Respiratory

• Match each intrinsic muscle of the larynx with its action on the vocal cord

o Thyroaretenoid=shortens
o Cricothyroid=elongates Function Innervation
o Posterior cricoarytenoid-=abducts
o Lateral cricoarytenoid=adducts Cricothyroid Elongates (tenses) true vocal cords SLN (external)
• The laryngeal musculature can be divided into the extrinsic and Thyroaretynoid Shortens (relaxes) true vocal cords RLN
intrinsic muscles Vocalis Shortens (relaxes) true focal cords RLN
o The intrinsic muscles control the movement of the
laryngeal cartilages and the vocal cords Posterior Cricoarytenoid Abducts vocal cords RLN
o The extrinsic muscles attach the larynx to the
Lateral Cricoarytenoid Adducts vocal cords and arytenoids RLN
surrounding anatomy and allow for movement of the
larynx within the neck.
Transverse Arytenoid Adducts arytenoids RLN
• Key Points to Remember Thyroepiglottic Open glottis RLN
o The true vocal cords attach anteriorly to the thyroid
Aryepiglottic Closes glottis RLN
cartilage and posteriorly to the arytenoids.
Oblique arytenoid Closes glottis RLN
o The cricothyroid muscle is the only intrinsic laryngeal
muscle that is innervated by the superior laryngeal
nerve (external branch). TIPS TO REMEMBER
§ Also a key component of the efferent limb of the
laryngospasm reflex!! • MUSCLES THAT TENSE AND RELAX THE VOCAL CORDS:
• We like to categorize the intrinsic laryngeal muscles according to their functions:
o Those that adjust the length of the vocal cords
o CricoThyroid: “Cords Tense”
o Those that abduct and adduct the vocal cords o ThyroaRytenoid: “ They Relax”
o Those that open and close the glottis • MUSCLES THAT ABDUCT AND ADDUCT THE VOCAL CORDS:
Four Nerves that innervate the Airway: o Posterior CricoArytenoid: “Please Come Apart”
o Lateral CricoArytenoid: “ Let’s Close Airway”
Recurrent laryngeal Nerve

• Left RLN courses underneath the aortic arch before it ascends the trachea towards the larynx • RLN Injury Either side:
• Causes of left RLN injury: PDA ligation, Left atrial enlargement secondary to mitral stenosis o External pressure from ETT
• Sensory innervation: below the vocal cordsàtrachea o External pressure from LMA
• Motor innervation: all intrinsic muscles except cricothyroid o Thyroid surgery
o Thyroaretynoid
o Parathyroid surgery
o Vocalis
o Neck stretching
o Posterior, lateral, transversecricoarytenoid
• RLN branches off vagus inside the thorax o Tumor
• The right RLN loops under subclavian artery, while left RLN loops under aortic arch. Both the ascend • RLN injury: Left Side Only
the tracheoesophageal groove to join the larynx. o PDA ligation
• The left RLN is more susceptible to injury due to location in thorax. o Left atrial enlargement (mitral stenosis)
• Clinical presentation o Aortic arch aneurysm
o Acute bilateral injury results in bilateral paralysis of the vocal cord abductors (posterior o Thoracic tumor
cricoarytenoid). Favors dangerous situation where the tensing action of cricothyroid
muscles act unopposed. Therefore, the patient with an acute injury to both RLN is at risk for stridor and respiratory depression.
o Unilateral injury results in paralysis of the ipsilateral vocal cord abductors. This
Trigeminal nerve (V)
does not cause respiratory distress
o Chronic injury is well tolerated and does not cause respiratory distress • V1: Ophthalmic (anterior ethmoidal)
Superior Laryngeal Nerve (internal and external branch) o Sensory: Nares and anterior 1/3 of nasal septum
• V2: Maxillary (sphenopalatine)
• SLN Internal branch: sensory nerve. Innervates underside of epiglottis up to (but not
o Sensory: tubrinates & septum
including) the vocal cords.
• SLN external branch: motor nerve. Innervates the cricothyroid muscles
• V3: Mandibular (lingual)
o Cricothyroid muscle is the “tuning fork” for the voice. Injury to the trunk of the o Sensory: anterior 2/3 of tongue
SLN or external branch causes hoarseness
o Most common cause of voice change following thyroidectomy: injury to SLN
external branch Glossopharyngeal nerve (IX)
• Branches off vagus n just beyond the jugular foramen at the skull base
• Sensory: soft palate, oropharynx, posterior 1/3 of
• At the level of the hyoid, it divides into the internal and external branches.
tongue, tonsils, vallecular, topside of epiglottis
• The internal branch penetrates the thyrohyoid membrane between the greater cornu of the
hyoid bone.
• *afferent limb of gag reflex
• The external branch enters the cricothyroid muscle.

1
3 Key Airway Blocks Laryngeal Structures
1. Glossopharyngeal o The adult larynx extends from C3-C6. It
2. Superior Laryngeal consists of bone, ligaments, and 9 cartilages (3
a. Below the border of the greater cornu of the hyoid bone. 1 outside thyrohyoid paired & 3 unpaired).
membrane. 2mL just beneath thyrohyoid membrane. o Anterior Ligaments
b. Aspiration of air=needle too deep! § Thyrohyoid ligament
3. Transtracheal § Cricothyroid ligament
a. Needle advanced in a caudal direction as it penetrates the cricothyroid o Unpaired artilages
membrane. After aspiration and before injection, patient should take a deep § Epiglottis
breath. During inspiration, 3-5mL of LA is injected. The patient will cough, § Thyroid
§ Cricoid
spraying the local up through the cords.
o Paired Cartilages
• Corniculate cartilage and cuneiform cartilages are actually what you mistake as the arytenoids
§ Corniculate
that are not seen during laryngoscopy. The cuneiforms are lateral to the corniculates.
§ Arytenoid
Laryngospasm & Larson’s Maneuver § Cuneiform
Risk Factors
• Laryngospasm is the sustained and involuntary contraction of the vocal cord
adductors that results in the inability to ventilate. This response often outlast the • Pre-Anesthetic
stimulus, and may result in complete airway obstruction, negative pressure o Active or recent URI (<2 wks)
pulmonary edema, gastric aspiration, cardiac arrest and death. It is more o Exposure to second hand smoke
o Reactive airway disease
common in children especially <1 year of age.
o GERD
o Result of stimulation of the internal branch of the SLN
o Age <1 year
• Signs of Laryngospasms • In the OR
o Inspiratory stridor o Light anesthesia with concurrent airway manipulation
o Suprasternal and supraclavicular retraction during inspiration o Saliva or blood in upper airway
o “rocking horse” appearance of chest wall o Hyperventilation
o increased diaphragmatic excursion o Hypocapnia
o lower rib flailing o Surgical procedures involving the airway
§ Tonsillectomy
• Factors that reduce the likelihood of laryngospasm
§ Adenoidectomy
o Avoidance of airway manipulation during light anesthesia
§ Nasal/sinus
o CPAP 5-10 mmHg during inhalation induction as well as immediately post
§ Laryngoscopy
extubation
§ Bronchoscopy
o Removal of pharyngeal secretions and blood prior to extubation
§ Palatal
o Tracheal extubation when deeply anesthetized or fully awake—not in-
between! Larson’s Maneuver—The laryngospasm Notch
o Laryngeal lidocaine (duration lasts ~30 min)
o IV lidocaine prior to extubation • First we’d like to point out that Larson’s maneuver is not a simple
o Hypercapnia/hypoventilation jaw thrust.
o PaO2<50mmHg • Larson’s maneuver is the application of firm pressure to the
• Treatment laryngospasm notch located just behind the earlobe. Pressure is
o It’s almost as though nature embedded a fail-safe mechanism wherby applied bilaterally towards the skull base.
hypercapnia and hypoxemia have a tendency to break laryngospasm. We do • This accomplishes two goals:
not recommend that you wait for nature to take its course. Instead, o 1. It displaces the mandible anteriorly to help open the
laryngospasm should be treated with the following interventions. airway
§ 1. FiO2 100% o 2. It often breaks laryngospasm by causing the lightly
§ 2. remove noxious stimulation anesthetized patient to sigh
§ 3. deepen anesthesia by increasing concentration of inhaled agent • Pressure should be applied for 3-5 seconds then released for 5-10
or with a small dose of propofol or lidocaine seconds. Repeat until relief of laryngospasm.
§ 4. CPAP 15-20 cm/H2O while instituting maneuvers that open the • Borders:
airway (head extension, chin lift, Larson’s maneuver) o Posterior—mastoid process
§ 5a. if IV access: succinylcholine 2 mg/kg (neonate and infant) or 1 Anterior—ramus of mandible
mg/kg (children or adult)
§ 5b. if no IV access: succinylcholine 5 mg/kg (neonate or infant) or 4 mg/kg (children or adult). Submental administration will produce the
fastest onset
§ 6. Children <5 years old should receive atropine 0.02mg/kg with succinylcholine.

Other Airway Maneuvers to Know

• Valsalva’s maneuver is exhalation against a closed glottis (or obstruction).

o Risk=increased pressure in the thorax, abdomen, and brain
• Muller’s maneuver is inhalation against a closed glottis (or obstruction).
o Risk=subatmospheric pressure in the thoraxànegative pressure pulmonary edema

2
• Upper Airway Anatomy
• The upper airway extends from the mouth and nares to the cricoid cartilage
• The primary functions of the upper airway include warming and humidifying During anesthesia, the upper airway can obstruct in three places:
inspired air, filtering particulate matter, and preventing aspiration. When the
• Soft palate: relaxation of the tensor palatine muscle
patient is intubated (bypassing the function of the upper airway), a heat and
moisture exchanger (HME) warms and humidifies inspired air, while the cuff on • Tongue: relaxation of the genioglossus muscle
the endotracheal tube protects against aspiration. • Epiglottis: relaxation of the hyoid muscles
• Upper Airway Patency
o During normal inspiration, diaphragmatic contraction and chest wall expansion create negative pressure to draw air into the lungs. What you should
appreciate is that the upper airway is also subjected to this negative pressure. In consequence, there is a tendency for the soft tissue in the upper
airway to collapse during anesthesia.
o You can think of the pharynx as a collapsible tube that lives inside a box. This box is formed by the borders of the surrounding anatomy such as the
tongue, soft palate, pharyngeal tissue, and cervical spine. Bone remains in a relatively fixed location, however the position of the soft tissue is
dynamic throughout the respiratory cycle.
• Factors that Impair Airway Patency
o Conditions that reduce the dimeter of the tube
§ Reduced pharyngeal dilator muscle tone Upper Airway Obstruction
§ Negative pressure during inspiration
• In the awake state, airway obstruction is prevented by 3 sets of dilator muscles
o Conditions that reduce the size of the box
o Muscle/Function
§ Increased soft tissue inside the box: obesity, large
§ Tensor palatine: opens the nasopharynx
tongue, hypertrophy of the tonsils and/or adenoids
§ Genioglossus: opens the oropharynx
§ Decreased size of the box: small craniofacial § Hyoid muscles: opens the hypopharynx
structures, craniofacial deformity

Lower Airway

• The lower airway begins at trachea and ends at the alveoli

• Let’s take a moment to introduce a powerful learning tool called the mind map. Instead of giving you a long list of facts about the lower airway, we’re going to
give you a mind map. The power of mind maps is that they convey a lot of information in a relatively small space. They’re also a great way to help you organize
your thoughts and make connection between interrelated concepts. You’re going to see a lot of these in the workbooks.
• Trachea:
o Begins at C6
o Ends at Tr-5 at the carina Alveoli:
o 2.5 cm wide o Humans have 300 million by age 9
o 10-13 cm long o Squamous epithelium
o cricoid is only complete ring o Pores of Kohn allow air movement between alveoli
o semi-circular rings open posteriorly
o ciliated columnar epithelium Pneumocytes:
o sensory innervation: vagus
o Type 1 cells are structural
o blood supply:
o Flat squamous cells
§ interior thyroida.
o Cover ~80% of alveolar surface
§ Superior thyroid a.
o Form tight junctions
§ Bronchial a.
o Type II cells produce surfactant
§ Internal thoracic a.
o Resistant to oxygen toxicity
• Carina:
o Capable of cell division
o T4-5
o Can produce type I cells
o Corresponds with angle of louis
o Type III cells are macrophages
o Ciliated columnar epithelium
o Fight lung infection
• Mainstem Bronchi
o Produce inflammatory response
o Right: 2.5 cm Long, 25 degree take off
o Neutrophils are present in the alveolus in smokers and with
o Left: 5 cm long, 45 degree take off
acute lung injury.
o Cuboidal epithelium Characteristics of Progressive Airway Division
• A Few Key Points
o The distance from the incisors to the larynx is ~13cm, and the distance from the larynx to the • Increased as the airway bifurcates:
carina is ~ 13cm. therefore, the distance from the incisors to the carina is ~26cm o Number of airways
o Neck flexion makes this distance shorter, while neck extension increases this distance (the tube o Cross sectional area
goes where the nose goes). o Muscular layer
o The right bronchus is 2.5cm in length and projects about ~ 25degrees from the long axis of the • Decreased as the airway bifurcates:
trachea, while the left bronchus is 5 cm in length and takes off at ~ 45 degrees o Airflow velocity
o This explains the greater likelihood for right mainstem intubation as well as aspiration of a o Amount of cartilage
foreign body to enter the right bronchus. o Goblet cells (produce mucos)
o In children up to 3 years of age, both bronchi take off 55 degrees from the long axis of the o Ciliated cells (clears mucus)
trachea.

Respiratory Physiology

3
 • Anatomic dead space begins in the mouth and ends in the terminal bronchioles.
o The airway is functionally divided into 3 zones: conducting, respiratory, transitional.
§ The conducting zone is anatomic dead space. This region extends from the nares and mouth to the terminal
bronchioles.
§ The respiratory zone is where gas exchange occurs. This region extends from the respiratory bronchioles to the
alveoli.

• Moving Air In and Out of the Lungs Conducting Zone Trachea

o Functional Divisions of the Airway Mainstem bronchi
§ The airway serves as a conduit to transfer gas between the Lobar bronchi
atmosphere and the blood. Small bronchi
§ Conducting Zone Bronchioles
• The conducting zone is anatomic dead space and Terminal bronchioles
does not participate in gas exchange. Respiratory Zone Respiratory bronchioles
Alveolar ducts
• Structures in the conducting zone include the
Alveolar sacs
mouth and nares and continue distally to the
Transitional Zone
terminal bronchioles.
• The terminal bronchioles are the last structure perfused by the bronchial circulation
§ Respiratory Zone
• The respiratory zone is where gas exchange takes place
• Gas exchange begins in the respiratory bronchioles.
• Gas exchange can only occur across the flat epithelium
§ Transitional Zone
• Some texts refer to the transitional zone as the portion of the airway that serves the dual function of
serving as an air conduit and an area where some gas exchange takes place.
• In this instance, the respiratory bronchioles and alveolar ducts would be considered part of the transitional
zone.
• Transferring Gas Between the Atmosphere and The Lungs
o Breathing is a process that creates cyclic pressure changes inside the thorax. This mechanism exchanges fresh gas in the upper
airway with alveolar gas in the distal airway. This serves 2 critical functions:
§ O2 is delivered to hemoglobin
§ CO2 is eliminated from the blood.
o For air movement (and gas exchange) to occur, the airways must remain patent; the pressure inside the airway must be greater
than the pressure outside of the airway. We can calculate this with the transpulmonary pressure equation.
Transpulmonary pressure= alveolar pressure – intrapleural pressure

o During tidal breathing:

§ Transpulmonary pressure is always positive (keeps airway open).
§ Intrapleural pressure is always negative (keeps lungs inflated).
§ Alveolar pressure becomes slightly negative during inspiration and slightly positive during expiration.
§ Note that there is no airflow at FRC (pre-inspiration) or at end-expiration.
o Aside from pathologic states, such as pneumothorax, the only time that intrapleural becomes positive is during a forced
expiration
Breathing Muscles

4
 o Inspiration
§ Contraction of the inspiratory muscles reduces thoracic pressure and increases thoracic volume. This is an example of
Boyle’s law.
§ The diaphragm and external intercostals contract during inspiration (tidal breathing).
• The diaphragm increases the superior-inferior dimension of the chest.
• The external intercostals increases the anterior-posterior diameter.
• Accessory muscles include the sternocleidomastoid and scalene muscles.
o Exhalation
§ Exhalation is usually passive; this process is driven by the recoil of the chest wall.
• Active exhalation is carried out by the abdominal musculature (rectus abdominis, transverse abdominis,
internal obliques, and external obliques).
• The internal intercostals serve a secondary role in active exhalation.
§ Exhalation becomes an active process when minute ventilation increases or in patients with lung disease, such as
COPD. A forced exhalation is required to cough and clear the airway of secretions. A vital capacity of at least 15 mL/kg
is required for an effective cough.
• Alveolar ventilation (NOT minute ventilation) determines the rate of removal of carbon dioxide from the body. Let’s examine why…
• Minute ventilation=tidal volume x respiratory rate
• Alveolar ventilation= (tidal volume – dead space) x Respiratory rate Which of the following is the primary
• The key here is to recognize that dead space doesn’t contribute to gas determinant of carbon dioxide elimination?
exchange, so only the fraction of the tidal volume that reaches the
respiratory zone contributes to gas exchange. o Tidal volume
o Respiratory rate
Ventilation
o Alveolar ventilation
• Ventilation is the process of exchanging gas between the atmosphere o Minute ventilation
and the lungs. This process supports two primary functions:
o 1. To acquire oxygen to support aerobic metabolism
o 2. To remove carbon dioxide- the waste product of aerobic metabolism
• a tidal volume (Vt) contains one volume of gas in the conducting zone and another in the respiratory zone.
o Gas that does not participate in gas exchange is called dead space (Vd).
o Vd is normally ~ 2mL/kg or 150 mL in a 70 kg patient.
o When the patient exhales, dead space gas is removed first.
o Any condition that increases Vd makes it more difficult to eliminate expiratory gases from the lungs.
o Increased Vd widens the PaCO2-EtCO2 gradient and causes CO2 retention.
• Minute Ventilation
o Minute ventilation (VE) is the amount of air in a single breath multiplied by the number of breaths per minute.
§ MV= Vt x RR or
o If a patient has a Vt of 500mL and a RR of 10 then his VE is: 500 x 10=5000ml/min
• Alveolar Ventilation
o Alveolar ventilation (VA) only measures the fraction of VE that is available for gas exchange. Said another way, it removes
anatomic dead space gas from the MV equation.
§ VA=(Vt – Vd) x RR
o Another way to conceptualize VA is to relate it to PaCO2
§ VA is directly proportional to carbon dioxide production
§ VA is inversely proportional to PaCO2
• VA=CO2 production/PaCO2
• CO2 production=VCO2
• Conditions that increase dead space tend to increase the volume of the conducting zone or reduce pulmonary blood flow:
o Hypotension reduces pulmonary blood flow, which increases alveolar dead space
o Atropine is a bronchodilator, so it increases anatomic dead space by increasing the volume of the conducting zone.
o Positive pressure ventilation increases alveolar pressure, which increases ventilation relative to perfusion. This is another
way of saying dead space increases.
o Dead space is reduced by anything that reduces the volume of the conducting zone or increases pulmonary blood flow
§ Examples: ETT, LMA, or neck flexion.

5
Dead Space & Vd/Vt

Dead Space (Vd) Definition Example

Anatomic Air confined to the conducting airways Nose/mouthàterminal bronchioles
Alveolar Alveoli that are ventilated but not perfused Reduced pulmonary blood flow (PE)
Physiologic Anatomic Vd + Alveolar Vd Variable
Apparatus Vd added by equipment Facemask, HME (heat moisture exchanger)

o Dead Space to Tidal Volume Ration (Vd/Vt)

§ Vd/Vt is the fraction of the tidal volume that contributes to dead space. It is affected by factors that alter dead space and the V/Q
relationship.
§ In the spontaneously ventilating patient, we assume dead space is 2 ml/kg or 150 mL in a 70kg patient. Therefore….
• Vd/Vt= 150 mL/450 mL=0.33
§ Mechanical ventilation increases alveolar pressure, which increases ventilation relative to perfusion. This explains why Vd/Vt
increases to 0.50 or 50%.
o Conditions that alter Vd
• Anything that increases the Vd/Vt ration increases dead space and by extension reduces alveolar ventilation. The most common
cause of increased Vd/Vt under general anesthesia is a reduction in cardiac output. If the EtCO2 acutely decreases, you should first
rule out hypotension before considering other causes of increased dead space.
• When thinking about Vd, consider how things change the volume of conducting airway relative to pulmonary blood flow. For
example:
o An LMA reduces V because it bypasses much of the anatomic Vd between the mouth to the glottis.
o Atropine increases Vd, because its bronchodilator action increases the volume of the conducting airway.
o Neck extension increases Vd, because it opens up the hypopharynx and increases its volume.

Causes of Increased Vd Causes of Decreased Vd

Airway Facemask Endotracheal tube
Heat and moisture exchanger (HME) LMA
Positive pressure ventilation Tracheostomy
Drugs Anticholinergics (bronchodilation)
Age Old age
Neck Position Extension Flexion
Pathophysiology Decreased cardiac output
Decreased pulmonary blood flow
COPD
Pulmonary embolus
• Thrombus
• Air
• Amniotic fluid
• Bone
Posture Sitting Supine
Head down positions
• If dead space increases, minute ventilation (RR, Vt or both) must increase to maintain a constant PaCO2. For example, if the Vd/Vt
ratio is 0.8-0.9 as a result of severe chronic bronchitis, then minute ventilation must increase to 30-50L/min in order to maintain a
normal PaCO2! Of course this is difficult task for even the healthiest lungs, but this explains why patients with chronic bronchitis
retain CO2.
• In the circle system, dead space begins at the y-piece. Anything proximal to the y-piece does not influence dead space nor does
increasing the length of the circuit. The only exception to this rule is an incompetent valve in the circle system. In this situation, the
entire limb with the faulty valve becomes apparatus dead space.

Bohr Equation

• Physiologic dead space can be calculated with the Bohr equation. This equation compares the partial pressure of carbon dioxide in the
blood vs the partial pressure of carbon dioxide in exhaled gas. The greater the difference between tehse values, the greater the amount
of dead space. Note that PeCO2 is not the same as end-tidal CO2, although EtCO2 may be used as a surrogate.
!" %&'(2 − %+'(2
=
!# %&'(2
• Many clinicians use the difference between PaCO2 and end-tidal CO2 as a gross estimation of dead space. This estimation does not
determine the cause of dead space, but only that dead space has changed.

6
Alveolar Compliance Curve

• In the textbook patient, ventilation is 4 L/min and perfusion is 5 L/min. this yields an overall V/Q ratio of 0.8
• Alveolar Perfusion
o Gravity and hydrostatic pressure affect the distribution of blood flow to the lung. When standing upright, there is less blood
flow towards the apex of the lung and there is more blood flow towards the base. This explains why there are higher V/Q ratios
towards the apex and lower V/Q ratios towards the base. An easy way to remember this is to think of tall person holding a
slinky. There is more air in between the rings towards the top, and this represents higher V/Q areas. There is less air in between
the spaces towards the bottom, and this represents low V/Q areas. As you’ll see in the next topic this explanation is a bit
simplified, but bear with us for now.
• Alveolar Ventilation
o Ventilation is a function of alveolar size and its position on the alveolar compliance curve.
§ The best ventilated alveoli are the most compliant. These smaller alveoli reside on the steep slope of the curve (note
the taller height of the red arrow near the bottom of the curve).
§ The poorest ventilated alveoli are the least compliant. These larger alveoli reside on the flat portion of the curve (note
the shorter height of the red arrow near the top of the curve).

Obviously, this relationship changes if the patient assumes the lateral decubitus position. In this position, the dependent lung receives the greatest
amount of ventilation and perfusion. Some of you will be asked to apply this information to the patient in the lateral decubitus position with a
double lumen endotracheal tube. Understand the relationships, and be able to apply this information.

Alveolar Surface Tension

• Law of Laplace
o Describes the relationship between
1. Pressure
2. Radius
3. Wall tension
• Surfactant
o Type II pneumocyte begin producing
surfactant between 22-26 weeks with peak production occurring at 35-36
weeks.
o Surfactant reduces alveolar surface tension and prevents alveolar collapse.
§ Each alveolus contains the same amount of surfactant.
§ Larger alveoli have a relatively smaller concentration of surfactant.
§ Small alveoli have a relatively larger concentration of surfactant.
o As the radius changes, the surface tension remains constant. This prevents
smaller alveoli from collapsing and emptying into larger alveoli.

7
Ventilation/Perfusion Mismatch

• V/Q Mismatch in Theory

o Before we delve into the West zones, it is important to understand that dead space and shunt rarely exist in the absolute form,
but rather ventilation and perfusion exist on a continuum. Most lung units have some degree of ventilation and some degree of
perfusion.

o It is the balance between ventilation and perfusion in each unit and throughout the
lung that determines the final partial pressures of oxygen and carbon dioxide in the
blood.
• V/Q Mismatch in Practice
o The image assumes the patient is in the sitting position
§ V and Q are perfectly matches where the lines intersect
§ Towards the apex: V>Q
§ Towards the base: V<Q
o Q can be replaced with pulmonary blood flow or cardiac output
o Position affects the V/Q relationship. Base could be replaced with the most dependent region, and apex could be replaced with
the least dependent region.
o Clinical Correlation
§ V/Q mismatch (specifically atelectasis) is the most common cause of hypoxemia in the PACU. As FRC becomes smaller
( the result of anesthesia and surgery), there is less radial traction to hold the airways open. The ultimate result is
atelectasis, right-to-left shunt, V/Q mismatch, and hypoxemia. Treatment includes humidified O2 and maneuvers
designed to reopen the airways (mobility, coughing, deep breathing, and incentive spirometry).
• Consequences of V/Q Mismatch
o Underventilated Alveoli
§ Blood passing through underventilated alveoli tends to retain CO2 and is unable to take in enough oxygen.
o Overventilated Alveoli
§ Blood passing through overventilated alveoli tends to give off an excessive amount of CO2. Remember that CO2
diffuses 20 times faster than oxygen.
§ Even though this blood can eliminate a large amount of CO2, it cannot take up a proportionate amount of O2. This is
explained by the flatness of the oxyhemoglobin dissociation curve. Once the PaO2 reaches 100mmHg, hemoglobin is
fully saturated and any additional oxygen that enters the blood must be dissolved in the blood (this is a very small
amount). Said another way, an alveolus can transfer much more CO2 than it can O2.
o Therefore…
§ A lung with V/Q mismatch eliminates CO2 from overventilated alveoli to compensate for the underventilated alveoli.
This is why the PACO2-PaCO2 gradient usually remains small with V/Q mismatch. CO2 retention indicates failure of
this compensation mechanism.
§ A lung with V/Q mismatch cannot absorb more oxygen from overventilated alveoli to compensate for underventilated
alveoli. This is why the PAO2-PaO2 gradient is usually large with V/Q mismatch.
• Compensation for V/Q Mismatch
o The body responds to these imbalances by attempting to match ventilation to perfusion.
§ To combat dead space (zone 1), the bronchioles constrict to minimize dead space.
§ To combat shunt (zone 3), hypoxic pulmonary vasoconstriction reduces pulmonary blood flow to minimize shunt.

8
West Zones

• In each alveolar unit, the ventilation to

perfusion ratio is determined by the
relative pressures between the:

1. Alveolus
2. Arterial capillary
3. Venous capillary
4. Interstitial Space

• Zone I= Dead space: PA > Pa > Pv

o There is ventilation, but there is no perfusion (V/Q=∞).
o This zone usually does not occur in normal lung.
o Zone 1 is increased by hypotension, pulmonary embolus, or excessive airway pressure.
o To combat zone 1, the bronchioles of unperfused alveoli constrict to reduce dead space.
• Zone II= Waterfall: Pa > PA > Pv
o There is ventilation and perfusion (V/Q=1)
o Think of a waterfall flowing over a dam, where Pa is the height of the upstream river and PA is the height of the dam. A greater
height of the upstream river translates into a higher rate of water flow over the dam.
o Like our waterfall analogy, blood flow is directly proportional to the difference of Pa-PA. The greater the difference between Pa-
PA, the greater the blood flow.
o Because the pulmonary capillary pressure and alveolar pressure change throughout the respiratory cycle, it is possible for a
zone II unit to transiently change to zone I or zone III.
• Zone III= Shunt: Pa > Pv > PA
o Blood flow is a function of the pulmonary arteriovenous pressure difference (Pa-Pv).
o In the absolute sense, shunt occurs when there is blood flow in the absence of ventilation (V/Q=0).
o Most zone III units are “shunt-like”-they are better perfused than they are ventilated (V<Q).
o To combat zone III, hypoxic pulmonary vasoconstriction reduces pulmonary blood flow to the underventilated units.
o Since the pressure in the capillary is always higher than the alveolus, the vessel is always open and blood is always moving
through it.
o This is why the tip of the pulmonary artery catheter should be placed in zone III.
o Not all shunt occurs in the lungs
o Anatomic shunt describes any venous blood that empties directly into the left side off the heart. Since this blood bypasses the
lungs, it never has the opportunity to saturate with oxygen. Sites of normal anatomic shunt include:
§ Thebesian veins (drain left heart)
§ Bronchiolar veins (drain bronchial circulation)
§ Pleural Veins (drain bronchial circulation)
o
• Zone IV= Pulmonary Edema: Pa > Pist > Pv > PA
o West later added zone IV to his schema.
o The pressure in the interstitial space exceeds the pressure in the pulmonary capillaries and the alveolus.
o Pulmonary edema is the classic example of zone IV. It occurs when the rate of fluid entry into the pulmonary interstitium
exceeds the rate of fluid removal by the lymphatic system.
o It is usually the result of 1 of 2 phenomena:
§ 1. Fluid is pushed across the capillary membrane by a significant increase in capillary hydrostatic pressure.
• Examples: fluid overload, mitral stenosis, and severe pulmonary vasoconstriction.
§ 2. Fluid is pulled across the capillary membrane by a profound reduction in pleural pressure.
• Examples: laryngospasm or inhalation against a closed glottis leading to negative pressure pulmonary
edema.

9
Alveolar Gas Equation

• The alveolar gas equation illustrates several very important points.

o 1. Hypoventilation can cause hypercarbia and hypoxemia.
o 2. Supplemental oxygen can easily reverse hypoxemia, however it does nothing to reverse hypercarbia.
o 3. Hypercarbia can go undetected in the patient breathing supplemental oxygen.
• The alveolar gas equation is used to determine the partial pressure of oxygen inside the alveolus. It tells us the maximal PAO2 that can be
achieved at a given FiO2. It also gives us a context for evaluating PaO2.
,-./0
Alveolar oxygen= FiO2 x (Pb-PH2O)-
12
o FiO2 Fraction of inspired oxygen
o Pb Barometric pressure
o PH2O humidity of inhaled gas (assumed to be 47mmHg)
o RQ respiratory quotient (assumed to be 0.8-detailed below)
• Understanding the Variables
o FiO2 is always higher than the partial pressure of oxygen in the alveolus (PAO2). This is because:
§ Inspired air becomes 100% humidified as it moves towards the alveoli. This water takes up space and dilutes the oxygen
concentration.
§ Furthermore, inspired air (lots of oxygen and no carbon dioxide) mixes with expired air ( a little oxygen and lots of carbon
dioxide). This dilutes the concentration of oxygen going towards the alveoli.
o As we can see from this equation, changes in FiO2, barometric pressure, PaCO2, or the respiratory quotient influence the final
concentration of oxygen in the alveolus.
§ For example, hypoventilation increases PaCO2. The increased PaCO2 competes with oxygen for space inside the alveolus and
dilutes the concentration of oxygen.
§ In this situation, supplemental oxygen can increase PAO2 as well as PaO2. You should understand that this only masks
hypoventilation and will not treat the cause.
• Calculation of Alveolar Oxygen
o Lets calculate the normal PAO2 then compare it to the patient in this question.
§ Normal PAO2
• 0.21 x (760-47) – 35/0.8 = 105.98 mmHg
§ This Patient’s PAO2
• 0.21 x (760-47) – 70/0.8 = 62.23 ~62
• Adding Supplemental Oxygen to this Patient
o This patient’s PaO2 is 60 mmHg, so he has a normal A-a gradient (more on this in the next question). If we increase the FiO2 to
40% then…
§ 0.40 x (760-47) – 70/0.8 = 197.7 mmHg
o By increasing the FiO2 to 40%, we fixed the hypoxemia but not the hypercarbia. The most appropriate intervention is to
increase his alveolar ventilation, which would remedy both the hypoxemia and hypercarbia.
• Respiratory Quotient (RQ)
.-3456 895:98; <358=>?956 0DDCE/C96
o Respiratory quotient= = = 0.8
5:@A;6 >56B=C<?956 0GD CE/C96
o An RQ>1 suggests lipogenesis. This occurs with overfeeding
o An RQ of 0.7 suggests lipolysis. This occurs with starvation.

A-a Gradient
• The A-a gradient is the difference between alveolar oxygen (PAO2) and arterial oxygen (PaO2). By relating partial pressure of oxygen inside the alveolus to
the partial pressure of oxygen in the arterial circulation , it helps us diagnose the cause of hypoxemia by indicating the amount of venous admixture.

Cause of Hypoxemia Explanation Fixed With Supplemental Oxygen

Normal A-a Gradient
Reduced FiO2 Not enough O2 in inspired gas Yes
Hypoventilation Inadequate air transfer in and out of lungs yes
Increased A-a Gradient
Diffusion Limitation Capillary thickening hinders O2 diffusion Yes
V/Q Mismatch Poor matching of V and Q Yes
Shunt Pulmonary blood bypasses alveoli No
With shunt there is no way for O2 to access the
pulmonary capillary. All of the other causes
allow O2 to transfer between the alveolus and
the pulmonary capillary.

10
 • When breathing room air, the normal A-a difference in less than 15 mmhg. The Thesbian, bronchiolar and pleural veins bypass the
alveolar-capillary interface and deliver doxygenated blood to the left heart. This accounts for a very small physiologic shunt.
• Let’s compare 2 hypothetical patients: one that has normal lungs and another that has V/Q mismatch.
o The healthy patient breathing room air has a PAO2 of 105 mmHg, PaO2 of 95 mmHg, and an A-a difference of 10 mmHg.
o The patient with V/Q mismatch has PAO2 of 313 mmHg, PaO2 of 95 mmHg, and a A-a difference of 218mmHg.
o This wide variation between PAO2 and PaO2 implies a significant degree of shunt, V/Q mismatch, or diffusion defect across the
alveolar capillary membrane.
• The A-a gradient is increased by:
o Aging (closing capacity increases relative to FRC)
o Vasodilators (decreased hypoxic pulmonary vasoconstriction)
o Right-to-left shunt (atelectasis, pneumonia, bronchial intubation, intracardiac defect)
o Diffusion limitation (alveolocapillary thickening hinders O2 diffusion)
• Sample Calculation
A-a Gradient= PAO2 – PaO2
§ PAO2=0.5 x (760mmHg – 46mmHg) 35/0.8=312.75mmHg
§ A-a gradient= 312.75 – 95= 217.75 if we round up =218mmHg
• Estimation of % Shunt
o Shunt increases 1% for every 20 mmHg of A-a gradient
o In our example, the A-a gradient is 218mmHg, so this roughly tanslates into a shunt of 11% (218/20=11)
Lung Volumes & Capacities

• The quantity of gas in the lungs can be divided into 4 volumes and 4 capacities. Each capacity consists of 2 or more volumes.

• The referenced values are from Nagelhout for a healthy 70 kg male. Some of these numbers are slightly different in Stoelting as well as
just about any other text you read. If you memorize the numbers we provided for you and are able to apply these, you’ll be good to go.
• Key Facts
o Tidal volume is 6-8 ml/kg
o Vital Capacity is 60-70 ml/kg
o Functional residual capacity is 35 ml/kg
o Lung volumes are ~25% smaller in females
o Lung volumes tend to change with body position—they are larger when sitting and smaller when supine
o Obstructive lung disease tends to cause air trapping. Patients with asthma, emphysema, and bronchitis have an increased
residual volume and total lung capacity.
o Spirometry cannot measure residual volume, therefore it also can’t measure total lung capacity or functional residual capacity.
These are drawn in blue in the image.
o Closing volume and capacity are dynamic measurements that assess small airway closure. They also can’t be measured with
spirometry.

11
Functional Residual Capacity

FRC=RV + ERV=35ml/kg
FRC is the volume of air in the lungs at end-expiration.
At FRC, the inward elastic recoil of the lungs is balanced by the outward elastic recoil of the chest wall—this is called static equilibrium.
Diaphragmatic tone and position also affects FRC.

FRC is the reservoir of oxygen that prevents hypoxemia during apnea.

• How to measure FRC

o FRC can be measured indirectly by: nitrogen washout, helium wash in, or body plethysmography.
o Since the RV cannot be exhaled and RV is a component of the FRC, spirometry cannot measure FRC>
• Factors that Alter FRC
o Conditions that reduce FRC have several things in common. They tend to reduce outward lung expansion and or reduce lung
compliance. When FRC is reduced, intrapulmonary shunt (zone 3) increases. PEEP acts to restore FRC by reducing zone III.

12
Closing Volume & Capacity

• As a person exhales, there is a point where pleural pressure exceeds airway pressure. This external force collapses the small airways that
lack cartilage and traps gas distally in the alveoli. Since pleural pressure is higher in the dependent region of the lung, the airways in this
region close first.
• Closing Volume is the point at which dynamic compression of the airways begins. Said another way, it is the volume above residual
volume where the small airways begin to close during expiration.
• Closing Capacity is the sum of closing volume and residual volume (CC=Closing volume + Residual volume)
• Factors that Affect Closing Volume & Capacity
o While CV is very important, the relationship between FRC and closing capacity is of much greater importance.
§ Under normal circumstances, the FRC is greater than CC.
§ When CC is greater than FRC, airway closure occurs during tidal breathing. This contributes to intrapulmonary
shunting and hypoxemia.
§ Anything that decreases FRC relative to CC or anything that increases CC relative to FRC will convert normal V/Q units
to low V/W units or shunt units.
§ PEEP can reverse this process by increasing the FRC relative to CC.

Factors that Increase Closing Volume

COPD
Left ventricular failure
Obesity
Smoking
Extreme age
Pregnancy

Mnemonic: CLOSE-P
§ In a young, healthy patient airway closure occurs just above residual volume. As we age, pleural pressure becomes
progressively higher such that the small airways begin to close sooner and at higher lung volumes. This explains the
progressive reduction in PaO2 that occurs with aging.

§ By age 30, CC ~ FRC when under general anesthesia

§ By age 44, CC ~ FRC when supine
§ By age 66, CC ~ FRC when standing

o How to Measure Closing Volume & Closing Capacity

§ Spirometry can’t measure closing volume and closing capacity ( it doesn’t measure residual volume), so you won’t be
able to identify these values with the traditional spirometer diagram that you reviewed in the last two questions.
§ Closing capacity is best measured by washout tracer gas, such as nitrogen or xenon-133. This gas is inhaled at residual
volume and the measurement is taken as the patient exhales from TLC.

13
OXYGEN CONTENT, DELIVERY & CONSUMPTION

• Oxygen Content (CaO2)

o Oxygen content is a measure of how much oxygen is present in 1 deciliter of blood. After oxygen diffuses through the alveolar
capillary membrane, it is transported by the blood in 2 ways:
§ 1. Dissolves in the plasma (3%)
§ 2. Reversibly binds with hemoglobin (97%)

CaO2 = (1.34 x Hgb x SaO2) + (PaO2 x 0.003)=20ml O2dL

o 1. Oxygen dissolved in the plasma
§ Dissolved O2 is measured by PaO2
• PaO2 should be used to determine gas exchange in the lungs and not as a measure of oxygen content in the
blood.
§ Oxygen dissolves in the plasma according to Henry’s law.
• This law states that the concentration of gas in a solution is difrectly proportional to the partial pressure of
the gas above the solution.
• The solubility coefficient for oxygen is 0.003ml/dl/mmHg
• Oxygen is 20 times less soluble than CO2
o 2. Oxygen Bound to Hemoglobin
§ Most of the oxygen contained in the blood forms a reversible bond to hemoglobin. The oxyhemoglobin dissociation
curve describes the characteristics of this bond.
§ Each gram ofhemoglobin can carry 1.39mL of molecular oxygen. Hemoglobin usually contains a small amount of
methemoglobin and carboxyhemoglobin, so you’ll often see 1.34 or 1.32 used instead.
§ Normal Hgb and Hct values:
• Male: 15 g/dL and 45%
• Female: 13 g/dL and 39%
• Oxygen Delivery (DO2)
o Again, CaO2 only tells us how much O2 is dissolved in the blood
o DO2 tells us how fast a quantity of O2 is delivered to the tissues.

DO2=CaO2 x CO x 10= ~ 1000mL O2/min

o Incorporating cardiac output in the equation gives us the “how fast.” Since hemoglobin is measured as g/dL and cardiac output
is measured as L/min, we need to convert all of the units to liters. The nuber 10 is a conversion factor that this equation
accomplishes this goal.
• Oxygen Consumption (VO2)
o We can use the Fick principal to calculate oxygen consumption. It assumes the VO2 is the difference between the amount of O2
that leaves the lungs and the amount of O2 that returns to the lungs. The difference between these values is the amount of O2
that was consumed by the body.
§ VO2= CO x (CaO2-CvO2)
o Numbers you must know:
§ VO2=3.5mL/kg/min
§ VO2 ~250 mL/min (assumes 70 kg male)

14
Oxyhemoglobin Dissociation Curve

o
o The oxyhemoglobin dissociation curve tells us the tendency of hemoglobin to bind oxygen. As you review this curve, we want
you to focus on several things:
§ 1. The P50 is the PaO2 where Hgb is 50% saturated by oxygen. A lower P50 reflects a left shift, and a higher P50
reflects a right shift.
§ 2. Maximum O2 loading occurs at a PaO2 of ~100mmHg. A PaO2 above this cannot improve O2 loading, but it does
increase the amount of O2 that is dissolved in the plasma.
§ 3. Many of the conditions that shift the curve are related to metabolic rate. Tissues with a high metabolic rate
consume more O2 and produce more CO2, hydrogen ions, and heat. This causes a right shift (right=rise in temp, 2,3-
DPG, CO2 and H+).
§ Most hemoglobinopathies cause a left shift.
o Bohr Effect
§ CO2 and hydrogen ions cause a conformational change in the hemoglobin molecule; this facilitates the release of
oxygen. Said another way, CO2 and H+ cause Hgb to release oxygen.
o Where does 2,3-DPG come from and why is it important?
§ 2,3 DPG is produced during RBC glycolysis (the Rapoport-Leubering shunt)
§ It maintains the curve in a slightly right shifted position at all times.
§ Hgb F doesn’t produce 2,3-DPG, which explains why it has a left shift (P50=19mmHg)
§ Hypoxia increases 2,3-DPG production. This facilitates O2 offloading.
§ 2,3DPG is an important compensation mechanism during chronic anemia.
§ In banked blood, the concentration of 2,3-DPG falls. This shifts the oxyhemoglobin dissociation curve to the left and
reduces the amount of O2 available at the tissue level.
Cellular Energetics

• You’ve learned how we get oxygen to the cells, but this is only half the story. Next we must review how the
cell consumes oxygen. To accomplish this goal, we’re going to give you a bird’s eye view of how the cell
produces ATP.
• ATP as “Energy Currency”
o Adenosine triphosphate (ATP) is the energy currency in the body.
§ It is produced by oxidation of proteins, carbohydrates, and fats (ADP + PiàATP).
§ It is consumed by reactions necessary for life (ATPàADP + Pi).
§ The phosphate bond is a high energy bond.
§ ATP can’t be stored, so the supply must be continuously replenished.
o Glucose is the primary substrate use for ATP synthesis.
o Aerobic metabolism produces much more ATP than anaerobic metabolism
o There are 3 key processes involved in aerobic glucose metabolism:
§ 1. Glycolysis
§ 2. Krebs cycle
§ 3. Electron transport

15
 §
• Glycolysis (Glucose àPyruvic Acid)
o The primary goal of glycolysis is to convert 1 glucose to 2 pyruvic acid molecules. The fate of pyruvic acid depends on whether
or not oxygen is available.
§ In the absence of oxygen, pyruvic acid is converted to lactate in the cytoplasm.
§ If oxygen is available, pyruvic acid is transported into mitochondria.
Net Gain: 2 ATP

o Next, 2 molecules of pyruvic acid are converted into 2 molecules of Acetyl Coenzyme A.
o 2, 3 DPG is produced in the Rapoport-Luebering shunt about half way through glycolysis. The more glucose molecules that go
through glycolysis, the more 2,3 DPG is produced.
• Krebs Cycle (Citric Acid Cycle)
o Krebs cycles tatkes place in the matrix of the mitochondria.
o The reaction begins when oxaloacetic acid and Aetyl coenzyme A react to produce citric acid.
o The reaction ends with the production of oxaloacetic acid (which is reused at the beginning of the next cycle) and NADH.
o The primary goal of this reaction is to produce a large quantity of H+ ions in the form of NADH. These are used in electron
transport.
o Products of protein and lipid metabolism can also enter Krebs cycle.

Net Gain: 2 ATP

• Oxidative Phosphorylation
o The primary goals of glycolysis and Krebs cycle is to liberate hydrogen from glucose. Up to this point, there has only been a net
gain of 4 molecules of ATP for 1 molecule of glucose so we haven’t produced very much ATP…yet…
§ NADH is split into NAD+, H+ and 2 electrons
§ The electrons are fed into the chemiosmotic mechanism. A proton gradient is generated across a membrane, which
drives ATP synthesis with the help of ATP synthase.
§ Oxygen serves as the final electron acceptor.
§ The end products of oxidative phosphorylation are CO2, water, and 34 ATP molecules.
§ ATP is used to carry out energy dependent processes in the body.
§ CO2 is removed from the body by alveolar ventilation.
NET GAIN: 34 ATP

• Lactic Acid Pathway

o Remember that oxygen is the final electron acceptor in electron transport, so if there is no oxygen, this reaction backs up. Since
pyruvic acid isn’t used, its concertation increases. The lactic acid pathway provides an alternative mechanism to convert pyruvic
acid to ATP, albeit a very small amount of it—just 2 molecules. In addition to producing less ATP, there is also another
problem—lactic acid is the end product of this pathway. So the lactic acid pathway doesn’t back up, lactate is released into the
extracellular space and the circulation. IF oxygenation isn’t restored, complications of lactic acidosis ensue.
§ The accumulation of lactic acid creates a lactic acidosis, which is an anion gap metabolic acidosis.
§ The body’s enzymes tend not to function properly in an acidic environment and serves as the basis of the altered
homeostasis during times of acidosis.
§ When the oxygen supply is re-established, intracellular lactate is converted back to pyruvic acid inside the cell and
aerobic metabolism starts again. Serum lactate is cleared primarily by the liver.

16
Carbon Dioxide Transport

• Carbon dioxide is the primary by-product of aerobic metabolism. Venosu blood tranpsorts it to the lungs, where it’s excreted into the
atmosphere.
• PvCO2 is about 5 mmHg higher than PaCO2, which explains why venous blood is more acidic

o Arterial pH=7.40 Method of Transport % Total Venous CO2

o Venous pH=7.36 Bicarbonate 70
• Mechanisms of CO2 Transport Bound to Hemoglobin 23
o 1. Bicarbonate: (70%) Dissolved in the Plasma 7
§ The vast majority of CO2 in the blood is in the form of bicarbonate. Recall that:

§ Carbonic anhydrase in erythrocytes is required for this reaction to take place.

• CO2 diffuses from the cells into the venous circulation and then diffuses into erythrocytes.
• Carbonic anhydrase is present in the erythrocyte but not in the plasma.
• In the presence of carbonic anhydrase, CO2 and H2O react to form carbonic acid or H2CO3.
• Carbonic acid rapidly dissociates into H+ and HCO3-.
• The H+ is buffered by hemoglobin and the HCO3- is transported to the plasma to function as a buffer.
• Cl- is transported into the erythrocyte to maintain electroneutrality. This is known as the chloride or
Hamburger shift.
• In the lungs, the chloride shift operates in reverse as CO2 is excreted from the body.

• Notice that the chloride shift adds osmotically active ions to the erythrocyte in the venous circulation.
Water follows isosmotically, causing the erythrocyte to swell. This increases cell volume relative to plasma
volume and explains why venous hematocrit is ~3% higher than arterial hematocrit. This process is reversed
in the lungs.
§ 2. Bound to Hemoglobin: (23%)
• Carbon dioxide binds with amino groups on hemoglobin as well as other plasma proteins.
o R-NH2 + CO2 <-> RNH – CO2- + H+
§ 3. Dissolved in the Plasma: (7%)
• Dissolved CO2 has a solubility coefficient of 0.067 mL/dL/mmHg. When compared to oxygen, CO2 is 20
times more soluble in the blood.
o Solubility is a function of Henry’s law.

17
The Haldane Effect & CO2 Dissociation Curve
• Don’t Confuse the Bohr Effect with the Haldane Effect!
o The Bohr effect describes oxygen carriage. It says that Co2 and decreased pH cause the erythrocyte to release oxygen.
o The Haldane is just the opposite. It describes CO2 carriage. It says that oxygen causes the erythrocyte to release CO2.
• Said Another way, the Haldane effect states that deoxygenated hemoglobin is able to
carry more CO2.

• CO2 Dissociation Curve

o Carbon dioxide has its own dissociation curve. And just like before, left is love and right is release.
o In the presence of oxygenated hemoglobin, the CO2 dissociation curve shifts to the right.
§ Hemoglobin has a decreased affinity for CO2.
§ This occurs in the lungs to facilitate unloading of CO2 to allow it to be excreted from the body.
o In the presence of deoxygenated hemoglobin, the CO2 dissociation curve shifts to the left.
§ Hemoglobin has an increased affinity for CO2.
§ This occurs in the systemic capillaries to facilitate the loading and subsequent transport of carbon dioxide.

Hypercapnia
./0 ,358=>?956
• Hypercapnia= PaCO2 >45 mmHg %&'(2 =
KEL;5E-3 M;6?9E-?956
• Consequences of Hypercapnia

Hypoxemia Remember the alveolar gas equation?

• Alveolar nitrogen is inert—its concentration remains constant
• Increased alveolar CO2 displaces alveolar O2àarterial hypoxemia
Increased P50 Curve shifts to the right—releases more O2 to tissues
• Partially compensates for hypoxemia
Cardiac & Smooth Muscle Depression Acidosis inside the muscle affects contractile protein and enzymatic function
• Myocardial depression
• Vasodilation
SNS Stimulation CO2 activates the SNS and increases catecholamine release
• Unless acidosis is severe. SNS stimulation offsets cardiac and smooth muscle depression)
• Tachycardiaàincrease myocardial O2 consumption & decrease myocardial O2 delivery
• Vasoconstrictionàincrease SVRàincrease myocardial O2 consumption
• Dysrhythmias
• Prolonged QT interval
• Oculocardiac reflex is more common following precipitating events
Increased Alveolar Ventilation CO2 is a respiratory stimulantàincreased minute ventilation
Increased (K+) Activates H+/K+ pump
• Buffers CO2 acid in exchange for releasing K+ into the plasma
Increased (Ca2+) Ionized Calcium competes with H+ for binding sites on plasma proteins
• Acidosisàplasma proteins buffer H+ and release Ca+2àincreased inotropy
• Alkalosisàplasma proteins release H+ and bind Ca+2àdecreased inotropy
Increased ICP CO2 freely diffuses across the BBB
• Decreased CSF pHà decreased cerebrovascular resistanceàincreased CBF and volume
Depression LOC CO2 narcosis when PaCO2 >90 mmHg
• Hypercarbia has the opposite effect on pulmonary blood vessels than in the peripheral circulation. In the lungs, CO2 is a direct acting vasoconstrictor,
where it can cause pulmonary hypertension and increase the right ventricular workload.
• Effect on Blood pH
o During respiratory acidosis, the kidneys excrete hydrogen and conserve bicarbonate to return pH to normal. This process begins within hours
but may require several days for full compensation to occur.

PaCO2 pH
Acute Respiratory Acidosis Increases 10 mmHg Decreases 0.08
Chronic Respiratory Acidosis Increases 10 mmHg Decreases 0.03 (renal HCO3- retention)
o You should be able to predict the pH or PaCO2 given a change in the other variable.

18
CO2 Ventilatory Response Curve

• The carbon dioxide ventilatory response curve describes the relationship between PaCO2 and minute ventilation.
o Chemoreceptors in the medulla (central) and the carotid bodies and transverse aortic arch (peripheral) monitor PaCO2
o The slope of the curve represents sensitivity of the entire respiratory apparatus to PaCO2
o When PaCO2 is between 20-80 mmHg, minute ventilation increases with PaCO2 in a linear fashion.
o Carbon dioxide is a respiratory depressant when PaCO2 exceeds 80-100 mmHg
o MAC of CO2 is 200 mmHg

o A left shift and increased slope indicates that Ve is higher than expected for a given PaCO2. This creates a respiratory alkalosis.
o A right shift and decreased slope indicates that Ve is lower than expected for a given PaCO2. This creates a respiratory acidosis.
• Apneic Threshold
o The apneic threshold is the highest PaCO2 at which a person will not breathe. Once the PaCO2 exceeds the apneic threshold,
the patient will begin to breathe.
o A left shift implies that the apneic threshold has decreased.
o A right shift implies that the apneic threshold has increased.
Control of Ventilation: Neural Control

• Alveolar ventilation and consequently the respiratory rate and pattern are determined by:
o 1. Neural control in the respiratory center – medulla
o 2. Chemical control in the central chemoreceptors – medulla
o 3. Chemical control in the peripheral chemoreceptors – carotid bodies and aortic arch
o 4. Baroreceptors – lungs
• We will elaborate on each of these over the next
several questions
• Think of breathing as a reflex arc that contains
sensors, afferent pathways, a control center, efferent
pathways, and effector organs.
• The respiratory center receives afferent input from
the central and peripheral chemoreceptors as well as
stretch receptors in the lungs. The respiratory center
integrates the incoming signals with its intrinsic
respiratory pattern and sends a coordinated response
via efferent pathways terminating in the diaphragm,
intercostals, and accessory muscles. The cerebral
cortex can modify these responses. The net result is a
mechanism that maintains PaCO2 and PaO2 within a
very narrow range.

19
Respiratory Center

• The respiratory center is located in the reticular activating system in the medulla and the pons. There are 4 key parts.

Control of Ventilation: Central Chemoreceptors

• The central chemoreceptors are located just a few microns below the surface of the anterolateral aspect of the medulla. This region
sends stimulatory impulses to the dorsal respiratory center.
o Central chemoreceptor primarily responds to PaCO2
o Peripheral chemoreceptors primarily respond to PaO2
• Volatile Acids and the Central Chemoreceptors
o The blood-brain-barrier is a highly selective barrier that separates the blood from the CSF. Some gases and lipid soluble
molecules freely diffused across the BBB, while ions, glucose, and amino acids are carried via active transport mechanisms.
§ CO2 freely diffuses through the BBB
§ H+ and HCO3-do not diffuse through the BBB
o Just like it does inside the erythrocyte, CO2 reacts with carbonic anhydrase and
dissociates into H+ and HCO-
§ The hydrogen ion concentration in the CSF is the most important
stimulus for the central chemoreceptor.
§ H+ drives the respiratory pacemaker in the dorsal respiratory center
§ As H+ rises, the rate and depth of respiration increases until a new
steady state for Ve is achieved.
§ An acute rise in PaCo2 à increase [H+] in the CSF and increases Ve.
§ An acute decline in PaCO2à decrease [H+] in the CSF and decreases Ve.
§ These changes occur within minutes and provide precise control of blood gas tensions.
• Non-Volatile Acids and the Central Chemoreceptor
o Non-volatile acids do not pass through the BBB. Because of this, they don’t influence Ve on a short term basis, however they do
influence Ve on a longer term basis.
• Bicarbonate and the Central Chemoreceptor
o HCO3- equilibrates between the blood and the CSF – this process begins after a few hours and peaks at ~ 2 days. Therefore, the
effect of hyperventilation on PaCO2 is limited to this window of time. After equilibration occurs, the pH of the CSF is restored to
normal (pH 7.32) as a result of active transport of HCO3- from the plasma to the CSF>
• Response to Excessive Hypercarbia and Hypoxemia
o The central chemoreceptor is stimulated by hypercarbia and hyoxemia, however it is depressed by profound hypercarbia and
hypoxemia.

20
Control of Ventilation: Peripheral Chemoreceptors

• The peripheral chemoreceptors are located in the carotid body at the bifurcation of the carotid artery. The transverse aortic arch also
contains chemoreceptors but its primary job is to monitor arterial blood pressure.
• The chief responsibility of the carotid body is to monitor hypoxemia (PaO2 <60 mmHg)
o They do not respond to SaO2 or CaO2
o Secondary responsibilities including monitoring PaCO2, H+, perfusion pressure.
• Response to Hypoxemia: The Hypoxic Ventilatory Response
o 1. PaO2 <60 mmHg closes the oxygen-sensitive K+ channels in Type I Glomus cells.
o 2. This raises resting membrane potential, opens Ca+2 channels, and increases neurotransmitter release (Ach and ATP)
o 3. An action potential is propagated along Hering’s nerve then along the glossopharyngeal nerve (CN IX).
o 4. The afferent pathway terminates in the inspiratory center in the medulla
o 5. Minute ventilation increases to restore PaO2.
• Conditions that Impair the Hypoxic Ventilatory Response
o Carotid endarterectomy severs the afferent limb of the hypoxic ventilatory response. This is why we don’t do bilateral CEA
simultaneously or very close to each other, it takes time for the body to recalibrate.
o Sub-anesthetic doses of inhalation and intravenous anesthetics (0.1 MAC) depress the hypoxic ventilatory drive, so
postoperative hypoxia is not always countered by a reflexive increase in minute ventilation. In addition, volatile anesthetics
impair diaphragmatic, intercostal, and upper airway muscle function.
• Conditions that DO NOT Impair the Hypoxic Ventilatory Response
o Even though CaO2 is reduced with anemia as well as carbon monoxide poisoning, the PaO2 is usually normal. This explains why
these conditions do not stimulate the hypoxic ventilatory response.

Pulmonary Reflexes
• Control of respiration is also influenced by sensors in the lung. Stretch receptors in the smooth
airway muscle transduce pressure conditions inside the airway. They transmit this information
along the vagus nerves (CN X) to the dorsal respiratory center (respiratory pacemaker).
• Hering-Breuer Inflation Reflex
o It provides a similar function as the pneumotaxic center, albeit by a different
mechanism.
o When lung inflation is >1.5 L above FRC (x3 normal Vt), this reflex “turns off” the
dorsal respiratory center. Said another way, it stops further inspiration.
o This reflex is not active during normal inspiration.
• Hering-Breuer Deflation Reflex
o This reflex is just the opposite. When lung volume is too small, this reflex helps
prevent atelectasis by stimulating the patient to take a deep breath.
• J Receptors (Pulmonary C fiber receptors)
o J receptor stimulation causes tachypnea. These receptors are activated by pulmonary
embolism or during pulmonary vascular congestion, such as CHF>
• Pardoxical Reflex of Head
o The paradoxical reflex of Head causes a newborn baby to take her first breath.

Hypoxic Pulmonary Vasoconstriction

• Hypoxic pulmonary vasoconstriction (HPV) is a local reaction that occurs in response to a reduction in alveolar oxygen tension (not arterial PO2).
o The pulmonary vascular bed is the only region in the body that responds to hypoxica with vasoconstriction.
o HPV selectively increase the pulmonary vascular resistance in poorly ventilated areas in an effort to minimize shutn flow to these regions. The
response begins within seconds and achieves its full effect in about 15 minutes.
o HPV is a protective mechanism that minimizes shunt flow during atelectsasis or one-lung ventilation.
• Factors that Impair HPV
o Drugs:
§ Voltatile anesthetics >1.5 MAC reduce the effectiveness of HPV (some texts say 1 MAC)
§ IV anesthetics do NOT affect HPV. Ketamine, propofol, fentanyl, etc. will not increase shunt.
§ Vasodilators, phosphodiesterase inhibitors, dobutamine, and some calcium channel blockers increase shunt flow by inhibiting HPV.
§ Vasoconstrictive drugs such as phenylephrine, epinephrine, and dopamine may constrict well oxygenated vessels and increase shunt
flow.
o Altered Physiology
§ Hypervolemia (LAP >25 mmHg) and elevated cardiac output may distend constricted vessels and increase shunt flow, although
hypovolemia may cause pulmonary vasoconstriction to well ventilated alveolar units. Therefore, euvolemia is best.
§ Excessive PEEP or high tidal volumes increase dead space (zone 1) and reduce optimal V/Q matching.

21
Control of Airway Diameter

• There are 3 systems that maintain airway caliber. An imbalance in any of these pathways alter airway diameter accordingly. Learning this
physiology is essential for understanding the basis of pharmacologic management for pulmonary diseases.
§ Airway diameter determines airway resistance
o Smooth muscle relaxationàincreases airway diameteràdecreases airway resistanceàimproves air flow
o Smooth muscle contractionàdecreases airway diameteràincreases airway resistanceàreduces air flow

• Bronchodilation
o Circulating Catecholamines
§ Although beta-2 receptors are well represented in airway smooth muscle, there are no sympathetic nerve endings here.
§ Instead, these receptors are activated by catecholamines circulating in the systemic circulation.
§ The Beta-2 receptor is coupled to a Gs protein. Activation of the beta-2 receptor turns on the Gs protein, and this activates
adenylate cyclase.
§ Adenylate cyclase activates cAMP. This is a second messenger.
§ Along with protein kinase A, cAMP reduces Ca+2 release from the sarcoplasmic reticulum.
§ In turn, this reduces smooth muscle contraction and promotes bronchodilation.
§ This pathway is turned off when phosphodiesterase 3 deactives cAMP by converting it to AMP.
o Nitric Oxide
§ NO is a potent smooth muscle relaxant
§ Non-cholinergic PNS nerves release vasoactive intestinal peptide onto airway smooth muscle.
§ This increases NO production.
§ NO stimulates cGMP, which fosters smooth muscle relaxation and bronchodilation
• Bronchoconstriction
o Parasympathetic Nervous System
§ The vagus n (CN X) supplies parasympathetic innervation to airway smooth muscle
§ Cholinergic nerve endings release Ach on to muscarinic-3
§ The M3 receptor is coupled to a Gq protein. M3 receptor activation turns on the Gq protein, and this activates phospholipase C
(PLC).
§ PLC activates inositol triphosphate (IP3). This is the second messenger.
§ IP3 stimulates Ca+2 release from the sarcoplasmic reticulum
§ Increased iCa+2 activates myosin light chain kinase, and this enzyme enables the contractile mechanismàbronchoconstriction.
§ This pathway is turned off when IP3 phosphatase deactivates IP3 to IP2.
o Other Mediators of Bronchoconstriction
§ Mast cells are highly concentrated in smooth airway epithelium. Coughing, allergy or infection activate igE, cytokines, and
complement, which in turn amplify the inflammatory response.
§ Non-Cholinergic c-fibers release chemicals that promote bronchoconstriction.

22
Pulmonary Pharmacology

• A solid understanding of the airway physiology covered on the last page should help this material fall into place.
o The drugs in red block the step that comes after it.
o The drugs in green potentiate the step that comes after it.

• The Drugs
o Pulmonary medications can be broken down into direct acting bronchodilators, anti-inflammatories, and methylxanthines.

23
Pulmonary Function Testing

• Pulmonary function test measure:

o Static Lung Volumes - how much air the lungs can hold at a single point in time.
o Dynamic Lung Volumes – How quickly air can be moved in and out of the lungs over time
o Diffusing Capacity – How well the lungs can transfer oxygen in and carbon dioxide out.
• Spirometry—Static Lung Volumes
o The static lung volumes are the 4 lung volumes and 4 lung capacities that we
discussed in the pulmonary physiology tutorial. These measure how much air
the lungs can hold at a single point in time.
• Spirometry—Dynamic Lung Volumes
o Dynamic means movement, so dynamic lung volumes measure airflow over
time. They provide an assessment of airway resistance and lung recoil. These measure how quickly air can be moved in and out
of the lung.
o Here is a list of the most clinically useful spirometric tests of airflow.
Dynamic Volumes—Tests of Airflow Normal Value

• Diffusing Capacity

Flow-Volume Loops

• Flow-volume loops allow us to differentiate between obstructive and restrictive respiratory diseases.
• Events Occurring on the Flow-Volume Loop
o 1. The patient inhales form residual volume to total lung capacity.
o 2. Then the patient exhales back to residual volume as fast as possible.
• We want to note several important things about the loop.
o Flow is zero at the line that transverse the loop.
o Flow occurs during inspiration (it moves away from 0).
o Flow becomes zero at end inspiration.
o Flow occurs during expiration (it moves away from 0).
o Flow is zero at end expiration.
o Volume becomes more positive from right to left
o RV is greater than zero, so the loop never gets to true zero.
o TLC is the max volume the lungs can hold.
o VC is the width of the loop.
• RV cannot be measured with spirometry. This is illustrated by the fact that the loop never reaches true zero. We included true zero on
the graph, so you can get a better understanding of the position of the loop relative to the lung volumes listed on the x-axis.

24
Postoperative Pulmonary Complications

• First let’s determine who is at risk, then we’ll consider strategies to reduce this risk during the perioperative period.
• Independent risk f actors for postoperative pulmonary complications can be categorized as patient related, procedure related, and
laboratory testing. Remember that an independent risk factor is statistically significant when adjusted for other known risk factors.

Patient Age > 60 years Consequences of Smoking

ASA III – V Respiratory
CHF
COPD • Risk factor for pulmonary disease
Cigarette smoking • Decreased mucociliary clearance
Procedure Aortic > thoracic > upper abdominal = neuro = peripheral vascular > emergency • Airway hyperreactivity
Duration of anesthesia >2.5 hrs • Reduced pulmonary immune function
General anesthesia Cardiovascular
Tests Albumin < 3.5 g/dL (indicates poor nutritional status)
• Note the ABGs and PFTs are not on this list. These are only useful in • Risk factor for cardiovascular disease
patients undergoing lung resection—not in patients undergoing • Carbon monoxide àdecrease DO2
nonthoracic surgery • Catecholamine release
• Risk Reduction Strategies: STOP SMOKING!!!! • Coronary vasoconstriction
• Decreased exercise tolerance
o Short Term Effects:
§ Carbon monoxide t1/2 – 4-6 hours Other
§ P50 returns to near normal in 12 hours
• Impaired wound healing
§ Short term cessation does not reduce pulmonary complications
o Intermediate Term Effects
§ Return of pulmonary function takes at least 6 weeks. This include:
• Airway function
• Mucociliary clearance
• Sputum production
• Pulmonary immune function
§ Hepatic enzyme induction also subsides after 6 weeks
• Reverse Anesthesia-Induced Atelectasis with ARMs
o Alveolar recruitment maneuvers (ARMs) are the best way to reverse anesthesia-induced atelectasis. Indeed, a peak airway
pressure of 30 cm H2O is required for initial reopening of the atelectatic regions, and increasing the PIP to 40cm H2O for 8
seconds appears to reverse anesthesia-induced atelectasis almost completely.
o For best results, use an ARM to open the atelectatic regions and apply PEEP to keep them open. PEEP by itself is not nearly as
effective.
• Other Risk Reduction Strategies
o Preoperative
§ Treat expiratory airflow obstruction with bronchodilation and corticosteroids
§ Treat active infection with antibiotics (no indication for prophylaxis for pulmonary infection).
§ Instruct patient on pulmonary recruitment maneuvers.
§ Treat RV failure.
o Intraoperative
§ Consider regional anesthesia instead of general anesthesia
§ Minimally invasive surgical approaches instead of open procedures when possible.
§ Avoid procedures lasting >3 hrs.
o Postoperative
§ Utilize effective analgesia (intercostal nerve block, neuraxial opioids, PCA).
§ Use pulmonary recruitment maneuvers (incentive spirometer, deep breathing, pulmonary toilet, CPAP).

25
Obstructive vs Restrictive Disease

• Obstructive disease is characterized by small airway obstruction and increased resistance to expiratory flow. Getting air out is the
problem
• Restrictive disease is characterized by a proportionate reduction in all of the lung volumes. Small lung volumes are the problem.

Spirometry for Obstructive and Restrictive Disease

• The normal waveform looks like an upside down ice cream cone.
• In the obstructive lesion, the expiratory limb has a concave shape.
o Example: COPD
o TIP: someone took a bite of my ice cream cone
• In the fixed lesion, the inspiratory and expiratory limbs are flat.
o Example: tracheal stenosis
o Tip: someone smashed my ice cream cone. It needs to
be “fixed.”
• In the restrictive lesion, the shape of the loop is similar to the
normal loop, however the restrictive loop is smaller and right shifted.
o Example: pulmonary fibrosis
o Tip: on a “restrictive” diet, you’ll have to eat a smaller ice cream cone.

A Few Words About Fixed & Variable Obstruction in the Upper Airway

• Sometimes an upper airway lesion is a problem during inspiration and expiration (like the loop
in the image to the right). Other times, the upper airway lesion is variable and only creates the
obstruction during inspiration or during expiration. Where the lesion is located will have a
significant impact.

• Extrathoracic Obstruction (Variable)

o The patient inhales and the airway collapses. This reduces flow.
o The patient exhales and pushes the obstruction open. Flow is normal.
o Notice the inspiratory limb is flat.
• Intrathoracic Obstruction (Variable):
o The patient inhales and pulls open the obstruction. Flow is normal.
o The patient exhales and collapses the airway. This reduces flow.
o Notice the expiratory limb is flat.

26
Asthma
• Asthmas is defined by an acute, reversible airway obstruction that is accompanied by chronic airway inflammation and bronchial hyperreactivity. Over
time airway remodeling leads to hypersection of mucus, fibrosis, smooth muscle hypertrophy, and angiogenesis.
• Atopy (the condition of being “hyper-allergic”) is the greatest risk factor for developing asthma.
• Sign & Symptoms:

o Wheezing Stimuli that Provoke S/Sx Examples

o Dyspnea Allergens Environmental
o Chest discomfort and/or tightness Drugs Aspirin, NSAIDs, Beta-antagonist, sulfites
o Productive or non-productive cough Infection Respiratory virus
o Prolonged expiratory phase Stress Vagal stimulation, cold air
o Eosinophilia Exercise Usually following exertion
• Diagnosis
o FEV1, FEV1/FVC ratio, and FEF 25-75% are reduced, but these improve following bronchodilator therapy.
o The most common ABG finding is respiratory alkalosis with hypocarbia.
o An elevated PaCO2 suggests air trapping, respiratory muscle fatigue, and impending respiratory failure.
o EKG may show right ventricular strain with right axis deviation during severe attack. Pulmonary vascular resistance increases, and this increases the
workload of the right heart.
o Tachypnea and hyperventilation and the result of neural reflexes- NOT hypoxemia.
o Severe bronchospasm can cause hypoxemia due to V/Q mismatch.
o PFTs are not predictive of postoperative pulmonary complications. The exception is for lung reduction surgery.
o A flow volume loop where the inspiratory or expiratory portion of the loop is flat suggests that wheezing is caused by upper airway obstruction (tracheal
stenosis, foreign body)- NOT asthma. If this doesn’t make sense, you’ll need to revisist flow-volume loops.
o FRC may increase as a result of air trapping, however TLC, remains wnl.
o CXR shows hyperinflated lungs with diaphragmatic flattening.
• Anesthetic Management
o Airway and Ventilator Management
§ Suppression of airway reflexes is paramount!
§ Avoidance of tracheal intubation is a good idea if the patient can safely receive regional, mask or LMA.
§ Deep extubation should be considered. If an awake extubation is selected, lidocaine and opioids will reduce airway reactivity.
§ Ventilator: limit inspiratory time, prolong expiratory time, and tolerate moderate permissive hypercapnia.
§ A heat-moisture exchanger retains airway humidity and may benefit patients with exercise induced asthma.
o Drugs:
§ All of the volatile agents dilate the airway and reduce airway resistance. Sevo reduces the risk of coughing, and may reduce the risk of
bronchospasm.
§ Ketamine is the only IV induction drug that causes bronchodilation, however it does increase secretions.
§ Propofol suppresses airway reflexes to a greater extent than thiopental.
§ Lidocaine 1-1.5mg/kg 1-3 minutes prior to extubation suppresses airway reflexes
§ Avoid histamine releasing drugs (sux, atracurium, morphine, meperidine, etc)
§ Differential diagnosis between light anesthesia and bronchospasms can be difficult. Neuromuscular blocks improve pulmonary compliance
with light anesthesia, but they do not treat bronchospasm.
§ Ketorolac can increase airway resistance and should be avoided in patients with aspirin intolerant asthma.
§ Presynaptic H2 receptor stimulation reduces histamine release. Avoid H2 antagonists (famotidine and ranitidine), as this allows H1
stimulation to occur unopposedàbronchospasm.
§ The textbooks caution the use of beta-blockers. Many question the validity of this. Because of its short t1/2 and beta1 selectivity, esmolol is
the best choice.
§ Beta-2 agonists relax the uterus. This can slow the progress of labor and contribute to post-delivery bleeding.
§ Ergot derivatives (ergonovine) and prostaglandins (F2-alpha) are used in OB, and they can induce bronchoconstriction.
§ Intravenous hydration reduces the viscosity of airway secretions.
§ Although anticholinesterases could precipitate bronchospasm, co-administration of anticholinergics negates the risk.

Intraoperative Bronchospasm
• Not all wheezing is asthma. Know the differential diagnosis.
• Treatment
o 100% FiO2
o deepen anesthetic (volatile agent, propofol, lidocaine, ketamine)
o short acting inhaled beta-2 agonist (albuterol)
Presentation
o inhaled ipratropium
o epinephrine 1 mcg/kg IV • Wheezing
o hydrocortisone 2-4 mg/kg IV (does not treat acute • Decreased breath sounds
symptoms, but prevents potential problems later). • Increased airway resistance
o Aminophylline (theophylline does not work well for acute • Increased PIP w/ normal plateau pressure
bronchospasm) (decreased dynamic pulmonary
o Helium-oxygen (Heliox) reduces airway resistance). compliance)
• Montelukast is NOT used in the treatment of acute bronchospasm. • Increased alpha angle on capnography
(expiratory upsloping)

27
Chronic Obstructive Pulmonary Disease: Pathophysiology
• COPD is characterized by a reduction in maximal expiratory flow and a slower forced emptying of the lungs. Unlike asthma, air flow obstruction is not fully
reversible.
• The name COPD is really an umbrella term for chronic bronchitis and emphysema. While these used to be considered separate clinical entities, many
patient present with features of both diseases.
• Etiology
o Cigarette smoking
o Respiratory infection
o Exposure to dust with higher risk in the coal mining, gold mining, and textile industries
o Alpha-1 antitrypsin deficiency
• Pathophysiology
o 1. Progressive deterioration of elastic components in the lung (decreased recoilàair trappingà increased residual volume)
o 2. Reduced airway rigidityàcollapse during exhalation àair trapping
o 3. Increased gas velocity through narrow airwaysàdecreased pressure in the airwaysàairway collapseàair trapping
o 4. Secretionsàairflow obstruction and bronchospasm
• See a common theme? Since getting air out of the lungs is the problem, these patients have hyperinflated lungs. Common findings include:
o Flattened diaphragm
o Increased AP diameter
o Pulmonary bullae
o Increased work of breathing
• Chronically elevated PaCO2 causes a respiratory acidosis. The kidneys reabsorb bicarbonate, which provides a compensatory metabolic alkalosis. If you put
this patient on a ventilator and restore PaCO2 to textbook “normal”, the bicarbonate in the blood hasn’t gone anywhere, so you’re putting the patient at
risk of severe alkalosis. This reduces oxygen unloading as well as causes apnea.
• Chronic hypercarbia blunts the chemoreceptor response to CO2. Some patients rely on PaO2 to maintain respiratory drive. Supplemental oxygen
theoretically could remove the stimulus to breathe, and this can cause hypoventilation and apnea. Keep in mind that patients with significant COPD wear
supplemental oxygen on a routine basis, so take this teaching with a grain of salt.
• Lung volume reduction surgery removes over distended tissue and allows normal lung tissue to function in a more regular way.
• Spirometry in COPD
o Increased: RV, FRC, TLC
o Decreased: FEV1, FEV1/FVC ratio, FEF 25-75%
o A FEV1/FVC ratio of <70% after bronchodilator therapy is diagnostic of COPD
• Chronic Bronchitis “Blue Bloaters”
o Chronic bronchitis is associated with hypertrophied bronchial mucus glands and chronic inflammation. Both processes liit air flow during
exhalation.
§ Chronic bronchitis is defined by the presence of cough and sputum production for more than three months for two consecutive
years.
§ Cigarette smoking is a common cause of chronic bronchitis.
§ RBCs are overproduced (erythrocytosis) to compensate for V/Q mismatch and hypoxemia. This increases blood viscosity as well as
myocardial work.
§ Chronic hypoxemia and hypercarbia increases PVRàpulmonary hypertensionàRV strain (right axis deviation) àcor pulmonale.
§ Left heart function is normal (normal PAOP).
§ A weak right heart creates a back pressure on the liveràliver congestion and ascites.
§ Oxygen therapy is more efficacious than any drug in terms of improving pulmonary hypertension and preventing erythrocytosis.
• Emphysema “Pink Puffers”
o Emphysema is associated with enlargement and destruction of the airways distal to the terminal bronchioles. Since the surface area for gas
exchange is reduced, dead space increases. Destruction of the pulmonary capillary bed contributes to pulmonary hypertension ( the same
amount of blood must travel to a smaller network of blood vessels).
§ The patient with emphysema generally has a normal (or slightly reduced) PaO2. The PaCO2 is usally normal or decreased as a result
of hyperventilation).
§ Late in the disease, hypoxemia and hypercarbia further increase pulmonary vascular resistance leading to right heart failure.
§ Alpha-1 antitrypsin deficiency can cause emphysema.
• A Few Words About Alpha-1 Antitrypsin Deficiency
o Alpha-1 antitrypsin is an enzyme produced by the liver
o Alpha-1 antitrypsin deficiency is a disease where an abnormal variant of the enzyme is produced. The hypatocyte is unable to secrete this
enzyme into the blood, so it accumulates inside the hepatocyte. This ultimately leads to cell death and cirrhosis.
• So what does this have to do with the lung?
o Alveolar elastase breaks down pulmonary connective tissue. This enzyme is kept in check by..you guessed it..alpha-1 antitrypsin.
o Alpha-1 antitrypsin deficiency allows a relative over activity of alveolar elastase activity.
o The net result is destruction of pulmonary connective tissue and the development of panlobular emphysema.

28
Chronic Obstructive Pulmonary Disease: Anesthetic Management
• Regional Anesthesia
o Always consider regional anesthesia for procedures involving the extremities and the lower abdomen.
o The benefits of regional anesthesia are eroded by ventilatory depression from excessive sedation.
o There are times where regional isn’t the best option. Do not consider neuraxial anesthesia if the patient requires sensory blockade >T6. This
impairs expiratory muscle function and reduces ERV. This hinders patient’s ability to cough and clear secretions.
• General Anesthesia
o To minimize postoperative respiratory depression, select a volatile agent with a low blood:gas solubility.
o All halogenated anesthetics are bronchodilators—they reduce airway resistance.
o Sevoflurane is less likely than desflurane or isoflurane to cause airway irritation.
o Emergence can theoretically be prolonged as exhaled agent is trapped in the alveoli.
o Nitrous oxide is associated with rupture of pulmonary blebsàpneumothorax
o Volatile agents may impair hypoxic pulmonary vasoconstriction (>1.5 MAC) and increase shunt. Unless shunt is severe, it can be overcome by
increasing FiO2. Keep in mind that nitrous oxide also limits the maximum FiO2 that can be used.
o Atelectasis is exacerbated by muscle relaxants and longer surgeries.
• Mechanical Ventilation
o Use a tidal volume of 6-8 mL/kg
o Slow inspiratory flow helps gas redistribute from high compliance areas to those with longer time constants. This maximizes matching of
ventilation and perfusion throughout the entire lung.
o PEEP maintains airway patency in alveoli at the flat portion (lower end) of the alveolar compliance curve. Without it, the alveoli at this region of
the curve would repeatedly open and close, predisposing them to atelectasis.
o Increase expiratory time to minimize air trapping and auto-PEEP. If you are using volume cycled ventilation, know that this comes at the cost of
higher peak inspiratory pressures (you have less time to get the same volume of gas into the patient).

Dynamic Hyperinflation (Auto-PEEP)

• If the patient is unable to fully exhale each breath, a portion of that previous breath remains in the lungs. If this occurs with subsequent breaths, the effect
is additive and airway pressure continues to rise. This is most evident by watching the waveform’s baseline increase with each breath.

• Treatment:
o Treatment includes any maneuver that increases expiratory time.
o For immediate treatment of auto-PEEP, you can disconnect the patient from the breathing circuit. This may be accompanied by a “whooshing”
sound as a substantial volume of air exits the lungs.

Restrictive Lung Disease

• Restrictive lung disease is an umbrella term for a collection of disorders that impair normal lung expansion during inspiration. Areas of restriction include
the pulmonary interstitium, pleura, rib cage, and/or abdomen.
• Characteristics of restrictive lung disease include:
o 1. Decreased lung volumes and capacities
o 2. Decreased compliance
o 3. Intact pulmonary flow rates
• An FEV1 and FVC <70% is diagnostic for restrictive lung disease. Although FEV1
and FVC are decreased, the FEV1/FVC ratio is unchanged.
• Work of breathing is increased, manifesting as a rapid and shallow breathing
pattern.
• Examples of Restrictive Ventilatory Defects
ßpregnancy, obesity, ascites
• Anesthetic Implications for Restrictive Lung Disease
o FRC is reduced, so patients are prone to rapid arterial desaturation
during apnea
o The best ventilatory strategy aims to minimize the risk of
barotrauma. This is best accomplished with a smaller tidal volume
(6ml/kg IBW) and faster respiratory rate (14-18 breaths/min)
o Keep peak inspiratory pressure below 30 cmH2O
o Prolong inspiratory time (I:E ratio of 1:1)

29
Aspiration Pneumonitis & Ventilator Associated Pneumonia
• Aspiration Pneumonitis
o Aspiration most commonly occurs during anesthetic induction and intubation or within 5 minutes of extubation. It causes three potential
problems:
§ 1. Gastric contents enter the airwayàrisk of airway obstruction
§ 2. Gastric contents cause a chemical burn to the airway and lung parenchymaàrisk of bronchospasm and impaired gas exchange
§ 3. Infectious material enters the airwayàbacterial infection (not all aspiration leads to infection)
o Mendelson’s syndrome is a chemical aspiration pneumonitis that was first described in OB patients receiving inhalation anesthesia. Risks
include:
§ Gastric pH <2.5
§ Gastric volume >25 mL (0.4 mL/kg)
• Treatment
o Tilt the head downward or to the side (first
action).
o Upper airway suction to remove particulate
matter
o Lower airway suction is only useful for removing
particulate matter. It doesn’t help the chemical
burn from gastric acid.
o Secure the airway to support oxygenation.
o PEEP to reduce shunt.
o Bronchodilators to reduce wheezing.
o IV lidocaine to reduce the neutrophil response.
o Steroids probably don’t help.
o Antibiotics are only indicated if the patient develops a fever or an increased WBC count >48 hours
• Outcomes
o 60% remain asymptomatic
o 20% require supportive care
o 15% require ventilation > 6 hours
o 5% die
• Patients who aspirate must be observed in the PACU. A patient can be safely discharged to home if he does NOT experience any of the following within 2-
hours of the aspiration event:
o New cough or wheeze
o Radiographic evidence of pulmonary injury
o SpO2 decrease > 10% of preoperative values on room air
o A-a gradient > 300mmHg
• Ventilator Associated Pneumonia
o The presence of an endotracheal tube bypasses the host’s defense mechanisms including cough and mucociliary clearance.
§ The endotracheal tube also allows orgnaisms direct passage between the mouth and the bronchopulmonary tree.
§ Microaspiration allows contaminants to slide between the ett cuff and the trachea.
§ Taken together, these factors increase the risk of ventilator associated pneumonia (VAP).
• Diagnosis
o The presence of leukocytosis (high white blood cell count) and/or fever should raise suspicion of VAP. Other early signs of VAP include
increased secretions in the endotracheal tube and increasing oxygen requirements.
o A chest x-ray alone is non-specific for VAP, as ARDS, atelectasis, or lung contusion could present a similar clinical picture. When coupled with
other signs of VAP, however, a chest x-ray is a powerful diagnostic tool.
• Prevention
o The best method to prevent VAP is to avoid intubation all together. If intubation is unavoidable, the next best preventative measure is to
minimize the duration of mechanical ventilation.
o Additional methods to reduce the incidence of VAP include:
§ Hand washing
§ Head of bed greater than 30 degrees
§ Daily spontaneous breathing trials
§ Limit sedation
§ Oropharyngeal decontamination
§ Subglottic suctioning
o GI bleed prophylaxis with gastric acid suppression therapy has the untoward side effect of bacterial overgrowth in the stomach. This increases
the risk of VAP. If the patient is at high risk for GI bleed, then sucralfate may be a more suitable alternative.
• Treatment
o Treatment with broad spectrum antibiotics that target organisms common to the ICU should begin as soon as clinical signs develop; early
intervention is key!
o The most common culprits are Pseudomonas aeruginosa and S. aureus. Once an organism is isolated, antibiotic therapy is then targeted to that
particular organism if it’s not already covered by initial broad spectrum therapy.

30
Pneumothorax & Flail Chest
• Pneumothorax
o There are 3 types of pneumothorax:
§ Closed
• A closed pneumothorax occurs when the lung collapses, but there is no communication between the pleural cavity and
the atmosphere.
• There is no mediastinal shift.
• Treatment includes observation, catheter aspiration, or chest tube insertion.
§ Communicating
• A communicating pneumothorax allows air to pass between the pleural space and the atmosphere.
• The lung collapses on inspiration and partially re-expands on expiration.
• Treatment includes an occlusive dressing that does not let air in,
but allows air to escape, supplemental O2, chest tube insertion,
and possibly tracheal intubation.
§ Tension
• A tension pneumothorax is created when air enters the pleural
space through a ball-valve defect in the chest wall—air is allowed
to enter, but not exit, the pleural space. The CXR in this question
shows a right tension pneumothorax with a leftward mediastinal
shift.
• Pathophysiology
o With a tension pneumothorax, intrathoracic pressure increases and compresses the
mediastinal structures. Increased intrathoracic pressure also decreases venous
return, cardiac output, and blood pressure which can precipitate cardiovascular
collapse.
o The hallmark characteristics of a tension pneumothorax include: hypoxemia,
increased airway pressures, tachycardia, hypotension, increased CVP.
o Emergency treatment of a tension pneumothorax includes insertion of a 14g
nd th th
angiocath into the 2 intercostal space at the mid-clavicular line or the 4 or 5
intercostal space at the anterior axillary line. This releases the tension and
relieves hemodynamic instability, but not the underlying pneumothorax. Chest
tube insertion is the definitive treatment.
o Pneumothorax can occur after:
§ Central line insertion
§ Supraclavicular, interscalene, and intercostal nerve blocks
§ Surgical procedures including: radical neck dissection, shoulder arthroscopy, mastectomy, axillary lymph node dissection,
mediastinoscopy, laparoscopy, and nephrectomy
§ Chest trauma—increasing peak inspiratory pressures following chest trauma should raise suspicion about a pneumothorax
§ Barotrauma, high peep, or high peak pressures
§ Lung cysts and bullae can expand and rupture when nitrous oxide is used
o The blood:gas partition coefficient of nitrous oxide is 0.47 and the blood:gas partition coefficient of nitrogen is 0.014. therefore, nitrous oxide is
34 times more soluble in the blood than is nitrogen. Indeed 75% nitrous oxide can double the size of a pneumothorax in 10 minutes. It should
be discontinued immediately upon suspicion of a pneumothorax.

• Chylothorax
o The thoracic duct empties lymph into the left subclavian vein. There’s another thoracic duct on the right side, but its much
smaller and often omitted from the texts.
o Injury to the thoracic duct during CVL insertion can cause chylothorax (subclalvian>internal jugular insertion). Again, injury is
more likely on the left side.
• Hemothorax
o Hemothorax is most commonly caused by bleeding intercostal vessels
o Indications for thoractotomy include initial drainage >1000mL, continued bleeding >200 mL/hr, white lung on CXR, and large air
leak.
o Hemodynamically stable patients with bleeding <150mL/hr may be managed with VATS

31
Flail Chest
• Flail chest is a consequence of blunt chest trauma with multiple rib fractures. The key characteristic is
paradoxical movement of the chest wall at the site of the fractures
• Inspiration (Negative Intrathoracic Pressure)
o Normal: the chest wall moves outward and lungs expand
o Flail chest: the injured ribs move inward & collapses affected region
• Expiration (positive intrathoracic pressure)
o Normal: the chest wall moves inward and lungs empty
o Flail chest: the injured ribs move outward and affected region doesn’t empty
• Consequences=alveolar collapse, hypoventilation, hypercarbia, and hypoxia
• Treatment includes reducing pain with an epidural catheter or intercostal nerve blocks. Remember, this
area is highly vascular and that the rate of local anesthetic uptake into the systemic circulation is high. Some patients may require mechanical ventilation
or surgical fixation.

Venous Air Embolism

• Pathophysiology
o When a gas embolism of significant size travels to the right heart, it lodges in the pulmonary
outflow tract.
o Air can be entrained into the bloodstream when there are open vessels above the level of the
heart. This is of even greater concern when the patient is spontaneously ventilating.
Consequences of air trapped in the pulmonary circulation include:
§ 1. Increased pulmonary artery pressure
§ 2. Increased right ventricular stroke work index
§ 3. Right ventricular failure
§ 4. Decreased pulmonary venous return
§ 5. Decreased left ventricular preload
§ 6. Decreased cardiac output
§ 7. Asystole and cardiovascular collapse
• The incidence of VAE varies with patient position
• In neurosurgical patients, here is the risk from highest to lowest: sitting > supine> prone > lateral
• Signs and Symptoms
o Air observed on TEE o hypotension
o “Mill wheel” murmur o dysrhythmias
o decreased EtCO2 o pulmonary edema
o increased ETN2 o hypoxia
o increased pulmonary artery pressure o cyanosis
• Treatment
o Administer 100% FiO2
o Flood surgical field with normal saline
o If surgical insufflation is used, discontinue gas insufflation and release pneumoperitoneum
o Place patient in the left lateral decubitus position (Durant maneuver). This causes the air to rise in the right heart and minimizes entry into the
pulmonary circulation
o Aspirate air from a central venous catheter.
o Hemodynamic support with vasopressors, inotropes, and intravenous fluids until the air is reabsorbed.

32
Pulmonary Hypertension
• Pulmonary artery hypertension is defined as a mean PAP>25mmHg
• Pulmonary vascular resistance increases as a function of increased vascular smooth muscle tone, vascular cell proliferation, and/or pulmonary thrombi.
• Increased right ventricular afterload leads to RV dilation, hypertrophy, and ultimately systolic impairment. As the volume of blood exiting the RV is
reduced, LV preload suffers and this can reduce CO and cause systemic hypotension. Bowing of the intraventricular septum towards the LV further
compromises LV filling. This patient has a relatively fixed cardiac output that is dependent on adequate preload.
• Another consequence of decreased RV stroke volume is an increased RV volume at the end of diastole. This stretches the tricuspid annulus, leading to
tricuspid regurgitation.
C;-6 ,K,O,K/, : PD
• %!N =
./
• Normal=150-250 dynes/sec/cm5
• Causes:
o COPD
o Hypoxemia and hypercarbia
o Left heart dysfunction
o Mitral valve disease
o Congenital heart disease
o Connective tissue disorders
o Chronic thromboembolism
o Portal hypertension
• Anesthetic Implications
o Do not hold preoperative medications that reduce PVR.
o Cardiac output is relatively fixed and patients can be sensitive to
inadequate preload.
o Treat hypotension aggressively
§ If decreased SVR, give vasopressors
§ If increased PVR or RV failure, give inhaled nitric oxide or iloprost
§ If loss of atrial kick, restore NSR
o Elevated RA pressure can open the foramen ovale, leading to a right-to-left intracardiac shunt. This is treated by reversing the cause of
increased pulmonary resistance. That is why the table above is so important!
o Neuraxial anesthesia is acceptable, but a slow sympathectomy is best (epidural is better than spinal). Remember the patient is preload
dependent.
o Too much preload can also be bad. Uterine contraction pushes a significant volume of blood towards the heart and may worsen PAH and RV
function. Nitroglycerine is the drug of choice in this context.

Carboxyhemoglobin
• Pathophysiology
o CO binds to the oxygen binding site on hemoglobin with an affinity 200 times that of oxygen.
o It causes a left shift in the oxyhemoglobin dissociation curve
o Oxygen cannot bind to or dissociate from the hemoglobin molecule, and the tissues become oxygen deprived
o Oxidative phosphorylation is impaired and metabolic acidosis results
• Diagnosis
o Think about CO in: burn victims, smokers, and patients exposed to dessicated soda lime
o A co-oximeter is required to measure CO
o A pulse oximeter does not measure CoHgb and may give a falsely elevated result
o Patients do not become cyanotic, but instead take on a cherry red appearance
o Signs of sympathetic stimulation may be confused with light anesthesia or pain
• Treatment
o Treatment include 100% oxygen until CoHgb is less than 5% or for 6 hours
o Hyperbaric oxygen is indicated if CoHgb exceeds 25% or the patient is symptomatic
o Hyperbaric oxygen may prevent delayed neurocognitive syndrome
• Production in Soda Lime
o Soda lime is hydrated to 13-15%
o As soda lime becomes dehydrated (desiccated), volatile anesthetics are more likely to react to form harmful compounds.
o The risk of carbon monoxide formation is greatest with desflurane (Des>Iso>>>Sevo)
o In the presence of desiccated soda lime, sevoflurane forms compound A and increases the risk of fire.

33
Indications for Mechanical Ventilation
• In the operating room, the requirement for mechanical ventilation is determined by a variety of factors including the site and duration of surgery. Outside
of the operating room, mechanical ventilation is indicated for respiratory failure. You need to know which clinical data suggest the need for mechanical
ventilation in these patients.
• Benefits of Endotracheal Intubation
o A patent airway
o Controlled ventilation
o Ventilation with high airway pressure
o Secured airway (protection from gastric aspiration)
o Removal of secretions
o Lung isolation
o Medication administration
• Although Hagberg says that medication administration via the ETT is not
recommended during resuscitation, we still think you should know what drugs
you can give down the endotracheal tube:
o NAVEL=narcan atropine vasopressin epinephrine lidocaine
• Subjective Signs of Respiratory Distress
o Anxiety and restlessness
o SNS stimulation (pupil dilation, diaphoresis)
o Dyspnea
o Accessory muscle use
o Mouth breathing during inspiratory efforts
o Pursed lip breathing or self-PEEP (pursed lips, grunting, groaning)
o Lip cyanosis
• Objective Measures of Respiratory Distress (table)

One Lung Ventilation: Part I

Assessment of Pulmonary Reserve

• Here are the best predictors of postoperative pulmonary complications for patients undergoing pulmonary surgery:
o Airflow: FEV1 <40% predicted
o Gas exchange: DLCO<40% predicted
o Cardiopulmonary reserve: VO2 max <15mL/kg/min
• Split lung V/Q function testing is indicated when preoperative assessment suggests an increased risk of postoperative pulmonary complications (anything
less than the values listed above)
• Indications for One-Lung Ventilation

DLT Size Men: 39-41 French

Women: 37-39 French
Insertion Depth Mend: 29cm
Women: 27cm
Tracheal Cuff Volume 5-10 mL air
Bronchial Cuff Volume 1-2 mL air
The bronchial cuff is a low volume, high
pressure cuff. Over inflation increases
the risk of mucosal injury. Keep this cuff
deflated whenever you don’t need it.

• Double Lumen Endotracheal Tube

o The double lumen endotracheal tube and one lung ventilation are NCE favorites, so you’d better know all of this material cold!
• OLV in Pediatrics
o As you know the pediatric airway is pretty narrow. Now imagine a child size ETT with two lumens instead of one. What’s the problem? The
narrow diameter of each lumen would make the resistance to airflow unacceptably high!
o Double Lumen Endotracheal Tubes
§ Children 8-9 years old=Size 26
§ Children 10+= Size 28 or 32
o Alternatives to DLTs
§ Some children younger than 8 years old will require lung separation. Here are some options:
• Bronchial blocker
• Single lumen endotracheal tube advanced into a mainstem bronchus

34
One Lung Ventilation: Part II
• Lateral Decubitus Position + Anesthesia
o Here’s the alveolar compliance curve. Observe what happens when the awake patient assumes
the lateral decubitus position, and then see how induction of anesthesia moves the lungs further
down the curve.
o Nondependent lung:
§ Moves from flatter region (less compliant) to an area of better compliance (slope)
§ Ventilation is optimal in this lung
o Dependent lung:
§ Moves from the slope to the lower, flatter area of the curve (less compliant).
§ Perfusion is best in this lung (effect of gravity)
§ A reduction of alveolar volume contributed to atelectasis.
o The net effect is that ventilation is better in the nondependent lung and perfusion is better in the
dependent lung. This creates V/Q mismatch and increases the risk of hypoxemia during OLV.
• Anesthetic Management of One Lung Ventilation
o Anyone who’s done their share of thoracic surgery understands just how fickle these tubes can be. You’ll need to be well versed in the possible
complications of their use. Chief among these are hypoxemia during OLV and complications of tube position.
§ 1. Use FiO2 of 100%. Some argue that this increases absorption atelectasis, so a FiO2 of 80% is acceptable if PaO2 is maintained.
§ 2. Vt 6-8 mL/kg to prevent alveolar trauma and acute lung injury
§ 3. Add PEEP 5 cmH2O. This increases FRC by pushing the lung up the compliance curve and prevents excess shearing stress of repeated
alveolar opening and closing.
§ 4. Respiratory rate 12-15 breaths/min to maintain PaCO2 35-35 mmHg
§ 5. Reconfirm placement after position changes
§ 6. If PIP >40cm H2O rule out distal occlusion
§ 7. If hypoxemia develops (PaO2 <60 mmHg or SpO2 <90%), first check the position of the DLT (poor position is the most common
complication of the DLT) and then rule out physiologic causes of hypoxemia. If hypoxemia is severe, then resume two lung ventilation.
§ 8. If the DLT is in good position, then apply 10 cmH2O CPAP to non-dependent (non-ventilated) lung
§ 9. If hypoxemia continues, add PEEP 5-10 cmH2O to dependent lung. This may improve FRC or may worsen shunt by directing more blood
flow towards the non-dependent (non-ventilated) lung, so pay attention
§ 10. Use alveolar recruitment techniques (sigh breaths)
§ 11. Some texts recommend TIVA to minimize inhibition of HPV
§ 12. If hypoxemia continues, consider ligation or clamping of the pulmonary artery supplying the non-dependent (non-ventilated) lung
§ 13. If this is not a suitable option and/or if hypoxemia continues, reinflate the lung. Do not tolerate prolonged hypoxemia!
o Avoid conditions that increase PVR:
§ Hypoxia
§ Hypercarbia
§ High levels of PEEP
§ High airway pressure
o Postpneumonectomy pulmonary edema is
associated with a high mortality rate. Risk factors
include:
§ Excessive hydration (restrict IVF in the
OR and limit IVF to <3 L in the first 24
hours)
§ PIP >25 cmH2O
§ Right pneumonectomy or lobectomy
• Complications of DLT Position
o While it’s important to understand trouble shooting techniques with auscultation of breath sounds, you should also know that direct
visualization with a fiberoptic scope is a significantly more reliable technique for identifying the correct tube position. Additionally, you must
reconfirm tube placement after you change the patient’s position.
o In a perfect world, what should you see with the bronchoscope?
§ Tracheal lumen (incomplete c-rings that open posteriorly)
§ Bronchial cuff is visible in the correct bronchus (no herniation is present)
§ When viewing the right bronchus, 3 take offs are present (1 for each lobe)
§ When viewing the left bronchus, 2 take offs are present (1 for each lobe)
o These are 3 key complications that you must be able to immediately recognize and rectify:
§ 1. The DLT is too faràupper lobe is not ventilated (increased risk of hypoxemia)
§ 2. The DLT is not deep enoughàfailure to achieve lung separation
§ 3. The DLT is in the wrong bronchus àwrong lung collapses
o The right upper lobe take off is only a few centimeters past the carina, so if the DLT is in the right bronchus, you must be careful not to occlude
the RUL. Indeed, this is why we opt for left sided DLTs unless we absolutely have to use a right sided DLT.

35
Mediastinoscopy

• Mediastinoscopy is performed to diagnose and stage lung cancer.

• The most common approach involves a small incision made at the midline of the lower neck at the suprasternal notch. The scope is placed
anterior to the trachea and posterior to the innominate artery and thoracic aorta. This region is rich in
high value real estate, so there are a number of serious complications that can result.
o Thoracic aorta (hemorrhage and reflex bradycardia)
o Innominate artery (decreased carotid blood flow and cerebral blood flow)
o Tracheal (airway obstruction)
o Vena cava (hemorrhage)
o Lung (tension pneumothorax)
o Thoracic duct (chylothorax)
o Phrenic and recurrent laryngeal nerve (paresis)
• The other name for the innominate a. is the brachiocephalic a.
• Contraindications
o Absolute: prveious mediastinoscopy (due to scaring)
o Relative: tracheal deviation, thoracic aortic aneurysm, and superior vena cava obstruction
• Anesthetic Considerations
o Central to understanding the anesthetic considerations is a solid understanding of the
vascular anatomy between the heart and the brain

Innominate a. à R. subclavian a. à R. Common carotid àR. Internal carotid àR. cerebral circulation at circle of Willis
o Innominate compression compromises circulation to the right side of the circle of Willis. This can be detrimental to patients with
cerebrovascular disease, where communication between the left and right side of the cerebral circulation is compromised.
o Place an arterial line or pulse oximeter on the right upper extremity. If the scope compresses the innominate a., the waveform will
dampen or disappear. If this happens, the scope must be repositioned.
o Place a non-invasive blood pressure cuff on the left upper extremity to measure blood pressure BP during compression.
o Have large bore IV access and PRBC available. If bleeding occurs, fluids and blood given in the upper extremity will pass through the
vascular injury and enter the mediastinum. A large bore IV catheter in the lower extremity circumvents this issue.
o There is an association between oat cell carcinoma and Eaton-Lambert syndrome.

AIRWAY MAINTENANCE

Airway Assessment Techniques:

§ Mallampati Classification
o The mallampatic exam assesses the oropharyngeal space. Said another way, it helps us quantify size of the tongue relative to
the volume in the mouth.
§ The more space the tongue occupies, the less space there is to work.
§ A higher Mallampati score (III or IV) is associated with a more difficult intubation.
§ By itself, Mallampati is a poor predictor of a difficult airway. Its predictive power increases when we use it in conjunction
with additional airway exams.
o How to Perform the Exam:
§ Sit upright
§ Extend the neck
§ Open the mouth wide
§ Stick out the tongue
§ NOT phonate
o Remember the mnemonic: PUSH
§ Class I: Pillars, Uvula, Soft Palate, Hard Palate
§ Class II: Uvula, soft palate, hard palate
§ Class III: Soft palate, hard palate
§ Class IV: hard palate
§ Inter-Incisor Gap
o The patient’s ability to open the mouth directly affects your ability to align the oral, pharyngeal and laryngeal axes. A smaller
inter-incisor gap creates a more acute angle between the oral and glottis openings, increasing the difficulty of intubation.
§ Normal=2-3 finger breaths or 4 cm
§ Long incisors reduce the gap
§ Buck teeth increase the risk of dental damage

36
 § Thyromental Distance
o To expose the glottis opening during laryngoscopy, you must displace the tongue into the submandibular space. If this space is
small or poorly compliant (tumor, radiation, or submandibular abscess) then you may not be able to move the tongue enough
to expose the glottis.
o The borders of the submandibular space include:
§ Superior border=Mentum
§ Inferior border=Hyoid bone
§ Lateral border=Either side of the neck
o The thyromental distance helps us estimate the size of the submandibular space. With the neck extended and mouth closed,
you can measure the distance from the tip of the thyroid cartilage to the tip of the mentum. Laryngoscopy may be more
difficult if the TMD is less than 6cm (3 fingerbreadths) or greater than 9 cm.
o Less than 6 cm:
§ Mandibular hypoplasia
§ Small submandibular space
o More than 9cm:
§ The larynx assumes a more caudal position
§ Because the tongue is fixed at the hyoid bone, the tongue moves caudally as well
§ These changes shift the glottis opening beyond the line of site, increasing the difficulty of laryngoscopy
§ Mandibular Protrusion Test (Upper Lip Bite Test)
o The MPT assesses the function of the temporomandibular
joint. The patient is asked to sublux the jaw, and the position
of the lower incisors it compared to the position of the upper
incisors.
§ Class I: Patient can move LI past UI and bite the
vermilion of the lip (where the lip meets the facial
skin)
§ Class II: Patient can move LI in line with UI
§ Class III: Patient cannot move LI past UI (increased risk of difficult intubation)
§ Antlanto-Occipital Joint Mobility
o The ability to place the patient into the sniffing position is highly dependent on the mobility of the atlanto-occipital joint.
§ Normal AO flexion (chin to chest)=90-165 degrees
§ Normal AO extension=35 degrees (laryngoscopy will be difficult if <23 degrees).
o Conditions that impair AO mobility
§ Degenerative joint disease
§ Rheumatic arthritis
§ Anklylosing spondylitis
§ Trauma
§ Surgical fixation
§ Klippel-Feil
§ Down Syndrome

Laryngeal Assessment Technique

§ Cormack and Lehane Score

o The Cormack and Lehane grading system helps us measure the view we obtain during direct vision laryngoscopy. Obviously you
can’t make this determination before performing laryngoscopy.
o Modification of the Cormack and Lehane Score
§ Sometimes this metric is modified to include:
• Grade IIA=you can see the posterior region of the
glottis opening
• Grade IIB= you can only see the corniculate
cartilages and posterior vocal cords. You cannot
see any part of the glottis opening.
§ You might see this as written as arytenoids, and this would
be correct if corniculate cartilages aren’t answer choice.
o How does this score correlate with intubation?
§ Grade I and IIA = easier intubation
§ Grade IIB & III = Harder intubation
§ Grade IV = Requires an alternative approach to intubation
37
Five Questions To Answer Before Providing Airway Management

§ 1. Will I Be Able to Mask Ventilate?

o Risk factors for difficult mask ventilation: (the mnemonic “BONES” should help)
§ Beard
§ Obese (most books say BMI > 26 kg/m2)
§ No teeth
§ Elderly (age >55 years)
§ Snoring
§ 2. Will I Be Able to Intubate?
o Risk factors for difficult laryngoscopy and endotracheal intubations:
§ Small mouth opening
§ Long incisors
§ Prominent overbite
§ High, arched palate
§ Mallampati class III or IV
§ Retrognathic jaw
§ Inability to sublux jaw
§ Short, thick neck
§ Short thyromental distance
§ Reduced cervical mobility
§ 3. Will I Be Able to Place A Supraglottic Airway and Will it Work?
o Risk factors for difficult suprglottic device placement:
§ Limited mouth opening
§ Upper airway obstruction (anything that prevents passage of the device into the pharynx)
§ Altered pharyngeal anatomy (anything that prevents a seal)
§ Poor airway compliance (requires excessive PIP)
§ Increased airway resistance (requires excessive PIP)
§ Lower airway obstruction
§ 4. Will I Be Able To Place An Invasive Airway?
o Risk factors for difficult invasive airway placement:
§ Abnormal neck anatomy (tumor, hematoma, abscess, history of radiation)
§ Obesity (difficult to identify the cricothyroid membrane)
§ Short neck (difficult to identify the cricothyroid membrane)
§ Laryngeal trauma
§ Limited access to cricothyroid membrane (halo, neck flexion deformity)
§ 5. How Fast Must I Secure The Airway?
o The Practice Guidelines for Preoperative Fasting and Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration
have been updated since their original publication in 1999. Here are the most current recommendations:
§ 2 hours=Clear liquids
§ 4 hours=Breast milk
§ 6 hours= nonhuman milk, infant formula, solid food
o Ingestion of clear liquids 2 hours before surgery reduces gastric volume and increases gastric pH. This reduces the risk of
Mendelson syndrome (risk factors=gastric pH<2.5 and gastric volume >25 mL (0.4mL/kg) ).
o Rapid Sequence Intubation
§ If the patient has a full stomach or other risk factors for aspiration, then a rapid sequence induction is indicated. The
patient is not ventilated, and the esophagus is compressed by applying pressure to the cricoid ring. Pressure is applied
before the patient loses consciousness and maintained until the tracheal intubation is confirmed.
• Pressure before LOC = 20 Newtons or ~2 kg
• Pressure after LOC = 40 Newtons or ~4kg
§ You must recognize that cricoid pressure is far from a benign procedure. Complications include:
• Esophageal rupture if patient is actively vomiting
• Airway obstruction
• Difficulty with laryngoscopy
• Impaired glottis visualization
• Difficult intubation

38
Angioedema, Ludwig’s Angina & Syndromes Associated with Difficult Airway Management

§ Angioedema
o Angioedema is the result of increased vascular permeability that can lead to swelling of the face, tongue, and airway. Airway
obstruction is an extreme concern.
o There are two causes of angioedema you should know for the NCE:
§ Angiotensin converting inhibitors (enalaprilat is the only ACEI available IV)
• Treatment=epinephrine, antihistamines, steroids (just like anaphylaxis)
§ Hereditary angioedema (C1 esterase deficiency)
• Treatment= C1 esterase concentrate or FFP (not epinephrine, antihistamines, or steroids)
§ Ludwig’s Angina
o Ludwig’s angina is a bacterial infection characterized by a is a rapidly progressing cellulitis in the floor of the mouth.
Inflammation and edema compress the submandibular, submaxillary, and sublingual spaces. The most significant concern is
posterior displacement of the tongue resulting in complete, supraglottic airway obstruction.
o The best way to secure the airway is with the patient awake:
§ Awake nasal intubation
§ Awake tracheostomy
o Retrograde intubation is contraindicated in patients with an infection above the level of the trachea
§ Syndromes
o You’ll need to understand how congenital conditions impact airway management. First, we’ll group a few together, then we’ll
detail the important considerations for each condition.

o Pierre Robin
§ Small/underdeveloped mandible (micrognathia or mandibular hypoplasia –can be used interchangeably)
§ A tongue that falls back and downwards (glossoptosis)
§ Cleft palate
§ Neonate often requires intubation
o Treacher Collins
§ Small mouth
§ Small/underdeveloped mandible
§ Nasal airway is blocked by tissue (choanal atresia)
§ Ocular and auricular anomalies
o Trisomy 21 (Down’s Syndrome)
§ Small mouth
§ Large tongue
§ Atlantoaxial instability
§ Small subglottic diameter (subglottic stenosis)
o Klippel-Feil
§ Congenital fusion of cervical vertebraeàneck rigidity
o Goldenhar
§ Small/underdeveloped mandible
§ Cervical spine abnormality
o Beckwith Syndrome
§ Large tongue
o Cri du Chat
§ Small/underdeveloped mandible
§ Laryngomalacia
§ Stridor
o *know the fancy words in the parentheses

39
Positioning for Airway Management

§ The Sniffing Position

o The “sniffing position” is widely believed to be the best position for direct vision laryngsocpy. The idea is the cervical flexion and
atlanto-occipital extension bring the oral, pharyngeal, and laryngeal axis into alignment. Not only should you know what the
sniffing position is, but you must also understand why it works and when it doesn’t.
§ Cervical flexion moves the chin towards the chest.
§ Atlanto-occipital extension extends the head on the neck.
o Let’s compare how various head and neck positions affect the oral, pharyngeal, and laryngeal axes.

o Modifications for Obesity

§ When the morbidity obese patient lays supine, excess adipose on the neck, shoulders, and back place the ehcest
higher than the head, contributing to misalignment of the OA, PA, and LA.
§ The HELP position (Head Elevated Laryngoscopy Position) solves this prolem by using blankets or a positioning device
to elevate the head and upper torso. Optimal positioning is achieved when the sternum and the external auditory
meatus are in the same horizontal plane.
§ Putting the bed in the reverse Trendelenburg position unloads the diaphragm and may prolong the time between
apnea and desaturation.
o How Does Head Position Affect the ETT After Intubation?
§ Just remember this: “The tube goes where the nose goes.”
• Nose to chest pushes the tip towards the carina (~2cm)
• Nose away from chest pulls the tip away from the carina (~2cm)
• Lateral rotation of the head moves the tip away the carina (~0.7cm)
§ Another thing to keep in mine is the position of the bed. The steep Trendelenburg position causes the abdominal
contents to shift towards the chest. This reduces thoracic volume and increases the risk of endobronchial intubation.

40
Oral & Nasal Airway

§ An oro- or nasopharyngeal airway is used to relieve upper airway obstruction. It opens the airway by displacing the tongue and epiglottis
from the posterior wall of the pharynx.
§ Types of Oropharyngeal Airways
o You must be able to identify each type of OPA as well as understand the unique benefits of each

o Notice the hole in the center of the Williams and Ovassapian airways? These openings are made to accommodate a fiberoptic
bronchoscope and endotracheal tube.
§ How to Size an Airway
o OPA: Measure from the corner of the mouth to the earlobe or the angle of the mandible.
o The flange should protrude outside of the lips and the pharyngeal end should rest at the base of the tongue
§ An OPA that is too short can obstruct the airway by causing the tongue to kink against the roof of the mouth
§ An OPA that is too long can obstruct the patient’s airway by displacing the epiglottis towards the glottis. It can also
cause trauma.
o NPA: Measure from the nare to the earlobe or the angle of the mandible
o Gently retract the tip of the nose and introduce the airway in line with the nasal passage (perpendicular to the face). Do not
push the airway towards the brain, as this can traumatize the turbinates.
§ An NPA that is too short to relieve the obstruction
§ An NPA that is too long can obstruct the patient’s airway by displacing the epiglottis towards the glottis. It can also
cause trauma.
o Complications (OPA & NPA)
§ Placing an airway into a lightly anesthetized patient can precipitate laryngospasms. A nasal airway is usually better
tolerated in this situation.
§ Other complications include:
• Vomiting (if the gag reflex is intact)
• Dental injury (if the patient bites down)
• Oropharyngeal trauma
• Ischemia (compresses blood flow to affected areas)
o Nasopharyngeal Airway Contraindications
§ Cribiform plate injury (risk of brain injury)
• LeFort II or III fracture
• Basilar skull fracture
• CSF rhinorrhea
• Raccoon eyes
• Periorbital edema
§ Coagulopathy (risk of epistaxis)
§ Previous transsphenoidal hypophysectomy
§ Previous Caldwell-Luc procedure
§ Nasal fracture

41
ETT Design

§ The Cuff
o Inflating the cuff occludes the trachea. This permits
positive pressure ventilation and protects the lungs from
aspiration of gastric contents. Tracheal ischemia can
occur if the cuff pressure exceeds tracheal mucosal perfusion pressure, so the cuff pressure should be less than 25 cm H2O.
o There are two types of cuffs: low-volume, high-pressure and high-volume, low-pressure. Be able to compare these.

Low-Volume, High-Pressure Cuff High-Volume, Low-Pressure Cuff

Which tubes use this cuff? Red rubber tube Nearly all tubes in modern practice
Silicone tube for LMA-Fastrach
Cuff compliance Low—it takes a smaller volume to High—it takes a larger volume to
increase the pressure inside the cuff increase the pressure inside the cuff
Can you measure the internal No Yes—best to use a manometer
pressure?
Benefits Better protection against aspiration Cuff pressure closely resembles the
Lower incidence of sore throat pressure exerted on the trachea. This is
Easier visualization during intubation why you can measure it with a
manometer.
Risks Prolonged intubationàtracheal Believing that you can accurately
ischemia estimate how much pressure is in the
cuff.
Adding too much air to the cuff or using
N2Oàincreased cuff
pressureàtracheal ischemia
It is easy to pass things around the cuff
(esophageal stethoscope, OGT, temp
probe)
Protection against aspiration isn’t as
good as a low-volume, high-pressure
cuff
o The microthin cuff is another type of high-volume, low-pressure cuff. Benefits over a standard high-volume, low-pressure cuff
include:
§ Lower pressure on the tracheal mucosa
§ Better protection against liquid aspiration
§ Ways to Minimize Cuff Pressure
o Don’t believe that you can accurately access the pressure inside of the cuff. The literature says you probably can’t, and that
you’re most likely underestimating the pressure exerted on the tracheal mucosa. Here are some better ways to protect the
patient:
§ Use a manometer after intubation and periodically during the case.
§ Fill the cuff with the same O2/N2O mixture that you will use during the case (assumes you’ll use N2O)
§ Fill the cuff with water or saline. This provides a more stable cuff pressure, but it takes longer to deflate (really bad if
there’s an airway fire)
§ Use a ETT with a Lanz pressure-regulating valve.
§ Murphy Eye
o The murphy eye is a small hole on the opposite side of the bevel
§ The purpose of the Murphy eye is to provide an alternate passage for air movement in case the tip of the ETT
becomes occluded or abuts the tracheal wall
§ Some ETTs don’t have a Murphy eye. This offers the advantatge of positioning the cuff closer to the tip, and this
architecture minimizes the risk of endobronchial intubation, which is useful in pediatrics.
§ A fiberoptic scope, forceps, or tube changer can get stuck in the Murphy eye. This is called Murphy’s law ;)

42
LMA: Design
§ The LMA is the most commonly used supraglottic airway. It can be used as a primary airway, rescue during difficult airway management, and as a
conduit for tracheal intubation. It’s value in difficult airway management stems from the fact that the conditions that make tracheal intubation
difficult do not correlate with those that make LMA placement difficult.
o The LMA consists of a curved airway tube that connects to a latex free mask.
o Two aperature bars across the tube’s orifice prevent the epiglottis from
obstructing the airway tube.
o A seal is created after air is added to the inflatable cuff.
§ Cuff Inflation
o Inflating the LMA cuff creates a seal over the larynx, which allows for positive
pressure ventilation. It also shields the larynx from pharyngeal secretions, however it does not reliably protect against gastric
regurgitation (it’s not a secure airway).
o The integrity of the seal is a primarily dependent on size and position and less dependent on cuff volume or pressure
§ Max PPV pressure = 20 cm H2O
§ Max cuff pressure = 60 cm H2O (target = 40-60 cm H2O)
§ If the cuff pressure exceeds 60 cm H2O and you cannot get a good seal, then the LMA is improperly positioned, the patient is
inadequately anesthetized, and/or there is a partial or complete laryngospasm
§ Nitrous oxide diffuses into the cuff, and this increases cuff pressure. Use a manometer when using N2O
§ Cuff overinflation is the most common cause of nerve injury. The lingual, hypoglossal, and recurrent laryngeal nerves are at
risk.
§ Other risk factors for nerve injury include
using an LMA that is too small, lidocaine
lubrication, and traumatic insertion.
§ Cuff overinflation also increase the risk of
sore throat and pharyngeal necrosis
§ LMA Size
o At a minimum, you must know how to size the LMA<
how much air to add to the cuff, and the largest size
endotracheal tube that fits through each LMA.
§ LMA Variations
o LMA ProSeal
§ The ProSeal is an adaptation of the classic
LMA. It’s a double lumen LMA with the following features:
• Gastric drain tube ( the second lumen) for easy gastric decompression
• Larger mask
• Bite block
§ Do NOT place suction directly to the drain tube. Instead you must pass an OGT through the tube
to decompress the stomach.
§ When compared to the LMA Classic, benefits of the ProSeal include a:
• Better seal
• Max pressure for PPV <30 cm H2O (LMA classic is <20 cm H2O)
o LMA Supreme
§ The disposable version of the ProSeal is called the LMA Supreme.
o LMA Fastrach
§ The Fastrach is an intubating LMA. After seating the LMA, the trachea is intubated with a specially designed endotracheal tube. The
LMA can be removed after intubation or it can remain in place throughout the procedure, although this is associated with a higher
incidence of sore throat and hoarseness.
§ Special features include:
• Metal handle (not suitable for use in the MRI suite)
• Specially designed endotracheal tube (uses a high pressure cuff)
• Tube pusher
• Epiglottic elevating bar
o LMA C-Trach
§ The C-Trach is very similar to Fastrach, but it includes a camera so you can visualize intubation
o LMA Flexible
§ The LMA flexible has an airway tube that is:
• Flexible
• Wire-reinforced (not suitable for use in MRI suite)
• Longer than the LMA classic
• Narrower than the LMA classic ( must use a small endotracheal tube or bronchoscope)
§ This device is useful for head and neck surgery where the airway tube of the LMA classic would limit access to the surgical site.

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§ LMA Special Considerations
o Contraindications
§ The LMA should not be used in the following situations:
• Risk of gastric regurgitation and aspiration: full stomach, hiatal hernia, small bowel obstruction, symptomatic
GERD, delayed gastric emptying
• Airway obstruction at the level of the glottis or below the glottis
• Poor lung compliance
• High airway resistance
§ In the event of a “cant ventilate and cant intubate” scenario, the LMA can be lifesaving and should be used even if the
patient is at risk for aspiration. In this situation, hypoxemia (not aspiration) is the greatest risk to the patient.
o What if Gastric Regurgitation Occurs After the LMA is in Place?
§ If you observe gastric contents inside the airway tube of the LMA, then you should perform the following interventions:
• Leave the LMA in place. There may be gastric contents behind the LMA cuff, and removing it can worsen the
situation.
• Place the patient in the Trendelenburg position and deepen the anesthetic if necessary.
• Give 100% oxygen via Ambu bag (if gastric contents are present inside the breathing circuit you don’t want to
push them into the lungs).
• Use a low FGF and low Vt.
• Use a flexible suction catheter to suction through the LMA.
• Use a FOB to evaluate the presence of gastric contents in the trachea. If present, then consider intubation and
aspiration protocols.
§ Even though an LMA does not provide a truly secure airway, it does shield the glottis opening. The risk of gastric aspiration is
low when used in patients with a low risk of gastric regurgitation. The incidence of gastric aspiration with an LMA parallels
the incidence during non-LMA general anesthetics (~ 2-6: 10,000 cases). Additionally, the LMA does a better job of
protecting the airway than a face mask.
o LMA & Asthma
§ Volatile anesthetics obtund the pulmonary reflexes. As the patient emerges from general anesthesia, these reflexes “wake-
up”, and if there is an endotracheal tube in the trachea, the patient may cough or suffer bronchospasm. Indeed, the patient
with asthma is most likely to experience wheezing during emergence. Since the LMA sits over the glottis, there’s nothing
inside the trachea to stimulate it during emergence.
o LMA & SNS Stimulation
§ We all know that direct vision laryngoscopy is an intensely stimulating procedure that can lead to increased catecholamines,
tachycardia, hypertension, dysrhythmias, bronchorrhea and bronchospasm. Did you know that the LMA is the least
stimulating airway device?
§ The tendency of airway device placement to activate the SNS (from most to least stimulating):
• Combitube
• DVL
• Fiberoptic Intubation
• LMA
o LMA & Laparoscopy
§ If you’re going to use an LMA for a laparoscopic procedure, then follow the guidelines described in Nagelhout:
• Observe the “15” rule: Use <15 degree tilt, <15 cm H2O intraabdominal pressure, and <15 minutes of insufflation
• Select an LMA that allows for gastric drainage (LMA ProSeal or Supreme)
• Use in patients with normal BMI (avoid in the obese population)
• Observe traditional NPO fasting guidelines
• Avoid light anesthesia
• Be an experienced LMA user

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Combitube

§ The Combitube is a supraglottic,double lumen device that is blindly placed in the hypopharynx. It is extensively utilized in prehospital
settings, but it’s also useful during difficult airway management.
o Size 37: Patient height = 4-6 ft
o Size 41: Patient height = >6 ft
o There are no options for patients <4 ft
§ How It Works
o The Combitube is blindly inserted into the hypopharynx
o Inflating the oropharyngeal balloon (proximal cuff)
occludes the hypopharynx
o Inflating the distal balloon (distal cuff) occludes the
esophagus (usually)
o The oropharyngeal balloon is inflated first. (size 37=40-85 mL and size 41= 40-100mL + option for additional 50 mL)
o The distal cuff is inflated second (both sizes = 5-12 mL air)
o Since the tip usually enters the esophagus, attempt ventilation through the blue (proximal or esophageal) lumen
o If the tip enters the trachea, then you can ventilate through the clear (distal or tracheal) lumen
o Cuff pressors should not exceed 60 cm H2O
o Overzealous inflation of the cuffs can rupture the esophagus
§ Benefits
o Provide a secure airway (aspiration protection)
o Ability to decompress the stomach
o Useful for the obese population
o Uses a blind insertion technique (minimal training required)
o Does not require neck extension
o Allows high ventilatory pressures (up to 50 cm H2O)
o Does not need to be taped to the patient
§ Contraindications
o Intact gag reflex
o Prolonged use (>2-3 hours) due to risk or ischemia from oropharyngeal balloon
o Esophageal disease (Zenker’s diverticulum)
o Ingestion of caustic substances
o Do not use a size 37-F in someone <4 ft
o Do not use a size 41-F in someone <6 ft
§ Zenker’s diverticulum is a condition where diverticulum (pouches) form in the pharyngeal mucosa.

Flexible Fiberoptic Bronchoscope

§ The flexible fiberoptic bronchoscope is used for indirect laryngoscopy in awake or asleep patients. Light from an external source travels
along the fiberoptic bundle and out from the distal tip. This light is reflected off the patient’s anatomy, allowing the operator to view the
anatomy from the eye piece or a camera attached to the eye piece.
§ Scope Movement
o Holding the scope:
§ Non-dominant = moves the lever
§ Dominant hand = holds the cord
o Vertical movement:
§ Push the lever down to point the tip up
§ Push the lever up to point the tip down
o Horizontal movement:
§ The FOB is rotated in either direction
§ Indications
o Flexible fiberoptic bronchoscopy in the awake, spontaneously ventilating patient is the gold standard for managing the difficult
airway.
o Other indications include:
§ C-spine limitation: severe cervical stenosis, cervical fracture, Chiari malformation, vertebral artery insufficiency
§ Limited mouth opening: TMJ disease, facial burns, mandibular-maxillary fixation

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 § Contraindications
o Although there are no absolute contraindications to fiberoptic bronchoscopy, you must be familiar with the relative
contraindications:
§ Hypoxia (lack of time)
§ Secretions not relieved by suction or an antisialagogue
§ Hemorrhage that impairs visualization
§ Uncooperative patient (for awake attempt)
§ Local anesthetic allergy (for awake attempt)
§ Key Points
o Anti-fog solution should be applied to the tip of the FOB
o An antisialagogue (glycopyrrolate 0.2mg IV) minimizes secretions.
o Vasoconstrictors minimize epistaxis during a nasal approach.
o The Williams or Ovassapian airway helps the FOB stay midline, although they may stimulate the gag reflex in the awake patient.
o A second provider can grab the tongue with a 4x4 and pull it anteriorly. This clears space for the FOB.
o An LMA can be used in conjuction with the FOB
o If bevel of the ETT hangs up on the right arytenoid, then you should pull back a little bit, rotate the ETT 90 degrees
counterclockwise, and advance the ETT again
o If the FOB gets stuck in the Murphy eye, then you must remove the FOB and the ETT and repeat the procedure
§ Applying Your Knowledge of Airway Innervation to Fiberoptic Bronchoscopy
o Know your anatomy, innervation, and the necessary blocks to anesthetize the airway structures. Revisit respiratory I: Airway
anatomy for more information.
§ Anterior tongue: trigeminal (V) V3-mandibular branch
§ Posterior tongue: glossopharyngeal (IX)
§ Soft palate: Glossopharyngeal (IX)
§ Oropharynx: Glossopharyngeal (IX)
§ Vallecula: Glossopharyngeal (IX)
§ Anterior epiglottis: Glossopharyngeal (IX)
§ Posterior epiglottis: superior laryngeal internal branch (X)
§ Vocal cords: superior laryngeal internal branch (X) and recurrent laryngeal (X)
§ Trachea: recurrent laryngeal (X)

Bullard Laryngoscope

§ The Bullard laryngoscope is a rigid, fiberoptic device used for indirect laryngoscopy.
§ When to use the Bullard
o Small mouth opening (minimum mouth opening = 7mm)
o Impaired cervical spine mobility
o Short, thick neck
o Treacher Collins syndrome
o Pierre-Robin syndrome
o Adult and pediatric sizes are available
§ There are no absolute contraindications to the Bullard, however the learning curve is high.
§ Considerations for Use
o The stylet and endotracheal tube sit to the right of the blade, but the stylet can be manipulated to position the ETT over the
glottis.
o Sometimes the endotracheal tube hangs up on the right arytenoid cartilage, but you can fix this with cricoid pressure and/or
lifting the blade anteriorly.
o There is a disposable tip extender which is useful for tall patients. Make sure you recover it after you’re done. Although it’s too
large to be aspirated, it can obstruct the upper airway. On numerous occasions, the tip got left behind only to be coughed up by
the patient several days later!
o Compared with DVL, the Bullard causes less cervical spine displacement.
o Compared to FOB, intubation with the Bullard is usually faster
§ Other Types of Rigid Fiberoptic Laryngoscopes
o These are very similar to the Bullard:
§ WuScope
§ UpsherScope

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Eschmann Introducer

§ The Eschmann introducer has several names. You should know them all.
§ In case you’re wondering, this device has nothing to do with gum, is not made from elastic, and really isn’t a bougie at all ( a bougie is a
device that dilates a lumen). Your guess is as good as ours.
§ When to use the Eschmann Introducer

o Understanding the Cormack-Lehane grading system is central in deciding when to use the EI.
§ Best time to use the Ei= Grade III view
§ Next best time to use the EI= Grade IIb view
§ Worst time to use the EI= Grade IV view (the chance of successful intubation is unacceptably low)

§ How to Use the Eschmann Introducer

o Hook the angled tip under the epiglottis (grade III view)
o Advance the tip into the trachea (23-25 cm)
o Feeling the click of the tracheal rings confirms placement
o If you don’t feel clicks, then you can look for the “hold-up sign” as a secondary way to confirm placement. You will feel the EI
“hold-up” as it encounters resistance at the carina (35-40 cm)
o You should only look for the “hold up” sign if you don’ feel the clicks but you think you’re in the trachea, as this technique
increases the risk of tracheal and/or bronchial trauma
o To summarize: if you feel clicks, then you’re in the trachea. If you don’t feel clicks, but you think you’re in the trachea, then you
can look for the “Hold-up” sign. If you don’t feel the “hold-up” sign then you are in the esophagus.
§ Trouble Shooting
o If the endotracheal tube catches on the soft tissue of the larynx, then you should rotate the ETT 90 degrees counter-clockwise.
This maneuver orients the bevel posteriorly, allowing it to more easily glide over the posterior laryngeal aperture.
o Keep the laryngoscope in place during the entire intubation process. If you remove it after placing the EI, but before placing the
ETT, the pharyngeal soft tissue will displace the EI and ETT posteriorly, causing it to catch on the posterior laryngeal aperture.
o The EI is also useful for nasotracheal intubation and orotracheal intubation through a supraglottic airway.

Lighted Stylet
§ The lighted stylet is a blind intubation technique that transilluminates the anterior neck to facilitate endotracheal intubation. It really
shines when conventional laryngoscopy is difficult but mask ventilation is easy.
§ Considerations for Use
o When the patient is supine, the trachea is anterior to the esophagus. Therefore, we can look at the quality of the light shining
through the neck to determine if the tip of the device is located in the
trachea or esophagus.
§ When the lighted stylet is in the trachea, the light has to
travel through less tissue, so you’ll observe a well-defined
circumscribed glow below the thyroid prominence.
§ When the lighted stylet is in the esophagus, the light has to
travel through more tissue, so you’ll observe a more diffuse
transillumination of the neck without the circumscribed glow

o Older iterations of this device required a dark environment, however

this is not a requirement when using the Trachlight. The light blinks
after 30 seconds to minimize heat product from the bulb as well as to give you a reminder of elapsed time.

47
 § Benefits of the Lighted Stylet
o Useful for the anterior airway
o Useful with small mouth opening
o Requires very little manipulation of the neck
o Less stimulating than direct vision laryngoscopy
o Less sore throat than direct vision laryngoscopy
o Can be used for oral or nasal endotracheal intubation
o Useful for cervical spine abnormality, Pierre-Robin syndrome, severe burn contractures
§ Disadvantages of the Lighted Stylet
o It should not be used in a can’t ventilate can’t intubate scenario
o More difficult to use in the patient with a short, thick neck
o It’s a blind technique and shouldn’t be used in the presence of tumor, foreign body, airway injury, or epiglottis
§ Use in Pediatrics
o When using the Trachlight in the adult, the tip should be bent to a 90 degree angle. When using this device in children, the
angle should be 60-80 degrees (more acute angle) to better accommodate a more cephalad glottis opening.
o Since the pediatric airway is smaller, the Trachlight should be bent closer to the tip. For the same reason, you should expect
that transillumination will occur sooner.
o Because of the thinner neck in the child, the circumferential glow will be more prominent. It’s possible that there are more false
positive results (you think the tip is in the trachea when it is really in the esophagus)

Bronchial Blocker

§ Lung separation and single lung ventilation can be accomplished with a bronchial blocker and a single lumen endotracheal tube. Under
many circumstances, this technique is a viable alternative to a double lumen endotracheal tube.
§ How to Place A Bronchial Blocker
o 1. Intubate the trachea with a single lumen ETT
o 2. Insert the bronchial blocker into the single lumen ETT. A fiberoptic bronchoscope may make your life easier.
o 3. After the bronchial blocker is in the correct position, inflate the balloon to isolate the lungs.
§ The lung on the opposite side of the bronchial blocker is ventilated
§ The lung on the same side of the bronchial blocker is NOT ventilated
§ About the Lumen
o It can be used to insufflate oxygen into the non-ventilated lung
o It can be used to suction air from the non-ventilated lung (improves surgical exposure)
o It cannot be used to suction blood, pus, or secretions from the non-ventilated lung
§ Indications
o Bronchial blockers are indicated for patients requiring lung separation who:
§ Are children <8 years of age (smallest DLT = 26 F for 8-10 years old)
§ Require nasotracheal intubation
§ Have a tracheostomy
§ Have a single lumen ETT in place
§ Require intubation after surgery, and you want to avoid changing the DLT to a single-lumen ETT at the end of the case
o The high pressure balloon can easily slip to enter the trachea (position change or surgical manipulation), and this can lead to
contamination and even block ventilation of both lungs! For these reasons, a bronchial blocker is not the best choice when a
lung must be isolated for concerns of contamination.
o There are several types of bronchial blockers; some are standalone products and some are incorporated into the design of the
ETT. Examples include:
§ EZ
§ Cohen
§ Arndt
§ Uniblocker

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Retrograde Intubation

§ Retrograde intubation is a blind procedure, where tracheal intubation is accomplished by passing the endotracheal tube over a wire.
§ Procedure
o Puncture the cricothyroid membrane with a 14-18g needle
o Aspirate for air to confirm proper placement inside the tracheal lumen
o Pass a wire through the needle and advance it in a cephalad direction
o The wire should travel in-between the vocal cords and exit through the mouth
o Load the endotracheal tube over the wire and advance it into the trachea
o Once the ETT is in the trachea and cannot be advanced any further, withdraw the wire and then
advance the ETT into its final position
§ Indications
o Unstable cervical spine (most common use of RI)
o Upper airway bleeding (can’t visualize the glottis)
o Since RI requires time ( ~ 5-7 minutes for experience practitioners), it is best used when intubation has failed but ventilation is
still possible.
o RI can also be performed in an awake patient.
§ Contraindications
o Poor Anatomy
§ Neck flexion deformity (unable to access the cricothyroid membrane)
§ Unable to identify neck landmarks (severe obesity)
§ Pretracheal mass (thyroid goiter)
o Laryngotracheal Disease
§ Tracheal stenosis under the puncture site
§ Tumor that obstructs the path of the wire
o Other
§ Coagulopathy
§ Infection (pretracheal abscess)
§ Complications
o Bleeding
o Pneumomediastinum
o Pneumothorax
o Trigeminal nerve trauma
o Breath holding
o Wire travels in the wrong direction

Invasive Airways
§ There are three ways to create a surgical airway:
o transtracheal jet ventilation (usually an emergen situation)
o cricothyroidotomy (usually an emergent situation)
o tracheostomy (usually a controlled situation)
§ Transtracheal Jet Ventilation
o TTJV is a percutaneous technique that requires a high pressure oxygen source.
§ A large bore needle is inserted percutaneously through the cricothyroid membrane
§ a jet ventilator is used to ventilate the patient
§ inspiration requires high pressure oxygen (~50 psi or wall pressure)
§ the pressure must be high, because the airway diameter is narrow
§ expiration is passive. Air exits through the glottis and upper airway.
§ Because ventilation can’t be controlled, the patient is at risk for hypercapnia.
o Contraindications
§ Upper airway obstruction
§ Laryngeal injury
o Complications
§ Upper airway obstruction or a space occupying lesion above the tip of the jet ventilator can act like a ball valve; air is
able to enter the lungs, but it is unable to exit the lungs. This can cause barotrauma, pneumothorax, subcutaneous
emphysema, and/or mediastinal emphysema
§ Other complications include: hemorrhage, aspiration, tracheal injury, and esophageal injury

49
 § Cricothyroidotomy
o Cricothyroidotomy is performed by creating a small, horizontal incision through the cricothyroid membrane, and then inserting
a cuffed endotracheal tube thorugh the hole.
o Contraindications
§ Children have more pliable and mobile laryngeal and cricoid cartilages, and this makes cricothyroidotomy incredibly
challenging. Additionally, the thyroid isthmus commonly covers the cricothyroid membrane in this population. For
these reasons, percutaneous transtracheal ventilation is the emergency surgical airway technique of choice for
children < 6 years old (some books say <10 years old)
§ Laryngeal fracture or neoplasm
o Complications
§ Tracheal stenosis
§ Tracheal or esophageal injury
§ Hemorrhage
§ Disordered swallowing
§ Subcutaneous or mediastinal emphysema
§ Tracheostomy
o Tracheostomy tends to require more time than cricothyroidotomy, which makes it less attractive for emergent situations.
Instead, this procedure is chosen when a patient requires a definitive airway, such as failure to wean from mechanical
ventilation in the intensive care unit.
nd rd
§ The incision is usually made between the 2 and 3 tracheal rings, and surgical dissection is more complex.
§ If there is an ETT in situ, it will need to be repositioned (pulled back or pushed down) when the surgeon enters the
trachea.
§ If the FiO2 is high and cautery is used, then an airway fire may result
§ If you must ventilate a patient with a tracheostomy in place, it will be easier if you used a cuffed trach tube.
Alternatively, you can replace the trach with a small diameter cuffed endotracheal tube.
o Contraindications:
§ There are no absolute contraindications to tracheostomy
o Complications:
§ Acute: airway obstruction, hypoventilation, pneumothorax, and bleeding
§ Long term: tracheal stenosis, tracheomalacia, tracheoesophageal fistula, and tracheal necrosis

Extubation

§ Advances in airway management have significantly reduced morbidity and mortality during endotracheal intubation, however the risks of
tracheal extubation remain unchanged.
§ When to Extubate: Awake vs Deep
o Extubation should be performed when the patient is deep or awake – NOT in-between!
§ Deep anesthetic plane (Guedel stage III)= airway reflexes attenuated
§ Light anesthesia plane (Guedel stage II) = airway reflexes are hyperreactive à increased risk of laryngospasm
§ Awake= airway reflexes intact
o A light plane of anesthesia is categorized by a disconjugate gaze, breath holding, and unable to follow commands

§ Preventing Complications of Awake Extubation

o CV & SNS stimulation: beta-blockers, calcium channel blockers, and vasodilators
o Coughing (and increased pressure noted above): lidocaine (IV or inside the ETT cuff) and opioids

50
 § Extubation of the Difficult Airway
o The risk of difficult extubation is increased if you can answer “yes” to any of the following questions:
§ 1. Was the airway abnormal or difficult during induction?
§ 2. Did anything change during surgery that would make the airway difficult to manage (edema, bleeding, restricted
access)?
§ 3. Does the patient have risk factors for increased extubation risk (known difficult airway, aspiration risk, OSA,
obesity, cardiopulmonary disease, neuromuscular disease, or metabolic abnormality such as acidosis, electrolyte
imbalance, hypothermia)?
§ Safer Extubation Techniques
o Extubate fully awake
o Extubate over a flexible fiberoptic bronchoscope
o Extubate then place a LMA
o Use an airway exchange catheter

Airway Exchange Catheter

§ The airway exchange catheter (or tube exchanger) is a long, thin, flexible, hollow tube that maintains direct access to the airway following
tracheal extubation. It is the most common device used to manage extubation of the difficult airway.
o The AEC is inserted into the in situ endotracheal tube.
o The distal end of the AEC remains in the trachea (~25- 26 cm at the lip)
o The endotracheal tube is removed.
o The patient maintains her own airway with the AEC in place (up to 72 hrs)
o By itself, the AEC does NOT provide a patient airway. Instead, think of it as a placeholder.
o If the patient requires re-intubation, the AEC is used as a stylet for re-intubation via the Seldinger technique
§ What You Can Do With An AEC
o end-tidal CO2 measurement
o jet ventilation (via Luer-lock adapter)
o oxygenation insufflation (via 15 mm adapter)
§ Complications
o Barotrauma/Pneumothroax
§ If you use jet ventilation in the patient with obstructed upper aiway, then air will get in but it wont get out.
§ Maneuvers that opent he upper airway should help: jaw thrust, oral airway, etc.
o Inability to Replace the Endotracheal Tube:
§ Replacing the ETT requires laryngoscopy to displace the supraglottic tissue
§ If the ETT hangs up on the arytenoids, then it should be rotated 90 degrees counterclockwise before advancing

51
Respiratory Notes:

52
Autonomic Nervous System
Cellular Communication
§ Cellular communication can be challenging topic. We want to make sure you understand it once and for all, so we’re going to approach this topic in a
series of questions and build upon each question in step-wise succession. If you aren’t using the workbooks yet, this is a great place to start.
§ To be able to respond to its environment, a cell must be capable of receiving and processing extracellular signals. An extracellular signal can take several
forms:
o Chemical: neurotransmitter, hormone, or drug
o Electrical: voltage change (think action potential)
o Mechanical: pressure
§ A Receptor receives the signal and instructs the cell to perform a specific function. Signal transduction is the process by which a cell converts this
extracellular signal into an intracellular response. Most receptors are embedded in the cell membrane, but there are few intracellular receptors as well.
we’ll cover all of the important categories here.
§ Membrane Bound Receptors
o There are 3 categories of membrane bound receptors:
§ Ion channel:
• An ion conducting pore is either open or closed
• A closed channel prevents ions from flowing along a concentration gradient
• An open channel allows ions to flow along a concentration gradient.
• Example: voltage-gated sodium channel in the neuron
§ G-Protein Coupled Receptor:
• The GPCR works in one of two ways:
o It opens or closes an ion channel
o Example: muscarinic-2 receptor in the SA node
o It activates or inhibits an enzyme inside the cell (shown in image)
o Example: alpha-1 receptor in vascular smooth muscle
§ Enzyme Linked Receptor:
• The receptor is also an enzyme
• At rest, the catalytic domain is inactive
• When the signal binds, the catalytic domain becomes activated
• Example: insulin receptor in skeletal muscle (linked to tyrosine kinase)
§ Intracellular Receptors
o A signal diffuses through the cell membrane and binds to a receptor located inside of the cell.
§ Example: steroids bind to receptors in the cytoplasm
§ Example: thyroid hormone binds to receptors in the cell nucleus
G-Protein Coupled Receptors
§ The Big Picture
o When organizing all of this in your head, it is helpful to think of the following sequence of events. Once you understand this,
you can use it as a scaffold to understand each of the GPCR system in greater detail.
First messenger àG-Protein Coupled Receptor àEffector àSecond Messenger à Cellular Response
§ First Messenger
o The first messenger is a ligand that binds to the GPCR> This ligand could be something endogenous to the body
(neurotransmitter or hormone) or something exogenous to the body ( a drug).
§ G-Protein Coupled Receptor
o Protein Structure:
§ The receptor portion is accessible outside of the cell membrane
§ The G-protein itself resides inside of the cell membrane. It consists of 3
subunits: alpha, beta, and gamma.
o Protein Function:
§ The G-protein either stimulates or inhibits an effector (enzyme or ion
channel).
• G stimulatory proteins (Gs and Gq) turn on an effector.
• G inhibitory proteins (Gi) turn off an effector
o What Happens When a Ligand Binds to the GPCR?
§ The ligand-receptor interaction activates the G-protein.
§ This causes the alpha subunit to dissociate from the beta and gamma subunits
§ The alpha subunit of a Gs or Gq protein will turn on an effector, while the alpha subunit of Gi protein will turn off an
effector
§ When the ligand unbinds from the receptor, the alpha subunit rejoins the beta and gamma subunits and its
interaction with the effector ends.

53
 § Effector
o The function of the effector is to activate the second messenger.
o Enzymatic effectors include adenylate cyclase and phospholipase C.
o Ion channel effectors include GABA-A and M2 receptor a the SA node.
§ Second Messenger, Enzymatic Cascade and Cellular Response
o The second messenger modulates a network of enzymatic activity, including phosphatase and protein kinases. This governs a
complex series of intracellular reactions that elicit a specific response within a particular cell type.
o Second messenger systems allow for signal amplification. This process allows a single molecule to initiate a process that
activates a large number of physiologic changes—each step progressively increases the magnitude of the response.
o The intracellular response to a second messenger is tissue specific. For example, increased cAMP may cause different effects in
different cell tyeps.
§ There are 5 second messengers that you should know:
o 1. Cyclic adenosine monophosphate (cAMP)
o 2. Cyclic guanosine monophosphate (cGMP)
o 3. Inositol triphosphate (IP3)
o 4. Diacyglycerol (DAG)
o 5. Calcium ion (Ca +2)
Signal Transduction: From Receptor to Second Messenger

§ In the last 2 questions we examined the big picture and types of receptors. Now let’s connect each receptor to its effector and second
messenger.

§ IP3=inositol triphosphate
§ DAG=diacylglycerol
§ cAMP=cyclic adenosine monophosphate
§ *remember that the cellular response is tissue specific, and we’ll cover these
responses in the next two questions.

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ANS Receptors and Physiologic Action: Part 1

§ Now that you reviewed receptors through second messengers, let’s take a look at the physiologic responses associated with each
receptor.
§ Memorize this table. You should be able to recite the entire thing in your sleep!

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Alpha-2 Receptor

§ The alpha-2 receptor is often poorly understood (making it great for test questions), so let’s give it the attention it deserves. The alpha-2
receptor is present throughout the body, and we can classify these locations in 3 ways.
o Presynaptic: NE releasing neurons in the CNS and PNS (negative feedback mechanism reduces NE release)
o Postsynaptic: Smooth muscle and several organs
o Nonsynaptic: platelets

§ Alpha-2 Receptor Stimulation & Transient Hypertension

o We all know that dexmedetomidine is a centrally acting alpha-2 agonist that reduces SNS tone and causes sedation, MAC
reduction, analgesia, bradycardia, and vasodilation. There is, however, more to this story…
o Rapid administration of dexmedetomidine can stimulate the postsynaptic alpha-2 receptors in the arterial and venous
circulations, leading to vasoconstriction and hypertension
§ The CNS effect (which ultimately produces vasodilation), temporarily lags behind.
§ Once it kicks in, the central alpha-2 effect overpowers the peripheral alpha-2 effect
§ Therefore, it is possible for dexmedetomidine to cause a transient rise in blood pressure.
Phosphodiesterase III
§ ATP (adenosine triphosphate) is the energy of life. Through its high energy phosphate bonds, ATP stores energy that we obtain from food and acts as the
molecular unit of currency of energy transfer. In the presence of oxygen, 38 moles of ATP can be produced from 1 mole of glucose.
§ How is ATP utilized by myocytes and vascular smooth muscle?
o Beta-1 receptors are present in the heart, while beta-2 receptors are present in skeletal muscle and other vascular beds.
o Epinephrine or norepinephrine can serve as the first messenger.
o Beta receptor stimulation activates a stimulatory G-protein (Gs) and instructs adenylate
cyclase to convert ATP into cAMP (cyclic adenosine monophosphate)
o cAMP is responsible for “turning on” a variety of protein kinases that instruct the cell to
perform a specific function
o Phosphodiesterase III metabolizes cAMP to AMP (adenosine monophosphate). This
“turns off” these protein kinases and the cell is no longer instructed to perform that
specific function.
o By inhibiting the “turn off” mechanism, inhibition of phosphodiesterase III indirectly
increases intracellular cAMP and maintains the protein kinases in the “turned on” state.
§ Inhibiting PDE III and Increasing cAMP has several beneficial effects:
o 1. In the cardiac muscle cell, cAMP augments myocardial performance by:
§ increasing intracellular calcium and the force of contraction
§ increasing the rate of relaxation by accelerating the return of calcium to the
sarcoplasmic reticulum—this is called lusitropy
o 2. In the vascular smooth muscle cell, cAMP inhibits myosin light chain kinase. This
causes:
§ vasodilation
§ decreased SVR
§ PDE III Inhibitors
o PDE III inhibitors, such as milrinone, are also called inodilators. They augment myocardial performance independently of the sympathetic
nervous system. This feature makes PDE III inhibitors useful in the following situations:
§ Beta-blocker induced myocardial depression
§ Acute heart failure
§ Unresponsiveness to IV catecholamines
§ Anytime the combination of increased inotropy and reduced afterload would be desirable
o In case you were wondering, there are five different varieties of phosphodiesterase (I—V). While PDE III is specific for cAMP, the other forms of
PDE are not specific cAMP. Theophylline is the prototype nonselective phosphodiesterase inhibitor.

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Norepinephrine Synthesis & Release

§ Norepinephrine is the primary neurotransmitter in the sympathetic nervous system.

§ You should understand how NE is synthesized, released, removed from the synaptic cleft, and metabolized. We will cover synthesis and
release here.

§ Norepinephrine Synthesis
o 1. Sympathetic neurons synthesize NE from tyrosine (an amino acid obtained from diet) or phenylalanine (converted to tyrosine
first)
o 2. Tyrosine is transported into the adrenergic nerve terminal and converted into DOPA by the enzyme tyrosine hydroxylase.
This occurs in the cytoplasm and is the rate limiting step in norepinephrine synthesis.
o 3. DOPA is converted to dopamine by the enzyme DOPA decarboxylase. This also occurs in the cytoplasm.
o 4. Dopamine is transported into a synaptic vesicle and is converted to norepinephrine by the enzyme dopamine beta-
hydroxylase.
* in the adrenal medulla, most of the norepinephrine is converted to epinephrine by the enzyme phenylethanolamine-N-
methyltransferase. The adrenal medulla secretes about 80% epinephrine and 20% norepinephrine into the circulation

§ Norepinephrine Release
o 1. The action potential depolarizes the nerve terminal
o 2. Voltage gated calcium channels open, and calcium flows into the nerve terminal
o 3. Increased neuronal calcium causes NE vesicles to fuse with the nerve terminal and release NE into the synaptic cleft via
exocytosis
o 4. NE inhibits its own release by stimulating the pre-synaptic alpha-2 receptor
o 5. NE can augment its own release by stimulating the pre-synaptic beta-2 receptor
Norepinephrine Termination of Action
§ Removal of Catecholamines from the Synaptic Cleft:
o 1. Reuptake into the presynaptic nerve
§ this is the primary mechanism that removes NE from the synaptic cleft
§ up to 80% of the NE released undergoes reuptake
§ most NE is recycled and repackaged into vesicles to be used again, however some NE
is metabolized by MAO in the nerve terminal
§ reuptake is blocked by tricyclic antidepressants and cocaine
o 2. Reuptake by extraneural tissues
§ these tissues contain MAO and COMT to metabolize NE
o 3. Diffusion away from the synaptic cleft
§ NE enters the circulation and is metabolized in the liver and kidney by MAO and
COMT
Catecholamine Metabolism
§ Metabolic Pathways
o There are 2 metabolic pathways for norepinephrine and epinephrine:
§ 1. Monoamine oxidase (MAO)
§ 2. Catechol-O-methyltransferase (COMT)
o the kidneys and liver are the principal sites of metabolism of catecholamines that have entered the circulation (this includes IV administration).
o Only ~5% of norepinephrine is excreted unchanged in the urine.
§ Final Metabolite
o The final byproduct of norepinephrine and epinephrine metabolism is vanilylmandelic acid (VMA). Another name for this compound is 3-
methoxy-4-hydroxymandelic acid
o Urine measurement of VMA permits a general assessment of overall SNS activity. The vast majority of VMA in the urine is the result of
deamination of norepinephrine in adrenergic postganglionic nerve endings.
o An elevated level of VMA in the urine aids in the diagnosis of pheochromocytoma

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Acetylcholine Synthesis, Release & Metabolism

§ Acetylcholine in the PNS

o Acetylcholine is the primary transmitter in the parasympathetic nervous system. It stimulates 3 different receptor types in the body:
§ Nicotinic type N (nerve)
• PNS ganglia
• SNS ganglia
• Central nervous system
§ Nicotinic type M (muscle)
• Neuromuscular junction
§ Muscarinic
• Postganglionic PNS effector organs
• Central nervous system
o Note that nicotinic receptors are ion channels, while muscarinic receptors are linked to G-proteins.
Ach Synthesis, Release & Metabolism
§ Ach Synthesis
o 1. Choline is transported from the blood into the cytoplasm of the nerve terminal.
o 2. Acetyl Coenzyme A is produced in the mitochondria and released to the cytoplasm.
o 3. In the presence of the enzyme choline acetyltransferase, choline and acetyl CoA are joined to
form acetylcholine
o 4. Acetylcholine is packaged into vesicles.
§ Ach Release
o 1. The action potential depolarizes the nerve terminal.
o 2. Voltage gated Ca+2 channels open and allow influx of Ca+2 into the nerve terminal.
o 3. Ca+2 is required for Ach vesicles to fuse with the nerve terminal and release Ach via exocytosis into the synaptic cleft.
o * Mg+2 is an antagonist of Ca+2 at the presynaptic nerve terminal. This explains why Mg+2 can cause muscle weakness or how it acts
synergistically with neuromuscular blockers
§ Ach Metabolism
o 1. Unlike norepinephrine, Ach is not reused and there is no uptake mechanism.
o 2. Ach must be rapidly metabolized to allow precise control of the effector organs.
o 3. Acetylcholinesterase (true cholinesterase) is positioned around the cholinergic receptors and quickly hydrolyzes Ach after it unbinds from
these receptors. The byproducts of Ach metabolism are choline and acetate.
o 4. Choline is transported back into the nerve terminal via reuptake and will serve as substrate for further Ach synthesis.
o 5. Acetate diffuses away from the synaptic cleft.
Autonomic Reflex Arc
§ The autonomic nervous system is a complex and well-coordinated network of visceral reflex arcs that work in concert to maintain whole body
homeostasis. Additionally, these reflex arcs are tightly integrated with the endocrine system.. the key points of integration include the renin-angiotensin
aldosterone axis as well as regulation of antidiuretic hormone, mineralocorticoids, glucocorticoids, and insulin.
§ The reflex arc allows for fine adjustments by positive and negative feedback mechanisms. It consists of 5 major components:
* you may want to remember the mneumonic “ACE” (Afferent – Control –Efferent_ to remember the order of afferent and efferent pathways.

§ Sensor
o Monitors the environment and informs the CNS of changes within the environment.
o When a change occurs, the stimulus alters the electrical potential of the sensor. Next, the sensor transduces the stimulus into an action
potential.
§ Afferent Pathway
o The afferent pathway links the sensor to the control center. It conducts the action potential towards the CNS.
§ Control Center
o The hypothalamus, brainstem, and spinal cord receive the bulk of sensory input from the body.
o While the cerebral cortex is not a component of the autonomic reflex arc per se, it can modulate autonomic output that may occur with
emotions, such as with fear and anxiety
§ Efferent Pathway
o The efferent pathway links the control center to the effector organ.
o It conducts the action potential towards the effector organ
o The efferent pathway almost always consists of two nerve fibers: 1 preganglionic and 1 postganglionic nerve
o The ganglion is the site where the preganglionic nerve and the postganglionic nerve form a synapse
o Preganglionic Neuron
§ The preganglionic neuron is a myelinated B-fiber
§ It exists the CNS and synapses with the postganglionic fiber in a n autonomic ganglion.
§ It releases acetylcholine onto a nicotinic type-N receptor in the ganglion
o Postganglionic Neuron
§ The postganglionic neuron is an unmyelinated C-fiber
§ It exits the ganglion and innervates the effector organ
§ In the PNS, a cholinergic postganglionic fiber releases acetylcholine onto its effector organ
§ In the SNS, an adrenergic postganglionic fiber releases norepinephrine onto its effector organ
§ There are some exceptions to this rule (adrenal medulla, sweat glands, piloerector muscles, and some blood vessels). These will be
covered shortly.
§ Effector Organ: Elicits a physiologic change in an effort to restore homeostasis

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Bird’s Eye View of the SNS & PNS

§ The efferent division of the autonomic nervous system is divided into two complementary pathways—the sympathetic nervous system
and the parasympathetic nervous system
§ You should think of the sympathetic and parasympathetic nervous systems as physiologic antagonists of each other. The relative balance
between these two systems determine how a particular organ will respond.
o Resting tone describes the relative balance of SNS and PNS input to a particular organ.
o Denervation is the absence of autonomic tone to a particular organ.

§ Comparative Anatomy & Physiology

SNS PNS
Origin Thoracolumbar: Craniosacral:
§ T1-L3 § CN III, VII, IX, X
§ Cell bodies arise from intermediolateral region of § S2-S4
spinal cord and axons exit via the ventral root
Ganglia Near spinal cord Near or inside effector organ
Post to preganglionic ratio 30:1 àpost-synaptic amplification contributes mass 1-3: 1 àprecise control of each organ
response
Preganglionic fiber Short Long
Myelinated Myelinated
B-fiber B-fiber
Post-ganglionic fiber Long Short
Unmyelinated Unmyelinated
C-fiber C-fiber
Neurotransmitter at ganglia Ach Ach
Receptor at ganglia Nicotinic –Type N Nicotinic –Type N
Neurotransmitter from NE Ach
post-ganglionic fiber § Ach at sweat glands, piloerector muscles, and
some vessels
§ There are no post-ganglionic fibers in the adrenal
medulla
§ Chromaffin cells release NE and Epi
Directly into the systemic circulation
Receptor at effector organ Alpha Muscarinic
Beta
Dopamine
Muscarinic (see above)

§ Sympathetic Ganglia
o In the efferent limb of the ANS, the ganglion is where the preganglionic and postganglionic neurons synapse.
o In the sympathetic nervous system, the preganglionic sympathetic fibers exit the spinal cord via the ventral nerve roots. These fibers enter the
sympathetic chain by way of the white communicating rami. They are called white rami, because they are myelinated.
o Once inside the sympathetic chain, a preganglionic fiber will travel one of three paths on its way to synapse with the
postganglionic fiber:
§ 1. It will synapse with the postganglionic fiber and exit at the same level.
§ 2. It will ascend or descend the sympathetic chain, then synapse at a higher or lower level before exiting.
§ 3. It will bypass the sympathetic chain entirely and synapse in a collateral ganglion.
o After synapsing in the ganglia, the postganglionic fiber will travel to its respective effector organ.
o Some fibers, such as those that innervate the sweat glands, piloerector muscles, and blood vessels to the skin and muscle, take a different path.
After exiting the sympathetic chain, they re-enter the spinal nerve via the grey communicating rami, and then they travel alongside somatic
nerves towards their effector organs. This is the purple nerve in the image.
o As you’ll see in the next question, the adrenal medulla follows its own rules.
§ The Stellate Ganglion—An NCE FAVORITE!
o The stellate ganglion is an important one to know. It provides sympathetic innervation to the ipsilateral upper extremity and a
portion of the head and neck.
o It is often blocked for treatment of upper extremity sympathetic dystrophy, complex regional pain syndrome, or to increase
blood flow to the upper extremity.
o Stellate ganglion blockade is often an unintended consequence of a brachial plexus block.
o Blockade of the stellate ganglion manifests as Horner’s syndrome: ptsosis, anhidrosis, miosis, and enophthalmos.
o Horner syndrome mnemonic: Very homely pam (Vasodilation Horner Ptosis Anhidrosis Miosis)
o Anhidrosis=inability to sweat normally, can lead to overheating
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Adrenal Medulla
§ There are 2 adrenal glands—one that sits atop each kidney.
§ The adrenal gland is divided into 2 key areas:
o Medulla: secretes catecholamines
o Cortex: secretes glucocorticoids, mineralocorticoids, and androgens (this is covered in endocrine)
§ Anatomy & Physiology

o Preganglionic sympathetic nerves are myelinated B-type fibers that arise from the thoracic region of the spinal cord (T5-T9)
o The preganglionic fibers release acetylcholine directly onto the chromaffin cells of the adrenal medulla.
o Chromaffin cells are derived from neural tissue
o There are no postganglionic neurons in the adrenal medulla
o SNS activation stimulates the chromaffin cells to release epinephrine and norepinephrine directly into the blood stream.
§ You can think of the adrenal medullas a sympathetic ganglion that is in direct contact with the systemic circulation. Therefore, any organ bearing
adrenergic receptors (except the brain) is activated by catecholamines released form the adrenal medulla. At rest, the adrenal medulla secrete:
o Epinephrine 0.2 mcg/kg/min
o Norepinephrine 0.05 mcg/kg/min
§ Catecholamines remain in the bloodstream 5-10 times longer than they do in the synaptic cleft.
o In the synaptic cleft, catecholamines are quickly removed via reuptake.
o Catecholamines in the circulation must travel to the kidneys and liver, where they’re metabolized by COMT and MAO
o Vanilylmandelic acid (VMA) is the final metabolite of epinephrine and norepinephrine metabolism
§ Pheochromocytoma
o Pheochromocytoma is a catecholamine secreting tumor (mostly NE) that usually originates in the chromaffin tissue in the adrenal gland.
§ The classic presentation reflects excessive SNS actiation and includes headache, diaphoresis, and tachycardia.
§ An elevated level of VMA in the urine aids in the diagnosis of pheochromocytoma
o Understanding the hemodynamic management of this patient is critical to the success of your anesthetic. You must alpha block before you beta
block! Just remember that A comes before B.
o Commonly used alpha antagonists include:
§ Non-selective: phenoxybenzamine and phentolamine
§ Alpha-1 selective: doxazosin and prazosin
o Problems that arise from blocking the beta receptor first:
§ Beta-2 blockade inhibits skeletal muscle vasodilation and increases SVR
§ Beta-1 blockade reduces inotropy and can precipitate CHF in the setting of increased SVR
o After the tumor is removed, all of the catecholamines that it was secreting go with it. Prepare for hypotension and hypoglycemia.
Transcellular Potassium Shift
§ Sympathetic stimulation causes hepatocyte to release glucose and potassium into the systemic circulation.
§ What Happens to Glucose?
o The glucose provides substrate for aerobic metabolism. For cells to utilize glucose, however, insulin must be present. Therefore,
it should make sense that SNS stimulation also increase insulin output from the pancreatic beta cells.
§ What Happens to Potassium?
o There are 2 phases to the potassium response:
§ Initially potassium release from the liver causes the serum [K+] concentration to rise. This effect is very short-lived.
§ Remember that SNS stimulation causes the adrenal medulla to secrete catecholamines into the systemic circulation.
§ When epinephrine binds to the beta-2receptor on skeletal muscle and erythrocytes, it activates the Na+/K+ pump and
shifts potassium into the cells. The end result is a decrease in serum potassium.
§ Causes of Transcellular Potassium Movement
o There are a variety of situations that promote the transcellular potassium shift. Some examples include:
§ Beta-2 receptor agonism (albuterol, ritodrine, epi)
§ Methylxanthines (theophylline)
§ Nicotinic type-m agonism (succinylcholine)
§ Destruction of cell membranes (rhabdomyolysis)
§ Activating the H+/K+ exchanger (acidosis)
§ Activating the Na+/K+ exchanger (epinephrine or insulin)
§ When reviewing for the NCE, you should always look for ways to build connections between topics. Instead of learning topics in isolation,
try to ask yourself how content from one area relates to another area. In this question, we are asking how the autonomic nervous system
affects serum potassium concentration. From here you may want to ask yourself what other situations might affect serum potassium and
then how each organ responds to those changes. The big picture becomes clear when you can visualize how everything is connected.

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Baroreceptor Reflex

§ Conventional teaching says that the baroreceptor reflex regulates short term blood pressure control, while longer term blood pressure
control is mediated by RAAS and ADH. There is emerging evidence, however, that suggests that BRR also contributes to longer term BP
control as well.
§ When the blood pressure rises, the baroreceptor reflex decreases heart rate, contractility, and systemic vascular resistance. Conversely,
when blood pressure falls, the baroreceptor reflex increases the heart rate, contractility, and total peripheral resistance.
§ This reflex is adaptable over time. In the patient with chronic hypertension, the baroreceptors readjust to a higher set point. A
consequence of this is that these patients autoregulate at a higher range of mean arterial pressure. This renders them less tolerant of
hypotension.
§ Sensors & Afferent Pathways
o Stretch receptors line the carotid sinus and the transverse aortic arch. As blood pressure increases, so does the amount of
stretch on these receptors. This changes their firing rates.
o There are 2 locations where pressure (stretch) is monitored: the carotid sinus and transverse aortic arch.
§ The carotid sinus is located at the origin of the internal carotid artery immediately distal to bifurcation of the internal
and external carotid arteries. This region is innervated by the carotid sinus nerves (nerve of Hering), which converge
with the glossopharyngeal nerve to send afferent impulses to the nucleus tractus solitatrius in the medulla.
§ The transverse aortic arch sends afferent information via the vagus to the same location.
§ Control Center & Efferent Pathways
o The vasomotor center in the medulla and the pons serves as the main control center for the baroreceptor reflex.
o There are 4 key functions of the vasomotor center: vasoconstriction, vasodilation, cardiac stiulation, and cardiac inhibition.
o Hypertension increases afferent traffic to the nucleus tractus solitatrius. This disinhibits inhibitory pathways and stimulates the
rostral ventrolateral medulla and the intermediolateral nucleus.
o Sympathetic output is decreased via inhibition of the cardioaccelerator nerves (T1-T4) and the neural network to the
vasculature. At the same time, there is a reciprocal rise in vagal tone. The net effect is a reduction in heart rate, inotropy and
systemic vascular resistance
Baroreceptor Reflex Effects of Drugs
§ You should know how drugs impact the baroreceptor reflex. As a general rule:
o If the heart rate increases in the setting of hypotension, then the baroreceptor is said to be preserved.
o If the heart rate does not increase in the setting of hypotension or does not decrease in the setting of hypertension, the baroreceptor reflex is
said to be impaired.
§ Keep in mind that this is not an all or none phenomenon, and these physiologic changes occur in varying degrees depending on drug dose, rate of
administration, and patient variability.
§ Volatile Anesthetics
o Volatile anesthetics decrease the effectiveness of the baroreceptor reflex in a dose dependent fashion.
o When the ability of the baroreceptor reflex is impaired, hemodynamic instability may result.
o Because isoflurane has mild beta-1 agonist properties, it impairs the baroreceptor the least.
§ IV Induction Agents:
o Thiopental preserves baroreceptor function. Induction with thiopental causes SVR to decrease with a compensatory rise in heart rate.
o Propofol usually depresses baroreceptor function. If the baroreceptor reflex was preserved, then you would expect to see the heart rate rise as
the SVR falls. Propofol can cause bradycardia and even asystole!
o Ketamine activates the SNS and will cause an increased heart rate with a minimal change in SVR. In the critically ill patient with an exhausted
catecholamine reserve, ketamine’s direct myocardial depressant effects may be unmasked.
o Etomidate administration is usually accompanied by an unchanged heart rate with a small decrease in SVR. Hypovolemic patients may
experience hypotension following etomidate induction.
§ Vasodilators
o Hydralazine is a potent vasodilator. The reduction in SVR is countered with an increase in heart rate via the baroreceptor reflex.
o Nitroprusside and nitroglycerine also preserve the baroreceptor reflex.
§ Beta Adrenergic Blockers
o By antagonizing the beta-1 receptor in the heart, beta blockers may, depending on the extent of beta blockade, prevent a compensatory rise in
heart rate in the setting of hypotension. Labetalol also antagonizes the alpha-1 receptor and may increase the risk of orthostatic hypotension.
§ Catecholamines
o The effect of norepinephrine on heart rate is dose dependent. In lower doses, the beta-1 chronotropic effects prevail. As the dose increases,
the alpha-1 vacoconstrictive effects overshadow the beta-1 effects. The net result is a baroreceptor-mediated fall in HR
o The other catecholamines (epinephrine, dobutamine, isoproterenol, and dopamine) cause the HR to increase regardless of their dose.
o Phenylephrine is not a catecholamine. Bradycardia is a common side effect and reflects preservation of the baroreceptor reflex.

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 Bezold-Jarisch & Bainbridge Reflexes
§ While the Bezold-Jarisch reflex slows the heart rate in the setting of profound hypovolemia (preload is too low), the Bainbridge reflex increases the heart
rate in the setting of venous congestion (preload is too high). These reflexes have a tendency to override the baroreceptor reflex.
Bezold-Jarisch: Empty heartàdecrease HR Bainbridge: Full heartàincreased HR
Stimulus Venous return too low Venous return too high
Myocardial ischemia
Purpose Allows heart adequate time to fill Minimizes venous congestion and promotes flow
A slow heart is a better perfused heart
Sensors Right ventricle SA node
• Mechanoreceptors (venous return) Right ventricle
• Chemoreceptors (ischemia) Pulmonary veins
• SA node stretch also directly increases intrinsic firing rate
Afferent Vagus—unmyelinated C-fibers Vagus—unmyelinated C-fibers
Control Center Medulla-vasomotor center Medulla-vasomotor center
Efferent Vagus Vagal inhibition
Effector SA node—decrease HR SA node—increased HR
AV node—decreased CV
Clinical Response Bradycardia Tachycardia
Hypotension
Coronary artery vasodilation
Treatment Restore preload None
• IVF
• Trendelenburg position
• Elevate legs above head
Increase heart rate
• Atropine
• Ephedrine
• epinephrine
Clinical examples Profound hypotension Autotransfusion during childbirth
Massive hemorrhage
Cardiac arrest with spinal anesthesia
Myocardial ischemia
Shoulder arthroscopy + interscalene block + sitting
position
For completeness, you should understand that cardiac congestion also leads to:

§ 1. Decreased ADH release from the posterior pituitary gland

§ 2. Increased atrial natriuretic peptide releaseàdiuresisàdecreased intravascular volume
Oculocardiac Reflex

o We believe that cardiovascular reflexes are prime NCE content, and the oculocardiac reflex is no exception.
o The oculocardiac reflex is otherwise known as the five & dime reflex:
Stimulus Traction to the extraocular muscles (especially the medial rectus)
Strabismus surgery—particularly in children
Pressure on the globe
Pressure on the conjunctiva
Ocular trauma
Pressure on the orbital tissue that remains following enucleation
A retrobulbar block can either cause or prevent the oculocardiac reflex
Afferent Limb Long & short ciliary n. àciliary ganglionàopthalmic division V1 of trigeminal n. (CN V)àGasserian ganglion
Control Center Medullar (vasomotor center)
Efferent Limb Vagus n. (CN X)
Effector Organ Heart (M2 receptor at SA and AV nodes)
Clinical Presentation Bradycardia
Hypotension
Junctional rhythm
AV block
Asystole
Factors that Worsen Severity Hypoxemia
Hypercarbia
Light anesthesia
Treatment 1. Ask the surgeon to remove the stimulus. This is usually enough to terminate the reflex.
2. Administer 100% oxygen, ensure proper ventilation, and deepen the anesthetic.
3. Administer an anticholinergic such as atropine or glycopyrrolate.
Other The reflex will fatigue with subsequent occurences.
Anticholinergic pretreatment may help prevent the reflex (Barash says “no” and Nagelhout says “yes “ for peds).

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Other Autonomic Reflexes
§ The Cushing reflex is a sign of intracranial hypertension. This reflex presents with hypertension, bradycardia, and irregular respirations.
Hypertension is the body’s attempt to restore CPP, bradycardia is from the baroreceptor reflex’s response to hypertension, and irregular
respirations are the result of brainstem compression.
§ The celiac reflex is initiated by traction to the mesentery or other abdominal organs. This reflex is mediated by the vagus nerve and causes
bradycardia and hypotension.
§ The chemoreceptor reflex is stimulated by hypoxia and hypercarbia. It increases minute ventilation and SNS tone.
Heart Transplant, Glomus Tumor & Multiple System Atrophy
Heart Transplant

• The transplanted heart is severed from autonomic influence, so the heart rate is determined by the intrinsic rate of the SA node. This explains why these
patients often have a resting tachycardia ( HR=100-120 bpm).
• If cardiac output is the product of heart rate and stroke volume (and the heart rate is fixed), then cardiac output becomes dependent on preload. Indeed,
CO is highly dependent on cardiac filling. This feature makes these patients very sensitive to hypovolemia.
• Which Drugs Can Be Used To Increase Heart Rate?
o Central to understanding this is knowing that there is no autonomic input from the cardiac accelerator fibers or the vagus nerve.
§ Drugs that directly stimulate the SA node can be used to increase the HR (epinephrine, isoproterenol, glucagon).
§ Drugs that indirectly stimulate the SA node can NOT be used (atropine, glycopyrrolate, and ephedrine).
• Other Considerations:
o Although cholinesterase inhibitors won’t cause bradycardia, they’ll still cause s/sx of PNS activation elsewhere in the body. You’ll need to
administer an anticholinergic with reversal of neuromuscular blockade to prevent these issues.
o You may see two P waves on the EKG; one corresponds to the recipient’s intrinsic SA node and one from the donor heart. The SA node of the
native heart may still react to fluctuations in autonomic input, but this will not affect cardiac function.
Glomus Tumor

• Glomus tumors release several vasoactive substances that can lead to exaggerated hyper- or hypotension
o Norepinephrine (similar to pheochromocytoma): hypertension
o Serotonin and kallikrein (similar to carcinoid tumor): bronchoconstriction, headache, hypertension, flushing, and diarrhea
o Histamine or bradykinin: bronchoconstriction and hypotension
o These tumors do not release epinephrine, because they lack the enzyme that converts NE to EPI (phenylethanolamine N-methyltransferase).
o Octreotide can be used to treat carcinoid-like s/sx
• Cranial nerve dysfunction (glossopharyngeal, vagus, and hypoglossal) can cause swallowing impairment, aspiration of gastric contents, and airway
obstruction. Surgical dissection of a glomus tumor that has invaded the internal jugular vein increases the risk of air embolism.
Multiple System Atrophy

• Multiple system atrophy (previously known as Shy-Drager syndrome) causes degeneration of the locus coeruleus, intermediolateral column of the spinal
cord (where the cell bodies for the SNS efferent nerves live), and the peripheral autonomic nerves.
• s/sx reflect autonomic dysfunction: orthostatic hypotension, urinary retention, impotence, and bowel dysfunction. Death from cerebral hypoperfusion
usually occurs within 8 years of the initial diagnosis.
• Autonomic dysfunction contributes to hemodynamic instability during anesthesia. Hypotension is treated with volume resuscitation and direct acting
sympathomimetics. Indirect acting adrenergic agonists (ephedrine) and possibly ketamine can cause an exaggerated hypertensive response.
Adrenergic Agonists & Vasopressin
Norepinephrine

• Norepinephrine is a naturally occurring catecholamine with a dose dependent affinity for alpha-1, alpha-2, and beta-1 receptors. This explains why
different doses produce different clinical effects.
o Dose=0.02-0.4 mcg/kg/min
o Low dose range: beta-1 selective (increased HR, increased inotropy)
o High dose range: stimulates alpha-1,alpha-2, and beta-1 receptors (increased SVRàincreased BPàdecreased HR via baroreceptor reflex)
• Key Points:
o Norepinephrine is an ideal drug for low SVR states like sepsis or post-cardiopulmonary bypass hypotension due to low afterload.
o Avoid NE in the setting of cardiogenic shock, because it increases afterload and MVO2.
o Extravasation of peripherally administered NE can cause tissue necrosis, so you should administer it via a central line.
o If extravasation occurs at a peripheral site, the area should be injected with phentolamine (2.5-10mg in 10mL of diluent) to vasodilate the
affected region. A stellate ganglion block is anoter treatment option.
Epinephrine

• Like norepinephrine, the dose of epinephrine determines its clinical effects

o Low dose (0.01-0.03 mcg/kg/min): beta-1 + Beta-2 (increased HR, CO, inotrophy, decreased SVR & wide pulse pressure)
o Intermediated dose (0.03-0.15mcg/kg/min): mixed alpha and beta effects
o High dose (>0.15mcg/kg/min): alpha effects predominate and supraventricular tachyarrythmias are common
• Key points:
o Bronchodilation (useful for bronchospasm)
o Mast cell stabilization (useful for anaphylaxis)
o Prolongs duration of local anesthetics
o Increases serum glucose
o Causes hypokalemia due to transcellular potassium shift

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Dopamine

• Like epinephrine and norepinephrine, the dose of dopamine determines its clinical effects.
o Low dose (1-2 mcg/kg/min): renal vasodilation and increased RBF (BP may decrease as more CO is delivered to the kidneys)
o Intermediate dose (2-10mcg/kg/min): cardiac stimulation (increased HR, inotropy, CO)
o High dose (10-20mcg/kg/min): vasopressor effect (alpha effects overshadow DA and beta effects)
• Key point:
o Renal dose dopamine does NOT reduce morbidity or mortality and it does NOT prevent renal failure.
Isoproterenol

o Isoproterenol is a synthetic catecholamine derived from dopamine. It stimulates beta-1 and beta-2 receptors.

§ Dose=0.02 – 0.5 mcg/kg min

§ Cardiac stimulation (increased HR, inotropy, CO)
§ Vasodilation decreases SVR
§ The reduction in SVR can be so severe as to drop diastolic blood pressure, and this can impair coronary perfusion pressure (CPP+
AoDB-LVEDP).
§ This also makes it a poor choice for septic shock.
§ It can cause severe dysrhythmias and tachycardia.
Dobutamine

• Dobutamine is a synthetic sympathomimetic amine with potent beta-1 and mild beta-2 agonistic effects
o Dose=0.5-15 mcg/kg/min
o Cardiac stimulation (increased HR, inotropy, CO)
• Key Points:
o Bolus dose=20-100 mcg
o Infusion=10-200mcg/min
o Increases SVR
o Increases coronary perfusion pressure
o Reflex bradycardia
o Useful for conditions where increased afterload is required, such as hypertrophic cardiomyopathy or tetralogy of Fallot
Ephedrine

• Non-catecholamine with direct and indirect effects at the alpha-1, alpha-2, beta-1, beta-2 receptors
• Key Points
o IV dose= 5-10 mg
o IM dose= 25-50mg
o Increased HR, increased inotropy, increased CO, increased SVR
o Uses endogenous catecholamine stores from the presynaptic sympathetic nerve
o Multiple doses can cause tachyphylaxis (progressively smaller response to a given dose after multiple administrations)
o Ephedrine doesn’t work well when neuronal catecholamine stores are depleted (sepsis) or absent (heart transplant)
o Risk of hypertensive crisis in patients on MAO inhibitors.
Vasopressin

• For the purposes of the NCE< vasopressin and arginine vasopressin are the same thing. It is produced by the hypothalamus and released by the posterior
pituitary gland.
• Vasopressin restores blood pressure in two ways:
o V1 receptor stimulation causes intense vasoconstriction
o V2 receptor stimulation sitmulates the synthesis and insertion of aquaporins into the walls of the collecting ducts. This increases water (but not
solute) reabsorption and lowers serum osmolarity.

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Beta Antagonists

• Beta antagonists are either cardioselective (they target the beta-1 receptor) or nonselective (they target the beta-1 and beta-2 receptors
equally). You should know which are which.
• Clinical use of Beta Blockers Beta-1 Selective Nonselective
o Essential hypertension Atenolol Carvedilol
o Angina pectoris Acebutolol Labetalol
o Coronary artery disease Betaxolol Nadolol
o Myocardial ischemia Bisoprolol Pindolol
o Dysrhythmias Esmolol Propranolol
o Congestive heart failure Metoprolol Timolol
o Hyperthyroidism
o Migraine headaches Menumonic: MABE AB (maybe-AB)
• Key Points
o Beta-1 receptor antagonism reduces heart rate, inotropy, conduction veolocity, and myocardial oxygen demand.
o Non-selective beta blockers increase airway resistance. In patients with asthma, a cardioselective beta blocker is the best
option.
o Atenolol is the only beta blocker that is metabolized by RBC esterases. This accoutns for a very short t1/2 of 9 min.
o Labetalol is a mixed alpha and beta antagonist with a beta to alpha block ratio of 7:1.
o Carvedilol is a mixed alpha and beta antagonists with a beta to alpha block ratio of 10:1.
o Beta blocker overdose can bet treated with glucagon, calcium, PEDI III inhibitors, epinephrine, isoproterenol, and/or cardiac
pacing.
o Preoperative beta blockade reduces the risk of cardiac morbidity and mortality, however it may increase the risk of stroke,
bradycardia, and hypotension.
o Patients currently on beta blocker therapy should continue their medication throughout the perioperative period.
• Membrane Stabilizing Properties
o Membrane stabilizing properties is another way of saying that a drug has local anesthetic-like effects.
o This effect reduces the rate of rise of the cardiac action potential, however this probably only occurs when these drugs reach
toxic levels. Examples: propranolol and acebutolol
• Intrinsic Sympathomimetic Activity
o Beta blockers that exert a partial agonist effect, while simultaneously blocking other agonists that have a higher affinity for the
beta receptor are said to have intrinsic sympathomimetic activity.
o Examples: labetalol and pindolol
Alpha Antagonists

• Phenoxybenazmine
o Phenoxybenzamine is a long acting, non-selective, noncompetitive antagonist of the alpha-1 and alpha-2 receptor.
o It causes vasodilation by decreasing SVR.
o It impairs the NE regulating effect of the presynaptic alpha-2 receptor à reflex tachycardia.
o Its primary role is to manage hypertension in the patient with pheochromocytoma (0.5-1 mg/kg PO)
o Side effects: orthostatic hypotension and nasal congestion
• Phentolamine
o Phentolamine is a short acting, non-selective, competitive antagonist of the alpha-1 and alpha-2 receptor.
o It causes vasodilation by decreasing SVR
o It impairs the NE regulating effect of the presynaptic alpha-2 receptoràreflex tachycardia.
o Clinical uses include treatment of pheochromocytoma or autonomic hyperreflexia (30-70 mcg/kg IV).
o Phentolamine can also be injected into tissue surrounding an infiltrated IV containing a vasoconstrictor (2.5-10mg in 10mL
diluent).
• Prazosin
o Prazosin is a selective alpha-1 blocker
o It causes vasodilation by decreasing SVR
o It does not impact the NE regulating effect of the presynaptic alpha-2 receptor, so reflex tachycardia is unlikely.
o Clinical uses include essential hypertension, especially in patients with benign prostatic hypertrophy.
• Yohimbine
o Yohimbine is an herb that antagonizes the alpha-2 receptor.
o It increases sympathetic tone by increasing NE release from the presynaptic nerve terminal.
o It is used to treat orthostatic hypotension.
o Overdose leads to tachycardia and hypertension.

65
ANS Notes:

66
Cardiovascular: Anatomy & Physiology
• The Myocyte
o Properties of Cardiac Muscle
§ Cardiac myocytes have properties of skeletal muscle as well as neural tissue.
o Like Skeletal Muscle:
§ It contains actin and myosin myofilaments
§ It is capable of contraction
§ The T-tubule system and the sarcoplasmic reticulum work to maintain Ca+2 homeostasis for contraction and relaxation.
o Unlike Skeletal Muscle
§ Tight junctions serve as low resistance pathways that help spread the cardiac action potential throughout the myocardium
§ Tight junctions are also called gap junctions or nexi
§ Cardiac myocytes contain more mitochondria than skeletal muscle cells
o Like Neural Tissue
§ It generates a resting membrane potential
§ It can initiate an action potential
§ It can propagate an action potential
• Terms to Know
o Automaticity: The ability to spontaneously generate an action potential
o Excitability: The ability to respond to an electrical stimulus by depolarizing and firing an action potential.
o Conductance: because of their charge ions do not freely pass through cell membranes. Instead an ion requires an open channel to
cross from one side of the membrane to the other. An open ion channel increases the conductance of that ion, while a closed
channel reduces conductance of that ion.
o Equilibrium potential: the Nernst equastion can be used to predict an ions equilibrium potential.
§ Equilibrium is achieved when there is no concentration gradient and therefore no net flow of ion across the cell
membrane. The charges inside the membrane balance the charges on the outside of the membrane

.
§ The only math you’ll need for the NCE is addition, subtraction, multiplication and division. Don’t fool yourself, however.
You may have to get creative with algebraic substitution (rearranging equations and solving for unknown variables). The
good news is that you won’t have to calculate the Nernst equation.
o Resting Membrane Potential
§ The difference in electrical potential between the inside and outside of the cell. The inside of the cell is negative relative to
the outside. RMP is established by three mechanisms:
• 1. Chemical force
• 2. Electrostatic counterforce
• 3. Sodium/potassium ATPase
o Threshold Potential
§ The internal voltage at which the cell depolarizes. Depolarization is an all or none phenomenon—once it begins, it cannot
be stopped.
• 1. When RMP is closer to TP, the cell is easier to depolarize.
• 2. When REMP is further from TP, the cell is harder to depolarize.
o Depolarization
§ Depolarization takes place when there is a reduced polarity across a membrane. There is less of a charge difference
between the inside and outside of the cell.
§ In excitable tissue, depolarization results in an action potential.
o Hyperpolarization
§ Hyperpolarization takes place when there is an increased polarity across a membrane. There is a larger charge difference
between the inside and outside of the cell.
o Repolarization
§ The restoration of membrane potential towards resting membrane potential following depolarization.

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• Sodium/Potassium Pump
o Potassium
§ The myocyte is permeable to potassium, but not other electrolytes or proteins. Because the cell continuously leaks potassium, it loses positive
charges. This is why the inside of the cell is negative and the outside becomes relatively positive. This also explains why K+ is the primary
determinant of resting membrane potential.
• When serum K+ decreases, RMP becomes more negative, and the myocytes become more resistant to depolarization.
• When serum K+ increases, RMP becomes more positive and myocytes depolarize more easily.
o Sodium
§ When the cell is at rest, Na+ permeability is very low compared to K+. When RMP approaches threshold potential, voltage-gated sodium
channels open and sodium conductance increases. This depolarizes the cell.
o Sodium-Potassium ATPase
§ The Na/K-ATPase is the same thing as the Na/K pump. It serves two purposes:
• 1. It removes the Na+ that enters the cell during depolarization.
• 2. It returns K+ that has left the cell during repolarization.
o For every 3 Na+ ions it removes, it brings 2 K+ ions into the cell.
o The Na/K-ATPase is always on.
o It is an active transport mechanism that requires energy in the form of ATP.
• Cardiac Action Potential: Ventricle
o The action potential for ventricular muscle is unique. There is a plateau phase where depolarization is prolonged. This gives the cardiac myocytes time to
contract, so the heart has enough time to eject its stroke volume.
o The SA node, AV node, and neural tissue do not have a plateau phase. We will cover these in the next topic.
o 5 Phases of the Ventricular Action Potential

The Bare Minimum

o Depolarization: Na+ in
o Initial repolarization: Cl- in
and K+ out
o Plateau: Ca+2 in
o Repolarization: K+ out

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• Cardiac Action Potential: SA Node
o The heart is made of contractile tissue (cardiac myocytes) and specialized conduction fibers that can generate and conduct
action potentials. These action potentials are propagated by the conduction system and spread through the entire myocardium
in a highly ordered and synchronized way.
§ SA Nodeàinternodal tractsàAV nodeàBundle of HisàLeft and right bundle branchesàpurkinje Fibers
o What determines the heart rate?
§ The heart rate is a function of: Intrinsic firing rate (BPM)
• The intrinsic firing rate of the dominant SA Node 70-80 (faster in the denervated heart)
pacemaker (usually the SA node) AV Node 40-60
• Autonomic tone Purkinje Fibers 15-40
§ Intrinsic Firing Rate of the SA Node:
• The SA node (Keith-Flack node) resides in the right atrium
o The rate of spontaneous phase 4 depolarization of the SA node determines the intrinsic heart rate.
o All of the cells in the myocardium are capable of automaticity (self-generating an action potential), however
each cell type has its own rate of spontaneous depolarization.
o The cells with the fastest rate of depolarization determine how often the heart depolarizes
o Each time the SA node fires, it depolarizes the rest of the conduction system as well as the cardiac myocytes.
o After the cardiac cycle is complete the SA node will be the first to fire again.
• SA nodal disease impairs its ability to function as the heart’s dominant pacemaker. In this situation, the cells
with the next highest rate of phase 4 spontaneous depolarization will assume the pacemaker responsibility.
This explains why a junctional rhythm is slow and does not have a P wave. We’ll provide you with extensive
coverage of cardiac dysrhythmias in Monitoring III: Cardiac Rhythms
§ Autonomic Influence
• The autonomic nervous system modulates the heart rate. At rest, PNS tone exceeds SNS tone.
o PNS tone: vagus nerve (CN X)- the right vagus innervates the SA node and the left vagus
innervates the AV node.
o SNS tone: cardiac accelerator fibers (T1-T4)
o We have illustrated the morphology of the SA node action potential. The AV action potential looks similar, but it has a lower slope during phase
4 and therefore a slower intrinsic firing rate.
o For the NCE, you should be able to compare and contrast the action potentials of the SA and AV nodes with the action potential of the
ventricular myocyte. For example, the morphology of each action potential is different. Also, note that the SA and AV nodes do not have a
plateau phase and that resting membrane potential is higher than ventricular muscle. While these are just a few differences, they should get
you thinking about all of the possible ways that the question writers might try to test your knowledge.

o The Na/K-ATPase helps re-establish the Na+ and K+ gradients after repolarization.
• How Does Heart Rate Change?
o We can alter the heart rate by manipulating 3 variables:
§ 1. The rate of spontaneous phase 4 depolarization
§ 2. Threshold potential
§ 3. Resting membrane potential
o There are 3 conditions that can increase heart rate. Each one causes threshold potential to be reached faster.
§ 1. The rate of spontaneous phase 4 depolarization increases.
§ 2. Rate of phase 4 remains constant, but threshold potential becomes more negative (shorter distance between RMP and TP).
§ 3. Rate of phase 4 remains constant, but resting membrane potential becomes less negative (shorter distance between RMP and
TP).
o SNS stimulation via norepinephrine increases heart rate by increasing Na+ and Ca+ conductance. This increases the rate of spontaneous phase 4
depolarization.
o PNS stimulation via acetylcholine slows heart rate by increasing K+ conductance and hyperpolarizing the SA node. This decreases resting
membrane potential and reduces the rate of spontaneous phase 4 depolarization.

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• Oxygen Delivery
o Our primary job in anesthesia is deliver oxygen to the tissues. Many of the problems that we encounter during the perioperative period are
related to inadequate oxygenation.
o What’s the Big Idea?
§ All of the cells in the body require oxygen to support aerobic metabolism, so the name of the game here is oxygen delivery. We
covered this concept extensively in the respiratory physiology tutorial, but here’s a quick refresher.

DO2 = Cardiac output x [(Hgb x SaO2 x 1.34) + (PaO2 x 0.003)] x 10

• * the 10 in this equation is a conversion factor that fixes (hgb g/dL and CO L/min) each gram of Hgb can carry 1.34 mL of
oxygen when 100% saturated
§ this equation illustrates the interrelationship between several organ systems (heart, blood vessels, lungs, kidneys) and how they work in
concert with the end goal of delivering oxygen to tissues. Don’t be intimidated. Let’s break it down.
o To understand the essence of DO2, we need to ask two questions:
§ 1. How much oxygen is in the blood?
§ 2. How fast is the oxygen being delivered to the tissues?
o 1. How Much Oxygen is in the Blood?
§ The oxygen content (CaO2) tells us how many grams per deciliter of oxygen are contained in the blood. Most oxygen is bound to
hemoglobin, while a small amount is dissolved in the blood. Remember the amount of gas dissolved in solution follow’s Henry’s law.
Amount of Oxygen Carried by Hemoglobin Amount of Oxygen Dissolved in the Blood
Hgb How many boxcars are available to carry O2? PaO2 Partial pressure of oxygen in the blood
SaO2 How full are the boxcars? 0.003 Solubility coefficient for dissolved oxygen
1.34 A constant that tells us the maximum
occupancy of the box cars

§ The normal DO2 is 1000ml/min. the normal oxygen extraction is 250ml/min, so we can say that the whole body O2 extraction ratio
is 25%.
o 2. How Fast is the Oxygen being Delivered to the tissues?
§ This is cardiac output. In the adult this is 5-6 L/min.
• What is the Heart’s Role in Oxygen Delivery?
o The heart generates a cardiac output to pump oxygen to the tissues as well as pump metabolic wastes to their clearing organs. Myocardial
function is determined by preload, afterload, and contractility.
o So to review…
o Oxygen Carrying Capacity: CaO2
§ How much O2 is carried in the arterial blood
CaO2=20 ml/dl
§ Reference value = 20 mL/dL
o Oxygen Delivery: DO2
§ How much O2 is carried in the blood and how fast it is being delivered to the tissues DO2=1000 mL/min
§ Reference value= 1000mL/min
o Oxygen Extraction Ratio: EO2
§
§
How much O2 is extracted by the tissues
Reference value for whole body = 25% (individual tissue beds will vary)
EO2=25% of whole
o Oxygen Consumption: VO2
§ How much oxygen is consumed by the tissues body
§ Reference value = 250 mL/min
o Venous Oxygen Content: CvO2
§
§
How much O2 is carried in the venous blood
Reference value = 15mL/dL
VO2= 250 mL/min
• Ohm’s Law & Poiseuille’s Law Applied to Hemodynamics
o Ohm’s law forms the basis for understanding hemodynamics

o We can translate Ohm’s law into some more familiar

hemodynamic terms.
o We need to point out it’s not quite as simple as we’ve lead you to believe.
If you were asked to calculate MAP and you simply multiplied CO and
SVR, you would be way off! If CO is 5 L/min and SVR is 1000
dynes/sec/cm-5, you’d have determined that the MAP is ~5000! There is
no way this is correct, but would you know what to do? The answer is
that you must understand the units for every variable that you calculate and that the units must
be correct in the final answer.
o Note that CO is measured in L/min and SVR is measured in dynes/sec/cm~5.
The number 80 is the conversion factor that you’ll need.

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• Poisuielle’s Law
o Poiseulle’s law is an adaptation of Ohm’s law that incorporates vessel diameter, viscosity and tube length.

o
• A Few Points About Flow
th
o Flow describes the movement of liquid, electricity, or air per unit time. It is directly proportional to the tube radius raised to the 4
power.
o Vascular resistance is primarily determined by the radius of the arterioles. Small changes in vessel diameter can yield profound
effects on tissue blood flow.
o Know that doubling radius increases flow by 16-fold and tripling the radius increases flow by 81-fold. Be sure to read the question
carefully. For example, the test may give you the diameter instead of the radius. If you were given the diameter, you’d have to cut it
in half before proceeding with the calculation.
o Flow can be laminar, turbulent, or transitional:
§ Laminar flow-molecules travel in a parallel path through the tube
§ Turbulent flow—molecules travel in a non-linear path and will create eddies
§ Transitional flow—laminar flow along the vessel walls with turbulent flow in the center
o Reynolds number (Re) can be used to predict if flow will be laminar or turbulent.
§ Re < 2000 predicts that flow will be mostly laminar
§ Re >4000 predicts that flow will be mostly turbulent
§ Re=2000-4000 suggests transitional flow
o When flow is turbulent, a greater amount of energy is lost via heat and vibration. The pressure gradient will be larger than what is
predicted by Poiseuille’s law.
o The vibrations that occur with turbulent flow may produce a murmur or bruit.
o Viscosity is the result of friction from intermolecular forces as a fluid passes through a tube. Blood viscosity is determined by the
hematocrit and body temperature.
o Blood viscosity is inversely proportionate to temperature—a cooler temperature increases viscosity and increases resistance. This
is important with cardiopulmonary bypass and hypothermia. Rewarming requires a higher shear stress to stimulate blood flow.
Reducing hematocrit will help counteract this.
• Interrelationship Between Hemodynamic Variables
o Now that you’ve reviewed the key concepts regarding blood flow, let’s start to put things together. A great way to do this is to link
concepts together. As you study this diagram, try to understand how each variable affects the next. It is one thing to simply
memorize it, but we really encourage you to go a step beyond and internalize it. Better yet, when you can explain it to your
classmate, friend, or even your dog, then you’ll really know what you know and what you don’t know!

o Question 1: What factors influence cardiac output (i.e. what comes before it)?
o Answer: Stroke volume and heart rate. Indeed, the product of SV and HR equals CO.
o Question 2: how does this cardiac output impact some variable that comes after it?
o Answer: it directly influences MAP. Indeed, the product of CO and SVR equals MAP.

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• Hemodynamic Calculations
o Sorry folks. There is no way around it. You have to know how to calculate each of these formulas. You’ll be expected to manipulate
these algebraically as well. Some parameters have more than one formula. And remember, you have to know the units for each
measurement and also the conversion factors that get you to the correct answer.

• Preload & The Frank-Starling Mechanism

o The functional unit of the heart: The Sarcomere
§ The sarcomere is the functional unit of the contractile tissue in the
heart. The amount of tension that each sarcomere can generate is
directly related to the number of cross bridges that can be formed
prior to contraction—the greater the tension produced, the greater
the force of contraction.
o Preload
§ Preload is the ventricular wall tension at the end of diastole (just
before contraction). Another way to think of tension is stretch or
tightness. Think about a rubber band. The more you stretch it, the
greater the snap after the tension is released. Stretching too far
defeats the mechanism.
§ While preload is NOT exactly synonymous with ventricular end-
diastolic volume, you’ll often find these terms interchanged.
§ There is a large list of factors that influence preload. Try to reason how each of these affects preload.
• Blood volume
• Atrial kick
• Venous tone
• Intrapericardial pressure
• Intrathoracic pressure
• Body position
• Skeletal muscle pumping action

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 o Ventricular Function Curve
§ The left ventricular function curve illustrates the relationship between ventricular volume and ventricular output. This is also known as the
Frank-Starling mechanism—an increased ventricular volume results in a large cardiac output. This occurs up to the plateau, after which
additional volume overstretches the ventricular sarcomeres, decreases the number of cross bridges that can be formed, and decreases
cardiac output.
§ Since we cannot measure ventricular volume without a TEE, we commonly use filling pressures as a surrogate. This isn’t without
limitations. Review the cardiovascular equipment tutorial for greater detail on the topic.
§ Contractility is the ability of the myocardial sarcomeres to perform work (shorten and produce force). It is independent of preload and
afterload. On the graph you should notice that increased contractility increases ventricular output even if preload remains the same. The
opposite is also true. Contractility is affected by chemicals. We’ll explore this more in the next topic.
§ Notice that there are a number of terms that can be used to
name the x- and y-axis. The NCE likes to test your vocabulary, so
you’ll need to know all of them.
o Conditions that Affect Ventricular Loading
§ Atrial contraction 9atrial kick) contributes to 20-30% of the final
LVEDV and, by extension, cardiac output.
• Think of atrial kick as “priming the pump.”
• Atrial kick is lost in the patient with atrial fibrillation.
Cardiac output typically declines as a result.
§ The non-compliant ventricle is stiff, so it is more dependent on a
wall-timed atrial kick to generate a sufficient stroke volume. The
extra pressure generated by the atrial kick helps prime a stiff
ventricle.
• Conditions associated with reduced myocardial
compliance include: myocardial hypertrophy, fibrosis,
and aging.
• These patients are more likely to experience a reduction in cardiac output with cardiac rhythm disturbances, such as junctional
rhythm and atrial fibrillation.
o Afterload
o Afterload is the force that the ventricle must overcome to eject its stroke volume. Don’t forget, there are two ventricles with drastically
different afterloads.

o Left ventricular afterload isn’t exactly synonymous with systemic vascular resistance. The reason for this is that SVR does not take blood
viscosity, blood density, or ventricular wall tension into account. Said another way, SVR is only a measure of arteriolar tone. Nevertheless, SVR
is commonly utilized as a surrogate for left ventricular afterload.
o The majority of the afterload is usually set by the systemic vascular resistance (arteriolar tone). You should know that aortic stenosis,
hypertrophic cardiomyopathy, or coarctation of the aorta can set the afterload proximal to the systemic circulation
• The Law of Laplace
o We can apply the law of Laplace to better understand myocardial afterload.
Wall stress= Intraventricular pressure x Radius
Ventricular thickness
o Explanation of terms:
§ Intraventricular pressure is the force that pushes the heart apart
§ Walls tress is the force that holds the heart together
§ Wall thickness and radius shouldn’t need explanations
o From this equation you can see that wall stress is reduced by:
§ Decreased intraventricular pressure
§ Decreased radius
§ Increased wall thickness

73
• Cardiac Cycle (Wiggers Diagram)
o The cardiac cycle is a sequence of electrical and
mechanical events that take place from the beginning of
one heart beat to the beginning of the next. It is divided
into systole (contraction) and diastole (relaxation).
o By convention, a discussion of the cardiac cycle details
the left heart. You can extrapolate these events to the
right heart as well.
o We have described the cardiac cycle in words and
pictures. We have intentionally separated these on the
screen so that you cannot see both side by side. You
should be able to explain the image with words and also
use the words to reconstruct the image. This exercise
may take a bit of time, but it will go a long way in
deepening understanding.
o You may be asking why this is such a critical concept.
One reason is that mastery of this material will
strengthen you understanding of pressure volume loops.
And you were hoping we might skip that? Not a chance!

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• Pressure-Volume Loop: Overview
o The pressure-volume loop is among the most feared topics in cardiac physiology. Some of
you will have one or even several pressure volume loops on the NCE, while others may not
see any. These are easy points if you know how to approach the questions, and the only way
to do that, is to understand them.
o What Does the Pressure-Volume Loop Tell Us?
§ By convention, it shows the pressure-volume relationship in the left ventricle
during one cardiac cycle—one systole and one diastole. It provides an assessment
of systolic and diastolic function as well as the integrity of the cardiac valves. It does NOT measure heart rate or linear time.
• Cardiac Cycle
o With the cardiac cycle fresh in your mind, let’s apply what you learned in the previous question to the pressure volume loop.

• Phase 1: Period of Ventricular Filling (Diastole)

o LV volume is ~50 mL (end-systolic volume)
o LV pressure is 2-3 mmHg
o Mitral valve opens and ventricular filling begins
o Aortic valve stays closed
o Since the LV is compliant, filling doesn’t increase pressure
o Atrial kick increases LV pressure to 5-7 mmHg
o LV fills to ~120 mL (end diastolic volume)
o There is a net gain of 70 mL during ventricular filling
• Phase 2: Period of Isovolumic Contractions (Systole)
o LV is stimulated to contract
o LV pressure exceeds LA pressure
o Mitral valve closes
o Aortic valve is still closed
o LV builds tension and increased LV pressure
o LV volume does not change
• Phase 3: Period of Ventricular Ejection (Systole)
o LV pressure exceeds aortic pressure
o Aortic valve opens
o Mitral valve still closed
o LV ejects stroke volume
o Normal stroke volume is 70 mL
o As stroke volume enters aorta, LV volume decreases
o Normal end systolic volume is 50 mL
o DBP is measured where the aortic valve opens External Work Output
o SBP is measured at the peak of the ejection curve
• EW stands for net external work output. This is measured by the area inside
• Phase 4: Period of Isovolumic Relaxation (Diastole)
the pressure-volume loop.
o Aortic pressure exceeds LV pressure
• If the ventricle accepts an increased volume, it will widen the area of the PV
o Aortic valve closes
loop. Since the area inside the PV loop has increased, we can predict that
o Mitral valve remains closed
the heart’s workload has also increased.
o LV volume does not change
• If the ventricle has to generate more pressure to open the aortic valve, this
o LV returns to starting pressure of 2-3 mmHg
will increase the height of the PV loop. Since the area inside the PV loop has
o LV returns to starting volume of 50mL
increased, we can predict that the heart’s workload has also increased.
• Ejection Fraction Calculation
o The ejection fraction can be calculated by the following equations:
o If you are asked to calculate stroke volume from a pressure-volume loop, then you got off easy. Just look at the width of the
pressure-volume loop to arrive at the correct answer.
§ Normal EF= 60-70%
§ Left ventricular dysfunction is present when EF <40%
75
• Coronary Circulation
o Arterial Circulation
§ The left and right coronary arteries supply blood to the entire heart.
• They are the first branches off the aorta.
• They arise at the sinus of Valsalva at the aortic root.
o What Vessel Supplies the SA node?
§ The SA nodal artery perfuses the SA node.
• Originates from the RCA in 50-60% of the population
• Originates from the CxA in 40-50% of the population.
o Coronary Artery Dominance
§ The coronary vessel that feeds the PDA determines dominance:
• RCA supplies PDA à right dominance (80% of population/shown in image)
• CxA supplies PDAà Left dominance
• RCA & CxA supply PDAà Co-dominance
o Assessment of Myocardial Ischemia
§ The RCA, LAD and LCx are called epicardial vessels because they lay on top of the heart’s surface. Coronary artery stenosis
that results from atherosclerosis and CAD affects the epicardial vessels. The epicardial vessels divide before penetrating
deeper into the myocardium. The coronary arterioles (not the epicardial vessels) provide the majority of coronary vascular
resistance.
§ Collateral vascular networks provide redundancy of blood flow. Collateral vessels can develop from different branches of
the same coronary artery or between two different coronary arteries. A collateral pathway that shares a single feeding
vessel is at risk if an occlusion develops proximal to the collateral branches.
§ You need to understand the vascular anatomy and how it impacts the conduction system and the myocardium. Be
prepared to answer questions that relate each coronary artery to an area of the myocardium and its corresponding EKG
leads. You must know this table!

o Transesophageal Echocardiography
§ While we don’t expect many (if any) questions on TEE, you should know that this image
represents the heart as seen in the midpapillary muscle level in short axis.
• This view is the best TEE view for diagnosing myocardial ischemia.
• The second best view is the apical segment also in short axis.
• Venous Circulation
o There are three main coronary veins. Each one runs alongside a coronary artery. It may help to
memorize these as pairs.
§ 1. Great cardiac vein (LAD)
§ 2. Mdidle cardiac vein (PDA)
§ 3. Anterior cardiac vein (RCA)
o Most of the blood returning from the left ventricle drains into the coronary sinus. It is located on the posterior aspect of the right
atrium just superior to the tricuspid valve.
o Most of the blood returning from the right ventricle is carried by anterior cardiac veins. They bypass the coronary sinus and empty
directly into the right atrium.
o A small amount of blood empties directly into all of the cardiac chambers via the Thebesian veins. Blood returning to the left side of
the heart by way of the Thebesian circulation contributes to anatomic shunt.

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• Coronary Perfusion
o The heart very efficiently matches its blood flow with its metabolic needs. Myocardial oxygen extraction is ~70%, therefore
increased O2 extraction is not a viable method of increasing oxygen supply. Instead, coronary blood flow must increase to meet an
increased metabolic demand
Coronary Blood Flow = Coronary Perfusion Pressure

Coronary Vascular Resistance

Coronary Perfusion Pressure = Aortic DBP – LVEDP

Look familiar? Yeah, that’s Ohm’s law again…
• Coronary Reserve
o Coronary reserve is the difference between coronary blood flow at rest and at maximal dilation. It is the ability of the coronary
circulation to increase blood flow in times of hemodynamic stress or exercise.
o Atherosclerotic vessels may already be maximally dilated and unable to dilate further with an increased O2 demand. Vessels that are
maximally dilated are completely dependent on coronary perfusion pressure.
• Autoregulation
o Coronary blood flow is autoregulated between a MAP of 60-120 mmHg. This allows a constant coronary blood flow over a wide
range of blood pressures. When MAP falls below the range of autoregulation, coronary perfusion becomes entirely dependent on
coronary perfusion pressure.
o Autoregulation is the net effect of three things: local metabolism, the myogenic response, and the autonomic nervous system.
o 1. Local Metabolism
§ local metabolism is the most important determinant of coronary vessel diameter. Adenosine is a byproduct of ATP
metabolism and is a potent coronary vasodilator. As MVO2 increases, the coronary endothelium release adenosine as well
as a variety of other vasodilator substances including nitric oxide, prostaglandins, hydrogen, potassium, and carbon
dioxide. Note that hypocarbia causes coronary vasoconstriction. It should make sense that as MVO2 increases, the tissue
has a mechanism to increase its own blood flow. Vasodilation decreases vascular resistance, increases coronary perfusion,
and flushes out products of metabolism.
o 2. Myogenic Response
§ the myogenic response refers to the vessel’s innate ability to maintain a constant vessel diameter. When the vessel’s
diameter is increased, it will have the tendency to contract, and when the diameter decreases, it will have the tendency to
dilate.
o 3. Autonomic Nervous System
§ the autonomic nervous system can affect coronary vascular tone, although these effects are overshadowed by the
products of local metabolism. There are, however, times when the ANS effects prevail. For example, patients with
Prinzmetal angina (vasospastic myocardial ischemia) are believed to have overactive coronary alpha receptors that cause
intense vasoconstriction and chest pain.

Coronary Perfusion: Left vs Right

77
• Myocardial Oxygen Supply & Demand
o Key Facts
§ The left and right coronary arteries supply oxygenated blood to the myocardium
§ Coronary blood flow is 225-250 mL/min or 4-7% of the cardiac output.
§ The coronary vasculature autoregulation between a MAP of 60-140.
§ At rest, the myocardium consumes oxygen at a rate of 8-10 ml/min/100g with an extraction ratio of ~70%. Coronary sinus
oxygen saturation is ~30%. Because of this, the myocardium cannot meaningfully increase its extraction ratio when oxygen
demand increases. Instead, coronary blood flow and CaO2 must increase to be able to satisfy the demand.
§ During ischemia, aerobic metabolisms shifts to anaerobic metabolism, increasing lactic acid production. Lactic acid is
presumed to be responsible for the perception of chest pain. Inadequate production of ATP and acidosis impairs
myocardial performance and leads to hemodynamic instability.
§ Most perioperative myocardial infarctions occur 24-48 hours following surgery and carry a 20% mortality.
§ You must know and understand all of the factors that affect myocardial supply and demand!

§ Diagrams like this make it easy to oversimplify complex concepts. It cant always be easy. There are a few circumstances
that affect both sides of the supply demand equation. These include, heart rate, aortic diastolic pressure and preload.
o Tachycardia: Decreased Supply, Increased Demand
§ Decreased Supply
• Tachycardia reduces diastolic filling time. Recall that the left ventricle, particularly the subendocardium, is best
perfused during diastole. A shorter diastolic time interval means that there is less time to deliver oxygen to the
left ventricle. The right ventricle usually isn’t affected, because it is well perfused throughout the cardiac cycle.
§ Increased Demand
• Cardiac contraction and relaxation require ATP. Increasing the number of cardiac cycles per minute increases
ATP and oxygen utilization.
o Increased Aortic Diastolic Pressure: increased Supply and decreased demand
§ Increased Supply
• An increased aortic pressure increases the pressure head that perfuses the coronary arteries (P1-P2).
• Increased Aortic DBP – LV End Diastolic Pressure = increased Coronary Perfusion Pressure
§ Increased Demand
• At the same time, an increased aortic pressure also increases wall tension and afterload. The myocardium
requires more oxygen as it generates a higher pressure to open the aortic valve.
• As a general rule, the benefit of an increased coronary perfusion pressure outweighs the drawback of an
increased wall tension.
o Increased Preload: Decreased Supply and increased Demand
§ Decreased Supply
• An increased end-diastolic volume decreases coronary perfusion pressure.
• Aortic DBP – increased LV-EDP = decreased coronary perfusion pressure
§ Increased Demand
• An increased preload increases wall stress

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Regulation of Vascular Smooth Muscle Tone

o Regulation of vascular smooth muscle tone is dependent on the successful integration of the autonomic nervous system, renin-
angiotensin-aldosterone system, local metabolism, and the myogenic response. All of these pathways either instruct the vascular
smooth muscle to contract or relax.
o But how does each accomplish this goal? How does alpha-1 stimulation or angiotensin II induce vasoconstriction? How does nitric
oxide induce vasodilation? Although we could go on for hours about this single topic, we want you to know that the most important
answer is regulation of intracellular calcium
• G Proteins Revisited
o In the autonomic A&P Tutorial, we discussed the role of G-protein in cellular communication. To recap, here is the basic schema:
§ First MessengeràG Protein Coupled Receptor àEffector àSecond Messenger à Cellular Response
o When you learn the physiology in this way, you’ll also gain a deeper appreciation of the related pharmacology. When you
understand the content on this level, you’ll no longer have to memorize a bunch of facts, because everything will begin to fit
together in a logical way. It takes some time, but the payoff is well worth the effort.
• The Importance of Calcium in Vascular Smooth Muscle
o Calcium plays a key role in the regulation of peripheral vessel diameter. As a general rule, increased Ca+2 causes vasoconstriction
and reduced intracellular Ca+ 2 leads to vasodilation.
o Its also important to recognize that inhibition fo vasoconstriction pathways results in vasodilation. The converse is also true.
o There are 3 important pathways that affect intracellular Ca+2 concentration:
§ 1. G-Protein cAMP PathwayàVasodilation
§ 2. Nitric Oxide cGMP Pathwayà Vasodilation
§ 3. Phospholipase C Pathway àVasoconstriction
• Vasodilation: G-Protein cAMP Pathway
o Recall that the intracellular effects of second messengers are tissue specific. When we discussed the cardiac myocyte just a few
pages back, we told you that increased cAMP and PKA increase intracellular calcium. In the vascular muscle cell, however, the
opposite is true—increased PKA decreases intracellular calcium. Here’s an example:
§ NEàBeta 2à Gs G-protienà adenyl cyclase àcAMPà protein kinase Aà decreased Ca+2à vasodilation
o PKA manipulates the excitation-contraction coupling pathway by:
§ Inhibition of voltage-gated Ca+2 channels in the sarcolemma
§ Inhibition of ca+2 release from the sarcoplasmic reticulum
§ Reduced sensitivity of the yofilaments to Ca+2
§ Facilitation of Ca+2 reuptake into the sarcoplasmic reticulum via the SERCA2 pump
• Vasodilation: Nitric Oxide cGMP Pathway
o Nitric oxide is a smooth muscle relaxant that induces vasodilation. Its production is increased by acetylcholine, substance P,
bradykinin, serotonin, vasoactive intestinal peptide, thrombin, and shear stress.

o Steps in the Nitric Oxide cGMP pathway

§ 1. Nitric oxide synthetase catalyzes the conversion of L-arginine to nitric oxide
§ 2. Nitric oxide diffuses from the endothelium to the smooth muscle
§ 3. Nitric oxide activates guanylate cyclase
§ 4. Guanylate cyclase converts guanosine triphosphate to cyclic guanosine monophosphate.
§ 5. Increased cGMP reduces intracellular calcium, leading to relaxation of smooth muscle
§ 6. Phosphodiesterase deactivates cGMP to guanosine monophosphate.
• Vasoconstriciton: Phospholipase C Pathway
o Activators of the PLC pathway include phenylephrine, norepinephrine, angiotensin II, and endothelin-1. Here’s an example:
§ Angiotensin II à ATII Receptor à Gq G-protienà Phospholipase Cà IP3 & DAG à Increased Ca+2à Vasoconstriction
o Activation of the enzyme PLC increases production of two second messengers: IP3 an dDAG, IP3 augments Ca+2 release form the sarcoplasmic
reticulum and DAG activates protein kinase C. This opens voltage-gated Ca+2 channels in the sarcolemma and increase Ca+2 influx.

79
Valvular Heart Disease

• Heart Sounds
o The heart sounds coincide with closure of the heart valves. Closure of the valve leaflets causes the valve, intracardiac blood,
and the heart’s walls to vibrate. This mechanical energy is transmitted throughout the chest, producing and audible sound.
Opening of the valves is a slower process and cannot be heard with a stethoscope.
o There are 4 heart sounds. The first and second are described as “lub dub” and are easily auscultated with a stethoscope. The
third and fourth heart sounds usually indicate pathology.
1st Heart Sound: S1 3rd Heart Sound: S3
Closure of mitral and tricuspid valves Suggests flaccid and inelastic heart—think heart failure
Marks onset of systole Heard during middle 1/3 of diastole—after S2
End of LV filling and beginning of isovolumic contraction Gallop rhythm—described as rumbling sound
Volume proportionate to force of contraction
• Sound is louder with a vigorously contracting ventricle
• Sound is softer with a poorly contracting ventricle
2nd Heart Sound: S2 4th Heart Sound: S4
Closure of aortic and pulmonary valves Caused by atrial systole
Marks onset of diastole Heard before S1
End of LV ejection and beginning of isovolumic relaxation
Volume proportionate to LV pressure decrease at the end of systole
• Sound is louder with hypertension
• Sound is softer with hypotension
o Where to Listen
§ you should know where to listen to
each valve. We’ve illustrated where you
should auscultate the valves to assess
their normal function. Where a
particular valve is heard best is NOT
directly over it, but rather a function of
how the blood vibrates and the
direction the sound waves are
transmitted through the chest.
• Concentric & Eccentric Hypertrophy
o Overview
§ The atrioventricular valves (mitral and tricuspid) separate the atria from the
ventricles. The valve leaflets are anchored to the interior of the ventricles by chordae tendineae and papillary muscles. These
structures prevent prolapse of the AV valve during ventricular systole.
§ The semilunar valves (aortic and pulmonary) open to let blood flow out from the ventricles. The valve leaflets are not anchored to
chordae tendineae or papillary muscles.
• When a valve opens, blood is propelled forward by a pressure gradient created inside the cardiac chamber.
• When a valve closes, blood is prevented from moving backwards.
o Mechanisms of Valve Failure
§ There are two ways that a valve can fail:
• 1. Stenosis: there is a fixed obstruction to forward flow during chamber systole. This
requires a higher transvalvular pressure gradient.
• 2. Regurgitation: The valve is incompetent, so some blood flows forward and some
blood flows backwards during chamber systole.
§ A valve lesion can be primary (due to a problem with the valve itself) or secondary (due to
supporting structures, such as ventricular dilation or papillary muscle infarction). Sometimes a valve will have elements of both
stenosis and regurgitation. Management targets the lesion of greater hemodynamic significance.
o Stenosisà Pressure Overloadà Concentric Hypertrophy
§ There is a fixed obstruction to forward flow.
§ In order to overcome the obstruction, the chamber must generate a higher transvalvular pressure gradient.
§ Blood flow passing through a more narrow opening (higher resistance) becomes turbulent and travels at a higher velocity.
§ The heart compensates by adding sarcomeres in parallel—the chamber wall becomes thicker. This reduces the radius of the
chamber.
o Regurgitationà Volume Overloadà Eccentric Hypertrophy
§ The valve is incompentent
§ When the chamber contracts, some blood flows forward and some blood
flows backward
§ During chamber diastole, there are two quantities of blood entering the
chamber—blood returning from the circulation AND the regurgitant fraction.
This causes volume overload.
§ The heart compensates by adding sarcomeres in series. To accept a larger
volume, the chamber radius increases (the chamber dilates).

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Aortic Stenosis

• Overview
o The normal valve orifice is 2.5-3.5 cm2. Aortic stenosis is considered severe when the valve orifice is <0.8cm2.
o The most common causes of AS is a bicuspid aortic valve and calcification of the valve leaflets. Other causes include rheumatic
fever and infective endocarditis.
• Pathophysiology
o Aortic stenosis is the result of an obstruction to blood flow across the aortic valve. Since the heart must generate more force to eject its stroke
volume, it suffers from pressure overload an an elevation in wall tension. Remember that an increase in ventricular pressure will present as an
increased height of pressure-volume loop. Also note that the end-systolic volume is higher as a function of elevated afterload. Replacing the
valve reduces afterload and the LV-Ao gradient. LVEDV is also decreased.
o In accordance with the law of Laplace, the left ventricle compensates with the law of Laplace, the left ventricle compensates with concentric
hypertrophy. This produces a thickened LV wall with decreased compliance and a narrowed chamber. Over time, this adaptation reduces
myocardial oxygen supply (subendocardial compression) and increases MVO2 (increased heart mass). The patient will experience myocardial
ischemia, LV failure, and pulmonary edema.
o We find it SAD that the triad of Syncope, Angina, and Dyspnea on
exertion is the classic presentation of severe aortic stenosis. The 50%
survival rate for each of these symptoms is 3, 5, and 2 years
respectively.
o Patients usually remain asymptomatic until left ventricular dysfunction
develops, so one should always listen for the murmur of AS,
particularly in the elderly and also before performing subarachnoid
blockade.
• Anesthetic Management
o Heart Rate & Rhythm: 70-80 bpm and NSR
§ A properly timed atrial contraction is absolutely required to
prime the non-compliant ventricle. Loss of atrial kick (junctional
rhythm or a-fib), will reduce ventricular filling and cause a decline in stroke volume.
§ Tachycardiaàdecreased time for ventricular filling à decreased LVEDVà decreased SV and decreased CO
§ Anesthetic Considerations:
• Cardioversion (if new onset and be sure to hit sync) or beta-blockade.
• If the HR is 70-80 bpm, drugs that increase heart rate further should be avoided.
§ Bradycardiaàdecreased COà LV over-distension with compression of subendocardiumà decreased myocardial oxygen supply
§ Anesthetic Considerations:
• Obviously if a patient is bradycardic, you’ll have to increase the heart rate. Use atropine, glycopyrrolate, or ephedrine.
o Preload: Increase
§ Adequate LVEDP is required to fill the non-compliant LV. LVEDP and PAOP overestimate LVEDV.
§ Anesthetic Considerations:
• Administer IVF to ensure adequate intravascular volume
o Systemic Vascular Resistance: Maintain or Increase
§ Stroke volume is fixed by the stenotic aortic valve, therefore Co is dependent on heart rate (BP = SVR X CO)
§ Hypotensionà decreased aortic root pressureàdecreased coronary perfusion pressureàmyocardial ischemia
§ Anesthetic Considerations:
• Hypotension should be treated with an alpha-1 agonist. This will increase SVR and coronary perfusion pressure without increasing
heart rate.
• Chest compressions during CPR won’t generate sufficient intracardiac pressure to overcome the stenotic aortic valve; stroke
volume and cardiac output will be inadequate.
• Remember that afterload is set at the valve, so valve replacement greatly improves afterload. Since the impedance to left
ventricular ejection (afterload) is reduced, the heart ejects more of its volume (stroke volume increases). Said another way, left
ventricular end-systolic volume will decrease.
o Contractility: Maintain
§ Usually not an issue until late in the disease.
§ Anesthetic Considerations
• Inotropes if LV dysfunction occurs.
o Pulmonary Vascular Resistance: Normal
§ Usually not an issue until late in the disease
§ Diastolic failure à increased LAP à pulmonary congestion
and dyspnea
o Regional Anesthesia
§ Spinal anesthesia is avoided with severe aortic stenosis (valve area <0.8cm2). Sympathectomy rapidly reduces SVR leading to profound
hypotension, reduced coronary perfusion pressure, and cardiovascular collapse.
§ Epidural anesthesia with a slow onset local anesthetic creates a more gradual sympathectomy. This decision should be made on an individual
basis and is reasonable as long as the patient doesn’t have severe AS> a lower block height is less likely to create hemodynamic instability.
o Arterial Waveform
§ When contrasted with a normal waveform, the arterial tracing of aortic stenosis exhibits a slower systolic upstroke (pulsus tardus)
with a delayed peak.
§ Stroke volume is typically reduced with aortic stenosis. This creates a narrow pulse pressure with a waveform of small amplitude
(pulsus parvus).
§ The dicrotic notch may be present, and the overall impression may be of a dampened waveform.

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Mitral Stenosis

• Overview
o The normal mitral valve orifice is 4-6cm2. Severe disease results when the valve area is <1.0 cm 2, the LAP-LV pressure gradient
exceeds 10 mmHg, and pulmonary artery systolic pressure is greater than 50mmHg.
o Asking about the most common cause of mitral stenosis is trick. In the United States, the incidence of rheumatic fever is quite
low, so the most common cause of mitral stenosis is endocarditis and calcification of the mitral annulus secondary to
atherosclerosis. In developing nations, rheumatic fever is the most common cause of mitral stenosis.
o Other causes include:
§ Rheumatoid arthritis
§ Systemic lupus erythematosus
§ Congenital defect
§ Left atrial myxoma
§ Carcinoid syndrome
§ Iatrogenic following mitral valve repair
• Pathophysiology
o Mitral stenosis is the result of an obstruction to
blood flow across the mitral valve. Early in the
disease, increased left atrial pressure is a sufficient
pressure head to maintain left ventricular filling. As
the valve orifice narrows even more, the pressure
gradient between the LA and LV increases, and the
left ventricle becomes chronically underfilled. We
have an overfilled left atrium and underfilled left ventricle. In addition, we have a lower end-diastolic volume, stroke volume, and cardiac
output (see pressure-volume loop). The body compensates by increasing systemic vascular resistance to maintain blood pressure (BP = CO x
SVR).
o An increased LA pressure and volume alters the anatomy of the atrial conduction system. This can precipitate atrial fibrillation. Loss of atrial
kick reduces ventricular filling and reduces cardiac output. Surgical options for treating atrial fibrillation include the Maze procedure and
pulmonary vein isolation.
o Increased left atrial pressure also creates a back pressure in the pulmonary venous system, contributing to an increased pulmonary venous
pressure. Increased pulmonary vascular pressure promotes fluid movement into the pulmonary interstitium. This reduces pulmonary
compliance and increases the work of breathing, resulting in dyspnea. Chronic pulmonary fluid overload causes anatomical changes in the
pulmonary vasculature, leading to pulmonary hypertension. Pulmonary hypertension increases the workload of the right ventricle, eventually
causing it to fail (cor pulmonale).
• Anesthetic Management – Full, Slow & Constricted
o Heart Rate & Rhythm: Low End of Normal with NSR
§ Tachycardiaàdecreased filling timeàdecreased time for blood to pass the stenotic MV à increased LA pressure
§ Anesthetic Considerations:
• Tachyarrhythmias are treated with: amiodarone, beta-blockers, calcium channel blockers, digoxin or cardioversion.
• Avoid drugs that increase heart rate, such as anticholinergics, ketamine, or atracurium.
• Any condition that increases cardiac output or heart rate will increase LAP and may lead to pulmonary edema.
• Clinical examples include: thyrotoxicosis, infection, and autotransfusion during uterine contraction in the pregnant patient.
o Preload: Maintain
§ LV is chronically underfilled. Decreased preload à decreased SV and CO
§ Hypervolemia increases LAP à pulmonary congestion
§ Anesthetic Considerations:
• Diuretics may be used to decrease LAP
• The LA undergoes concentric hypertrophy. PAOP overestimates LVEDV.
• The PAOP waveform may reveal a prominent a wave and decreased y descent.
o Afterload: Maintain
§ In the setting of low SV and CO, the systemic vasoconstriction increases SVR and preserves BP
§ Anesthetic Considerations:
• A rapid decrease in SVR will elicit a baroreceptor mediated rise in heart rate (this isn’t good).
• Treat hypotension with a vvasoconstrictor such as phenylephrine or vasopressin. Ephedrine isn’t the best choice here.
o Contractility: Maintain
§ Usually not an issue.
o Pulmonary Vascular Resistance: Avoid Increase
§ Pulmonary hypertension increases the workload of the right ventricle.
§ Anesthetic Considerations:
• Avoid conditions that increase PVR: acidosis, hypercarbia, hypoxia, lung hyperinflation, nitrous oxide, Trendelenburg
position
o Regional Anesthesia
§ Blood stasis in the left atrium is prone to thrombus formation. The rate of embolic phenomenon is 7-15%. Patients with atrial
fibrillation will be anticoagulated (INR 2.5-3.0). do not put a needle in the backs of these patients!!!!
§ If the INR is <1.5, neuraxial anesthesia can be a safe option and should be considered on an individual basis. Epidural anesthesia is
preferred over spinal anesthesia due to the slower onset of Sympathectomy.

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Mitral Insufficiency

• Overview
o Mitral insufficiency occurs when blood re-enters the left atrium through an incompetent mitral valve during ventricular systole.
This lesion is associated with volume overload and eccentric hypertrophy.
o Etiologies of Mitral Insufficiency:
§ Rheumatic fever
§ Ischemic heart disease
§ Papillary muscle dysfunction
§ Ruptured chordae tendineae
§ Endocarditis
§ Mitral valve prolapse
§ Left ventricular hypertrophy
§ Systemic lupus erythematosus
§ Rheumatoid arthritis
§ Ankylosing spondylitis
§ Carcinoid syndrome
• Pathophysiology
o During normal ventricular systole, the mitral valve is closed and blood is ejected into the aorta. With mitral insufficiency, the
stroke volume goes in two directions—towards the aorta and through the incompetent mitral valve towards the left atrium.
This leads to volume overlaod of the left atrium and left ventricle.
o The regurgitant volume is increased with a/an:
§ 1. Slower heart rate
§ 2. Increased pressure gradient between the LV and LA
§ 3. Increased SVR
§ 4. Increased size of valve orifice
o On the pressure volume loop of mitral
regurgitation, note that the end-diastolic volume
gets smaller during isovolumic contraction of the
left ventricle ( it shouldn’t change at all). We put
an “M” there to help you remember this. Also,
remember that a pressure problem is depicted by
an increased height, while a volume problem is
depicted by an increase in width. Last, the acute
loop is always smaller than the chronic loop
• Anesthetic Management
o Heart Rate and Rhythm: High HR with NSR
§ Regurgitation occurs during systole
(isovolumic contraction). A faster heart rate reduces time spent during
systole, and this reduces the regurgitant fraction.
o Preload: Maintain or Increase
§ Not all of the stroke volume goes to the systemic circulation; some is lost to the LA. A higher preload helps
compensate for the lost volume.
§ Anesthetic Considerations:
• PAOP over estimates LVEDP and cannot be used as a reliable measure of LV filling pressure.
• The PAOP waveform will have an enlarged v wave. This represents the regurgitation volume passing
through the incompetent mitral valve.
o Afterload: Decrease
§ Blood flows along the path of least resistance. Systemic vasodilation promotes forward flow, while systemic
vasoconstriction increases the regurgitant volume.
§ Anesthetic Considerations:
• Following mitral valve repair, there is a risk of systolic anterior motion (SAM) of the anterior leaflet. In this
condition, the anterior leaflet obstructs the left ventricular outflow tract during systole. If SAM is suspected
or verified with TEE, treatment consists of increasing intravascular volume and increasing afterload with an
alpha agonist such as phenylephrine. SAM is very similar to hypertrophic cardiomyopathy.
o Contractility: Maintain
o Pulmonary Vascular Resistance: Avoid Increase
§ Avoid conditions that increase PVR: acidosis, hypoxia, lung hyperinflation, nitrous oxide, Trendelenburg position
o Regional Anesthesia
§ Sympathectomy reduces SVR, promotes forward flow, and reduces the regurgitant fraction.
§ Drastically reducing AoDBP can compromise coronary perfusion pressure.

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Aortic Regurgitation

• Pathophysiology
o In the patient with aortic insufficiency, a portion of the previously ejected stroke volume re-enters the left ventricle during
diastole. This causes volume overload and eccentric hypertrophy in the left ventricle. Additionally, since a portion of the stroke
volume returns to the left ventricle, cardiac output is reduced.
o The size of the regurgitant volume is made worse by:
§ 1. Bradycardia (longer diastolic filling time)
§ 2. Increased SVR (increased aorta-LV pressure gradient)
§ 3. Large valve orifice (larger area for the blood to return though)
o Aortic insufficiency is either the result of an incompetent valve or dilation of the aortic root or its supporting structures. Unlike
stenosis, which takes decades to develop, valvular insufficiency can either occur acutely or develop over many years.
o If this patient has an intact mitral valve, there will not be pulmonary symptoms. If the mitral valve becomes incompetent
(usually from dilation of the mitral annulus), then an elevated LVEDP will reflect back into the pulmonary circulation, causing
congestion.
o If cardioplegia is injected into the aorta, it will pass through the incompetent aortic valve and enter the LV. In the patient with
aortic regurgitation, cardioplegia must be injected
retrograde (through the coronary sinus0 or directly into
each coronary ostia.
o On the pressure-volume loop of aortic regurgitation, note
that end systolic volume gets bigger during isovolumic
relaxation. This is because the regurgitant volume is added
to the blood volume entering from the left atrium. We
added an “A” to help you remember this. Again, since this
is a volume issue, the pressure-volume loop becomes
wider. Like mitral regurgitation, the loop for the acute
presentation is smaller than that of chronic disease.
o Acute Aortic Regurgitation
§ Acute AI leads to rapid cardiovascular instability. The left ventricle becomes acutely dilated and experiences increased
wall tension and impaired contractility. Left ventricular failure may result.
§ Acute AI is usually caused by endocarditis, but it may also result from aortic root dissection from aneurysm or trauma.
o Chronic Aortic Regurgitation
§ In the patient with chronic AI, the left ventricle has had time to compensate with LV dilation (eccentric hypertrophy).
The diameter of the chamber increases to a greater degree than the wall thickens. This normalizes wall tension while
preserving stroke volume and contractility. The rise in LVEDP coupled with a reduction in aortic diastolic blood
pressure decreases coronary perfusion pressure. As the LV continues to dilate beyond the range of compensatory
mechanisms, wall tension and cardiac mass increase. This reduces compliance and contractility ultimately culminating
in left ventricular failure.
§ Chronic AI develops slowly, so the volume overloaded ventricle is better able to compensate for a progressively
increasing regurgitant fraction.
• Anesthetic Management—Full, Fast & Forward
o Heart Rate & Rhythm: Increase with NSR
§ A faster heart rate reduces the regurgitant volume and increases AoDBP and CPP.
§ A slower heart rate gives more time for the stroke volume to pass back into the LV instead of moving forward. This
reduces CO. additionally, this reduces pressure at the aortic root and can compromise CPP.
o Preload: Maintain or Increase
§ Some of the stroke volume is lost to the LV, so avoid hypovolemia.
o Afterload: Decrease
§ Blood flows along the path of least resistance. An elevated afterload increases the regurgitant volume, while a lower
afterload promotes forward flow. Phenylephrine or vasopressin aren’t ideal choices.
o Contractility: Maintain
§ LV failure is treated with an inotrope and a vasodilator.
o Pulmonary Vascular Resistance: Maintain
§ Acute LV dilation stretches the mitral annulus. LV pressure will reflect to the LA and pulmonary circulation. Pulmonary
congestion will result.
o Regional Anesthesia
§ Sympathectomy reduces afterload and will reduce the regurgitation fraction.
o Arterial Pressure Waveform
§ In patients with aortic regurgitation, the arterial waveform has a sharp upstroke, a low diastolic pressure and a wide
pulse pressure. This is secondary to ease of ejection followed by retrograde flow of blood towards the left ventricle.
This arterial pressure waveform may also have a biphasic systolic peaks (bisferiens pulse) because of an additional
reflective wave from the periphery.

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Pathologic Murmurs

• If you understand the cardiac cycle, and by now you should, it is possible to reason your way through this.
• Aortic Stenosis: Systole
o LV generates significant pressure to overcome the stenotic aortic valve.
o LV pressure can exceed 350mmHg
o High velocity through a narrow opening creates “nozzle” effect
o Sound transmitted through upper aorta and carotid arteries. May be confused with carotid bruit.
o Sound can vibrate intensely to the chest and may be palpated as a thrill.
o Murmur may decrease in intensity with very severe disease—not enough flow passes through the valve to make a sound
o Mneumonic “ASSS” Aortic Stenosis is a Systolid mumur heard at the right Sternal border
• Aortic Regurgitation: Diastole
o Turbulent retrograde flow across the aortic valve
o High pitch “blowing” murmur
o Not as loud as aortic stenosis—there is less of a pressure gradient.
o Mneumonic “ARDS” Aortic Regurgiation is a Diastolic murmur heard at the right Sternal border
• Mitral Stenosis: Diastole
o LA generates increased pressure to overcome the stenotic mitral valve.
o LA pressure can reach up to 35 mmHg
o Opening snap followed by low intensity rumbling murmur.
o Mnemonic “MSDA” Mitral Stenosis is a Diastolic murmur heard at the Apex and left Axilla
• Mitral Regurgitation: Systole
o Retrograde flow across the incompetent mitral valve during ventricular contraction
o Holosystolic murmur characterized by a loud “swishing” sound
o Sound similar to aortic regurgitation but occurs during systole
o Mnemonic: “MRSA” Mitral Regurgitation is a Systolic murmur heard at the Apex and left Axilla
Cardiac Pathophysiology

Assessment of Perioperative Cardiovascular Risk

• You should be able to stratify cardiac risk by the patient’s history and type of surgery. Risk is defined as perioperative myocardial
infarction, congestive heart failure, or death.
• Risk Factors for Perioperative Cardiac Morbidity and Mortality for Non-Cardiac Surgery
o General Risk Factors:
§ High risk surgery (see below)
§ History of ischemic heart disease (unstable angina confers the greatest risk of perioperative MI)
§ History of CHF
§ History of cerebrovascular disease
§ Diabetes mellitus
§ Serum creatinine > 2 mg/dL
o Unstable angina is defined as angina at rest, new onset angina (<2 months) , increasing symptoms (intensity, frequency, duration), duration
exceeds 30 min, and symptoms have become less responsive to medical therapy.
o Risk of Perioperative MI in the Patient with Previous MI:
§ General population = 0.3%
§ MI if > 6 months = 6%
§ MI if 3-6 months = 15%
§ MI <3 months = 30%
o The highest risk of reinfarction is greatest within 30 days of an acute MI. for this reason, the ACC/AHA guidelines recommend a minimum of 4-6
weeks before considering elective surgery in a patient with a recent MI.
• AHA/American College of Cardiology Guidelines Based on Surgical Procedure
o High (Risk > 5%)
§ Emergency surgery (especially in the elderly)
§ Open aortic surgery
§ Peripheral vascular surgery
§ Long surgical procedures with significant volume shifts and/or blood loss
o Intermediate (Risk = 1-5%)
§ Carotid endarterectomy
§ Head and neck surgery Modified New York Association Functional
§ Intrathoracic or intraperitoneal surgery Classification of Heart Failure
§ Orthopedic surgery
§ Prostate surgery Class I: Asymptomatic
o Low (Risk <1%)
§ Endoscopic procedure Class II: Symptomatic with moderate activity
§ Cataract surgery
§ Superficial procedures Class III: Symptomatic with mild activity
§ Breast surgery
Class IV: Symptomatic at rest
§ Ambulatory procedures

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Myocardial Oxygen Imbalance

• O2 Delivery vs Demand
o While we covered this in detail in the Cardiac Anatomy & Physiology Tutorial, let’s revisit the highlights here. You cant see this
information too many times

• EKG and Myocardial Ischemia

o Here are the best leads to monitor for intraoperative ST changes:
§ Normal EKG or no EKG on file (listed in order of preference): V3>V4>V5>III>aVF
§ Abnormal EKG: Monitor the regions at greatest risk of ischemia
o In patients with CAD, Nagelhout suggests the following lead combinations provide the best assessment of intraoperative ST changes:
§ 5 cable EKG: V3, aVF, and MCLS or III
§ 3 cable EKG: aVF and MCL5
o Lead II is best for monitoring dysrhythmias with a narrow QRS where P wave analysis is critical for diagnosis (junctional, a-flutter, or a-fib)
• Laboratory Assessment of Myocardial Ischemia
o A cell requires oxygen to maintain the integrity of its cell membrane, and a cell deprive of oxygen dies and releases its contents into the
systemic circulation
§ Infarcted myocardium releases 3 key
biomarkers: creatine kinase-MB, troponin I,
and troponin T.
§ Cardiac troponins are more sensitive than
CK-MB for the diagnosis of myocardial
infarction.
§ These values must be evaluated in the context of
the patient’s EKG
• Treatment of Myocardial Ischemia
o Treatment of intraoperative myocardial ischemia should
focus on interventions that make the heart slower, smaller,
and better perfused.
o Most perioperative myocardial infarctions are undiagnosed
and undertreated. According to the POISE study, most
myocardial infarctions occur in the postoperative period (within 48 hours after surgery).
Diastolic Compliance
• Diastolic compliance describes the ventricular filling pressure that results from a given end-diastolic volume.
o Decreased Cv shifts curve up and left
o Increased Cv shifts the curve down and right
• Decreased Compliance
o The diastolic pressure-volume relationship is affected by:
§ Age >60 years
§ Ischemia
§ Pressure overload hypertrophy (aortic stenosis or HTN)
§ Hypertrophic obstructive cardiomyopathy
§ Pericardial pressure (increased external pressure)
o The clinical take away here is that higher filling pressures are required to prime the
ventricle.
§ Preservation of NSR and atrial kick are critically important to maintain the priming function.
§ Elevated filling pressures put patients at higher risk of pulmonary edema.
§ For any condition that reduces ventricular compliance, the CVP and PAOP may overestimate LVEDV.
• Increased Compliance
o Compliance is increased by conditions that dilate the heart, such as aortic insufficiency and dilated cardiomyopathy. These patients have a
lower EDP for a given EDV.

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Heart Failure: Systolic vs Diastolic

• Heart failure results when the myocardium’s pumping action fails to satisfy the body’s metabolic demands. Since a properly functioning
ventricle must be able to accept and eject preload, the failing ventricle has a defect in its ability to fill and/or empty.
• Systolic Heart Failure—The Ventricle Doesn’t Empty Well
o The hallmark of systolic heart failure is a decreased ejection fraction with an increased end-diastolic volume. Volume overload
commonly causes systolic dysfunction.
§ Since the heart can’t squeeze well, a greater volume of blood remains in the ventricle after each contraction.
§ This also means that less oxygen rich blood is delivered to the periphery.
§ The arterial-venous oxygen content difference is increased.
§ Compensatory mechanisms include: increased SNS, increased RAAS, and increased preload.
• Diastolic Heart Failure—The ventricle Doesn’t Fill Properly
o Diastolic failure occurs when the heart is unable to relax and accept the incoming volume because ventricular compliance is
reduced. The defining characteristic of diastolic dysfunction is symptomatic heart failure with a normal ejection fraction.
Contractility is generally preserved until the late stage of the disease.
• Etiology, Cardiac Compensation & Hemodynamic Management
o The failing heart changes its size, shape, and function in an attempt to preserve cardiac output. This is known as cardiac
remodeling. Overtime, these compensatory mechanisms create problems of their own, and a decline in myocardial function
ensues.
o Remodeling can be reversed by:
§ ACE inhibitors (-pril drugs)
§ Aldosterone inhibitors (spironolactone)

• The Right Heart

o The right heart is thinner, more compliant, and weaker than the left heart. Anything that increases pulmonary vascular
resistance can impair RV function:
§ Hypoxia
§ Hypercarbia
§ Acidosis
o Nitrous oxide can increase PVR
o Treatment for RV failure includes inotropes and decreasing PVR (reversing the causes mentioned above and nitic oxide).
o The most common cause of right heart failure is left heart failure.

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Hypertension
• Hypertension affects up to 30% of the adults in the US, yet less than a third of these individuals realize they have high blood pressure. A high afterload increases
myocardial work and an elevated arterial driving pressure damages nearly every organ in the body.
• Diagnosis
o In the adult, hypertension is Complications include:
diagnosed when blood pressure
exceeds 140/90mmHg. To confirm • Left ventricular hypertrophy
the diagnosis, the blood pressure • Ischemic heart disease
should be measured on two • Congestive heart failure
separate occasions no sooner than • Arterial aneurysm (aorta, cerebral circulation)
1-2 weeks apart. • Stroke
• Etiology • End-stage renal disease
o Hypertension can be classified as
primary or secondary.
§ Primary hypertension has no identifiable cause. Incidence = 95% of all HTN cases.
§ Secondary HTN has an identifiable cause. Incidence = 5% of all HTN cases.
• Pathophysiology—Primary Hypertension
o Blood pressure is regulated by a feedback network consisting of the SNS (baroreceptors),
RAAS, and vasopressin
§ Hypertension is caused by an increased CO or SVR or both. Of the two, an
elevated SVR is almost always the cause.
§ Vascular smooth muscle tone (intracellular Ca+2 concentration) plays an
integral role in an elevated SVR.
o Although the exact cause of primary HTN is unknown, here are a few common explanations
§ Chronic vasoconstrictionàincreased renin releaseàincreased angiotensin I,
angiotensin II, and aldosteroneà increased sodium and water retention
§ SNS overactivity àchronic vasoconstrictionàincreased SVR
§ Vasodilator deficiency (decreased nitric oxide, prostaglandins)àincreased SVR
§ Collagen and metalloproteinase deposition in the arterial intimaàincreased vascular
stiffnessàincreased SVR
§ Diet (increased Na+ intake and/or decreased K+ or Ca+2 intake)
• Effects on Cerebral Autoregulation
o The cerebral autoregulation curve describes the range of blood pressure where cerebral perfusion pressure
remains constant. Chronic hypertension shifts this curve to the right. This adaptation helps the patient’s brain
tolerate a higher range of blood pressures, however this comes at the expense of not being able to tolerate a
lower blood pressure. Remember that BP past the range of auto regulation is pressure dependent.
§ Malignant hypertension increases the risk of hemorrhagic stroke and cerebral edema
§ Hypotension increases the risk of cerebral hypoperfusion
§ As an aside, the texts would lead you to believe that the width of the curve remains the same in the
hypertensive patient, however there is good evidence that the width of the curve (range of
autoregulation) becomes narrower.
Hypertension: Secondary Secondary HTN Clinical Findings Diagnostic Tests
Coarctation of the aorta Upper limb BP > lower limb BP Aortography
• Secondary hypertension is an elevated BP that
Weak femoral pulse Echocardiography
has a definitive cause. Treating this cause
Systolic bruit CT/MRI
usually restores BP to a normal range.
Renovascular Disease Bruit (epigastric or abdominal) CT angiography
• Etiology
Severe HTN in young patient MRA
o When you’re reading this chart,
don’t just think of it in relation to Aortography
secondary hypertension. You Duplex ultrasonography
should also use it as a brief review Hyperadrenocorticism Weight gain (truncal obesity) Dexamethasone suppression test
of each disorder. In your head, try Cushing’s syndrome Hyperglycemia Glucose tolerance test
to recall the key points about each Muscle and bone weakness Urinary cortisol
disease process. This is one way to Weakened immunity Adrenal CT/MRI
build connections in your mind. Hirsutism
Moon face
Hyperaldosteronism Hypertension Cp aldosterone
Conn’s disease Hypokalemia Cp renin
Alkalosis Cp potassium
Fatigue/weakness Urinary potassium
Paresthesia
Nocturnal polyuria and polydipsia
Pheochromocytoma Headache Plasma metanephrines
Palpitations Urinary catecholamines
Diaphoresis Urinary vanillylmandelic acid (VMA)
Pregnancy-induced HTN Peripheral and pulmonary edema Urinary protein
Headache Platelet count
Seizure Uric acid
RUQ pain Cardiac output

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Antihypertensive Agents

• Antihypertensive agents target blood pressure in several locations: ANS, kidney, adrenal gland, myocardium, and vascular smooth
muscle.
• Drugs that Target the Adrenergic Receptors
Drug Class Examples How BP is Reduced
α1 Antagonists Suffix àzosin Decreased vascular [iCa=@] àvasodilation
And… Decreased SVR (afterload)
Phenoxybenazmine
Phentolamine (α1 & α2)
β1 Antagonists Suffix àlol Decreased inotropy (contractility)
β1 Selective Decreased chronotropy (heart rate)
acebutolol, atenolol, bisoprolol, esmolol, Decreased dromotropy (conduction velocity)
metoprolol Decreased renin release by juxtaglomerular
apparatus
β1 & β2 Non-selective
nadolol, pindolol, propranolol, sotalol, In addition to β1 effectàvasoconstriction in
timolol muscle (this doesn’t decreased BP)
Mixed α1/β1, β2 antagonists Bucidolol, carvedilol, labetalol Mixed α1/β1, β2 effects
Labetalol α:β antagonistic potency:
IV 1:7
PO 1:3
α2 Agonists Clonidine, dexmedetomidine Decreased SNS outflow
αβ
• Drugs that Target the Myocardium and Vascular Smooth Muscle

• Drugs that Target the Kidney

Drug Class Examples Effects
ACE Inhibitors Suffixà pril Inhibits ATII mediated vasoconstriction
Inhibits aldosterone release
At-2 receptor blockers Suffixà sartan Inhibits ATII mediated vasoconstriction
Inhibits aldosterone release
Loop diuretics Furosemide, bumatenide, ethacrynic acid Inhibits Na-K-2Cl tranporter in thick portion of the
ascending loop of Henle
Diuresisàdecreased venous return (preload)
Thiazide diuretics HCTZ, metolazone, indamide, chlorthalidone Inhibits Na-Cl transporter in the distal convoluted
tubule
Diuresisàdecreased venous return (preload)
Potassium sparing diuretics Triamterene, amiloride Inhibits K excretion and Na reabsorption by the
principal cells in the collecting ducts
Acts independently of aldosterone
Aldosterone antagonists Spironolactone Inhibits K excretion and Na reabsorption by the
principal cell sin the collecting ducts

Blocks aldosterone at mineralocorticoid receptors

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Calcium Channel Blockers
• Mechanism of Action
o There are 3 types of voltage-gated calcium channels:
§ L-type=Long lasting or slow channel
§ N-type=Neural
§ T-type=transient
o All of the clinically used CCBs bind to the alpha-1 subunit of the L-type
calcium channel. This prevents calcium from entering cardiac and
vascular smooth muscle cells.
• How CCBs Affect Hemodynamics
o The effects of calcium channel blockers vary widely. While some are
better for controlling heart rate or contractility, others are more appropriate for modifying vascular tone. So which drug to use when?
o Control of Heart Rate
§ Verapamil and diltiazem are great choices to reduce heart rate in the patient with tachycardia, atrial fibrillation, or atrial flutter.
o Control of Contractility
§ Do you need to preserve contractility when you’re reducing heart rate? In the patient with a reduced EF, this is probably a wise idea.
§ CCB impair contractility in the following order (ranked highest to lowest): verapamil>nifedipine>diltiazem>nicardipine
§ In the patient with decreased contractility, diltiazem is a better choice than verapamil
o Control of Vascular Tone
§ Nifedipine, amlodipine, and nicardipine are vasodilators and are best used in the treatment of hypertension from elevated SVR
§ Nicardipine is useful as a coronary antispasmodic
§ Nimodipine is the only CCB proven to reduce M&M from cerebral vasospasm.
Pericarditis you must know 3 conditions that can affect the pericardium. All of
• The pericardium surrounds the heart. It provides a minimal friction environment in which the them limit the heart’s ability to move within the pericardial sac
heart can move with ease. The pericardium is composed of two layers that are separated by 10- 1. Acute pericarditis
50 mL of clear fluid:
1. The visceral layer is attached to the myocardium 2. Constrictive pericarditis

2. The parietal layer is anchored in the mediastinum 3. Cardiac tamponade (covered in next question)

Pathophysiology

• Constrictive pericarditis is caused by fibrosis or any condition where the pericardium becomes thicker. During diastole, the ventricles cannot fully relax, and this
reduces compliance and limits diastolic filling. Ventricular pressures increase and this creates a backpressure to the peripheral circulation. The ventricles adapt by
increasing myocardial mass, but over time this impairs systolic function.
• Acute pericarditis is usually the result of inflammation. It does not impair diastolic filing unless inflammation leads to constrictive pericarditis or cardiac tamponade.
Constrictive Acute
Cause Cancer (radiation) Infection (viral most common)
Cardiac surgery Dressler’s syndrome—inflammation from necrotic myocardium s/p MI
Rheumatoid arthritis Rheumatoid arthritis
Tuberculosis Systemic lupus erythematosus
Uremia Scleroderma
Trauma
Cancer (radiation)
Signs & Due to increased venous pressure and decreased CO Acute chest pain with pleural component:
Symptoms Kussmaul’s Sign • Increased pain with inspiration and postural changes
• Increased CVP during inspiration • Relieved by leaning forward or supine
• JVD during inspiration • Pericardial friction rub
Pulsus paradoxus (less common) • ST elevation with normal enzymes
• Decreased SBP>10mmHg during inspiration • fever
• Indicative of impaired diastolic filling
Increased venous pressure
• Distended neck veins
• Hepatomegaly
• Ascites
• Peripheral edema
Atrial dysrhythmias d/t atrial distension
Pericardial knock
Treatment Pericardiotomy Usually resolves spontaneously
• hemorrhage and dysrhythmias common Drugs to relieve pain: salicylates, oral analgesics, corticosteroids
• morality = 6-19%
Anesthetic CO is dependent on HR (avoid bradycardia) None
Management Preserve HR and contractility
• Ketamine
• Pancuronium
• Volatile agents with caution
• Opioids, benzos, and etomidate OK
Maintain afterload
Aggressive PPV can decrease venous return and CO

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Cardiac Tamponade

• The pericardium is a sac that surrounds the heart.

o The outside is called the parietal pericardium.
o The inside is called the visceral pericardium.
o It secretes serous fluid that reduces friction between the epicardium and the visceral pericardium.
• Pericardial Effusion
o A pericardial effusion is the accumulation of fluid inside the pericardial sac.
§ It is not associated with increased pericardial pressure, so it doesn’t impair diastolic filling or
ventricular compliance.
§ Therefore, it’s not an emergency and seldom requires
intervention.
• Cardiac Tamponade
o Cardiac tamponade also results from fluid accumulation inside
the pericardium, however the pericardial pressure is high
enough to compress the myocardium. This interferes with its
ability to fill and act like a pump.
o Key Points
§ CVP rises in tandem with pericardial pressure. As ventricular
compliance deteriorates, left and right sided cardiac diastolic pressures (CVP and PAOP) begin to equalize.
§ TEE is the best method of diagnosis.
• Pressure Volume Loop
o The pressure volume loop of cardiac tamponade results from
§ Decreased LVEDV (shifts loop to the left)
§ Decreased stroke volume (the loop is narrower)
§ Decreased ventricular compliance (notice the slop during ventricular filling)
• Presentation of Cardiac Tamponade
o BECK’s TRIAD
§ Hypotension decreased stroke volume
§ Jugular venous distension impaired return to the right heart
§ Muffled heart tones fluid accumulation attenuates sound waves
o Pulsus Paradoxus Decreased SBP by >10 mmHg during inspiration
Negative intrathoracic pressure on inspiration àincreased venous return to RV
àBowing of ventricular septum toward the LV àdecreased SVàdecreased COàdecreased SBP
o Kussmaul’s Sign Increased CVP + JVD during inspiration
o Reduced EKG Voltage excess fluid around the heart attenuates the electrical signal recorded by the electrodes
o Compression of the Heart, Lungs, mass effect
Trachea,and Esophagus
• Surgical Treatment
o Removing the excess pericardial fluid is the definitive treatment for cardiac tamponade. This is accomplished by:
§ Pericardiocentesis—a needle is used to aspirate pericardial fluid
§ Pericardiostomy—surgical opening and drainage of the pericardium (subxiphoid,thoracoscopic, or thoracotomy)
o Complications of these procedures include: pneumothorax, re-accumulation of pericardial fluid, and puncture of the coronary vessels or
myocardium.
• Anesthetic Management Drugs to Avoid Drugs that are Safer to use
o Local anesthesia is the preferred technique for pericardiocentesis. Halogenated anesthetics Ketamine (activation of the SNS makes
o If a general anesthetic is required, your primary goal is to preserve Propofol this the best choice)
myocardial function. Recall from the last question that SV is Thiopental
severely decreased and increased SNS tone (increased contractility High dose opioids Nitrous oxide
and increased afterload) provide compensation. Any drug that Neuraxial anesthesia Benzodiazepines
depresses the myocardium or reduces afterload can precipitate opioids
cardiovascular collapse.
o Positive pressure ventilation can impair venous return and cardiac output. It is best to maintain spontaneous ventilation until
the tamponade is relieved.
• Hemodynamic Goals for Cardiac Tamponade

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Infective Endocarditis

• Endocarditis is an infection where bacteria enter the blood stream and find their way to a heart valve, chamber, or blood vessel.
• The American Heart Association Guidelines for ineffective endocarditis prophylaxis determined that very few cases of IE can be prevented
with prophylactic antibiotics. For this reason, the indications for antibiotics in these patients was scaled down considerably.
• When considering who should receive antibiotic prophylaxis for endocarditis, we must consider 3 areas:
o 1. Who is at risk?
o 2. Does the surgical procedure increase the risk?
o 3. What is the appropriate treatment?
• Who is at Risk?
o The following conditions are associated with the highest risk for developing ineffective endocarditis. These patients would
receive pre-operative antibiotic prophylaxis.
§ Previous ineffective endocarditis
§ Prosthetic heart valve
§ Unrepaired cyanotic congenital heart disease
§ Repaired congenital heart defect if the repair is <6 months old
§ Repaired congenital heart disease with residual defects that have impaired endothelialization at the graft site
§ Heart transplant with valvuloplasty
o Antibiotic prophylaxis against endocarditis is NOT required for:
§ Unrepaired cardiac valve disease including mitral valve prolapse
§ CABG
§ Coronary stent placement
• Does the Surgical Procedure Increase the Risk?
o High risk procedure are thought to be “dirty” procedures where the risk of transient bacteremia outweighs the risk of antibiotic
therapy.
§ Dental procedures involving gingival manipulation and/or damage to mucosa lining.
§ Respiratory procedures that perforate the mucosal lining with incision or biopsy
§ Biopsy of infective lesions on the skin or muscle.
o Antibiotic prophylaxis against endocarditis is NOT required for:
§ GI endoscopic procedures without infection
§ GU procedures without infection
• What is the Treatment?

*please note that these guidelines change frequently, and what is cited in texts may not be the most up to date information.

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Obstructive Hypertrophic Cardiomyopathy

• The Name Game

o Hypertrophic Cardiomyopathy is the most common autosomal dominant cardiovascular disease, and it is the most common
cause of sudden cardiac death in young athletes. This disease process goes by several names. Learn them all.
§ Obstructive hypertrophic cardiomyopathy (OHCM)
§ Hypertrophic obstructive cardiomyopathy (HOCM)
§ Asymmetric septal hypertrophy (ASH)
§ Idiopathic hypertrophic subaortic stenosis (IHSS)
• Pathophysiology
o Left ventricular outflow tract (LVOT) obstruction is caused by:
§ Congenital hypertrophy of the interventricular septum
§ Systolic anterior motion (SAM) of the anterior leaflet of the mitral valve
o When the ventricle contracts forcefully or quickly, there is a greater tendency of
the anterior leaflet of the mitral valve to reduce flow through or completely obstruct the LVOT, understand that this occurs
during systole and that the problem is proximal to the aortic valve—NOT at the valve itself.
• Systolic Anterior Motion (SAM)
o SAM is likely caused by the Venturi effect as blood rapidly flows across the LVOT. Remember that velocity increases through a
point of stricture.
§ SAM is easily diagnosed with TEE>
§ It can also occur following mitral valve repair (not replacement).
• Factors that Determine Blood Flow through the LVOT
o There are 3 determinants of blood flow through the LVOT: systolic
LV volume, force of LV contraction, and the transmural pressure
gradient. Things that distend the LVOT are good, while things that
narrow the LVOT are bad.
o If some of the LV stroke volume can’t pass into the aorta, it takes a
retrograde path across the mitral valve. This leads to mitral
regurgitation. A systolic murmur can be a sign of turbulent flow through the LVOT obstruction or mitral regurgitation.
o LV hypertrophy leads to diastolic dysfunction. Because the LV takes longer to relax and is less compliant, preservation of left atrial contraction is
very important. Promptly treat a-fib or a junctional rhythm.
• Treatment
o Appreciating the pathophysiology should ease your understanding of anesthetic management. You’ll notice many similarities to aortic stenosis.
Problem Treatment Things That Cause the Problem
Increase heart rate Beta blockers Beta agonists
Calcium channel blockers Ketamine
o Verapamil Pancuronium
o Diltiazem Desflurane
Oxytocin
Light anesthesia
Histamine releasing drugs:
o Morphine
o Meperidine
o Thiopental
o atracurium
Decrease preload Volume resuscitation Vasodilators
Phenylephrine Neuraxial anesthesia
Hypovolemia (blood loss)
Postural changes (reverse T-burg)
Positive pressure ventilation
valsalva
Increase contractility Beta blockers Beta agonists
Calcium channel blockers Digoxin
o verapamil Light anesthesia
o diltiazem
Decrease afterload phenylephrine Neuraxial anesthesia
oxytocin

o *Hines incorrectly states that afterload reduction improves LVOT obstruction. In the next sentence, it correctly states that vasodilation worsens
LVOT obstruction (p 137).
• Surgical Repair
o Options include:
§ Septal myomectomy removes a portion of the interventricular septum and improves the transmural pressure gradient.
§ Alcohol injection into the septal perforator arteries causes ischemic injury to the septum and improves the transmural pressure
gradient.
§ Mitral valve replacement can reduce SAM.

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Percutaneous Coronary Interventions (Stents)
• Patients who’ve received a coronary stent are placed on dual antiplatelet therapy consisting of:
o 1. Aspirin—irreversible cyclooxygenase inhibitor Procedure Duration to Wait Until
o 2. Thienopyridine (usually clopidogrel or ticlopidine)—ADP receptor antagonist Elective Surgery
• Timing of Surgery after PCI Angioplasty—no stent 2-4 weeks
o When is it ok to proceed with surgery after percutaneous coronary intervention? You Bare metal stent 6 weeks minimum
must consider the implications of withholding antiplatelet therapy. 12 weeks preferred
§ Withholding therapyà increase risk of thrombus formation and myocardial Drug eluting stent 1 year
infarction CABG 6 weeks minimum
§ Continuing therapy àincreased bleeding risk *included for completeness 12 weeks preferred
o Elective surgery is best delayed until the recommended time has elapsed.
o *Miller says 30 days for bare metal stents, while Hines says a minimum of 6 weeks.
• When to Discontinue Therapy Before Surgery
o Always consult with a cardiologist before stopping dual antiplatelet therapy.
o Aspirin
§ If not absolutely contraindicated, continue ASA throughout the perioperative period
§ If absolutely contraindicated, stop ASA at least 3 days before surgery
o Clopidogrel
§ Stop 7 days before surgery
o Ticlopidine
§ Stop 14 days before surgery
o If the patient presents for emergency surgery, platelets can be used to reverse platelet inhibition.
o Unfractionated heparin and/or LMWH should NOT be used to “bridge” patients who’ve stopped all antiplatelet therapy. Interestingly, heparin
paradoxically increases platelet aggregation in the stent leading to an increased risk of thrombosis.
o The best treatment for stent thrombosis is PCI. The best outcome is achieved if blood flow is restored in <90 min.
o We discuss the implications of regional anesthesia in patients on anticoagulation therapy in the neuraxial anesthesia tutorial.
Cardiopulmonary Bypass

• Cardiopulmonary bypass allows the surgeon to operate on an immobile heart.

• Once the blood flows into the bypass circuit, oxygen is added and CO2 is removed, so that the blood returning to the patient resembles arterial blood.
1. Venous Line
a. Venous blood (usually SVC/IVC) is drained into the venous reservoir by gravity.
i. An airlock can occur if air enters the venous line.
2. Pump
a. The pump propels the blood through the patient’s circulation (it replaces the heart).
b. Roller Pump
i. A roller pump compresses the blood tubing, which creates an occlusion point as it mechanically
propels the blood forward.
ii. This is traumatic to blood cells.
iii. Additionally, pump flow remains constant regardless of the patient’s afterload, so if the arterial
inflow line is clamped, the pump continues pushing blood forward, and this can rupture the
arterial inflow tubing.
iv. Last, a roller pump is more likely to entrain air if the venous reservoir runs dry, which can lead to air embolism.
c. Centrifugal Pump
i. A centrifugal pump is nonocclusive—it uses gravity and spins the blood through a cone.
ii. This is less traumatic to blood cells
iii. Since a centrifugal pump can’t produce excessive negative pressure, it tends not to entrain air, thus reducing the risk of air
embolism.
iv. Additionally, this type of pump is unable to produce excessively high positive pressure, so pump flow decreases when it is
confronted by excessive afterload. This reduces the risk of line rupture if the arterial inflow line is clamped.
v. For all of these reasons, a centrifugal pump is preferred over a roller clamp.
vi. One disadvantage of the centrifugal configuration is the lack of an occlusion point—if there is an excessively high afterload, blood
backs up towards the venous circulation, which reduces the patient’s circulating blood volume.
3. Oxygenator
a. The oxygenator is the component of the CPB machine where gas exchange occurs (it replaces the lungs).
i. A membrane oxygenator uses a blood-membrane-gas interface. It’s more expensive, but it’s safer.
ii. A bubble oxygenator uses a blood-gas interface (no membrane). This architecture carries a risk of cerebral air embolism, which
explains why a membrane oxygenator is preferred.
4. Heat Exchanger
a. This device regulates the patient’s temperature by warming or cooling the blood.
i. Patients on CBP are rendered hypothermic to reduce the metabolic rate (this protects the critical organs).
5. Priming the Bypass Circuit
a. Because the CBP bypass circuit becomes an extension of the patient’s circulation, it must be primed with enough volume to de-air the pump.
The priming solution can be a balanced salt solution (+ mannitol, albumin, heparin, HCO3-) or blood.
b. Priming with anything other than blood produces hemodilution, which has the following effects:
i. Decreased hematocrit
ii. Decreased oxygen carrying capacity
iii. Decreased blood viscosity (good if hypothermia is used)
iv. Decreased plasma concentration of drugs and plasma proteins
v. Increased microvascular flow ( a function of reduced viscosity)

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CPB Key Facts

• While we can’t possibly detail everything you need to execute a cardiac anesthetic here, we’re going to hit the highlights of what we feel is most important
for testing situations. As an aside, our favorite book on this subject is A Practical Approach to Cardiac Anesthesia by Hensley and Martin
• Prebypass
o Awareness
§ Awareness is most common during sternotomy ( due to intense surgical stiulation)
§ The next most common time for awareness is probably during rewarming.
o Heparinization
§ The patient must be adequately heparinized before transitioning to cardiopulmonary bypass.
• This is defined as an activated clotting time (ACT) > 400 seconds
• Heparin allergy or a history of heparin induced thrombocytopenia requires an alternative such as bivalirudin, hirudin, or
another factor X inhibitor.
o Aortic Cannulation
§ Before CBP, the aorta must be cannulated. Hypertension during cannulation can lead to aortic dissection, so it is imperative that the
systolic blood pressure be less than 100mmHg during this time (Ideal range: SBP= 90-100 mmHg or MAP <70mmHg)
o Blood Conservation
§ Blood transfusion is not without risk, so we must employee methods to reduce these risks
• Antifibrinolytics, such as aminocaproic acid, reduce bleeding and the need for transfusion
• Cell saver is also used to reduce the need for transfusion
• On Bypass
o Cardioplegia:
§ The goal of myocardial preservation is to reduce myocardial damage that occurs during cardiopulmonary bypass.
§ Antegrade cardioplegia is introduced into the aortic root, where the solution then enters the coronary arteries. For this to occur, the
aortic valve must be competent (no AI) and the aorta clamped. Alternatively, retrograde cardioplegia may be administered through a
cannula placed in the coronary sinus.
§ Potassium in the cardioplegia solution arrests the heart in diastole. Recall that K+ increases resting membrane potential. This initially
activates the voltage-gated Na+ channels, but then it maintains the Na+ channels in an inactive state. Said another way, the voltage-
gated Na+ channels are unable to depolarize again until the RMP returns to normal. When the surgical procedure is complete, the
heart is “restarted” by infusing the coronary circulation with warm, normokalemic blood.
o Blood Gas Management:
§ Because the solubility of a gas is a function of temperature, it should make sense that hypothermia complicates our interpretation of
blood gas results during CPB. As temp decreases, more CO2 is able to dissolve in the blood. By extension, this affects the pH.
Knowing this poses an interesting question about how to best manage blood pH during CPB with hypothermia. Should the
temperature of the sample be corrected or not?
• Alpha-stat does not correct the patient’s temperature. This technique aims to keep intracellular charge neutrality acros
all temperatures. It is associated with better outcomes in adults.
• pH-stat corrects for the patient’s temperature. This technique aims to keep a constant pH across all temperature. It is
associated with better outcomes in peds.
o Key Points:
§ Blood flow is non-pulsatile, so we rely on MAP.
§ Full bypass is when all of the venous return is drained in the venous reservoir, while partial bypass describes a situation where the
heart receives ( and pumps) a fraction of the venous return.
§ A left ventricular vent removes blood from the LV. This blood usually comes from the Thebesian veins and bronchial circulation
(anatomic shunt).
§ CBP produces systemic inflammation that can result in critical organ injury and/or failure.
• After Bypass
o Protamine
§ Protamine is used to reverse heparin at the conclusion of cardiopulmonary bypass. It does this via a neutralization reaction ( it forms
an acid/base complex with heparin).
• As a general rule, 1 mg of protamine will reverse every 100 units of heparin that was given.
• If 30,000 units of heparin remain in the patient’s circulation, then the calculated dose of protamine is 300mg.
§ There are two ways to calculate the protamine dose:
• It is calculated from the initial heparin dose or…
• It is calculated from the amount of heparin that is predicted to remain in the patient’s circulation at the conclusion of
cardiopulmonary bypass.
• Because protamine has anticoagulant properties, basing the protamine dose from the initial heparin dose (not what
remains after CBP) may contribute to protamine overdose (prolonged ACT).
§ Administering protamine over 10-15 minutes reduces the likelihood of systemic vasodilation as well as pulmonary vasoconstriction
(both side effects of protamine). The rate of administration does not impact the probability of anaphylaxis.
o Key Points
§ Radial artery pressure may be artificially low just after CPB
§ Heart block (after the heart is restarted) is a side effect of the cardioplegia solution. For this reason, the heart is often paced in the
post-bypass period.

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Mechanical Cardiac Support

Intra-Aortic Balloon Pump

o The intra-aortic balloon pump is a counter pulsation device that improves myocardial oxygen supply while reducing myocardial oxygen demand.
• Pump Function
o Diastole: inflation increases coronary perfusion
o Systole: deflation allows ejection of stroke volume
o Indications
§ Cardiogenic shock
§ Myocardial infarction
§ Intractable angina
§ Difficult separation from cardiopulmonary bypass
o Contraindications
§ Severe aortic insufficiency
§ Descending aortic disease
§ Severe peripheral vascular disease
§ Sepsis
• Placement
o The balloon is inserted through the femoral artery and advanced along the
descending aorta. You wouldn’t want to push through plaque or compress an
aneurysm with the balloon.
o The tip of the balloon should be positioned 2 cm distal to the left subclavian artery. A more proximal position causes the balloon to occlude
perfusion of the left common carotid, and/or the brachiocephalic arteries.
o Proper position is confirmed with CXR, fluoroscopy, or TEE.
• How it Works
o InflationàDiastole
§ The aortic valve closes at the onset of diastole, and this is when the balloon inflates.
• Inflation correlates to the dicrotic notch on the aortic pressure waveform
• The inflated balloon creates a back pressure on the coronary arteries that augments coronary perfusion pressure—this
increases myocardial oxygen supply
• Note that this pressure is higher than during unassisted systole

o DeflationàSystole
§ The balloon deflates just before the onset of systole.
• This correlates with the R wave on the EKG
• Balloon deflation causes a vacuum like effect that reduces afterload and reduces left ventricular work—this reduces
myocardial oxygen demand
• Note that the aortic pressure dips lower than after an unassisted systole. It also reduces aortic end-diastolic pressure.
• Other Key Facts
o The balloon may be timed to inflate during every cardiac cycle (1:1) or at some other ratio (1:2, 1:3, etc) to facilitate weaning.
o Timing is generally unaffected by pacemaker spikes or electrocautery. Irregular heart rhythm, such as atrial fibrillation or rapid heart rate, can
make proper timing more challenging.
o The most common complication of IABP are: vascular injury, infection at the insertion site, and thrombocytopenia.
o Patients on long term IABP therapy require anticoagulation.
Left Ventricular Assist Device

• An LVAD is a mechanical device that aids the failing heart by pumping blood from the left ventricle to the aorta.
o This device can be used as a bridge to recovery, bridge tot transplant, or destination therapy (this is as good as it gets).
o The presence of an intracardiac shunt (PFO), aortic insufficiency, or tricuspid regurgitation requires surgical correction before an LVAD can be
placed.
o LVAD flow is highly dependent on LV volume. A underfilled LV compromises C, while an overfilled LV compromises RV function.
o Depending on the patient’s native cardiac function, flow can be pulsatile or non-pulsatile. In the absence of a pulse, a pulse oximeter and NIBP
will be ineffective. An arterial line and frequent blood gas analysis will be required.
o Sepsis (infection) is the most common cause of death in the patient with an LVAD> aseptic technique and prophylactic antibiotics are
mandatory.
o These patients require anticoagulation (usually warfarin) and gastrointestinal bleeding is common in this population.

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Abdominal Aortic Aneurysm

• The incidence of AAA in the United States is between 3-10% for patients over 50 years of age.
• Independent risk factors include cigarette smoking, male gender, and advanced age.
• Diagnosis
o AAA is generally symptomless and detected as a pulsatile abdominal mass during routine examination. CT, ultrasound, and MRI are useful for
determining its size.
• Pathophysiology
o The primary mechanism for the development of AAA is the destruction of elastin and collagen that form the matrix of the vessel wall.
Atherosclerosis, inflammation, endothelial dysfunction, and platelet activation also contribute to the pathologic changes that cause the vessel
wall to weaken and dilate. Thrombus formation may reduce the diameter of the aortic lumen.
o Applying the law of Laplace, we know that the diameter of the AAA correlates with the risk of rupture.
Wall tension= transmural pressure x Vessel radius
Increased diameteràincreased transmural pressureàincreased wall stress
o Since mortality increases significantly once the AAA reaches 5.5cm, surgical correction is recommended when the aneurysm exceeds 5.5cm or if
it grows more than 0.5-0.8 cm/year.

• AAA Rupture
o The classic triad of AAA rupture consists of: hypotension, back pain, and pulsatile abdominal mass. This is only present in ~50% of patients.
Most aneurysms rupture in the left retroperitoneum. Rapid exsanguination is usually prevented by clot formation and the tamponade effect of
the retroperitoneum. Myocardial infarction is the most common cause of postoperative death.
Aortic Cross Clamp

• The patient’s physiologic response to the aortic cross clamp (AoX) is related to 3 factors:
o 1. Location of AoX placement (infrarenal most common)
o 2. Intravascular volume status
o 3. Cardiac reserve
• Application of AoX creates a central hypervolemia by:
o Reducing venous capacity
o Shifting a greater proportion of the blood volume proximal to the clamp
o Venous return increases
• Removal of AoX creates a central hypovolemia by:
o Restoring venous capacity
o Shifting a greater proportion of blood to the lower body
o Capillary leak contributes to the loss of intravascular volume
o Venous return decreases
• Clamping starves distal tissues of oxygen. These cells convert to anaerobic metabolism, which
results in:
o Increased lactic acid productionàmetabolic acidosis
o Increased prostaglandins
o Increased activated complement
o Increased myocardial depressant factors
o Decreased temperature
• Physiologic Changes Associated with AoX

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Aortic Surgery & Anterior Spinal Artery Syndrome

• Spinal Cord Circulation

o The spinal cord’s circulation consists of
§ 2 posterior spinal arteries
§ 1 anterior spinal artery
§ 6-8 radicular arteries
o Posterior Spinal Arteries (2)
§ Aortaàsubclavian a. à vertebral a. àposterior spinal a.
§ Aortaà segmental a. àposterior radicular a. à posterior spinal a.
§ Perfuses the posterior 1/3 of the spinal cord (green)
o Anterior Spinal Artery (1)
§ Aortaàsubclavian a. àvertebral a. à anterior spinal a.
§ Aorta à segmental a. à anterior radicular a. à anterior spinal a.
§ Perfuses the anterior 2/3 of the spinal cord (yellow)
o Artery of Adamkiewicz
§ It is the most important radicular artery
§ It perfuses the anterior spinal cord in the thoracolumbar region
§ It most commonly originates on the left side between T11-T12
§ In 75% of the population, it originates between T8-T12, and in another 10% it arises at L1-2.
o It’s critical to understand that the spinal cord is perfused at each segment, but not necessarily along its entire length. Some regions of the cord
have only a single blood supply. These are called watershed areas, and they’re particularly vulnerable to ischemia.
o For example, the thoracolumbar region of the anterior spinal cord is highly dependent on the radicular arteries. Interruption of radicular flow
can cause ischemia or infarction to the corresponding spinal cord segments.
• Anterior Spinal Artery Syndrome
o An aortic cross clamp placed above the artery of Adamkiewicz can cause ischemia to the lower portion of the anterior spinal cord. This can
result in anterior spinal artery syndrome—otherwise known as Beck’s syndrome. Classic signs and symptoms include:
§ Flaccid paralysis of the lower extremities
§ Bowel and bladder dysfunction
§ Loss of temperature and pain sensation
§ Preserved touch and proprioception
o We tend to generalize that the anterior cord contains motor neurons and the posterior cord contains sensory neurons. While this is enough to
get you by in most situations, we need to dig deeper to help you understand the presentation of anterior spinal artery syndrome.
§ The corticospinal tract is perfused by the anterior blood supply. This explains why the patient presents with flaccid paralysis of the
lower extremities.
§ Autonomic motor fibers are perfused by the anterior blood supply. This explains why the patient experiences bowel and bladder
dysfunction.
§ The spinothalamic tract is perfused by the anterior blood supply. This explains why the patient loses pain and temperature
sensations.
§ The dorsal column is perfused by the posterior blood supply. This explains why touch and proprioception are spared in this patient.
• Anesthetic Considerations for Aortic Surgery
o Thoracic cross clamp times >30 minutes pose a significant risk for cord ischemia and protective strategies should be employed.
o Spinal cord protection strategies include:
§ Moderate hypothermia (30-32 degrees C) to reduce cord oxygen consumption.
§ CSF drainage—spinal cord perfusion is dependent on the pressure gradient between anterior spinal artery and CSF pressure, so a
CSF drain will reduce CSF pressure and increase the pressure gradient.
§ Proximal hypertension during cross clamping (MAP ~100 mmHg).
§ Avoidance of hyperglycemia
§ SSEP and MEP monitoring (recall that SSEP will only monitor the posterior cord and MEP may be useless if neuromuscular blockers
are used).
§ Partial CPB (left atrium to femoral artery).
§ Drugs –corticosteroids, calcium channel blockers, and/or mannitol
o There is conflicting data regarding spinal cord ischemia with endovascular repair.

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Carotid Endarterectomy & Carotid Angioplasty Stenting

• Patients with carotid stenosis are at a higher risk of transient ischemic attacks or stroke. In symptomatic patients, CEA significantly reduces stroke risk when the
degree of carotid stenosis exceeds 70%.
• Amaurosis Fugax
o Amaurosis fugax (blindness in one eye) is a sign of impending stroke.
o Emboli travel from the internal carotid artery to the ophthalmic artery. This
impairs perfusion of the optic nerve and causes retinal dysfunction.
o It occurs in 25% of patients with high grade stenosis.
• Type of Anesthesia
o CEA can be performed under regional or general anesthesia. While neither
method is superior over the other, you should understand the relative merits
of both.
• Monitoring Cerebral Perfusion and Neurologic Integrity
Key Points
Awake patient This is the best method to assess cerebral perfusion and neurologic integrity
EEG Monitors cortical electrical function (does not detect subcortical problems).
Risk of cerebral hypoperfusion with loss of amplitude, decreased beta-wave activity, and/or appearance of slow wave activity.
High incidence of false-negatives. Possible causes include:

Increased Frequency (Hz) Decreased Frequency (Hz)

Mild hypercarbia Extreme hypercarbia

Early hypoxia Hypoxia
Seizure activity Cerebral ischemia
Ketamine Hypothermia
N2O Anesthetic overdose
Light anesthesia Opioids
Cerebral Oximetry Uses near-infrared spectroscopy (NIRS) to monitor cerebral oxygen saturation (rSO2) in the frontal lobe.
Cerebral perfusion is at risk when rSO2 is reduced > 25% from baseline
Transcranial Doppler Assessment of continuous blood flow velocity in the middle cerebral artery (this is where most emboli lodge).
May indicate when a shunt should be placed.
SSEP Monitors sensory pathways only
Requires light plane of general anesthesia, as volatile agents decrease amplitude and increase latency – both of which can
mirror ischemia
• Key Considerations
o Head rotation, flexion, or extension can compress the carotid and/or vertebral arteries. This can reduce cerebral perfusion
o Hyperglycemia the day of surgery (>200 mg/dL) has been associated with a n increased risk of stroke and death. Therefore, hyperglycemia should be treated with
insulin and glucose containing solutions avoided.
o Normocapnia or mild hypocapnia should be maintained. The cerebral vessels distal to the point of stenosis may be maximally dilated. Since hypercarbia dilates all of
the cerebral vessels, it can create a “steal” phenomena by shunting blood away from the hypoperfused cerebral tissue.
• Carotid Cross Clamp
o After the carotid artery is cross clamped, ipsilateral cerebral perfusion relies on collateral flow from the circle of Willis.
o Cerebral perfusion pressure = MAP – CVP (or ICP whichever is higher)
o During cross clamping: maintain BP normal or slightly elevated. We do this because blood vessels in ischemic regions of the brain are maximally vasodilated (loss of
autoregulation). Said another way, perfusion to these regions is pressure dependent.
§ Actions: give phenylephrine and reduce anesthetic depth
o After cross clamping: reduce BP < 145 mmHg (HTN à reperfusion injury à cerebral edema)
§ Agents to use: vasodilators or labetalol
• Stump Pressure
o Monitors perfusion pressure in the carotid artery on the operative side
o Risk of cerebral hypoperfusion if <50 mmHg
o A shunt placed distal to the carotid cross clamp increases cerebral perfusion
o shunt placement increases risk of embolic stroke
o some surgeons do not routinely use shunts and may employ cerebral perfusion monitors to guide this decision.
• Post-Operative Considerations
o Hematoma
§ Hematoma at the surgical site can compromise airway patency. This is an airway emergency. A cricothyroidotomy or tracheostomy may be required.
§ If the surgeon isn’t available, you’ll need to remove the sutures and decompress the wound.
o Recurrent Laryngeal Nerve Injury
§ The ipsilateral recurrent laryngeal nerve may be injured during CEA
§ Remember the RLN innervates all of the intrinsic laryngeal muscles except for the cricothyroid muscle
§ Unilateral injury paralyzes the ipsilateral vocal cord and may result in hoarseness and inspiratory stridor
o Hemodynamic Instability
§ Exposing the previously covered baroreceptors alters their sensitivity.
§ Hyper-and hypotension are common, but hypertension is more common. Both usually subside within 24 hours.
§ Hypertension can lead to reperfusion injury, cerebral edema, and hematoma at the surgical site.
§ Hypotension can reduce cerebral perfusion pressure
§ Postoperative stroke is usually the result of an embolic phenomena—not hypotension or hyperperfusion.
o Carotid Denervation
§ Carotid body denervation reduces the ventilatory response to hypoxia. This is a problem in the patient with a h/o bilateral CEA

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Carotid Artery Angioplasty Stenting

• CAS uses percutaneous transvascular access to pass the stent into the carotid artery.
• Anticoagulation is maintained with heparin (50-100 units/kg) to maintain ACT > 250-300 seconds
• Balloon inflation can activate the baroreceptor response, leading to bradycardia and hypotension. Pretreatment with atropine or glycopyrrolate can attenuate this
response.
• The most common complication is thromboembolic stroke, as atherosclerotic debris lodges in the cerebral vasculature.
• A distal protection filter placed beyond the angioplasty balloon will catch most of the debris.
• Embolic stroke is treated with recombinant tissue plasminogen activator.
Subclavian Steal Syndrome

• Subclavian steal occurs when there is an occlusion of the subclavian or innominate artery proximal to the origin of the ipsilateral vertebral artery. This
disease usually occurs on the left side.
o This results in a reversal of blood flow, where vertebral blood (usually goes to the brain) follows a pressure gradient towards the ipsilateral
subclavian artery.
o Said another way, arterial blood is “stolen” from the posterior cerebral circulation when it’s diverted to the ipsilateral arm.

o the blood pressure is much lower in the ipsilateral arm—the pulse may be diminished.
o Subclavian endarterectomy is the treatment of choice.

100
CV Notes

101
Pharmacokinetics

Volume of Distribution

• The volume of distribution (Vd) describes the relationship between a drug’s plasma concentration following a specific dose. It is a
theoretical measure of how a drug distributes throughout the body. Vd assumes two things:
o 1. The drug distributes instantaneously (full equilibration occurs at t=0)
o 2. The drug is not subjected to biotransformation or elimination before it fully distributes
• Vd is a calculated value. It is not something we can directly measure.
• Concentration is a measure of amount per volume. A drug is in its most concentrated
form before we administer it to the patient. When the drug enters the blood stream it
becomes diluted, and as the drug penetrates the tissues, it becomes diluted even
further.
• To provide context, let’s review the distribution of body water in a 70 kg patient:

• A drug with a Vd that exceeds total body water (>0.6 L//kg or >42 L) is assumed to be lipophilic. It Vd is affected by
distributes into the total body water as well as into the fat. It will require a higher dose to achieve a
given plasma concentration. For example, propofol has a very large Vd. • Drug characteristics
o Molecular size
• Conversely, a drug with a Vd that is less than total body water (<0.6 L/kg or <42 L) is assumed to be
o Ionization
hydrophilic. It distributes into some or all of the body water, but it does not distribute into fat. It will
o Protein binding
require a lower dose to achieve a given plasma concentration. For example, neuromuscular blockers
are restricted to the ECF (plasma + ISF) and have a comparatively small Vd. • Patient characteristics
o Pregnancy
• Since you can use your favorite pharmacology textbook to look up the Vd for any drug, we can
o Burns
rearrange this formula to calculate the loading dose that will provide a predetermined plasma
concentration. As you can see from the equation, the higher the Vd, the higher the loading dose must be given to achieve the
predetermined plasma concentration.
Loading Dose = Vd x Desired Plasma Concentration
Bioavailability
• For an IV medication, bioavailability equals 1 since it is injected directly into the bloodstream. A drug administered by any other route
may not be absorbed completely and/or it may be subjected to the first pass metabolism in the liver. These conditions reduce
bioavailability and explain why the dose that achieves a given plasma concentration is dependent on the route of administration.
Clearance & Steady State

• Clearance
o Clearance is the volume of plasma that is cleared of drug per unit time.
CL is Directly Proportional to: CL is Inversely Proportional To:
Blood flow to clearing organ Half-life
Extraction ratio Drug concentration in the central compartment
Drug dose
o For our purpose, the most important clearing organs include:
§ Liver
§ Kidney
§ Organ independent (Hofmann elimination and ester hydrolysis in the plasma)
• Steady State
o The concept of clearance is vital when calculating a continuous infusion of determining a dosing interval. To maintain a steady
state concentration in the plasma, the infusion rate or dosing interval must equal the rate of drug clearance by metabolism and
elimination.
(SS) Rate of Administration = Rate of Elimination
o Steady state occurs when the amount of drug entering the body is equivalent to the amount of drug being eliminated from the
body – there is a stable plasma concentration. Each of the compartments has equilibrated, although the total amount of drug
may be different in different compartments.
o Steady state is achieved after 5 half-times.

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Multi-Compartment Models

• Two Compartment Model

o The plasma concentration curve graphically depicts the biphasic decrease of
a drug’s plasma concentration following a rapid IV bolus.
o A: Line A is redistribution.
§ Drugs are not confined to the plasma. Instead, they distribute into
multiple theoretical compartments in the body. When we give a
rapid IV bolus, the drug follows its concentration gradient from
the central compartment (the plasma) to the peripheral
compartments (the tissues).
• This quickly reduces the Cp, which is reflected by the
steep slope of line A.
• The slop of line A is influences by a drug’s volume of distribution. As a general rule, the more lipophilic the
drug, the larger the Vd, and the steeper the slope.
o B: Line B represents elimination:
§ As soon as a drug enters the plasma, part of its redistributes based on the concentration gradient between the
plasma and the tissues.
§ At the same time, some of the drug in the plasma is already undergoing elimination.
§ As Cp continues to decline as a result of continued elimination, the concentration gradient reverses and drug
redistributes from the peripheral compartment and re-enters the central compartment.
§ The relatively flatter slope (beta phase) represents drug elimination from the central compartment.
o A + B: represents plasma concentration over time; it is the summation of line A and line B
§ The alpha portion of the curve represents distribution. It is also called t1/2a
§ The beta portion of the curve represents elimination. It is also called t1/2b
o Rate Constants
§ Rate constants communicate the speed at which a reaction occurs (or how fast a molecule moves between
compartments)
• K12—rate constant for drug transfer from central to peripheral compartment
• K21—rate constant for drug transfer from peripheral to central compartment
• Ke—rate constant for drug elimination from body

• Three Compartment Model

o If you extrapolate what you’ve learned about the two compartment model, you can predict a drug’s behavior that distributes
into a three compartment model. This becomes very complex very quickly! These models are constructed via computer
simulation.

103
Elimination Half-Time & Context Sensitive Half-Time

• What is the Difference Between Half-Life and Half-Time?

o Elimination Half-Life is the time it takes for 50% of the drug to be removed from the body after a rapid IV injection
o Elimination Half-Time is the time it takes for 50% of the drug to be removed from the plasma during the elimination phase
o When the rate of drug removal from the plasma is not the same as the rate of drug removal from the body, the elimination
half-life and half-times will be different.
o Note that the concepts are very similar. So similar in fact, that some of the texts don’t even make this distinction and only use
the term half-life. Don’t get bogged down by this. Learn to apply the general concept and you’ll be in great shape.
• How Long Until the Drug is Eliminated? Half-Time Amount of Drug Amount of Drug
o By convention, we say that a drug has been cleared from the body Eliminated % Remaining %
when 96.9% of the dose has been eliminated from the plasma. This 0 0 100
occurs after 5 half-times. 1 50 50
o The half-time measures a constant fraction and NOT a constant 2 75 25
amount. It takes the same period of time for the plasma 3 87.5 12.5
concentration of a drug to fall from 200mg/L to 100mg/L as it does 4 93.75 6.25
for the same drug to fall from 50mg/L to 25 mg/L
5 96.875 3.125
• The Problem with Half-Times
o Even though you need to know this stuff for the NCE, you should also know that the concept of half-times oversimplifies the
movement of drugs inside the body and is, dare we say it, almost clinically meaningless. Here’s the rub….
o The concept of half-times is really only applicable to drugs that follow a 1 compartment model. The problem is that the body is
so much more complex than a single homogenous compartment. In the last question, we said that most drugs we give
distribute into and out of different compartments at different rates. The bottom line is that we cannot determine the offset of
anesthetic drugs by half-times alone.

• Context Sensitive Half-Time

o The concept of context-sensitive half-time takes the duration of drug administration into account. It is the time required for the
plasma concentration to decline by 50% after the infusion is stopped. The “context” is time. Context-sensitive half-time is
calculated with the aid of complex computer algorithms.
• Clinical Example: Context-Sensitive Half-Time of Opioids
o The context-sensitive half-time for a fentanyl infusion increases as a function of how long it was infused. A longer infusion had
more time to fill up the peripheral compartments, therefore more fentanyl has to be eliminated and it will have a longer
elimination half-time. This is also true for alfentanil and sufentanil. Remifentanil is an exception. Even though it is highly
lipophilic, it is quickly metabolized by plasma esterases and has a similar context-sensitive half-timie regardless of how long it is
infused.

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pKa, pH & Ionization

• What is the Difference Between a Strong and Weak Acid or Base?

o If you put a strong acid or a strong base in water, it will ionize
completely.
o If you put a weak acid or a weak base in water, a fraction of it
will be ionized and the remaining fraction will be unionized.
• Ionization
o Ionization describes the process where a molecule gains a positive or negative charge, and this molecular change affects a molecule’s ability to
diffuse through lipid membranes.
o The amount of ionization is dependent on two things:
§ 1. The pH of the solution
§ 2. The pKa of the drug (another name for the pKa is the dissociation constant)
When pKa and pH are the same, 50% of the drug will be ionized and 50% will be unionized
o Same changes in pH can have a profound impact on the degree of ionization.
§ This is more pronounced if the pKa and pH are very close to each other.
§ It is less significant if the pKa is very far from the pH
• How Does Ionization Affect Pharmacokinetics and Pharmacodynamics?

• What Happens When We Put Weak Acids and Bases in Solution? Just Remember that…
“Like Dissolves Like”
o An Acid in a Basic Solution
§ An acidic drug will be highly ionized in a basic pH
§ The acidic drug wants to donate protons and the basic solution wants to accept protons
§ The acidic drug happily donates its protons and will become ionized
o An Acid in an Acidic Solution
§ An acidic drug will be highly unionized in an acidic pH
§ The acidic drug wants to donate protons and the acidic solution wants to do the same
§ Since there are no proton acceptors, the acidic drug retains its proton and will remain unionized.
o A Base in an Acidic Solution
§ A basic drug will be highly ionized in an acidic pH
§ The basic drug wants to accept protons and the acidic solution wants to donate protons.
§ The basic drug happily accepts the protons and will become ionized.
o A Base in a Basic Solution
§ A basic drug will be highly unionized in a basic pH
§ The basic drug wants to accept protons and the basic solution wants to do the same.
§ Since there are no proton donors, the basic drug will remain unprotonated and will remain unionized.
• Drug Preparations
o Most of the drugs that we give are weak acids and bases. Ionization affects a drug’s pharmacologic activity as well as its ability to pass through
cell membranes. Drugs are usually prepared as a salt that dissociates in solution.
o A weak acid is paired with a positive ion such as sodium, calcium, or magnesium
§ Example: Sodium thiopental
o A weak base is paired with a negative ion such as chloride or sulfate
§ Example: lidocaine hydrochloride
• Now Let’s Get Back to the Question…
o Now that we’ve reviewed the essentials of acid-base chemistry, we hope that it appears pretty easy.
o The unionized fraction predominates if:
§ The molecule is a weak base and the pH of the solution is > the pKa of the drug (a base dissolved in a base)
§ The molecule is a weak acid and the pH of the solution is < the pKa of the drug (an acid dissolved in an acid)
o The ionized fraction predominates if:
§ The molecule is a weak base and the pH of the solution < the pKa of the drug ( a base dissolved in an acid)
§ The molecule is a weak acid and the pH of the solution > the pKa of the drug (an acid dissolved in a base)

105
Ion Trapping

• Imagine two different solutions separated by a lipid bilayer. The solution on the left side has a pH of 7.4 and the solution on the right side
has a pH of 5.4.
• Only the lipophilic, unionized fraction of a drug will freely diffuse across the cell membrane. After it does, it will ionize according to its pKa
and the pH of the solution on this side of the membrane. Therefore, the drug concentration, as well as the degree of ionization, will be
different on each side of the membrane.

• Fetal Ion Trapping

o Let’s look at the classic example of the mother and fetus.
§ If the mother receives an IV injection of lidocaine (pKa=7.9), the unionized fraction freely diffuses across the placenta
§ Fetal pH is normally a little lower than the maternal pH
§ Since a weak base has entered a more acidic environment, there will be a greater degree of ionization inside the
fetus.
§ Since the ionized lidocaine cannot freely cross the placenta back to the mother, it becomes trapped inside the fetus.
§ Furthermore, the concentration gradient for unionized lidocaine favors the passage of even more unionized lidocaine
into the fetus.
§ As the fetus becomes distressed, it becomes more acidotic, which traps even more lidocaine within it. A vicious cycle
ensues.
o Maternal alkalosis increases the unionized fraction in the maternal circulation; more lidocaine is available to diffuse across the
placenta. Fetal acidosis increases the ionized fraction inside the fetus. Therefore, the combination of maternal alkalosis and
fetal acidosis creates the strongest diffusion gradient.
Plasma Protein binding

• Plasma proteins are synthesized by the liver. They are too large to pass through cell membranes and therefore remain confined to the
circulation.
• You can think of plasma proteins as an intravascular drug storage compartment. The drug and protein form a weak bond, such as an
ionic, hydrogen, or van der Waals bond. A drug bound to a plasma protein cannot bind to a receptor, so any bound drug can be
considered inert. Only when the drug is released from the protein, is it able to affect the body.
• Plasma Proteins
o Albumin Increased Decreased
§ Is the most plentiful plasma protein Albumin na Liver disease
§ Is the primary determinant of plasma oncotic *primarily binds acidic Renal disease
pressure drugs, but will bind some Old age
§ T ½ is 3 weeks basic and neutral drugs Malnutrition
§ Serves as a measurement of protein Pregnancy
synthesis—will reflect chronic but not acute
changes
a1-acid glycoprotein
Surgical stress
Myocardial infarction
Neonates
Pregnancy
*binds basic drugs Chronic pain
§ Carries a negative charge
§ Primarily binds to acidic drugs, however it also Rheumatoid arthritis
binds to some neutral and basic drugs Advanced age
o a1-acid glycoprotein beta-globulin na na
§ binds to basic drugs *binds basic drugs
o beta-globulin
§ binds basic drugs

• Conditions that Alter Plasma Protein Concentrationàtable

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 • Changes in Plasma Protein Binding
o Alterations in plasma protein binding can theoretically affect a drug’s therapeutic effect. For drugs highly bound to plasma
protein, we must conceptualize the bound and the unbound fractions. Only the unbound fraction (free fraction) of a drug is
available to cross lipid membranes where the drug can ultimately engage its receptor and exert its physiologic effect.
§ [Free drug] + [ Unbound protein binding sites] <-> [Bound drug]
o if a drug is 98% bound and the bound fraction is reduced to 96%, the unbound or free fraction has increased by 100%! Said
another way, if the free fraction is 2% and it increases to 4%,the the free fraction has increased by 100%. Clinically this would
manifest as an observed increase in potency.
o Changes in protein binding can result from: decreased plasma protein content or competition for binding sites on the protein.
o 1. Decreased plasma protein
§ reduced synthetic function (liver disease, malnutrition)
§ increased protein excretion (renal disease)
rd
§ altered distribution (3 trimester of pregnancy)
o [Link] for binding sites
§ there are no clinically relevant interactions that result from competition for binding sites. If a drug is displaced from
the plasma protein, its serum concentration will rise. During this time, the drug is subjected to a higher rate of
metabolism and elimination. Steady state between the bound and unbound fractions will be re-established after 5
half-lives have elapsed.
o Other important facts include:
§ Volume of distribution is inversely related to the degree of plasma protein binding
§ Highly protein bound drugs typically have a slower rate of metabolism and elimination.
Zero vs First Order Kinetics

• For the majority of drugs, the rate of metabolism is dependent on 2 factors:

o 1. The concentration of drug at the site of metabolism. This is influenced by blood flow to the site of metabolism.
o 2. The intrinsic rate of the metabolic process. This is influenced by genetics, enzyme induction, and enzyme inhibition.
• Kinetic models take into account that there is a finite quantity of enzymes available to metabolize a drug.
• Zero Order Kinetics (Linear)àConstant Amount per Time
o Zero order kinetics describes the situation where there is more drug than enzyme.
o The biotransformation process becomes saturated.
o Not enough enzyme is available to metabolize all of the drug that is delivered to it.
o The enzyme will metabolize a constant amount per unit time.
o Think of a bus (enzyme) and people at the bus stop (drug molecules). The bus only has 10 seats, so it can only
pick up 10 passengers at a time. No matter how many people are standing in line, only 10 can ride the bus at any
given time.
o The concentration scale on the y-axis is linear.
o Examples: aspirin, phenytoin, alcohol
• First Order Kinetics (Logarithmic) àConstant Fraction per Time
o First order kinetics describes the situation where there is less drug than enzyme
o No saturation occurs
o The enzyme will metabolize a constant fraction per unit time
o The concentration scale on the y-axis is measured as the log concentration
o Just about all of the drugs we administer follow first order kinetics.
• It is possible for a drug that follows first order kinetics to change to zero order kinetics if the enzymatic
pathway becomes saturated.

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Phase I, II & III Reactions
• Sites of Metabolism
o Metabolism, otherwise known as biotransformation, is the enzymatic process of altering the chemical structure of a molecule. The liver is the primary
organ of metabolism. The hepatic microsomal enzymes of the P450 system are generally confined to the smooth endoplasmic reticulum, although they
also present in the kidney and GI tract.
o The plasma is another important site of drug metabolism. Key reactions include Hofmann elimination (pH and temperature dependent) as well as
hydrolysis reactions catalyzed by non-specific plasma esterases, and pseudocholinesterase
• How Metabolism Facilitates Drug Elimination
o The primary role of metabolism is to change a lipid soluble, pharmacologically active compound into water soluble, pharmacologically inactive byproduct.
Creating molecules with greater water solubility increases ionization and decreases their volume of distribution. In turn, this increases their delivery to
the kidneys for elimination. Since the molecule is ionized, it will be eliminated in the urine instead of undergoing reabsorption from the renal tubule. The
gastro intestinal tract is capable of elimination as well.
o If the body was unable to change a lipid soluble drug into a water soluble byproduct, the
lipid soluble drug would be continuously reabsorbed by the renal tubules into the
pericapillary fluid and returned to the plasma; the drug could theoretically remain in the
body for a very long time. It should be noted that sometimes the body converts an
inactive molecule into a pharmacologically active molecule. This is called a prodrug.
Fospropofol is a prodrug that is metabolized by alkaline phosphatases to its active
metabolite—propofol.
• Phases of Metabolism
o There are 3 phases of metabolism: modification, conjugation, and elimination.
o Phase 1: Modification
§ Phase 1 reactions result in small molecular changes that increase the
polarity (water solubility) of a molecule to prepare it for a phase 2
reaction – it creates a location on the molecule that will allow the phase
2 reaction to take place. Most phase I biotransformations are carried out
by the P450 system.
§ There are 3 phase I reactions that you should understand:
• Oxidation—adds an oxygen molecule to a compound
• Reduction—adds electrons to a compound
• Hydrolysis—adds water to a compound to split it apart (usually an ester)
o Phase II: Conjugation
§ The phase 2 reaction conjugates (adds on) an endogenous, highly polar, water soluble substrate to the molecule. This results in a
water soluble, biologically inactive molecule ready for excretion.
§ Common substrates for conjugation reactions include: glucuronic acid, glycine, acetic acid, sulfuric acid, or a methyl group. Some
drugs do not require preparation by phase I reactions and may proceed directly to phase II reactions.
o Phase III: elimination
§ Phase 3 elimination involves ATP dependent carrier proteins that transport drugs across cell membranes. These are present in the
kidney, liver, and GI tract.
Hepatic Clearance
• Hepatic clearance is the product of:
o Liver blood flow—how much is delivered to the liver
o Hepatic extraction ratio—how much is removed by the liver
• Extraction Ratio
o The extraction ratio is a measure of how much drug is delivered to clearing organ vs how much drug is removed by that organ

§ ER of 1.0 means that 100% of the drug delivered to the clearing organ is removed.
§ ER of 0.5 means that 50% of the drug delivered to the clearing organ is removed.
o Hepatic clearance is categorized as flow limited elimination or capacity limited elimination.
§ Increased liver blood flowà increased clearance
§ Decreased liver blood flowàdecreased clearance
o Capacity Limited Elimination (ER < 0.3)
§ For a drug with a low hepatic extraction ratio (<0.3), clearance is dependent on the ability of the liver to extract drug from the blood.
Changes in hepatic enzyme activity or protein binding have a profound impact on clearance of these drugs.
§ Since only a small amount of drug is removed per unit time, alterations in liver blood flow minimally effect clearance.
§ Changes in the liver’s intrinsic ability to remove drug from the blood is influenced by the amount of enzyme present.
• Enzyme inductionàincreased clearance
• Enzyme inhibitionà decreased clearance
• The Effect of Oral Administration
o When administered orally, high extraction ratio drugs are subject to first pass metabolism. After the drug is absorbed from the gastrointestinal
tract, it is delivered to the portal circulation where a portion of it’s metabolized before the drug can reach the biophase. The oral dose must be
adjusted upwards to compensate for this effect. This explains the discrepancies between oral and IV dose regimens.

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 o Remifentanil undergoes hydrolysis in the plasma by non-specific tissue esterases. It is not affected by liver blood flow or hepatic
enzymatic activity.
P450 Enzymes

• The P450 system is the most important mechanism of drug biotransformation in the body. You may see it called the mixed-function
oxidase system or monooxygenases. It carries out most of the body’s phase I biotransformations. It also contributes in some conjugation
reactions.
• The P450 enzymes are located in the smooth endoplasmic reticulum of the hepatocyte. They are also located in extrahepatic tissue such
as the lung, kidneys, skin, adrenal gland, and gastrointestinal tract. Genetic polymorphisms contribute to variations in enzyme efficiency
from person to person.
• CYP Variants
o CYP 3A4 is the most important cytochrome P450 enzyme, metabolizing nearly 50% of the drugs that we administer. CYP 2D6
also has important clinical implications. While there are over 20 different P450 enzymes, we believe that you should have a
basic understanding of CYP 3A4 and CYP 2D6.
o A unique feature of the P450 system is that exogenous chemicals can influence the expression of these enzymes. This can be a
significant source of drug interactions.
§ An enzyme inducer stimulates the synthesis of additional enzyme. This increases drug clearance and reduces t1/2.
§ An enzyme inhibitor competes for binding sites on an enzyme. Since there are fewer binding sites available, drug
clearance is reduced and t1/2 is increased.

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Renal Elimination
• Elimination of metabolic waste into the urine is a key function of the kidney.
• A drug’s fate is determined by its polarity and the pH of the glomerular fluid.
o Hydrophilic drugs will be excreted unchanged.
o Lipophilic drugs must undergo biotransformation reactions to increase their water solubility before they can be excreted by the kidneys
o Lipophilic drugs that have not undergone biotransformation will be reabsorbed into the peritubular fluid by diffusion.
• Getting the Drug to the Urine
o There are 2 processes that deliver drug to the urine: glomerular filtration and organic ion transporters.
o 1. Glomerular Filtration
§ drugs not bound to plasma proteins will be freely filtered by the glomerulus
§ drugs that are highly protein bound are resistant to glomerular filtration; only the free fraction will be filtered.
o 2. Organic Anion and Cation Transporters:
§ transport proteins located in the proximal renal tubules actively secrete organic acids and bases into the urine.
§ Organic anion transporters (OAT): furosemide, thiazide diuretics, and penicillin
§ Organic cation transporters (OCT): morphine, meperidine, and dopamine
• Urine pH
o Urine pH influences whether drugs are excreted in the urine or reabsorbedinto the peritubular capillaries. Remember that like dissolves like.
o Acidic urine favors:
§ Reabsorption of acidic drugs
§ Excretion of basic drugs
o Basic urine favors:
§ Reabsorption of basic drugs
§ Excretion of acidic drugs
o How to Alter Urine pH
§ Ammonium chloride or cranberry juice will acidify the urine. This helps eliminate basic drugs.
§ Sodium bicarbonate or acetazolamide will alkalize the urine. This helps eliminate acidic drugs.
Metabolism in the Plasma

• The plasma is an important site of drug metabolism, specifically hydrolysis. Hydrolysis uses water to cleave an ester linkage.
• There are 4 key metabolic pathways in the plasma.
o All of these involve an enzymatic pathway except for Hofmann elimination.
o Unlike hepatic enzymes, plasma enzymes do not undergo enzyme induction.
o Pseudocholinesterase deficiency extends the duration of action of succinylcholine and ester local anesthetics.

PHARMACODYNAMICS

Overview
• Pharmacokinetics
o Pharmacokinetics can be thought of as “what the
body does to the drug”
o It explains the relationship between the dose that
you administer and the drug’s plasma concentration over time.
o This relationship is affected by absorption, distribution, metabolism, elimination.
• Pharmacobiophasics
o The biophase, otherwise known as the effect site, is the specific area of the body where the drug engages its receptor.
o The drug concentration in the biophase (not the plasma) determines its clinical effect.
o Let’s look at an example where we administer a cisatricurium bolus and continuously measure its serum concentration. After one minute, you’ll
notice that the plasma concentration is already decreasing, while the clinical effect (degree of muscle relaxation) continues to rise. This is direct
evidence that the plasma concentration does not equate
to clinical effect.
• Pharmacodynamics
o Pharmacodynamics can be thought of as “what the drug
does to the body”
o It explains the relationship between the effect site
concentration and the clinical effect.
• Concepts You Must Understand
o We will cover all of these concepts in the pharmacokinetics
and pharmacodynamics tutorials.

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Dose Response Curve

• The dose response curve illustrates the relationship between the drug dose and its clinical
effects. It tells us about potency, efficacy, and slope.
• Potency
o Potency is represented by the x-axis. It is the dose required to achieve a given
clinical effect.
o Potency is affected by the absorption, distribution, metabolism, elimination, and
receptor affinity.
o The ED50 and ED 90 are measures of potency. They represent the dose required to
achieve a given effect in 50% and 90% of the population respectively.
o The curve shifts left with à increased affinity for receptoràhigher potencyàlower
dose required
o The curve shifts right withàdecreased affinity for receptoràlower potencyàhigher
dose required.
• Potency becomes clear when we compare two drugs. For example, let’s compare drug A and
drug B. both are excellent analgesics that share a similar efficacy (they reach the same height
on the y-axis). Drug A is more potent that drug B, and this explains why the curve for drug B is shifted to the right.

• Efficacy
o Efficacy is a measure of the intrinsic ability of a drug to elicit a given clinical effect.
o The height of the plateau on the y-axis represents efficacy.
o A higher plateau implies a greater efficacy, while a lower plateau reflects a lower efficacy.
o Once the plateau phase is reached, additional drug does NOT produce additional effect. Additional drug will increase the risk of
toxicity.
• Efficacy becomes clear when comparing two drugs. For example, let’s compare drug A with drug B. although both drugs provide
analgesia, drug A does a better job—it is more efficacious. If we compared the dose response curves of these drugs, we would see that
drug A’s plateau would be higher on the y-axis than that of drug B. Also, the drug B curve is shifted to the right because it is less potent
than drug A.

• Slope
o The slope tells us how many of the receptors must be occupied to elicit a clinical effect.
o A steep slope implies that most of the receptors must be occupied before we observe the clinical response.
o Once the effect is observed, small increases in the dose can have a profound clinical effect.
o Neuromuscular blockers and inhaled anesthetics have a steep slope.
• Individual Variability
o A particular dose ma provide an excellent clinical effect in one patient, but offer no benefit in another.
o Differences between pharmacokinetics and pharmacodynamics between patients explains individual variability.
o You need dose response curves from multiple patients to get an accurate representation of individual variability.

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Agonists, Partial Agonists, Antagonists & Inverse Agonists

• A drug that binds to a receptor follows the law of mass action. There is a rate constant for drug binding (k1) and a rate constant for
dissociation from the receptor (k2)

• Drugs may be classified based on their degree of efficacy. Remember that efficacy is measured by the height of the y-axis of the dose
response curve.

• Full Agonist
o Binds to a receptor and turns on a specific cellular response
o Mimics an endogenous ligand.
o A full agonist instructs the receptor to produce its maximal responses.
o Different drugs may produce the same clinical effect, but each may require a
different dose to do so. This is a difference in potency.
o Continuous administration of an agonist may cause down-regulation of the
target receptors.
o Examples: norepinephrine, propofol, dopamine, alfentanil
• Partial Agonist
o Binds to a receptor, but it is only capable of partially turning on a cellular
response.
o It is less efficacious that a full agonist.
o A partial agonist is also called an agonist-antagonist.
o It can block the effects of an agonist by competing for binding sites. For
example, giving a partial opioid agonist to an opioid addicted patient can
precipitate withdrawal.
o Example: nalbuphine
• Antagonist
o The antagonist sits in the receptor and prevents an agonist from binding to it. It does not tell the cell to do anything.
o By definition, it does not have efficacy.
o Continuous administration of an antagonist may cause up-regulation of the target receptors.
o Competitive Antagonism
§ Competitive antagonism is reversible
§ If a patient receives a competitive antagonist, the dose response curve for the agonist shifts to the right.
§ Increasing the concentration of the agonist can overcome competitive antagonism (the agonist can achieve the same efficacy), but
since it requires more drug molecules to achieve the desired clinical effect, the dose response curve would reflect a reduction in
potency.
§ Example: atropine, vecuronium, rocuronium
o Noncompetitive Antagonism
§ Noncompetitive antagonism is not reversible.
§ Noncompetitive antagonists permanently bind to a receptor (usually through covalent bonds) and their effects cannot be overcome
by increasing concentration of agonist. This shifts the dose response curve for the agonist down, so that it resembles a partial
agonist.
§ The effects of a noncompetitive antagonist can only be reversed by producing new receptors. This explains why these drugs have
long durations of action.
§ Examples: aspirin and phenoxybenzamine
• Inverse Agonist
o Binds to the receptor and causes an opposite effect to that of a full agonist
o It has negative efficacy
o Many drugs that were previously believed to be antagonists are actually inverse agonists
o Examples: propranolol
• Putting it All Together
o Let’s look at a hypothetical receptor. It is a G-protein that modulates cAMP production.
§ An agonist completely activates the receptor and increases cAMP production.
§ A partial agonist partially activates the receptor. It increases cAMP production, but not as much as a full agonist.
§ An inverse agonist activates the receptor, but because it causes the opposite effect of the agonist, it decreases cAMP production.
§ An antagonist blocks the ability of the agonist to bind with the receptor, but it does not increase or decrease cAMP production.
• What Happens When We Administer Drugs Together?
o The presence of one drug can have a profound effect on the behavior of a second drug. Here are 4 concepts you need to know.
§ Addition: effect of two drugs given at the same time are added to each other (1 +1=2)
§ Synergism: effect of two drugs given at the same time is greater than the sum of their individual effects (1+1=3)
§ Potentiation: effect of one drug is enhanced by a drug that has no effect of its own (1+-=3)
§ Antagonism: simultaneous administration of one drug cancels out the effect of a second drug (1+1=0)

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ED50, LD50 & Therapeutic Index

• Effective Dose 50
o The ED50 is the dose that produces the expected clinical response in 50%
of the population.
o This is a measure of potency.
• Lethal Dose 50
o The LD50 is the dose that will produce death in 50% of the population.
o When we index the ED50 to the LD50, we can determine the median
therapeutic safety margin for a desired clinical effect.

• Therapeutic Index
o The therapeutic index is a measure of a drug safety. It is the ratio of the LD50 to the ED50.
§ A drug with a narrow therapeutic index has a narrow margin of safety. Examples include volatile anesthetics and
chemotherapy.
§ A drug with a wide therapeutic index has a wide margin of safety.
Sterochemistry, Enantiomerism & Racemic Mixtures

• Stereochemistry is the study of the three-dimensional structure of molecules.

• Chirality
o Chirality is a division of stereochemistry. It deals with molecules that have a center of three-dimensional asymmetry. In biologic
systems, this type of asymmetry generally stems from the tetrahedral bonding of carbon—carbon binds to 4 different atoms.
§ A molecule with 1 chiral carbon will exist as 2 enantiomers.
§ The more chiral carbons in a molecule, the more enantiomers that are created.
• Enantiomerism
o Enantiomers are chiral molecules that are non-superimposable mirror images of one another.
o Look at your hands. On each hand, you most likely have a palm, thumb, and four fingers. Although your hands are mirror
images of each other, you cannot superimpose one on top of the other. While the left and right hand are constructed from the
same building blocks, they are not the identical in all respects. These principals apply to chiral compounds.
o D & L and R & S

§ Enantiomers in solution are distinguished from each other by the

direction they rotate when exposed to polarized light.
• The dextrorotatory enantiomer (+) rotates clockwise.
• The levorotatory enantiomer (-) rotates
counterclockwise.
§ Understand that optical rotation does not necessarily describe
the spatial arrangement of the atoms on the chiral carbon.
Instead, we use the R and S designations to describe the
orientation of a specific stereocenter within a molecule. A molecule with more than one chiral carbon will have
multiple R and/or S designations in the chemical name (one for each chiral carbon).
• Racemic Mixtures
o a racemic mixture contains 2 enantiomers in equal amounts. About one third of the drugs we administer are enantiomers, and
just about all of these are prepared as racemic mixtures. Some exceptions include levobupivacaine and ropivacaine, which are
prepared as single enantiomers.
o Examples:
§ Ketamine § Bupivacaine
§ Thiopental § Cisatracurium
§ Methohexital § Morphine
§ Isoflurane § Methadone
§ Desflurane § Ibuprofen
§ Mepivacaine § Ketorolac
§ Prilocaine
o You have no doubt learned about the “lock and key” theory that can be applied to enzymes and substrates or receptors and their agonists. This
theory assumes that physiologic systems are intrinsically stereospecific. Therefore, drugs that exist as enantiomers often function as 2 different
drugs—with different affinities for the target receptor and different side effects.
o Clinical Examples:
§ S-bupivacaine (levobupivacaine) is less cardiotoxic than the R-bupivacaine or the racemic mixture
§ The S enantiomer of ketamine is less likely to cause emergence delirium than the R form. The S form is also more potent.

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Local Anesthetics

• Peripheral Nerves

• Conduction Velocity
o Conduction velocity is a measure of how fast an axon transmits the action
potential
o CV is increased by myelination and a larger fiber diameter.
• Classification of Peripheral Nerve Fibers
o We can subdivide peripheral nerves into 3 major classes based on their diameter and
myelination. A, B, and C. this allows us to better understand differential blockade, or
why some nerves are blocked before others.
o Differential blockade cannot be explained on the basis of diameter and myelination
alone. Instead, it likely results from other variables such as the ability of local
anesthetics to penetrate a nerve, the anatomical position of each axon within the
nerve, and the nerve’s intrinsic sensitivity to stimulation.

• Minimum Effective Concentration (Cm)

o Cm is a unit of measure that quantifies the concentration of local anesthetic that is required to block conduction. It is analogous to ED50 for IV
drugs and MAC for volatile anesthetics.
§ Fibers that are more easily blocked have a lower Cm.
§ Fibers that are more resistant to local anesthetic blockade have a higher Cm.
o Cm is typically higher in nerves with a wider diameter. Cm is reduced by higher tissue pH or a high frequency of nerve stimulation.
o In the clinical setting, epidural bupivacaine serves as an excellent examples of differential blockade. In lower concentrations, it provides
analgesia, yet spares motor function. As the concentration is increased, it anesthetizes resistant nerve types, such as those that control motor
function and proprioception.
o In vivo, local anesthetics inhibit the peripheral nerves in the following order:

B fibers > C fibers > Small diameter A fibers > large diameter A fibers

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The Voltage-Gated Sodium Channel
• Local anesthetics reversibly bind to the alpha subunit of the voltage-gated sodium channel. Plugging the channel reduces sodium conductance and blocks
nerve conduction.
• The voltage-gated sodium channel contains 1 alpha subunit and several beta subunits. The alpha subunit forms the entire ion conducting pore. As a point
of comparison, the nicotinic (N-m) receptor has 5 subunits that form the ion conducting pore. In the N-m receptor, there are 2 alpha subunits.
• Sodium Channel Configurations
o The sodium channel can exist in 3 possible states: resting, active, and inactive. As its name suggests, the voltage near the
sodium channel determines the state of the channel.

o 1. Resting State (-70 mV):

§ at resting membrane potential, the channel is closed
o 2. Active State (-70 to + 35 mV):
§ when threshold potential is reached, the channel opens.
§ The open channel allows Na+ to follow its concentration gradient (outside to inside).
o 3. Inactive State (+35 to -70 mV):
§ the channel is closed.
§ the inactivation gate plugs the channel until resting membrane potential is re-established.
§ The return of resting membrane potential converts the channel from the inactive state to the resting state. At this
point, the nerve is ready to be stimulated again.
• How & When Local Anesthetics Bind to the Sodium Channel
o The guarded receptor hypothesis states that local anesthetics can only bind to sodium channels in their active (open) and inactive (closed
refractory) states.
o Local anesthetics cannot bind to sodium channels in their resting states.
o The more frequently the nerve is depolarized and the voltage-gated sodium channels open, the more time there is available for local anesthetic
binding to occur, and the faster the nerve will become blocked. This is called a use-dependent or phasic blockade.
The Action Potential & Effects of Local Anesthetics
• Resting Membrane Potential
o In the neuron, resting membrane potential is – 70 mV. This is established by 2 things:
§ 1. The membrane is selectively permeable to potassium (it is allowed to leave the cell), but it is impermeable to sodium.
§ 2. The Na/K-ATPase extrudes 3 Na+ ions for every 2 K+ ions it brings back into the cell.
o The net result is a cell interior that is negative with respect to its exterior.
• Depolarization
o An action potential is a temporary change in transmembrane potential followed by a return
to transmembrane potential.
o An action potential is created when a stimulus opens sodium channels.
o In order for a neuron to depolarize, sodium must be allowed to enter the cell. Once
threshold potential is achieved, the cell depolarizes and propagates an action potential.
This is an all or none phenomenon; the cell either depolarizes or it doesn’t.
o Since the upstream portion of the neuron is in its refractory period (Na+ channels are in the
inactive state), the wave of depolarization can only go in one direction.
• Repolarization
o The voltage gated sodium channels inactive after a set period of time.
o Potassium conductance is increased, and this restores transmembrane potential to resting
membrane potential.
o Another key role of the Na/K-ATPase is to remove all of the sodium that has entered during
depolarization.
• Local Anesthetic Effects on Depolarization
o Local anesthetics bind to the alpha-subunit on the inside of the sodium channel when it’s in
either the active or inactive state.
o When a critical number of sodium channels are blocked, there aren’t enough open channels for sodium to enter the cell in sufficient quantity.
The cell can’t depolarize and the action potential can’t be propagated.
o Local anesthetics do NOT affect resting membrane potential or threshold potential.

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Local Anesthetic Mechanism of Action

• Local Anesthetic in the Vial

o Local anesthetics are weak bases.
o They are packaged as hydrochloride salts in aqueous solutions.
o The solution has a low pH to guard against precipitation.
• Local Anesthetic in the Patient
o 1. After you inject local anesthetic around a nerve, the local anesthetic rapidly dissociates into an uncharged base (LA) and an ionized,
conjugate acid (LA+).

LA+ <-> LA + H+
§ the pKa is the pH where 50% of the drug exists as the uncharged base and 50% of the drug exists as the conjugate acid. You can use
the Henderson-Hasselbach equation to predict the ratio of each molety.
pH=pKa + log ( [ base] / [conjugate acid] )
§ Since local anesthetics are weak bases with pKa values higher than 7.4, we can predict
that >50% of the local anesthetic will exist as the ionized, conjugate acid.
o 2. Some of the local anesthetic molecules diffuse through the lipid rich axolemma, while other
molecules diffuse into surrounding tissues or into the systemic circulation. Diffusion into the
bloodstream is called uptake. Highly vascular areas remove local anesthetic as a faster rate than
sites with less blood flow. While this reduces local anesthetics duration, it also increases its plasma
concentration.
o 3. The uncharged base enters the axoplasm by diffusing through the lipid rich axolemma. Once
inside, a new equilibrium is established. Since the ICF is slightly more acidic than the ECF, there is a
greater fraction of the ionized, conjugate acid inside the cell.
o 4. Only the ionized, conjugate acid binds to the local anesthetics binding site (alpha-subunit) on
the inside of the voltage-gated sodium channel.
o 5. The sodium channel remains in the closed, inactivated state until enough local anesthetic
diffuses away.
Esters & Amides

• the local anesthetic molecule is constructed from 3 key components: benzene ring, intermediate side chain, and tertiary amine.

• Here’s another fun way to remember the ester-type local

anesthetics: “Ester and Ben are Pros at Toking Coke”
• Local Anesthetic Allergy
o Although true allergy to local anesthetics is rare, it is more
common with the esters. The ester-type local anesthetics are
derivateives of para-aminobenzoic acid (PABA). PABA is an
immunogenic molecule capable of causing an allergic
reaction. This sis why there is cross sensitivity within this
class.
o The incidence of allergy to amides is incredibly rare. Some
multi-dose vials contain methylparaben as a preservative.
This compound is similar to PABA and can also precipitate an
allergic reaction.
o If a patient has experienced a true allergy with an ester, all
other esters should be avoided. Since there is no cross
sensitivity between the esters and amides, it is safe to select
an amide that does not contain methylparaben. Conversely, a
patient who’s allergic to an amide (if one even exists), may
safely receive an ester-type local anesthetic.

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Onset, Potency & Duration of Action

• Onset of Action
o pKa
§ if the pKa of the local anesthetic is closer to pH of the blood, a larger fraction of molecules will exist as the lipid soluble, uncharged
base. In this situation, more molecules diffusing across the axolemma translates to a faster onset of action.
§ If the pKa of the local anesthetic is further away from pH of the blood, there will be less molecules available to peneterate the cell
membrane. This prolongs the onset of action.
§ Once the local anesthetic reaches the inside of the neuron, it is the conjugate acid (not the nonionized base) that binds to the alpha
subunit on the inside of the voltage-gated sodium channel.
o Dose & Concentration
§ Chloroprocaine has a high pKa – in isolation suggests a slow onset. At the same time, chloroprocaine is not very potent, so we have
to give a large dose. Giving more molecules creates a mass effect that explains why chloroprocaine has a rapid onset of action even
though it has a high pKa.
§ 0.75% bupivacaine has a faster onset than 0.25% bupivacaine – again more molecules are given.
• Potency
o Lipid Solubility
§ A lipid soluble drug has an easier time diffusing through the epineurium, and more drug inside the nerve means more molecules are
available to bind to the receptor.
§ Agents that are more lipophilic tend to be more potent and have longer durations of action.
§ Lipid solubility is increased with alkyl group substitution on the amide group and the benzene ring.
§ Stereoselectivity also plays a role in potency.
o Intrinsic Vasodilating Activity
§ For most of the drugs that we administer, systemic absorption begins the process of delivering a drug to its site of action. Local
anesthetics are different. We administer these drugs directly to their site of action. Absorption into the systemic circulation removes
the local anesthetic from its site of action and contributes to the termination of its effect.
§ Nearly all local anesthetics have a biphasic response on vascular smooth muscle:
• - at lower concentrations (below what we use clinically), they cause vasoconstriction by inhibiting nitric oxide.
• At higher concentrations (what we use clinically), they cause vasodilation. Some Las cause more vasodilation than others.
• Cocaine is an exception, as it inhibits NE reuptake and always causes vasoconstriction.
• Some texts also say chloroprocaine and ropivacaine also do not have intrinsic vasodilating activity.
§ Drugs with a greater degree of intrinsic vasodilating effects (lidocaine) undergo a faster rate of vascular uptake, preventing some of
the administered dose from accessing the nerve. This may explain why in vitro and in vivo potecy and duration of action are
sometimes different.
• Duration of Action
o Protein Binding
§ After local anesthetic injection, some of the molecule penetrate the epineurium, some diffuse away into the systemic circulation,
and some bind to tissue proteins. The molecules that bind to the plasma proteins serve as a tissue reservoir that extends the
duration of action.

ProteinLA+ <-> Protein + LA+ <-> LA + H+

o Lipid Solubility
§ A higher degree of lipid solubility also correlates with a longer duration of action.
o Intrinsic Vasodilating Activity
§ A drug with intrinsic vasodilating activity will increase its rate of vascular uptake and shortens its duration of action.
The addition of vasoconstrictors, such as epinephrine, will prolong the durations of these drugs.

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Acid Base Chemistry & Physicochemical Properties of Local Anesthetics

• Acid base chemistry applied to local anesthetics perplexes many students. We covered this topic in detail in the pharmacokinetics
tutorial, so if you feel like you need a little more detail than you’ll find here, that’s a great place to start.

• Strong vs Weak Acids & Bases

o If you put a strong acid or a strong base in water, it will dissociate completely.
o If you put a weak acid or a weak base in water, a fraction will ionize and the remaining fraction will be unionized.
o Ionization is Dependent on 2 Factors
§ 1. The pH of the solution
§ 2. The pKa of the drug
o just so we’re clear, local anesthetics are weak bases and the pH of the blood is 7.4
• The Importance of pKa
The pKa is the pH where 50% of the drug exists as the uncharged base and 50% of the drug exists as the conjugate acid
o When a basic drug is placed into a relatively more acidic environment, the Henderson-Hassalbalch predicts that the conjugate
acid will predominate.
§ pH= pKa + log ( [ base] / [conjugate acid] )
o The Unionized Fraction Predominates:
§ If the molecule is a weak base and the pH of the solution is > the pKa of the drug (a base dissolved in a base)
§ If the molecule is a weak acid and the pH of the solution is < the pKa of the drug (an acid dissolved in an acid)
o The Ionized Fraction Predominates:
§ If the molecule is a weak base and the pH of the solution < the pKa of the drug (a base dissolved in an acid)
§ If the molecules is a weak acid and the pH of the solution > the pKa of the drug (an acid dissolved in a base)
o You just need to remember that “like dissolves like” and that an acid mixed with a base ionizes.
• Physiochemical Properties of Local Anesthetics

• Take Away Points from this Chart

o Notice that as pKa gets further away from physiologic pH, the degree of ionization increases.
o Remember the closer the pKa is to the pH of the blood, the faster the onset. The exception to this is chloroprocaine.
o Chloroprocaine does not undergo protein binding.
• Benzocaine is Unique
o You already know that local anesthetics are weak bases that are ionized (charged) at physiologic pH, but did you also know that
benzocaine is the odd man out? It’s the only clinically available local anesthetic with a pKa well below physiologic pH
(benzocaine pKa = 3.5).
o What s the significance of this? Benzocaine is unionized at physiologic pH, yet it possesses anesthetic activity. for all other local
anesthetics, the charged species is required to produce the anesthetic effect.
o Benzocaine is useful for topical anesthesia of the mucus membranes during endoscopy, TEE placement, and bronchoscopy.

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Uptake and Termination of Action

• For most drugs that we administer, systemic absorption begins the process of delivering a drug to its site of action. Local anesthetics are
different. We administer these drugs directly to their site of action. Absorption into the systemic circulation removes the local anesthetic
from its site of action and contributes to the termination of its effect. At the same time, a higher amount of vascular uptake contributes
to a higher plasma concentration. This may result in toxicity.
• Factors that Influence Vascular Uptake & Cp
o Site of injection
o Tissue blood flow
o Physiochemical properties of local anesthetic
o Metabolism
o Addition of vasoconstrictor
• Site of Injection and Tissue Blood Flow
o A greater amount of local anesthetic transferred into the blood stream correlates with a higher potential for toxicity.
Understand that the same amount of local anesthetic injected at two different sites will result in different plasma
concentrations as a direct result of the amount of blood flow each location receives. This should make you question standard
maximum doses for a given local anesthetic.
o The total dose of anesthetic, but not its concentration or speed of injection, also determines the final plasma concentration. For
example, 100mg of bupivacaine will achieve the same plasma concentration whether 40 mL of 0.25% or 20 mL of 0.5% were
used.

o Mneumonic: irresponsible trails ignite inside creepy estuaries because fires scare snakes.
• Protein Binding
o At the site of injection, local anesthetics dissolve in tissues, which behave like a reservoir.
o In the circulation, plasma protein binding helps limit the peak plasma concentration.
o Local anesthetics preferentially bind to alpha1-acid glycoprotein, but will also bind to albumin.
o The lungs also act as reservoir that removes local anesthetic from the circulation and limits plasma concentration.
• Metabolism
o Metabolism decreases plasma local anesthetic concentrations.
o Amides and cocaine are metabolized by P450 enzymes.
o Esters are metabolized by pseudocholinesterase.
• Vasoconstrictor
o The addition of a vasoconstrictor, such as epinephrine or
phenylephrine, will decrease systemic absorption by up to one
third and prolong duration. This effect is the greatest with local
anesthetics that have significant intrinsic dilating activity.
o The addition of dexamethasone extends the duration of a
brachial plexus block.
• Maximum Allowable Dose
o Systemic blood levels depend on the drug selected, dose, the
site of injection, and technique.
o It can be tough to estimate blood levels with a weight based
approach. The same amount of local anesthetic injected at two different sites will result in different plasma concentrations as a
direct result of the amount of blood flow each location receives. Some clinicians observe the total maximum dose
recommendations for adults and reserve weight based dosing for pediatric patients only.
o What will you see on the NCE? Depends who’s writing the question, so learn both.
o We ordered these according to their relative potencies for the
weight-based calculation.

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Local Anesthetic Systemic Toxicity (LAST)
o Overview
§ The plasma concentration of local anesthetic is the net balance of vascular uptake relative to redistribution and metabolism. High plasma
concentrations of local anesthetic quickly overwhelm the body’s buffering capacity, allowing toxicity to occur in the heart and the brain.
• The most common cause of toxic plasma concentrations is inadvertent intravascular injection during regional anesthesia.
• The most frequent symptom is seizure. Bupivacaine is the exception—cardiac arrest can occur before seizure.
• LAST is more common with peripheral nerve blocks than with epidural anesthesia.
§ Sequence of Signs & Symptoms of Lidocaine Toxicity

§ CNS Toxicity
• Factors that Increase Risk: Hypercarbia, Hyperkalemia, and Metabolic Acidosis
o Hypercarbia increases cerebral blood flow and increases drug delivery to the brain.
o Hypercarbia also decreases protein binding and increases the free fraction available to enter the brain.
o Hyperkalemia raises resting membrane potential, making them more likely to depolarize.
o Metabolic acidosis decreases the convulsion threshold and favors ion trapping inside the brain.
*If you were thinking that acidosis should increase the fraction of the conjugate acid and decrease the amount of
uncharged base that is available to pass through the blood brain barrier, then you were right! Unfortunately, this alone it
is not enough to decrease the risk of CNS toxicity.

• Factors that Decrease Risk: Hypocarbia, Hypokalemia, and CNS depressants

o Hypocarbia decreases cerebral blood flow and reduces drug delivery to the brain. Hyperventilation may be helpful.
o Hypokalemia lowers resting membrane potential, requiring a larger stimulus to depolarize the nerve.
o CNS depressants such as benzodiazepines and barbiturates raise the seizure threshold.
§ Cardiovascular Toxicity
• Local anesthetics disrupt hemodynamics by altering the cardiac action potential, myocardial performance, and vascular
resistance. Local anesthetics:
o Decrease automaticity, conduction velocity, action potential duration, and the effective refractory period.
o Depress the myocardium by impairing intracellular calcium regulation.
o Produce a biphasic effect on vascular smooth muscle. Low concentrations of low anesthetic produce
vasoconstriction, while higher doses produce vasodilation and a reduction in systemic vascular resistance.
• Two Features Determine the Extent of Cardiotoxicity
o 1. Affinity for the voltage-gated sodium channel in the active and inactive state.
o 2. Rate of dissociation from the receptor during diastole.
• When compared to lidocaine, bupivacaine has a greater affinity for the voltage-gated sodium channel and a slower rate of
dissociation from this receptor during diastole. The result is that more bupivacaine remains at the receptor for a longer period
of time. This explains why cardiac morbidity is higher with bupivacaine and why resuscitation is so difficult.
Difficulty of cardiac resuscitation: Bupivacaine > Levobupivacaine > Ropivacaine > Lidocaine
• The risk of bupivacaine toxicity is increased with: pregnancy, beta blockers, calcium channel blockers, and digitalis.
o Cocaine Toxicity
§ Cocaine (an ester) is the only local anesthetic with vasoconstrictive properties (it inhibits NE reuptake into the presynaptic nerve
terminal). Because of this, excessive SNS stimulation is the primary risk of cocaine toxicity.
• Cocaine should be avoided with MAOIs, TCAs, or sympathomimetic drugs.
• Beta-blockade in the setting of cocaine overdose is a questionable practice that allows for unopposed alpha-1
stimulation. High SVR (alpha-1 stimulation) and reduced inotropy (beta-1 antagonism) set the stage for cardiovascular
collapse.
• A vasodilator such as nitroglycerine is best, but if you are given a list of beta-blockers, then labetalol (or another mixed
alpha and beta antagonist) is the correct choice.
§ Topical Anesthesia
• Cocaine is an excellent vasoconstrictor, which explains why it’s sometimes used in clinical practice.
• Barash says that the dose range of cocaine is 1.5-3.0 mg/kg, not to exceed 200 mg.
• Stoelting says that the maximum dose is 150 mg.

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• Treatment for LAST
• Risk Reduction
o local anesthetic systemic toxicity can be reduced by using a test dose and/or incremental dosing with periodic aspiration.
• Treatment
o 1. Manage the Airway
§ FiO2 100%
§ Hypoxia and acidosis will worsen the symptoms of LAST
o 2. Treat Seizures with Benzodiazepines
§ if benzodiazepines are ineffective, a small dose of succinylcholine or a nondepolarizer should be given to stop muscle contraction.
This minimizes oxygen consumption, hypoxemia, and acidosis, although it will not stop seizure activity in the brain.
§ Avoid propofol. While small doses may abate seizure activity, larger doses of propofol augment myocardial depression.
§ In clinically relevant doses, propofol does not contain a high enough lipid content and should not be used as a substitution for
standard lipid emulsion therapy.
o 3. ACLS with Specific Modifications
§ Epinephrine can hinder resuscitation from LAST and it also reduces the effectiveness of lipid emulsion therapy.
§ If epinephrine is used, it should be given in doses of <1 mcg/kg.
§ Avoid vasopressin.
§ For treatment of ventricular arrhythmias, avoid lidocaine and procainamide.
§ Amiodarone is agent of choice.
o 4. Lipid Emulsion
§ bolus 20% 1.5 mL/kg (lean body mass) over 1 minute
§ infusion 0.25 mL/kg/min
§ if symptoms are slow to resolve, repeat bolus up to 2 more times and increase infusion rate to 0.50 mL/kg/min
§ continue infusion 10 min after achieving hemodynamic stability.
§ Maximum recommended dose is 10 mL/kg in the first 30 min
§ Mechanism of action:
• Lipid sink- an intravascular reservoir that sequesters local anesthetic and reduces plasma concentration of local
anesthetic.
• Metabolic effect- enhanced myocardial fatty acid metabolism.
• Inotropic effect- increased calcium influx and intracellular calcium concentration
• Membrane effect- impairs local anesthetic binding to voltage-gated sodium channels.
§ Safe in pregnancy.
§ Pancreatitis is a theoretical complication secondary to hyperlipidemia and/or hyperamylasemia.
§ Careful post resuscitation monitoring is essential. If the duration of the local anesthetic exceeds that of the lipids, then
hemodynamic instability may reoccur.
o 5. Other
§ avoid beta blockers and calcium channel blockers. These enhance local anesthetic induced cardiac disturbances.
§ If the patient is unresponsive to modified ACLS and lipid emulsion therapy, prepare for cardiopulmonary bypass.
• Tumescent Anesthesia
o Overview
§ Liposuction is associated with a mortality rate of 19.1 per 100,000 procedures. Of these, pulmonary embolism is the most common cause of
death.
§ Tumescent anesthesia provides patient comfort during liposuction. A dilute solution of sodium Max Dose of Lidocaine
chloride, lidocaine, epinephrine, and bicarbonate is injected into the adipose tissue. This large
volume of injectate firms the adipose tissue, thereby increasing the ease of its removal. Lidocaine
prevents discomfort, and epinephrine minimizes vascular uptake of both the local anesthetic and Tumescent Anesthesia
the large volume of tumescent solution.
o Dose Guidelines
§ For all other applications, the maximum dose of lidocaine with epinephrine is 7 mg/kg with a maximum dose of 500 mg. for use with
tumescent anesthesia, the maximum dose of lidocaine remains open for debate. The American Academy of Dermatology currently
recommends that lidocaine should not exceed 55 mg/kg, although some patients have received up to 70-80 mg/kg without incident.
Nagelhout says that the maximum lidocaine dose may be as high as 50 mg/kg, while Miller and Stoelting state the maximum dose is 55
mg/kg.
o Pharmacokinetics of Tumescent Anesthesia
§ Serum lidocaine levels seldom exceed 1.5 mcg/mL. This is below the threshold for CNS and cardiovascular toxicity.
§ Cp peaks at 12 hours, and it is completely eliminated by 36 hours.
§ Lidocaine is metabolized by cytochrome 3A4 and 1A2. Patients currently on medications that inhibit these metabolic pathways should receive
a dose reduction.
o Anesthetic Plan
§ Monitored anesthesia care may be selected if a small volume of tumescent is used.
§ General anesthesia is recommended if > 2-3 L of tumescent are injected.
§ Indeed, fluid overload and pulmonary edema may occur as a result of intravascular volume expansion. Pay attention to fluid management.

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• Methemoglobinemia
o Pathophysiology
§ The oxygen binding site on the heme portion of the hemoglobin molecule contains an iron molecule in its ferrous form (Fe+2).
§ Methemoglobin is formed when the iron molecule becomes oxidized to its ferric form (Fe+3).
§ It decreases oxygen carrying capacity and shifts the oxyhemoglobin dissociation curve to the left.
§ Methemoglobin cannot bind or release oxygen and creates a physiologic anemia.
§ Methemoglobin absorbs 660 nm and 990 nm infrared wavelengths equally, and a significant concentration of methemoglobin can
lead to pulse oximetry measurement errors typically resulting in a SpO2 reading of
85%.
§ A co-oximeter is required to diagnose methemoglobinemia.
o Causes, Signs & Symptoms
§ *Cyanosis in the presence of a normal PaO2 is highly suggestive of
methemoglobinemia.
o Treatment
§ Methylene Blue
• Methylene blue 1-2 mg/kg over 5 minutes with a maximum dose of 7-8 mg/kg.
• Methylene blue is metabolized by methemoglobin reductase to form
leucomethylene blue. This metabolite functions as an electron donor, which
reduces a methemoglobin back to hemoglobin.
§ Other Considerations
• Patients with glucose-6-phosphate reductase deficiency do not possess
methemoglobin reductase, so an exchange transfusion may be required.
• Fetal hemoglobin is relatively deficient in methemoglobin reductase, making it
susceptible to oxidation. Therefore, neonates are at higher risk for toxicity.
• EMLA Cream
o 5% EMLA cream is a 50/50 combination of 2.5% lidocaine and 2.5% prilocaine.
o The melting point of EMLA is lower than either of its constituents. This property facilitates its absorption. After topical application, an occlusive
dressing should be applied.
o Uses include: arterial or venous cannulation, lumbar puncture, or myringotomy.
o It produces analgesia within 1 hour and achieves maximum effect after 2-3 hours.
o It should not be applied to mucus membranes and instead only be applied to intact skin. Skin conditions such as eczema, psoriasis, or skin
wounds can alter EMLA pharmacokinetics and may increase the
risk of toxicity.
o Nitroglycerin may be applied simultaneously to hasten the
absorption of EMLA.
o Prilocaine is metabolized to o-toluidine, which oxidizes
hemoglobin to methemoglobin. Infants and small children are
more likely to become toxic.
o Dose Recommendations
Additives
• You should be familiar with common additives to local anesthetic solutions.
Additives are selected based on their ability to prolong duration, hasten onset,
provide supplemental pain relief, and improve drug transfer through tissues.
• Drugs that Prolong Local Anesthetic Duration of Action
o Local anesthetics have an intrinsic vasodilating ability and produce
a biphasic effect on vascular smooth muscle. Low doses of local
anesthetic produce vasoconstriction, while higher dose produce
vasodilation.
o Epinephrine
§ the alpha-1 agonist effect of epinephrine makes it a
potent vasoconstrictor that can decrease systemic uptake of local anesthetic, prolong block duration, and enhance block quality.
§ Decreased systemic uptake allows for better matching of uptake and metabolism. This decreases plasma concentration of local
anesthetics.
§ Epinephrine does a better job of prolonging local anesthetics of intermediate duration when compared to those of long duration.
For example, epinephrine will more greatly extend the duration of lidocaine than bupivacaine.
§ Cocaine does not possess intrinsic vasodilating properties. Some texts also include chloroprocaine and ropivacaine in this group.
§ *Nagelhout states that lidocaine does not possess intrinsic vasodilating properties. Many other books contradict this, and we believe
Nagelhout is incorrect.
o Dexamethasone
§ The ability to extend local anesthetic duration of action correlates with glucocorticoid activity.
§ It acts on the steroid receptor and/or affects systemic uptake of the local anesthetic.
§ Dexamethasone can increase the duration of brachial plexus blockade by up to 50%.
o Dextran
§ Low molecular weight dextran prolongs block duration by decreasing systemic uptake of local anesthetics
o Other Facts to Know
§ Cocaine inhibits norepinephrine reuptake and causes profound vasoconstriction. It is only used topically.

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 • Drugs that Provide Supplemental Analgesia
o Clonidine
§ Analgesia is produced by the alpha-2 receptor agonism in the brain and spinal cord.
§ Dose: 100 mcg added to the local anesthetic solution.
o Epinephrine
§ Alpha-2 agonism
o Opioids
§ Opioids provide supplemental analgesia for spinal and epidural anesthesia. When used in peripheral nerve blocks, the results have
been mixed.
§ Chloroprocaine is an exception, as it reduces the effectiveness of opioids in the epidural space.
• Drugs that Shorten Onset Time
o Sodium Bicarbonate
§ Alkalization increases the number of lipid soluble molecules, which speeds up the onset of action. In practice, however, there is a
limit to how much a local anesthetic solution can be alkalized before it precipitates, so this technique only produces a modest
benefit.
§ You can alkalize local anesthetic by mixing 1 mL of 8.4% sodium bicarbonate with 10 mL of local anesthetic.
§ By increasing the fraction of nonionized base, this also increase the quality of the block.
• Drugs that Improve Diffusion through Tissues
o Hyaluronidase
§ Hyaluronic acid is present in the interstitial matrix and basement membrane. It hinders the spread of substances through tissue.
§ Hyaluronidase hydrolyzes hyaluronic acid, which facilitates diffusion of substances in the tissues.
§ It is commonly used in ophthalmic blocks to increase the speed of onset, enhance block quality, and mitigate any rise in intraocular
pressure.
§ It also reduces hematoma size as well as decreases the risk of postoperative strabismus.
§ It has an allergic potential.
NEUROMUSCULAR BLOCKERS

Neuromuscular Junction Physiology

o Pre-and Postsynaptic Nicotinic Receptors

§ There are 2 different types of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction.
• 1. The prejunctional Nn receptor is present on the presynaptic nerve. (n=nerve)
• 2. The postsynaptic Nm receptor is present at the motor end plate on the muscle cell (m=muscle)
§ the postsynaptic nicotinic receptor (Nm) is a pentameric ligand-gated ion channel located in the motor
endplates at the neuromuscular junction. It is comprised of 5 subunits that align circumferentially around an ion
conducting pore. There are 2 alpha, 1 beta, 1 delta, and 1 epsilon subunits – a2b1d1e1 subtype.
§ Each alpha subunit binds with one Ach molecule. When two Ach molecules simultaneously occupy two alpha
receptors, the channel opens. Na+ and Ca+ enter the cell and K+ exits the cell.
§ Anions, such as chloride, do not pass through the nicotinic receptor. They are repelled by the strong negative
charges situated inside the channel.
§ At rest, the inside of the muscle cell is negative relative to the outside of the cell. When the Nm receptor is activated by Ach, Na+ flows down its concentration
gradient and enters the cell. This makes the cell interior more positive, activates voltage-gated sodium channels, depolarizes the muscle cell, and initiates an
action potential. Depolarization of the myocyte instructs the endoplasmic reticulum to release Ca+ into the cytoplasm, where it engages with the myofilaments
and initiates muscle contraction.
§ For every ligand-receptor interaction, there has to be an off switch. We’ve already caused the muscle to contract, so now we need it to relax.
Acetylcholinesterase is strategically positioned around the pre-and postsynaptic nicotinic receptors; it hydrolyzes Ach almost immediately after it activates
these receptors. At the Nm receptor, this mechanism ensures that muscular contraction can be turned off and on like a
light switch, so the muscle can be instructed to contract and relax repeatedly over very short time periods. If Ach was
allowed to bind to the receptor for a longer period of time, the muscle would contract once and not be able to be
stimulated again until Ach dissociated from the receptor. And for those of you a step ahead, this is how succinylcholine
causes muscular paralysis.
o Extrajunctional Receptors
§ There are 2 pathologic variants of the nicotinic receptor
• The a2b1d1e1 subtype has a gamma subunit in lieu of an epsilon subunit.
• The a7 subtype consists of 5 alpha subunits.
• Extrajunctional receptors resemble those that are present early in fetal development. Once innervation takes
place, fetal nicotinic receptors are replaced by the adult a2b1d1e1 subtype. Denervation later in life or
prolonged immobility allow for the return of both types of extrajunctional receptors. Notice
how they’re distributed at the NMJ and the sarcolemma.
• You must be familiar with the conditions that allow for the re-expression of extrajunctional
receptors. Examples include:
o Upper or lower motor neuron injury
o Spinal cord injury
o Burns
o Skeletal muscle trauma
o Cerebrovascular accident
o Prolonged chemical denervation (magnesium, long term NMB
infusion, clostridial toxin)
o Tetanus
o Severe sepsis
o Muscular dystrophy

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 § Succinylcholine and Extrajunctional Receptors
• In the absence of extrajunctional receptors, succinylcholine can transiently increase serum potassium by 0.5-1.0 mEq/L for
up to 10-15 minutes.
• Extrajunctional receptors are much more sensitive to succinylcholine; they remain open for a longer period of time. This
augments the potassium leak and may precipitate life-threatening hyperkalemia. The a2b1d1g1 receptor is depolarized by
succinylcholine, while the a7 receptor is depolarized by both succinylcholine and its metabolite- choline. Choline
stimulation is likely a significant contributor of the hyperkalemic response.
• As a general rule, succinylcholine is avoided 24-48 hours after the injury and at least 1 year after (the texts range from 6-
12+ months). Burns may be an exception to this rule, as the risk of hyperkalemia may persist for several years after the
burn (especially if the patient has contractures).
§ Nondepolarizers and Extrajunctional Receptors
• Patients with upregulation of extrajunctional receptors are resistant to nondepolarizers—their potency is reduced.
• Mechanism of Fade
o Fade during train-of-four stimulation is caused by antagonism of presynaptic Nn receptors.
o Acetylcholine is synthesized from choline and acetyl CoA in the presence of the enzyme choline acetyltransferase. It is packaged in vesicles,
which are anchored by specialized proteins inside the presynaptic nerve terminal.
o There are two supplies of Ach vesicles:
§ 1. Ach that is available for immediate release
§ 2. Ach that must be mobilized before it can be made available for immediate released
o You can think of this second supply as a stockpile that must be transported to
the front line before it can be used.
o When an action potential arrives at the nerve terminal, voltage-gated calcium
channels open and calcium enters the nerve terminal. Increased intracellular
calcium destabilizes the proteins that hold the Ach vesicles in place. Next, the
vesicles exit the nerve via exocytosis and each vesicle releases 5,000-10,000 Ach
molecules into the synaptic cleft. Ach diffuses toward the postsynaptic Nm
receptors on the motor endplate, where it depolarizes the motor endplate and
initiates skeletal muscle contraction.
o Not all of the Ach released diffuses towards the motor endplate, however,
instead a fraction of the Ach molecules bind to prejunctional receptors on the
nerve terminal (Nn receptor). Ach binds to these receptors and causes mobilization of Ach vesicles inside the presynaptic nerve. Mobilization
moves the part of the stockpiled Ach to the front line where it is available for immediate release the next time the nerve is stimulated.
o Nondepolarizaing neuromuscular blockers competitively antagonize the presynaptic Nn rectpors. This impairs the mobilization process, so now
only the vesicles that are available for immediate release are able to be used. Since this is a limited quantity, nerve stimulation can quickly
exhaust this supply. With each successive stimulation, less Ach is released. Clinically this manifests as fade with train-of-four, double burst, and
tetanus.
o In contrast to nondepolarizers, succinylcholine stimulates the prejunctional receptors – has the same effect as Ach. When succinylcholine binds
to the presynaptic Nn receptor, it facilitates the mobilization process, so there is always Ach available for immediate release. This explains why
fade is not observed with a depolarizing neuromuscular blocker.
• Phase 1 vs Phase 2 Block
o The presence of absence of fade distinguishes between a phase I and phase II block.
o Recall that the presynaptic nicotinic receptor is an integral component of the fade mechanism. As an agonist of the presynaptic nicotinic
receptor, succinylcholine produces a phase I block. In this situation, the mobilization of Ach functions as it normally does – there is an ample
supply of Ach.
o By contrast, nondepolarizers competitively antagonize the presynaptic nicotinic receptor and cause a phase II block. The Ach mobilization
mechanism is impaired, so the nerve terminal can only release the fraction of Ach that is immediately available. Because this supply exhausts
quickly, fade is observed with the nerve stimulator.
o High doses of succinylcholine can cause a phase II block. In doing so, it likely inhibits the presynaptic nicotinic receptor, impairs acetylcholine
mobilization and release from the presynaptic nerve terminal, and/or creates a
conformational change in the postsynaptic receptor. A phase Ii block with succinylcholine is
indistinguishable from a phase II block with a nondepolarizer.
o There are 2 situations that favor the development of (although do not guarantee) a phase II
block with succinylcholine:
§ 1. Dose > 7-10 mg/kg
§ 2. 30-60 minutes of continuous exposure (IV infusion)
o the following chart compares the phase I and phase Ii blocks as observed by a
nerve stimulator. Notice that the phase I responses to stimulation are diminished
but equal—there is no fade. The phase Ii response to stimulation is characterized
by fade. Also, there is no post-tetanic potentiation with a phase I block, but this is
present with a phase II block.

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 • Testing Recovery from Neuromuscular Blockade
o Historically, it was believed that a TOF ratio of 0.7 correlated with a full recovery from neuromuscular blockade. More recent
evidence suggests that full recovery doesn’t occur until a TOF ratio is > 0.9 at the adductor pollicis. Therefore, residual
neuromuscular blockade is defined as a TOF ratio <0.9.
o Inadequate recovery places the patient at risk for airway obstruction and pharyngeal dysfunction (increased risk of aspiration).
o Sequence of Neuromuscular Block
§ Muscle groups respond differently in terms of onset, duration, and sensitivity to neuromuscular blockade. As a general rule, more
central muscles are paralyzed faster and recover sooner than peripheral muscles. This is complicated by the amount of blood flow
that each muscle receives, as this impacts drug delivery and removal. Save yourself a trip down the rabbit hole. Here’s what you
have to know:
• Best place to measure onset of blockade (intubation conditions);
o Muscle = Orbicularis oculi (closes eyelid) or corrugator supercilii (eyebrow twitch)
o Nerve= Facial nerve
• Best place to measure recovery of blockade (return of upper airway muscle function)
o Muscle= adductor pollicis (thumb adduction) or flexor hallicus (big toe flexion)
o Nerve= ulnar nerve or posterior tibial nerve
th
o *relying on the flexion of the 5 finger overestimates recovery
o Bedside Test of Neuromuscular Function
§ We are unable to precisely determine the TOF ratio at the bedside. Instead, we must rely on a variety of bedside tools
that we can correlate with the degree of recovery. The return of spontaneous ventilation with a normal tidal volume
is not a reliable indicator of recovery. You should always use a nerve stimulator!

§ Barash cites a study where holding a tongue blade in the mouth against force may be more sensitive than a sustained
head lift (TOF ratio 0.86 and 0.62 respectively). If you are asked which test is best, we would go with the tongue blade
test over any other qualitative assessment of recovery.
Succinylcholine

• Side Effects
o Succinylcholine is two acetylcholine molecules joined together. It should be no surprise that this serves as the basis for a wide
range of side effects.
o Bradycardia
§ By stimulating the M2 receptor on the SA node, succinylcholine can cause bradycardia or asystole. A second dose of
succinylcholine increases this risk. Its primary metabolite, succinylmonocholine, is probably most responsible for this
effect. Antimuscarinics may prevent or reverse these bradyarrhythmias.
§ Since children have a higher baseline of vagal tone, they are more susceptible to bradycardia with succinylcholine.
Atropine should always sprecede a second dose of succinylcholine in children.
o Tachycardia
§ By mimicking the action of Ach at the sympathetic ganglia, succinylcholine can cause tachycardia and hypertension. In
adults, tachycardia is more common than bradycardia.
o Potassium release
§ Opening of the nAChR at the neuromuscular junction can increase serum potassium by 0.5-1.0 mEq/L for up to 10-15
min. in patients with upregulation of extrajunctional receptors, the potassium concentration may rise even further.
Hyperkalemia increases the resting membrane potential of excitable tissue. This increases the risk of dysrhythmias.
§ Succinylcholine is safe in patients with renal failure and a normal potassium level. Renal failure patients with an
elevated potassium do not have an increased release, however the normal response to succinylcholine may increase
serum potassium to a dangerous level.

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 o Increased Intraocular Pressure
§ Succinylcholine transiently increases intraocular pressure by 5-15 mmHg for up to 10 min. while some argue that pretreatment with a
nondepolarizing NMB attenuates the rise in IOP, the texts say that it’s controversial and/or provides little to no benefit.
§ A classic scenario debates the use of succinylcholine in the patient with an open globe injury—this is further complicated by the patient with
a difficult airway. This patient should be considered a full stomach and requires a rapid sequence intubation. Also, you want to minimize the
rise in intraocular pressure, as it can cause extrusion of intraocular contents and permanent blindness. In reality, there is little evidence to
support this fear. At the same time, you don’t want to be the one to publish this case report either! Securing the airway is the first priority,
and prevention of increased IOP is a close second. It is important to point out that light anesthesia, laryngoscopy, intubation, coughing and/or
straining causes a greater rise in IOP than succinylcholine.
§ Bottom line—now that sugammedex is available, this may be a non-issue. If that’s not an option, then securing the airway is the top priority.
Give the succinylcholine and prevent the rise in IOP with a sufficiently deep anesthetic, brief laryngoscopy and intubation, and prevent
bucking, straining, and movement.
o Increased Intracranial Pressure
§ Succinylcholine temporarily increases intracranial pressure. This is minimized or prevented with a defasciculating dose.
o Increased Intragastric Pressure
§ Contraction of the abdominal muscles increases intragastric pressure. At the same time, succinylcholine raises lower esophageal sphincter
tone. These processes cancel each other out, so barrier pressure at the gastroesophageal junction is unchanged. The risk of aspiration is not
increased.
o Malignant Hyperthermia
§ Succinylcholine is a trigger of malignant hyperthermia.
§ It may increase masseter muscle tone and induce spasm. Occasionally this is followed by malignant hyperthermia, however the presence of
masseter spasm in the absence of other s/sx of MH does not warrant cancellation of the planned surgical procedure.
• Synonyms for Pseudocholinesterase and Acetylcholinesterase
o A rose by any other name..you probably aren’t thinking about roses when you’re studying for the NCE, but you get the idea.
o Acetylcholine and succinylcholine are metabolized by different enzymes, and each of these enzymes go by several different names. We know this is
confusing, but you never know exactly which term you’re going to come across on the NCE.
o Useful facts about Pseudocholinesterase:
§ It is produced in the liver and serves as an indicator of Metabolizes Acetylcholine Metabolizes Succinylcholine,
hepatic synthetic function. MIvacurium, and Ester Local Anesthetics
§ In the plasma, it has a reference concentration range of Type 1 cholinesterase Type 2 cholinesterase
2900-7100 units/L Acetylcholinesterase Butyrylcholinesterase
§ Neuromuscular symptoms begin at 60% of normal and True cholinesterase False cholinesterase
become serious at 20% of normal. Specific cholinesterase Plasma cholinesterase
§ It is also found in smooth muscle, intestines, white matter Genuine cholinesterase Psudocholinesterase
of the brain, heart, and pancrease
§ It is not located in the CSF.
• Factors that Reduce Pseudocholiensterase Activity
o While this stuff is important for the NCE, in clinical practice the prolongation Drugs Co-existing Conditions
of succinylcholine is insignificant for all but the shortest procedures. The
obvious exception here is the patient who has a homozygous variant of Metoclopramide Atypical PChE
atypical Pseudocholinesterase. Esmolol Severe liver disease
• Dibucaine Test Neostigmine (NOT edrophonium) Chronic renal disease
o Atypical PChE variants cannot hydrolyze succinylcholine, so the Echothiophate Organophosphate poisoning
duration of succinylcholine will be prolonged. A tentative bedside
diagnosis can be made if the response to train-of-four stimulation is
Oral contraceptives/estrogen Burns
absent for a longer than expected period of time following the use Cyclophosphamide Neoplasm
of succinylcholine. The dibucaine test is used to make the definitive Monoamine oxidase inhibitors Advanced age
diagnosis. Nitrogen mustard Malnutrition
o Dibucaine is an amide local anesthetic that inhibits normal plasma Pregnancy (late stage)
cholinesterase. It has no effect on atypical PChE. The number
reflects the percentage of normal enzyme that is inhibited by dibucaine.
o Normal Test
§ A normal dibucaine number is 80. This means that dibucaine has inhibited 80% of Pseudocholinesterase in the sample
and suggests that the normal enzyme is present.
o Abnormal Test
§ Dibucaine does not inhibit atypical plasma cholinesterase. If the patient has a dibucaine number of 20, this means
that dibucaine did not inhibit the patient’s PChE and that an atypical variant is present.
PChE Variant Genotype Incidence Dibucaine # Duration of Succinylcholine
Typical homozygous UU 70-80 5-10 min
Heterozygous UA 1/480 50-60 20-30 min
Atypical homozygous AA 1/3200 20-30 4-8 hours
§ U=usual variant A=atypical variant
o Atypical plasma cholinesterase is a qualitative defect. Pseudocholinesterase is produced in sufficient quantity, however the enzyme that is
produced is not functional.
o Although whole blood, fresh frozen plasma, or purified human cholinesterase will restore plasma Pseudocholinesterase levels in a patient with
an atypical variant, postoperative mechanical ventilation and sedation is the treatment of choice. It is the safest and least expensive option.

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• Succinylcholine Black Box Warning: Duchenne Muscular Dystrophy
o Succinylcholine sports a block box warning that details the risk of cardiac arrest and sudden death secondary to hyperkalemia in children with
undiagnosed skeletal muscle myopathy. The most common is Duchenne muscular dystrophy. This is an X-linked, recessive disease that results from the
absence of the dystrophin protein. Although we will focus our discussion on Duchenne, you
should be aware of the other forms of skeletal muscle myopathy including Becker, Emery-
Dreifuss, facioscapulohumeral, and limb-girdle muscular dystrophy.
o Dystrophin is a critical structural component of the cytoskeleton of skeletal and cardiac
muscle cells. It helps anchor actin and myosin to the cell membrane. The absence of
dystrophin destabilizes the sarcolemma during muscle contraction and increases membrane
permeability. The breakdown of the sarcolemma allows creatine phosphokinase (a marker of
skeletal muscle breakdown) and myoglobin to enter the systemic circulation. Also, calcium
may freely enter the cell, which leads to activation of proteases that destroy the contractile
elements and causes inflammation, fibrosis, and cell death. This is observed by the presence
of skeletal muscle weakness, conduction abnormalities, cardiomyopathy, and sometimes
cognitive impairment.
o The absence off dystrophin also alters the type and number of postjunctional nicotinic receptors on the muscle cell. This predisoposes these patients to
hyperkalemia following succinylcholine administration. Hyperkalemia raises resting membrane potential, so excitable tissues are closer to threshold
potential and depolarization. Administration of IV calcium increases threshold potential, which helps re-establish the normal difference between
transmembrane potentials.
o Mild hyperkalemia presents with peaked T-waves and PR prolongation. This may progress to severe hyperkalemia and cause ventricular fibrillation
and/or asystole. If a healthy infant or small child develops cardiac arrest following succinylcholine, particularly a boy < 8 years old, immediate treatment
of hyperkalemia should begin.
o Mortality approaches 40-50%, so succinylcholine should be reserved only for select situations including difficult intubation, laryngospasm, need for rapid
sequence induction, and intramuscular use when intravenous access is unattainable.
• Postoperative Myalgia with Succinylcholine
o Succinylcholine is a well-recognized cause of postoperative myalgia
that may persist up to 24-48 hours. Myalgia manifests as muscle
soreness in the neck, shoulders, subcostal region, upper abdominal
muscles, and trunk muscles.
o Succinylcholine causes uncoordinated muscle contraction before
causing flaccid paralysis. It is believed that these contractions are
the origin of the myalgia.
o Who is at Risk?
§ Those with the highest risk of myalgia include young
adults undergoing ambulatory surgery (women>
men) and those that do not routinely engage in
strenuous activity. Children, the elderly and pregnant patients seem to have the lowest rate of occurrences.
o Can Myalgia be Reduced?
§ The incidence of myalgia might be minimized, but not entirely eliminated, by pretreatment with a nondepolarizing neuromuscular blocker.
Other methods that may reduce the risk of myalgia include: NSAIDs, lidocaine 1.5 mg/kg, and use of a higher dose rather than a lower dose of
succinylcholine. Opioids do not decrease the incidence of myalgia.
§ One tenth of the ED95 of a nondepolarizer will reduce fasciculations. This can be accomplished with rocuronium 2 mg, 1.5 mg atracurium, or
0.3 mg vecuronium. To allow it adequate time to penetrate the neuromuscular junction, it should be administered 3-5 minutes prior to
succinylcholine.
o Dose Adjustment for Succinylcholine
§ When using a defasciculating dose of a nondepolarizer, the dose of succinylcholine should be increased to 1.5-2.0 mg/kg. since the
nondepolarizer will competitively antagonize the nicotinic receptor, more succinylcholine must be given to overwhelm the
nondepolarizer in order to produce sufficient muscle relaxation.
o When NOT to Use a Defasciculation Dose
§ The use of defasciculating dose of a NMB should be carefully balanced against potential complications. Patients may experience
muscle weakness, dyspnea, dysphagia, and diplopia. Those with pre-existing skeletal muscle weakness, such as those with
myasthenia gravis, should probably not receive a defasciculation dose.
• Disease with Altered Responses to Neuromuscular Blockers
Succinylcholine Nondepolarizer
Amyotrophic lateral sclerosis Hyperkalemia Sensitive
Charcot-Marie-Tooth Hyperkalemia Normal
Duchenne’s muscular dystrophy Hyperkalemia rhabdomyolysis Sensitive
Guillain-Barre Hyperkalemia Sensitive
Huntington chorea Sensitive Sensitive
Hyperkalemic periodic paralysis Hyperkalemia Normal
Hypokalemic periodic paralysis Normal Normal
Malignant hyperthermia MH Normal
Multiple sclerosis Hyperkalemia Sensitive
Myasthenia gravis Resistant Sensitive
Myotonic dystrophy Muscle contractures Normal or sensitive
Up-regulation of AChRs Hyperkalemia Resistant or Normal
(depends on timing of injury)

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• Potency
o When thinking about the potency of any drug, all you have to do is compare the dosages. The higher the dose you have to give
to achieve a given effect, the lower the potency.
§ The ED95 is a Measure of Potency – They are inversely related
o In the context of neuromuscular blockers, the ED95 is the dose at which there is a 95% decrease in twitch height.
o In some instances, the ED95 can be used to predict onset. The higher the ED95, the lower the potency and the faster the onset.
This inverse relationship occurs because there are more molecules to diffuse from the plasma to the biophase at the
neuromuscular junction. This explains why rocuronium has the fastest onset of all the non-depolarizers. It also explains why
high dose rocuronium (1.2 mg/kg) has a similar onset as succinylcholine.
o The dose required to provide optimal conditions for tracheal intubation is ~ 2-3 times the ED95.
ED95 Intubation Time to max block Time to return to 25% control
(mg/kg) (mg/kg) (~onset) (~duration)
Short Acting
• Mivacurium 0.067 0.15 3.3 min 16.8 min
Intermediate Acting
• Cisatracurium 0.04 0.1 5.2 min 45 min
• Vecuronium 0.043 0.1 2.4 min 45 min
• Atracurium 0.21 0.5 3.2 min 45 min
• Rocuronium 0.305 0.6 1.7 min 35 min
Long Acting
• Pancronium 0.067 0.08 2.9 min 85 min

• Metabolism of Nondepolarizers
o Nondepolarizing neuromuscular blockers are divided into 2 classes:
Benzylisoquinolinium Compounds Aminosteroid Compounds
Atracurium Rocuronium
Cisatracurium Vecuronium
Mivacurium Pancuronium
o Perhaps the biggest difference among these classes is how they are metabolized and excreted from the body. Methods of metabolism and
excretion include: Hofmann elimination, non-specific ester hydrolysis, liver metabolism, biliary excretion, and renal excretion.
o Since all of these drugs are ionized, each one undergoes some degree of renal elimination as unchanged drug. For this reason, renal
insufficiency can prolong the duration of any of these drugs, although this issue is negligible with the benzylisoquinolinium compounds.
o Benzylisoquinolinium Compounds
§ Benzylisoquinolinium compounds (those that end with –curium) undergo spontaneous degradation in the plasma.
They are not dependent on hepatic or renal function for metabolism and elimination.
§ Atracurium is hydrolyzed by Hofmann elimination (33%) and non=specific plasma esterases (66%). These are the same
enzymes that degrade esmolol and remifentanil. Furthermore, you should note that non-specific plasma esterases are
NOT the same as Pseudocholinesterase that metabolizes succinylcholine and ester type local anesthetics. Therefore,
patients with Pseudocholinesterase deficiency do not experience a prolonged block with atracurium.
§ Cisatracurium breakdown is dependent on Hofmann elimination.
§ Mivacurium is metabolized by pseudocholiesterase. It’s the only nondepolarizing NMB metabolized by this enzyme.
• This explains why it has a relatively short duration of action
• A reversal agent may not be required.
o Hofmann Elimination
§ Hofmann elimination is a base-catalyzed reaction that is dependent on normal blood pH and temperature.
• The reaction is faster with alkalosis and hyperthermia.
• The reaction is slower with acidosis and hypothermia.

o Toxic Metabolite of Benzylisoquinolinium Compounds

§ Laudanosine is a metabolite of both atracurium and cisatracurium, although atracurium produces more. As a CNS
stimulant, laudanosine is capable of producing seizures. This is not a problem during routine administration of these
drugs in the operating room, however, it may be a valid concern wit a prolonged infusion in the intensive care unit.
Laudanosine has no muscle relaxant properties.
Metabolism Liver Elimination Renal Elimination Metabolites
Atracurium Ester hydrolysis None 10-40% Laudanosine
(66%)
Hofmann (33%)
Cisatracurium Hofmann (77%) None 16% of total Cl Laudanosine

§ Mivacurium does not produce an active metabolite.

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• Aminosteroid Compounds
o The termination of action for aminosteroid neuromuscular blockers depends on hepatic metabolism, biliary excretion, and/or
renal excretion. It should follow suit that hepatic dysfunction, renal failure, and extremes of age will reduce clearance and
prolong the elimination half-times of these drugs.
o Rocuronium does not undergo significant (if any) deacetylation by the liver. Its primary method of elimination from the body is
the biliary excretion as an unchanged molecule.
o Vecuronium undergoes hepatic deacetylation to 3-OH vecuronium. This compound is half as potent as its parent compound,
however it is rapidly metabolized to inactive metabolite.
o Pancuronium also undergoes hepatic deacetylation to 3-OH pancuronium. This compound is half as potent as it parent
compound.
Metabolism Liver elimination Renal Elimination Metabolites
Rocuroium None >70% 10-25% None
Vecuronium Liver (30-40%) 40-50% 50-60% 3-OH vecuronium
Pancuronium Liver (10-20%) 15% 85% 3-OH pancuronium

• Factors that Potentiate Neuromuscular Blockade

o Factors that potentiate neuromuscular blockade increase the difficulty of reversal as well as the risk of residual weakness.
• Cardiovascular Effects of NMBs
o When selecting a neuromuscular
blocker, one must be cognizant of
how it affects the cardiovascular
system. Some NMBs influence
hemodynamics by inducing histamine
release or affecting ANS tone.
o Histamine Release
§ Succinylcholine,
atracurium, and
Mivacurium release
histamine. Histamine
release is generally short-
lived (1-5 min) and can be
minimized by slow drug
administration. Even so,
patients who are sensitive
to a higher heart rate or
reduced afterload should
not receive histamine
releasing drugs, unless
the clinical benefit of the
drug outweighs the risk.
o Autonomic Nervous System
§ In contrast to histamine
releasing drugs, the rate
of administration does
not affect the autonomic
response.
o Tachycardia
§ Pancuronium is a unique
in that it has a vagolytic
effect. It inhibits M2
receptors at the SA node, stimulates the release of catecholamines, and inhibits catecholamine reuptake in adrenergic nerves. This
increase heart rate and cardiac output with no or minimal effect on the systemic vascular resistance. This drug is sometimes used to
mitigate opioid induced bradycardia in cardiac surgery.
§ The patient with hypertrophic cardiomyopathy (idiopathic hypertrophic subaortic stenosis) should not receive pancuronium. In this
disease process, there is a hypertrophied ventricular septum and systolic anterior motion of the anterior leaflet of the mitral valve.
When the ventricle contracts forcefully or quickly, there is a greater tendency for the anterior leaflet to occlude the LVOT, which
reduces the flow through the aortic valve. This reduces cardiac output and blood pressure. Pancuronium’s vagolytic effect can be
detrimental in this patient.
o Bradycardia
§ In rare instances, vecuronium and atracurium have caused asystole, in all of these cases, an opioid was also administered. It isn’t
that vecuronium or atracurium caused asystole, it is more likely that the vagal effects of the opioid were left unchecked.

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 • Anaphylaxis & Neuromuscular Blockers
o Neuromuscular blockers are the most common cause of perioperative allergic reactions. Their structures contain one or more antigenic
quaternary ammonium groups that interact with Ig-E, causing mast cell and basophil degranulation. This would be reflected by an elevated
typtase level in the blood (peak=15-120 minutes after exposure).
o Drugs with a single quaternary ammonium group (rocuronium, vecuronium, and pancuronium) are less likely to cause anaphylaxis than
succinylcholine. Cross sensitivity may occur in up to 70% of those who have experienced a previous allergic response related to neuromuscular
blockers. It is possible that sensitivity to any NMB may develop following exposure to soaps or cosmetics, as these compounds often contain
antigenic quaternary ammonium groups.
o Some of what we’re about to say may conflict with what you’ve learned in school. Let’s examine what the most current textbooks have to say…
o Of all of the neuromuscular blockers, anaphylaxis is most common with succinylcholine – NOT rocuronium. The incidence of anaphylaxis with
succinylcholine is estimated to range from 1: 5,000 to 1:10,000.
o The following NMBs are ordered from highest to lowest likelihood of cause anaphylaxis (Nagelhout).
Succinylcholine > atracurium > cisatracurium > rocuronium > vecuronium
o As a class of drugs, neuromuscular blockers account for 11% of anaphylactic reactions in the United States, however European data raises this
estimate to 58%! There are several French and Norwegian studies suggesting that rocuronium has a much higher rate of allergic reactions than
any other NMB. Indigenous population characteristics and a high frequency of false-positive results stemming from the gross inaccuracy of skin
testing have caused many to question the validity of these findings. In the United States, the incidence of anaphylaxis to rocuronium may be as
low as 1:1,000,000
o The bottom line is that Barash, Nagelhout, and Stoelting state that succinylcholine is the most common cause of anaphylaxis among the
neuromuscular blockers. If we encountered this question on the NCE< we would opt for succinylcholine before selecting rocuronium or any
other neuromuscular blocker.
NEUROMUSCULAR BLOCKER REVERSAL AGENTS

• AchE Inhibitors: Mechanisms of Action

o Acetylcholinesterase hydrolyzes Ach into choline and acetate. This enzyme is concentrated around the nicotinic receptors at the neuromuscular junction.
o Drugs such as edrophonium, neostigmine, and pyridostigmine reversibly inhibit AchE, which indirectly increases the concentration of Ach at the neuromuscular junction. Since
more Ach is present, it is better able to compete for the alpha binding sites on the nicotinic receptor and antagonize the block. It is important to note that, even though the
concentration of Ach is increased, the neuromuscular blocker still needs to be eliminated from the body.
o Not to be confused with acetylcholinesterase, Pseudocholinesterase is located in the plasma. This enzymes metabolizes succinylcholine. Pseudocholinesterase is inhibited by
neostigmine and pyridostigmine, but not edrophonium. Therefore, if ssuccinylcholine is given after neostigmine or pyridostigmine, the duration of succinylcholine will be
prolonged.
o There are 2 ways that AchE inhibitors increase the concentrations of Ach at the nicotinic receptor; enzyme inhibition and resynaptic effects
• Enzyme Inhibition
o There are 3 Ways to Inhibit AchE:
§ 1. Electrostatic attachment
• competitive inhibition
• edrophonium
§ 2. Formation of carbamyl esters
• competitive inhibition
• neostigmine, pyridostigmine, physostigmine
§ 3. Phosphorylation
• non-competitive inhibition
• organophosphates and echothiophate
• Presynaptic Effects
o In addition to increasing the concentration of Ach at the neuromuscular junction, there is some evidence of a presynaptic site of action. There
are 2 possible mechanisms:
§ 1. Similar to succinylcholine, AchE inhibitors stimulate the presynaptic receptor and cause it to release additional Ach.
§ 2. Inhibition of AchE near the presynaptic receptor increases the concentration of Ach in this region, so it is actually Ach that
stimulates this receptor.
o The primary mechanism of edrophonium is most likely presynaptic.
• Pharmacokinetics & Pharmacodynamics
o Renal failure prolongs the duration of action for both AchE inhibitors and
NMBs. Since both drugs will remain in the body for a longer period of
time, there is no need to adjust the dose of the AchE inhibitor or re-dose
it.
o AchE inhibitors have a ceiling effect above which additional drug does
not produce a better recovery.
o The onset of action is inversely related to the depth of the block. For
example, neostigmine will take longer to reach peak effect with a 990%
twitch suppression when compared to a 50% twitch suppression.
o Mixing AchE inhibitors yields an additive (not synergistic) effect.
o When compared to adults, antagonism with neostigmine is faster in
infants and children.
o Neostigmine doses > 2.5 mg may be associated with a higher incidence of PONV. Even so, minimizing the risk of postoperative weakness with
an appropriate dose of neostigmine trumps any risk of PONV.
o Edrophonium, neostigmine, and pyridosigimine are quaternary amines—they do not pass through the blood brain barrier.

o Physostigmine is a tertiary amine-it does pass through the blood brain

barrier.
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• Other Uses in the OR:
o Intrathecal neostigmine (50-100 mcg) produces analgesia. Side effects include nausea and vomiting, pruritus, and prolongation
of sensory and motor block.
o Physostigmine (40 mcg/kg) reduces the incidence of postoperative shivering. Its efficacy matches meperidine and clonidine.
• Cholinergic Side Effects D Diarrhea
o By increasing the concentration of Ach at the muscarinic receptor, AchE inhibitors U Urination
cause a predictable set of parasympathetic side effects. M Miosis
Mnemonic: DUMBBELLS B Bradycardia
• Muscarinic Antagonists: Side Effects B Bronchoconstriction
o Atropine and scopolamine are naturally occurring tertiary amines. Because they are E Emesis
lipophilic, they easily cross lipid membranes including the BBB, GI tract, and placenta. L Lacrimation
o Glycopyrrolate is different. As a quaternary ammonium derivatives, it is ionized. This L Laxation
limits its ability to cross cell membranes. Therefore, it does not possess CNS activity or S Salivation
cross the placenta.
o Small doses of atropine can cause a paradoxical bradycardia.
This is probably due to inhibition of the presynaptic M1
receptor on vagal nerve endings. This receptor’s job is to
reduce Ach release via negative feedback loop. Blockade of
the presynaptic M1 receptor “turns off” this negative
feedback loop and allows for continued Ach release and
bradycardia.
o Muscarinic antagonists do not affect the heart rate of the
patient with a previous heart transplant. Even so, these
patients will still experience other cholinergic effects from
AchE inhibitors, so they should receive a muscarinic
antagonist with an AchE inhibitor.
• Sugammadex
o Sugammadex selectively binds to the aminosteroid
nondepolarizing neuromuscular blockers (rocuronium >
vecuronium > pancuronium). It has no effect on succinylcholine or the benzylisoquinolines (atracurium, cisatracurium, and
Mivacurium).
o Mechanism of Action
§ Sugammadex is a gamma-cyclodextrin made of 8 sugars assembled in a ring. The ring encapsulates the neuromuscular blocker,
rendering it inactive and unable to engage with the nicotinic receptor. It’s like Febreze for aminosteroid neuromuscular blockers.
§ Encapsulating rocuronium decreases the free concentration of the drug in the plasma. This
augments the concentration gradient between the neuromuscular junction and the plasma,
thereby increasing the rate of transfer of rocuronium from the neuromuscular junction towards
the plasma. The affinity for rocuronium is strong, but not irreversible. It is not understood if pH,
temperature, or other factors affect the rate of dissociation. Because it does not interact with
neuromuscular receptors and neurotransmitters, it has no major systemic side effects.
§ Sugammadex improves safety in 3 ways:
• 1. Rocuronium can be used for difficult intubation without the drawbacks
of succinylcholine.
• 2. It can reverse a dense neuromuscular block quickly, thus greatly
reducing the risk of residual paralysis.
• 3. It allows for a dense block until the very end of the surgical procedure
without the concerns of a delayed extubation. Now those whiny surgeons
can have it both ways!
§ Metabolism
• Unlike rocuronium, which is primarily excreted by the biliary system, sugammadex and the sugammadex-
rocuronium complex are excreted unchanged by the kidneys.
§ Risks
• Of course no drug is a panacea. Sugammadex is extremely expensive. While it’s been available in Europe for several
years, the FDA approved Sugammadex for clinical use on Dec. 15, 2015.
• Hypersensitivity reactions have been reported.
• In the even that additional surgery is required shortly after sugammadex administration, there is a concern about the
ability to re-paralyze the patient with an aminosteroid NMB. A larger dose of rocuronium may be required in this
situation. It will have a longer onset and a shorter duration. It would make more sense to select a Benzylisoquinolinium
compound instead.

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OPIOIDS

• Mechanism of Action
o Pain Transmission Recap
§ The experience of pain can be divided into four steps: transduction, transmission, modulation, and perception.
Transduction Injured tissues release a variety of chemicals that activate peripheral nerves and/or cause immune
cells to release proinflammatory compounds. The peripheral nerves transduce this chemical soup
into an action potential, so that the extent of tissue injury can ultimately be interpreted by the
brain.
• A-delta fibers transmit “fast pain” that is sharp and well localized
• C-fibers transmit “slow pain” that is dull and poorly localized
Inflammation also contributes to:
• Reduced threshold to pain stimulus (allodynia)
• Increased response to pain stimulus (hyperalgesia)
Transmission The pain signal is relayed through the three-neuron afferent pain pathway along the
spinothalamic tract
• First-order neuron: periphery to dorsal horn (cell body in dorsal root ganglion)
• Second-order neuron: dorsal horn to thalamus (cell body in dorsal horn)
• Third-order neuron: thalamus to cerebral cortex (cell body in thalamus)
Modulation The pain signal is modified (inhibited or augmented ) as it advances towards the cerebral cortex
The most important site of modulation is the substantia gelatinosa in the dorsal horn (Rexed
lamina II and III)
• The descending inhibitory pain pathway begins in her periaqueductal gray and the
rostroventral medulla. It projects to the substantia gelatinosa.
Pain is inhibited when:
1. Spinal neurons release GABA and glycine (inhibitor neurotransmitters)
2. The descending pain pathway releases NE, 5-HT, and endorphins
Pain is augmented by:
1. Central sensitization
2. Wind-up
Perception Describes processing of afferent pain signals in the cerebral cortex and limbic system
*How we “feel” about pain

o Opioid Receptors
§ We will cover the specifics of each receptor after the next question, but for now we’d like you to know that there are four
types of opioid receptors.
1. Mu (MOP)

2. Delta (DOP)

3. Kappa (KOP)

4. ORL1 (NOP)

• There is no evidence to support the existence of distinct Mu-1 and Mu-2 receptors. Indeed, the newer texts
usually lump Mu-1 and Mu-2 effects together.
• The ORL1 (NOP) is an opioid-like receptor, however there is little information about it in the texts.
• The sigma receptor is no longer considered an opioid receptor.
o Opioid Mechanism of Action
§ Each opioid receptor is linked to a G protein, and agonism of the receptor
instructs the G protein to “turn off” adenylate cyclase. This reduces the
intracellular concentration of cAMP (second messenger), which alters ionic
currents and reduces neuronal function.
1. Opioid binds to receptor
2. G protein is activated.

3. Adenylate cyclase is inhibited.

4. Less cAMP is produced.

5. Ca+2 conductance is decreased.

6. K+ conductance is increased.

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• Systemic Effects
o Opioid Receptors
§ There are 4 types of opioid receptors: mu, delta, kappa, and OLR-1. While the mu receptor contributes to most of the
classic signs of opioid administration, you should be familiar with the unique features of the delta and kappa receptors.
The texts speak very little of the OLR-1 receptor, so we won’t waste your time with speculation.
o Where are Opioid Receptors Located?
§ Brain: periaqueductal gray, locus coeruleus, and rostral ventral medulla
§ Spinal Cord: primary afferent neurons in the dorsal horn and the interneurons
§ Peripheral: sensory neurons and immune cells
o What are the Precursors of the Endogenous Opioids?
§ Pre-proopiomelanocortinàEndorphins (Mu receptor)
§ Pre-enkephalinàenkaphalins (delta receptor)
§ Pre-dynorphinàDynorphins (kappa receptor)
o What are the Physiologic Functions of the Opioid Receptors?
Mu (µ) Delta (d) Kappa (K)
Endogenous Ligand Endorphin Encephalin Dynorphin
• beta-endorphin • leu-enkephalin • Dynorphin A
• endomorphin • met-enkephalin • Dynorphin B
• Neodynorphin
Analgesia Supraspinal Supraspinal Supraspinal
Spinal Spinal Spinal

Respiratory Depression Depression Depression???

Cardiovascular Bradycardia 0 0
CNS Sedation 0 Sedation
Euphoria Dysphoria
Prolactin release Hallucinations
Mild hypothermia Delirium
Pupil Miosis 0 Miosis
Genitourinary Urinary retention Urinary retention diuresis
Gastrointestinal N/V 0 0
Increased biliary pressure
Decreased peristalsis
Pruritus Yes Yes 0
Antishivering 0 0 Yes
§ In case you are asked about the differences between mu-1 and mu-2 receptors, you should know:
• Mu-1: supraspinal analgesia, bradycardia
• Mu-2: spinal analgesia
o What are the Systemic Effects of Opioids?

o Gender Differences
§ Gender plays a role in the PK/PD differences among opioid agonists. In women, morphine is associated with a:
• Greater analgesic potency
• Slower onset of action
• Longer duration of action
• Lower post-operative opioid consumption

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• Relative Potency & Dependence
o Relative Potency
§ Morphine is the standard by which all of the other opioids are compared. In order from most to least potent:
• Sufentanil>Fentanyl= Remifentanil > Alfentanil >Hydromorphone >Morphine >Meperidine
o Equinanalgesic Dosing

o Important Considerations
§ You will find these numbers vary throughout the anesthesia textbooks. The values we’ve presented here are
easy to remember and will serve you well on test day.
§ The IV dose and relative potency of methadone is variable and based on the patient’s daily opioid
requirements and duration of therapy.
o Dependence
§ Tolerance occurs when a patient requires higher doses of a drug to achieve a given effect.
§ Tolerance and physical dependence are most likely due to receptor desensitization and increased synthesis of cAMP. These
phenomena are not due to enzyme induction.
§ Tolerance develops to nearly all of the side effects associated with opioids. This includes analgesia, sedation, euphoria,
respiratory depression and emetic effects. There are 2 exceptions to this rule – tolerance does NOT develop to miosis or
constipation.
§ Withdraw
• Patients who are physically dependent on opioid agonists will experience s/sx of withdraw upon discontinuation
of these drugs.
o Early s/sx: diaphoresis, insomnia, restlessness
o Later s/sx: abdominal cramping and N/V
• The time course of opioid withdraw is a function o fthe drug’s half-life. Withdraw s/sx occur as follows:
o Fentanyl and meperidine: onset 2-6 hrs – Peak 6-12 hrs – Duration 4-5 days
o Morphine and heroin: Onset 6-18 hrs – Peak 36-72 hrs – Duration 7-10 days
o Methadone: onset 24-48 hrs – peak 3-21 days – duration 6-7 weeks
• Metabolism
o Except for remifentanil, all of the opioids undergo hepatic biotransformation. If Have Active Metabolite Do Not Have Active Metabolite
a drug produces an active metabolite, the metabolite is excreted in the urine. Morphine Fentanyl
o Morphine
Meperidine Sufentanil
§ Morphine is conjugated to morphine-3-glucoronide (inactive*)and
morphine-6-glucoronide (active). Alfentanil
• Compared to morphine, M6G is more water soluble, so it Remifentanil (unique pathway)
tends not to cross the blood brain barrier at normal hydromorphone
concentrations.
• Patients on dialysis are unable to excrete M6G, so they are prone to accumulation of this metabolite. A larger concentration
gradient between the blood and the brain helps M6G ender the CNS (law of mass action).
• This is why renal failure patients are more likely to experience respiratory depression and toxicity after morphine.
• Chronic morphine administration to patients with normal renal function can also cause M6G accumulation and toxicity.
§ *While Hemmings and Naglehout state that M3G is inactive. Barash says the following:
• M3G causes hyperalgesia, agitation, myoclonus, and delirium.
• M6G causes respiratory depression, drowsiness, N/V and coma.
o Meperidine
§ Meperidine is demethylated in the liver to normeperidine.
• Normeperidine is one half as potent as its parent compound.
• It reduces the seizure threshold and increases CNS excitability.
• Signs and symptoms of CNS excitability include: muscle twitches, tremors, and seizures.
• It should be avoided in patients on dialysis and used with caution, if at all, in the elderly.
o Remifentanil
§ Remifentanil is hydrolyzed in the plasma by erythrocyte and tissue esterases.
• It is not metabolized by Pseudocholinesterase, therefore its metabolism is unaffected by Pseudocholinesterase deficiency.
• Although it is very lipophilic, it is rapidly metabolized in the plasma. This explains why it behaves like a drug that has a low Vd.
Therefore, remifentanil is always dosed at lean body weight.

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• Meperidine
o Meperidine is a synthetic phenylpiperidine opioid that stimulates the mu and kappa receptor.
o Normeperidine
§ Meperidine is demethylated to normeperidine by the CYP450 system in the liver.
• Normeperidine is ½ the potency of its parent compound.
• The elimination half time is 15 hours, but it can exceed 35 hours in the patient with renal failure.
• Normeperidine causes myoclonus, reduces the seizure threshold, and increases CNS excitability, therefore it
should be avoided in the dialysis patient, and used with caution, if at all, in the elderly.
• Repeated dosing can cause accumulation and increase the risk of toxicity. Meperidine is therefore not
recommended for patient-controlled analgesia (PCA)>
o Co-Administration with MAO inhibitors
§ Meperidine is a weak serotonin reuptake inhibitor.
• Since MAO deaminates serotonin in the synaptic cleft, co-administration of meperidine and an MAO inhibitor
can cause serotonin syndrome.
• s/sx include: hyperthermia, mental status changes, hyperreflexia, seizures, and death.
• MAO inhibitors: phenelzine, isocarboxazid, and tranylcypromine.
o Anticholinergic Effects
§ Meperidine is structurally related to atropine.
• It exhibits anticholinergic effects such as: tachycardia, mydriasis and dry mouth.
o Antishivering Effect
§ Stimulation of the kappa receptor reduces postoperative shivering.
• Shivering increases oxygen consumption, so meperidine reduces oxygen consumption in the shivering patient.
o Histamine
§ Meperidine is one of several opioids that cause histamine release from mast cells (others include morphine, codeine and
oxycodone)
• Alfentanil
o Rapid Onset of Action
§ Alfentanil is a weak base whose pKa (6.5) is less than physiologic pH. All of the other opioids have a pKa greater than 7.2.
• At physiologic pH, ~90% of alfentanil is unionized and only ~10% is ionized.
• Remember it’s the unionized fraction that is able to diffuse across the blood brain barrier.
• It also has a low Vd and high degree of plasma protein binding (alpha-1-acid glycoprotein).
• Since it doesn’t widely distribute to the rest of the body, more drug is available to enter the brain.

§ Alfentanil’s effect site equilibration is ~1.4 minutes. Fentanyl and sufentanil achieve this end point in 6.8 and 6.2 minutes
respectively.
o Metabolism
§ Alfentanil undergoes N-dealkylation and O-demethylation by the hepatic cytochrome P450 system, specifically CYP3A4.
• Because it has a comparatively lower hepatic extraction ratio, alfentanil metabolism is more susceptible to
CYP3A4 function.
• Erythromycin inhibits alfentanil’s metabolism and co-administration can result in prolonged respiratory
depression.
• Alfentanil does not produce an active metabolite.
• Renal failure does not alter alfentanil clearance
§ Alfentanil is useful for blunting the hemodynamic response to short, but intense, periods of stimulation, such as tracheal
intubation or retrobulbar block.

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• Remifentanil
o Remifentanil is a rapid-on and rapid-off mu agonist.
§ Potency is similar to fentanyl.
§ Maintenance infusions is 0.1 -1.0mcg/kg/min
§ The context-sensitive half time is about 4 minutes regardless of infusion duration.
§ Even though it is highly lipophilic, it behaves as though it has a small Vd. This is due to a very fast rate of clearance in the
plasma.
§ In the obese patient, the rate of remifentanil infusion is calculated with lean body weight (it does not distribute
throughout the body fat because it is metabolized so quickly).
o Metabolism
§ Remifentanil contains an ester linkage. This renders it susceptible to hydrolysis by erythrocyte and tissue esterases.
• It is not metabolized by Pseudocholinesterase, so it isn’t affected by Pseudocholinesterase deficiency.
• Biotransformation is unaffected by hepatic or renal disease.
o Opioid Induced Hyperalgesia
§ Remifentanil causes acute opioid induced hyperalgesia following discontinuation.
• Postoperative opioid requirements are particularly high in these patients
• OIH can be prevented with ketamine or magnesium sulfate.
o Preparation
§ Remifentanil powder is mixed with a free base and glycine to provide a buffered solution following reconstitution.
• Glycine is an inhibitory neurotransmitter.
• It can cause skeletal muscle weakness, so it should not be administered in the epidural or intrathecal space.
• Methadone
o Methadone is prepared as a racemic mixture. It is useful in the following circumstances:
§ Chronic treatment of opioid abuse (prevention of withdrawal)
§ Chronic pain syndromes
§ Cancer pain
o Unique Mechanism of Action
§ Methadone decreases pain by 3 mechanisms:
• 1. Mu receptor agonist
• 2. NMDA receptor antagonist (dextrorotatory isomer)
• 3. Inhibits reuptake of monoamines in the synaptic cleft
o Metabolism
§ When administered orally, it has a bioavailability of 80%. There is also an IV preparation.
§ The duration of action is 3-6 hours, however chronic administration prolongs its elimination half-life as well as its duration
of analgesia.
§ It is metabolized in the liver by the CYP450 system.
§ It does not have an active metabolite.
o QT prolongation
§ Although a rare event, methadone can potentially increase the QT interval.
• It inhibits the delayed rectifier potassium ion channel (IKr)
• This can lead to Torsades de pointes
• Skeletal Muscle Rigidity
o Rapid IV administration of opioids can cause skeletal muscle rigidity.
§ This condition is more common with the potent (lipophilic) compounds, such as sufentanil, fentanyl, remifentanil, and
alfentanil.
§ Historically, this complication has been described as the chest wall rigidity or stiff chest syndrome, however current
evidence suggests that the greatest resistance to ventilation occurs at the larynx.
§ Opioid induced muscle rigidity is believed to result from mu receptor stimulation in the CNS (ultimately influencing
dopamine and GABA motor pathways).
§ Opioids do not directly affect motor nerve conduction, the neuromuscular junction, or skeletal muscle.
§ The best treatment for opioid induced skeletal muscle rigidity is paralysis and intubation.
§ Naloxone can also reverse rigidity, but giving this just before surgery seems counterproductive given that there is a better
alternative.

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 o Complications
§ Complications of opioid induced
muscle rigidity can be anticipated
based on the physiology of a
“stiff chest” and sustained muscle
contraction.
• Partial Agonists
o Opioid partial agonists (agonist-antagonist)
function just as their name suggests. They
can never achieve the same intensity of effect at a specific receptor as a full agonist.
o Common Characteristics
§ Produce analgesia with a reduced risk of respiratory depression
§ Have a ceiling effect beyond which additional analgesia is not possible.
§ Reduce the efficacy of previously administered opioids
§ Can cause acute opioid withdrawal in the opioid dependent patient.
§ Can cause dysphoric reactions.
§ Carry a low risk of dependence.
§ Are used in patients who cannot tolerate a full opioid agonist.
o Specific Drugs

Other examples from this drug

class include:

• Pentazocine
• Nalorphine
• Bremazocine
• Dezocine
• meptazinol

• Antagonists
o Naloxone
§ Naloxone is the prototype opioid antagonist. It competitively antagonizes the mu, kappa, and delta opioid receptors, however it has the
greatest affinity at the mu receptor.
• Indications
o Acute reversal of opioid induced respiratory depression
o Reversal of respiratory depression in the neonate whose mother received an opioid
o Treatment of opioid overdose
• Key Facts
o Dose= 1-4 mcg/kg (it’s better to give 20-40 mcg at a time, as this will prevent overshoot)
o Duration = 30-45 min
o Metabolism= Liver (significant first pass metabolism)
• Naloxone’s duration may be shorter than the opioid you’re trying to reverse. Consider an infusion if a long acting opioid is the
cause of respiratory depression.
§ in the patient with pain, analgesic reversal activates the SNS.
• This is the mechanism by which naloxone causes neurogenic pulmonary edema, tachycardia, cardiac dysrhythmias and sudden
death.
• Slow titration minimizes these effects.
§ It can also cause nausea and vomiting. Slow titration over a 2-3 minutes causes less N/v.
§ Naloxone cross the placenta. If it is given to an opioid abusing mother, it can precipitate acute opioid withdrawal in the neonate.
o Methylnaltrexone
§ Methylnaltrexone has a quaternary amino group that prohibits its passage across the blood brain barrier.
• Since it doesn’t enter the brain, it does not reverse respiratory depression.
• It’s useful for mitigating the peripheral effects of opioids, such as opioid induced bowel dysfunction.
o Nalmefene
§ Nalmefene (0.1-0.5 mcg/kg) has a profile similar to naloxone, however its duration of action is much longer—about 10 hours.
• It can be used to maintain recovering opioid abusers.
o Naltrexone
§ Unlike naloxone, naltrexone does not undergo significant first pass metabolism.
• It can be given orally and has a duration of up to 24 hours.
• An extended release may be used for alcohol withdrawal treatment.
• It can also be used to maintain recovering opioid abusers.

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Inhaled Anesthetics
Chemical Structures
o Inhaled anesthetics are categorized into 3 groups: ethers, alkanes, and gases.
o At atmospheric pressure and room temperature, the ethers and alkanes exist as liquids. The gases (obviously) exist in gaseous
form.
Ethers (R-O-R’) Alkanes (R-H) Gases
Desflurane Halothane Nitrous oxide
Isoflurane Chloroform Cyclopropane
Sevoflurane Xenon
Enflurane
Methoxyflurane
Ether

• Tips to Help You Identify the Correct Agent

o Number of Carbons:
§ Isoflurane has 5 fluorine atoms + 1 chlorine atom
§ Desflurane has 6 fluroine atoms
§ Sevoflurane has 7 fluorine atoms (sevo=7)
o Chiral Carbons
§ Desflurane and isoflurane contain chiral carbons
§ Sevoflurane does not contain a chiral carbon
• Isoflurane
o The addition of the heavier chlorine atom increases potency. Indeed, isoflurane is nearly twice as potent as sevoflurane and five
times as potent as desflurane. The chlorine atom also increases blood and tissue solubility.
• Desflurane
o Notice that desflurane is nearly identical to isoflurane, but the chlorine atom has been replaced by a fluorine atom, making
desflurane fully fluorinated.
o Full fluorination has the following effects:
§ Decreased potency (decreased oil: gas solubility)àincreased MAC
§ Increased vapor pressure (decreased intermolecular attraction) àrequires heated vaporizer
§ Increased resistance to biotransformation (decreased metabolism) àdecreased trifluoroacetate makes an immune
mediated hepatitis extremely unlikely
• Sevoflurane
o As we’ve learned, fluorination tends to reduce potency. Even though sevoflurane is heavily fluorinated, it’s still ~3 times as
potent as desflurane. This is most likely due to the bulky propyl side chain.
Physical Properties

• The physiochemical characteristics of each inhaled anesthetic affect how each drug behaves outside and inside of the body. We need to
define 4 key physiochemical concepts: vapor pressure, boiling point, partial pressure, and stability.
• Vapor Pressure
o The pressure exerted by a vapor in equilibrium with its liquid or solid phase inside of a closed container.
§ Vapor pressure is directly proportional to temperature
§ Increased temperatureàincreased vapor pressure
• Boiling point
o At high altitude, a liquid will boil at a lower temperature as a function of the reduction in atmospheric pressure. Boiling requires
an open container.
• Partial Pressure
o The fractional amount of pressure that a single gas events within a gas mixture. Dalton’s law of partial pressures states that the
total gas pressure in a container is equal to the sum of the partial pressures exerted by each gas.
P total = P1 + P2 + P3…
o The depth of anesthesia is determined by the partial pressure of anesthetic agent in the brain and NOT the volume percent!
When you set the vaporizer dial, you are setting the vol%. this isn’t a problem near sea level, however at elevation, it may lead
to underdosing desflurane but not sevoflurane or isoflurane. This is because the conventional variable bypass vaporizer
automatically compensates for elevation, however the Tec 6 desflurane vaporizer does not.
Vol% x Total gas pressure = Partial pressure of that particular gas
o 6% desflurane at sea level results in a delivered partial pressure of 45.6 mmHg (0.06 x 760 mmHg=45.6 mmHg)
o 6% desflurane in Denver (1 mi. above sea level) results in a delivered partial pressure of 37.2 mmHg (0.06 x 620
mmHg=37.2mmHg)

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• Stability
o Carbo dioxide absorbent as well as the liver are capable of transforming volatile anesthetics into toxic compounds. Stability
refers to the ability to resist breakdown or metabolism.
o Even in hydrated soda lime, sevoflurane is unstable and capable of producing compound A. this is the basis for the minimum
fresh gas flow requirements with sevoflurane. Desflurane and isoflurane can become unstable in desiccated soda lime. They can
produce carbon monoxide (des > iso).
• Physiochemical Properties of Inhalation Anesthetics

• Solubility & the Blood: Gas Coefficient

o Solubility is the tendency of a solute to dissolve into a solvent. In the case of inhalation anesthetics, it’s the ability of the
anesthetic agent to dissolve into the blood and tissues.
o How easily a solute will dissolve into a solvent depends on the physiochemical characteristics of both compounds ==”like
dissolves like.”
§ A polar solute will be more soluble in a hydrophilic solvent
§ A nonpolar solute will be more soluble in a lipophilic solvent
• How Do We Measure Solubility?
o The partition coefficient is a measure of solubility. It describes the relative solubility of a solute in 2 different solvents.
o The blood : gas partition coefficient (l) describes the relative solubility of an inhalation anesthetic in the blood vs. in the
alveolar gas when the partial pressures between the 2 compartments are equal.

• FA/FI Curves
o When administering a volatile anesthetic, our main objective is to produce a state of anesthesia by building up a partial
pressure of anesthetic agent inside the patient’s brain and spinal cord.
o To do this, we must be concerned with the partial pressure of anesthetic in two locations: leaving the vaporizer and inside the
alveoli.
FA= the partial pressure of anesthetic inside the alveoli
FI= the concentration of anesthetic exiting the vaporizer
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• Why Do We Measure Alveolar Concentration?
o The concentration of an agent inside the alveoli is proportional to its concentration inside the blood and this is proportional to
the anesthetic inside the brain. While we cannot directly measure the anesthetic in the brain, we use the alveolar concentration
(FA) as a surrogate.
Alveolar partial pressure ~ Blood partial pressure ~ Brain partial pressure
• How Do We Establish an Anesthetic Concentration Inside the Alveolus?
o 1. Turn the vaporizer on. This creates a concentration gradient that pushes anesthetic agent
from the vaporizer towards the alveoli. This is FI.
o 2. The anesthetic is washed into the alveoli. This is called FA.
o 3. The buildup of anesthetic partial pressure inside the alveoli is being opposed by continuous
uptake of agent into the blood. This is uptake.
o 4. The cardiac output distributes the anesthetic agent throughout the body. This is
distribution.
• The Importance of Solubility
o The speed of induction is a function of the solubility of the anesthetic
agent.
§ Low solubility àless uptake into the bloodà increased
rate of rise àfaster equilibration of FA/FIàfaster onset
§ High solubilityàmore uptake into the bloodàdecrease
rate of riseàslower equilibration of FA/FIàslower onset
o ***it is tempting to think that a greater amount of anesthetic agent
dissolved in the blood equates to a greater effect on the brain. This is
NOT the case. Instead, it is the partial pressure of the anesthetic
agent in the blood that equates to a greater effect.
o The FA/FI curve allows us to appreciate the speed at which alveolar
partial pressure equilibrates with the partial pressure leaving the
vaporizer. You must be able to identify this curve for each inhalation
agent.

o Did you notice that desflurane has a lower blood: gas partition coefficient than nitrous oxide, yet the rate of rise of FA/FI for
nitrous oxide is higher? How do you explain this? If you can’t remember, hang on and we’ll cover that point shortly.
• Factors Affecting FA/FI
o It is critically important that you understand the factors that influence the rate of anesthetic delivery to
the alveoli as well as the factors that influence uptake away from the alveoli.
o FA is a function of:
§ 1. The rate of delivery to the alveoli
§ 2. The rate of removal from the alveoli
o Determinants of Delivery to the Alveoli:
§ Setting on the vaporizer
§ Time constant of the delivery system
§ Anatomic dead space
§ Alveolar ventilation
§ Functional residual capacity
o Determinants of Removal from the Alveoli:
§ Solubility of anesthetic in the blood (blood: gas partition coefficient)
§ Cardiac output
§ Partial pressure gradient between the alveolar gas and the mixed venous blood

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Distribution

• After inhalation anesthetic enters the blood, it is distributed to nearly all the tissues in the body.
• The rate of anesthetic uptake into the tissues is unique for each tissue type. For each tissue type, uptake is dependent on:
o Tissue blood flow
o Solubility of the anesthetic in the tissue
o Arterial blood: tissue partial pressure gradient
• We can divide the body into 4 tissue groups. Each group is defines by
how much cardiac output it receives relative to it percentage of body
weight.
• The vessel rich group consists of the heart, brain, kidneys, liver, and endocrine
glands. It is only 10% of the body mass, yet it receives 75% of the cardiac
output. Because the VRG receives a disproportionately large amount of the
cardiac output relative to body mass, these organs receive most of the
anesthetic agent during induction and are the first to equilibrate with FA. After the VRG becomes saturated with anesthetic, the muscle group is
responsible for the majority of continued tissue uptake. The muscle group is slower to saturate because it receives a disproportionately lower amount of
cardiac output and has a much larger capacity. The fat group is also soaking up anesthetic agent, but at a slower rate. Once the muscle group is saturated,
fat is responsible for any additional uptake. Because the halogenated agents are lipid soluble, the fat group functions as a high capacity sink capable of
storing large amounts of agent. The vessel poor group consists of tendons, ligaments, cartilage, and bone. It does not receive enough blood flow to
meaningfully contribute to anesthetic uptake.
• What About Nitrous Oxide?
o The uptake of nitrous oxide by any of these groups is
minimal. It partitions nearly the same into all of the
compartments. Nitrous will quickly diffuse into the gas
containing areas of the body, such as the
gastrointestinal tract and the middle ear.
• Let’s look at a clinical example.
o You don’t have to memorize these numbers. We only
included this example so you can attach meaning to
what you’re learning.
o After 10 minutes of 2.56% sevoflurane anesthesia in
100% oxygen at 8 L/min, the following tissue partial
pressures and concentrations are observed.
o If the sevoflurane was continued until it fully equilibrated throughout the body, the partial pressure would be equal in all compartments. The
vol% will differ based on the tissue: gas partition coefficients.
Hepatic Metabolism of Inhalation Anesthetics
• Inhaled anesthetics are eliminated from the body in 3 ways:
o 1. Elimination from the alveoli
Agent Hepatic Biotransformation %
o 2. Hepatic biotransformation
Nitrous oxide 0.004
o 3. Percutaneous loss
Desflurane 0.02
• exhalation through the lungs is the primary mechanism by which inhalation anesthetic is removed
Isoflurane 0.2
from the body. Hepatic metabolism is a secondary mechanism for anesthetic removal.
Percutaneous loss is minimal and not clinically significant. Sevoflurane 2-5
• You should remember this as “the rule of 2’s—(0.02,0.2, and 2.0).” additionally you should notice
that halogenated agents are in alphabetical order beginning with desflurane undergoing the least amount of biotransformation (D-I-S)
• How are Halogenated Anesthetics Metabolized in the Liver?
o The halogenated anesthetics undergo metabolism by the P450 system, and this is primarily carried out by CYP2E1. During anesthetic induction,
it is unlikely that metabolism significantly counters the rise in FA> metabolism plays a more important role during recovery.
• Metabolites of Desflurane and Isoflurane:
o Desflurane and isoflurane are metabolized to inorganic fluoride ions and trifluoroacetic acid (TFA). Up to 40% of halothane undergoes hepatic
biotransformation, and a high concentration of TFA in the liver is in the mechanism for halothane hepatitis. Although desflurane and isoflurane
undergo a much smaller degree of hepatic biotransformation, there remains a very minute possibility that TFA could precipitate an immune
mediated hepatic dysfunction, especially in a patient with previous TFA exposure.
• Metabolites of Sevoflurane:
o Sevoflurane is not metabolized to TFA< but its biotransformation does result in the liberation of inoraganic fluoride ions. Because sevoflurane
has a relatively higher degree of metabolism, there are theoretical concerns of fluoride induced high output renal failure. This type of renal
failure is characteristically unresponsive to vasopressin. Signs of high output renal failure include: polyuria, hypernatremia, hyperosmolarity,
increased plasma creatinine, and inability to concentrate the urine. To date, these concerns seem unjustified.
• Metabolites of Nitrous Oxide:
o for all intents and purposes, nitrous oxide is not metabolized by the body.
• How Does Soda Lime Contribute to the Breakdown of Halogenated Anesthetics?
o Sevoflurane generates compound A when exposed to soda lime. Desiccated soda lime accelerates the production of compound A.
o Desflurane and isoflurane produce carbon monoxide in the presence of desiccated soda lime.
o It is important to recognize that fluoride ions and TFA are produced during biotransformation inside the body, while compound A and carbon
monoxide are produced following exposure to soda lime outside of the body.

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Concentration Effect

• Working along the theme of altering the speed of anesthetic induction and emergence, we’d like you to be familiar with several confusing
terms. This is classic board stuff.
o 1. Concentration effect
o 2. Concentrating effect
o 3. Augmented gas inflow effect
o 4. Ventilation effect
• Concentration Effect:
o The higher the concentration of inhalation anesthetic delivered to the alveolus, the faster its onset of action. This effect is probably only
clinically relevant with nitrous oxide.
o There are 2 components to the concentration effect:
§ 1. Concentrat”ing” effect:
• when the patient is breathing room air, nitrogen is the primary gas in the alveolus.
• Nitrous oxide is ~34 times more soluble in the blood than nitrogen
• When nitrous oxide is introduced into the lung, the volume of nitrous oxide going from the alveolus to the pulmonary
blood is much higher than the amount of nitrogen moving in the opposite direction. This causes the alveolus to shrink
and the reduction in alveolar volume causes a relative increase in FA>
• The concentrating effect explains why nitrous oxide (not desflurane) achieves the faster rate of rise of FA/FI, even though
desflurane is less soluble in the blood. Simply put, the sheer volume of nitrous oxide movement more than compensates
for the small difference in blood solubility.
§ 2. Augmented gas inflow:
• the concentrating effect temporarily reduces alveolar volume
• on the subsequent breath, the concentrating effect causes an increased inflow of tracheal gas containing anesthetic
agent to replace the lost alveolar volume. This increases alveolar ventilation and augments FA> alveolar volume is
restored quickly, so this is only a very temporary phenomenon.
• Ventilation Effect:
o The ventilation effect describes how changes in alveolar ventilation can affect the rate of rise of FA/FI
§ The greater the alveolar ventilation, the greater the rate of rise of FA/FI
§ In the spontaneously ventilating patient, as the anesthetic is deepened, alveolar ventilation decreases and this decreases anesthetic
input to the alveolus. This can be thought of as a protective effect that minimizes the risk of anesthetic overdose.
Second Gas Effect
• It’s easy to confuse the concentration effect with the second gas effect. While the concentration effect deals with a single gas (usually nitrous oxide), the
second gas effect describes the consequences of the concentration effect when a second gas is co-administered.
• Second Gas Effect
o The use of nitrous oxide during anesthetic induction will hasten the onset of a second gas.
§ When nitrous oxide and the second gas are introduced into the alveolus, the rapid uptake of N2O will cause the alveolus to
temporarily shrink. The reduction in the alveolar volume and augmented tracheal inflow causes a relative increase in concentration
of the second gas.
§ The partial pressure of alveolar oxygen also increases when the alveolus shrinks. This, too, is a transient effect.
§ The end result is the alveolar concentration of the other gases are higher than if they were administered alone.
• Diffusion Hypoxia
o The gas containing areas of the body can absorb up to 30 L of nitrous oxide within 2 hours, and most of this will be eliminated from the body
within 5 minutes after nitrous oxide is discontinued. As this tremendous volume of nitrous oxide is transferred into the alveoli, it dilutes
alveolar oxygen and carbon dioxide. This can cause a temporary diffusion hypoxia and hypocarbia.
o Administration of 100% oxygen for 3-5 minutes after nitrous oxide has been discontinued will mitigate the dilution of alveolar oxygen.
Cardiac Shunts & FA/FI
• A right-to-left cardiac shunt causes some of the deoxygenated blood leaving the right heart to bypass the lungs. Because this fraction of blood does not pick up
oxygen or inhalation agent, it will dilute the non-shunt fraction when it mixes in the left heart. The result is a reduction in PaO2 as well as a reduction in the partial
pressure of anesthetic in the arterial blood.
• Examples of Right-to-Left Shunts:
o Tetralogy of Fallot
o Foramen ovale
o Eisenmenger’s syndrome
o Tricuspid atresia
o Ebstein’s anomaly
• Which Anesthetics are Most Impacted by a Right-to-Left Shunt?
o In the presence of a right-to-left shunt, the FA/FI of an agent with lower solubility will be more affected than an agent with higher solubility.
o More soluble agents experience a greater degree of uptake by the blood, which partially offsets the dilution effect. Said another way, there is more agent
dissolved in the blood.
o Less soluble agents undergo very little uptake by the blood, and the effect of dilution is unchecked.
o Desflurane has the lowest blood : gas partition coefficient (0.42), so its FA/FI curve is affected the most. Isoflurane has the highest blood : gas partition
coefficient (1.46), so its FA/FI curve is affected the least.
• How Does a Left-to-Right Shunt Affect Anesthetic Uptake?
o A left-to-right shunt will not have a meaningful effect on anesthetic uptake of induction time.

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Nitric Oxide: Peculiarities

• How Nitrous Oxide Affects Closed Air Spaces

o Nitrous oxide is ~ 34 times more soluble than nitrogen. This means that for every 1 molecule of nitrogen
that leaves a closed space, 34 molecules of nitrous oxide enter to take its place.
§ Nitrogen blood:gas partition coefficient = 0.014
§ Nitrous oxide blood:gas partition coefficient = 0.46
o Why Does This Matter?
§ In a compliant airspace, nitrous oxide increases the volume of the space.
§ At some point, the compliant airspace will convert to a fixed airspace.
§ In a fixed airspace, nitrous oxide increases the pressure of the space.
• The rate of pressure change inside the space is dependent on: the compliance of the space, the partial pressure of
nitrous oxide, the perfusion of the surrounding tissue, and time. Knowing this allows you to predict the situations where nitrous is potentially harmful.
• The Middle Ear:
o Nitrous oxide quickly increases middle ear pressure, which
can damage a tympanic membrane graft. Conversely,
discontinuation of nitrous oxide can quickly decrease
middle ear pressure, and can result in serous otitis.
• Ocular Gas Buddle Placement:
o During retinal detachment surgery, a gas bubble is placed
over the site of the retinal break. This functions as a
“splint” to hold the retina in place while healing occurs.
Because nitrous oxide can diffuse into the bubble faster
than the other gases in the bubble can diffuse out, nitrous oxide can expand the SF6 bubble, compromise retinal perfusion, and cause
permanent blindness.
§ Discontinue N2O 15 minutes before the SF6 bubble is placed.
§ Avoid N2O for 7-10 days after the SF6 bubble is placed.
o Alternatives to SF6 and When to Avoid N2O:
§ Air: 5 days
§ Perfluoropropane: 30 days
§ Silicone oil: no contraindications to N2O
• Fire Risk
o Nitrous oxide is not flammable, but it does support combustion. There is a fire risk when nitrous oxide is administered during laparoscopy with
pneumoperitoneum if the electrocautery is used.
• How Does Nitrous Oxide Affect Anesthetic Equipment?
o Nitrous oxide can increase the volume and pressure in the following anesthesia equipment:
§ Endotracheal tube cuff
§ LMA cuff
§ Balloon-tipped pulmonary artery catheter
o That the most reliable way to check the internal pressure of the endotracheal tube or LMA cuff is to attach a manometer to the pilot balloon.
Palpation is grossly inaccurate.
• Vitamin B12 Inhibition
o Nitrous oxide irreversibly inhibits B12, which inhibits methionine synthase (enzyme required for folate metabolism and myelin production). This
has several potential side effects:
§ Megaloblastic anemia (bone marrow suppression)
§ Neuropathy
§ Immunocompromised
§ Impaired DNA synthesis
§ Concern of teratogenicity (clinical data is lacking)
§ Possible risk of spontaneous abortion (many clinicians avoid N2O in the first two trimesters)
§ Homocysteine accumulation (no strong data that clinical use of N2O increases cardiovascular m&m)
o The risk of complications is increased by prolonged exposure and in patients with pre-existing B12 deficiency: pernicious anemia, alcoholism,
strict vegan diet, and recreational use of N2O.
Minimum Alveolar Concentration: A Measure of Potency

• Minimum alveolar concentration (MAC) is the concentration of inhalational anesthetic that prevents the nociceptive withdrawal reflex
following a supramaximal painful stimulus in 50% of the population. Remember that this is In the absence of residual midazolam,
fentanyl, propofol, ect.
• MAC is a measure of potency—it is akin to the ED50. Drug MAC for 40 Year Old (%) Relative Potency
• The essential triad of anesthetic action includes: Isoflurane 1.2 ++++
o 1. Amnesia Sevoflurane 2.0 +++
o 2. loss of consciousness Desflurane 6.6 ++
o 3. Immobility Nitrous Oxide 104 +
• Volatile agents also modulate autonomic function and may
provide some analgesia.

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 • These effects are dose-dependent. For example, supraspinal effects such as amnesia and loss of consciousness occur at lower
concentrations, while immobility requires a higher concentration. This suggests anesthetics exert these effects in different regions of the
CNS.
• Key Facts
o MAC is additive. 0.5 MAC isoflurane + 0.5 MAC N2O= 1 MAC
o MAC-awake is the alveolar concentration at which a patient opens his or her eyes. This shows hysteresis in that MAC awake is
0.4-0.5 during induction, but during recovery MAC-awake is as low as 0.15 MAC
o MAC-bar is the alveolar concentration required to block the autonomic response following a supramaximal painful stimulus. It
is ~1.5 MAC
o Movement can be prevented in 95% of the population at ~1.3 MAC
o Awareness and recall is generally assumed to be prevented at 0.4-0.5 MAC
• Factors that Affect Potency
o Study the chart to review all of the factors that influence MAC. We’d like to point out a few points of interest here.
§ MAC tends to be increased by factors that increase central neurotransmitter concentrations, neurotransmission, and
cerebral metabolism.
§ MAC tends to be decreased by factors that decrease central neurotransmitter concentrations, neurotransmission, and
cerebral metabolism.
§ MAC is decreased by 6% for each decade of life.
§ MAC is increased ~19% in red heads presumably due to mutations in the melanocyte stimulating hormone receptor
and an increased production of pheomelanin
§ Hyper- and hypothyroid do NOT directly affect MAC, however changes in cardiac output associated with these
conditions may affect anesthetic uptake and subsequent onset of action. For example, profoundly hypothyroid
patients have a reduced CO leading to decreased uptake into the blood and a faster rate of rise of rise of FA/FI.
Because of this, these patients are more susceptible to anesthetic overdose.
Factors that Increase MAC Factors that Decrease MAC Factors that Do NOT Affect MAC
Drugs Chronic alcohol consumption Nitrous oxide
Acute amphetamine intoxication Opioids
Acute cocaine intoxication IV anesthetics
MAOIs Alpha-2 agonists
Ephedrine Acute alcohol use
Levodopa Lithium
Cyclosporine Lidocaine
Neuraxial opioids
Verapamil
Hydroxyzine
THC
Electrolytes Hypernatremia Hyponatremia Hyperkalemia
Hypokalemia
Hypomagnesemia
hypomagnesemia
Age Peaks at 6 months Increasing age
Body temperature Hyperthermia Hypothermia
Other Red hair Hypotension Gender
PaO2<38 mmHg PaCO2 15-95 mmHg
Anemia PaO2>38 mmHg
Cardiopulmonary bypass Hyperthyroid
Metabolic acidosis Hypothyroid
Hypo-osmolality Hypertension
Pregnancy à postpartum (24-72 hrs)

Mechanism of Action: Old Way of thinking—Lipophilic Action

• The old theory of anesthetic action suggested that anesthesia was produced by the interaction between the anesthetic agent and the lipid bilayer. Even
though our understanding of anesthetic action has moved well beyond this simplistic explanation, we believe this is still critical information that you
should know.
• Meyer-Overton Rule
o The Meyer-Overton rule states that lipid solubility is directly proportional to the potency of an inhaled anesthetic.
o Said another way, the greater the lipid solubility, the lower the MAC value.
o This theory implies that depth of anesthesia is determined by the number of anesthetic molecules that are dissolved in the brain and not
necessarily the particular anesthetic agent that is used. Indeed, a wide variety of dissimilar agents can produce anesthesia.
• Unitary Hypothesis
o The unitary hypothesis states that all anesthetics share a similar mechanism of action, but each may work at a different site.

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Mechanism of Action: New Way of Thinking—Protein Based Mechanism
• Our current understanding of anesthetic action highlights the enormous complexity involved.
• General anesthesia is produced by membrane bound protein interactions in the brain and spinal cord. The stereoselectivity of anesthetic potency suggests a chiral
binding site. In addition, they probably affect specific areas of the cell membrane.
• As a general rule the volatile anesthetics have the following effects on their target receptors:
o 1. They stimulate inhibitory receptors
o 2. They inhibit stimulatory receptors
• So if you know if a neurotransmitter is stimulatory or inhibitory, you can easily
deduce how an anesthetic will affect it.
• In the Brain
o In the brain, the most important site of volatile anesthetic action is the
GABA-A receptor.
§ The GABA-A receptor is a ligand gated chloride channel.
§ Stimulation of the GABA-A receptor increases chloride influx and hyperpolarizes neurons. This impairs the ability of these neurons to fire.
§ Volatile anesthetics most likely increase the duration that the chloride channel remains open.
• In the Spinal Cord
o In the spinal cord, volatile anesthetics produce immobility in the ventral horn.
o The most important sites of volatile anesthetic action in the spinal cord are:
§ Glycine receptor stimulation
§ NMDA receptor inhibition
§ Na+ channel inhibition
o Immobility is NOT due to GABA-A receptors in the spinal cord.
• What About Nitrous Oxide and Xenon?
o The effects of gaseous anesthetics (nitrous oxide and xenon):
§ NMDA antagonism
§ Potassium 2P-channel stimulation
o Nitrous oxide and xenon do not stimulate the GABA-A receptor.
Site of Anesthetic Action
• The essential triad of general anesthetic action includes:
o 1. Unconsciousness
o 2. Amnesia
o 3. Immobility
• volatile agents also modulate autonomic function and may provide some analgesia.
• Volatile anesthetics produce these effects by altering the function of the following neuroanatomical structures.
Pharmacodynamic Effect and Target Region Function of Target Region
Unconsciousness
Cerebral Cortex Higher order cerebral functions
Thalamus Relay station of sensory and motor input to the cortex
Reticular activating system Influences consciousness and arousal
Amnesia
Amygdala Emotion, response to pain, formation of stress response
Hippocampus Memory formation
Immobility
Ventral Horn Upper and lower motor neurons synapse here
Analgesia
Spinothalamic tract Nociceptive signals along the ascending pain pathways are inhibited
Autonomic modulation
Pons and medulla Control center for autonomic reflexes
Cardiovascular Effects
• In cardiac muscle and vascular smooth muscle, volatile anesthetics decrease Ca+2 influx though the sarcolemma and reduce Ca+2 release from the
sarcoplasmic reticulum.
• They also modulate nitric oxide release, inhibit Ach-induced vasodilation, and impair the Na+/Ca+2 pump decreasing intracellular Ca+2 concentration.
• We’re going to give you the summary first, then we’ll delve into the details.

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 • Blood Pressure
o Halogenated Anesthetics
§ The halogenated anesthetics decrease MAP in a dose dependent fashion. At equivalent doses, there is little difference
between agents.
• Primary cause: decreased intracellular Ca+2 in vascular smooth muscleàsystemic vasodilationàdecreased
SVR and decreased venous return
• Secondary cause: decreased intracellular Ca+2 in the myocyte àmyocardial depressionàdecreased
inotropy
o Nitrous Oxide
§ The hemodynamic effects can be explained by SNS activation
§ Nitrous oxide + volatile agent causes less blood pressure reduction when compared to the MAC equivalent of the
volatile agent alonge.
• Heart Rate
o Halogenated Anesthetics
§ Halogenated anesthetics directly affect cardiac conduction in a dose dependent fashion. They do this in several ways:
• Decreased SA node automaticity
• Decreased conduction velocity through Av node. His-Purkinje system and ventricular conduction pathways
• Increased duration of myocardial repolarization by impairing an inward K+ current. This prolongs the QT
interval
• Altered baroreceptor function
§ Desflurane and isoflurane increase heart rate form baseline by 5-10%. This is most likely due to SNS activation from
respiratory irritation.
§ Rapid increases in desflurane, and to a lesser degree, isoflurane cause tachycardia. Pulmonary irritation àSNS
activationàincreased norepinephrine releaseàbeta-1 stimulation
• Tachycardia can be minimized, but not abolished, with opioids, alpha=2 agonists, or beta-1 antagonists
o Nitrous Oxide
§ Nitrous oxide activates the SNS and increase heart rate
• Contractility
o There is a small decrease in baseline contractility, however the myocardium remains preload responsive. Myocardial depression
is dose dependent.
o Nitrous oxide + opioid can cause myocardial depression.
• Systemic Vascular Resistance
o Decreased intracellular Ca+2 in vascular smooth muscleàsystemic vasodilation àdecreased SVR
o Sevoflurane causes the least reduction in SVR
• Coronary Vascular Resistance
o Volatile anesthetics increase coronary blood flow in excess of myocardial oxygen demand. They preferentially dilate the small
cardiac vessels that are 20-50 micrometers in diameter.
o Isoflurane is the most potency coronary artery vasodilator (from greatest to least): Isoflurane > Desflurane >Sevoflurane
o Since isoflurane is the most potent coronary artery vasodilator, there have been concerns that it might induce a coronary steal
phenomenon. Current thinking suggests that isoflurane does not contribute to coronary steal. In fact, the volatile anesthetics
precondition the myocardium and protect it against ischemia.
o The Idea Behind Coronary Steal
§ As myocardial oxygen demand increases, healthy vessels dilate. Recall that the heart’s oxygen extraction is ~75%. Since it cannot
significantly increase its extraction ratio, the heart increases its own blood flow to satisfy its oxygen requirement.
§ Severely stenotic vessels are maximally dilated beyond the point of stenosis. When myocardial oxygen demand increases, the
diseased vessels will not be able to dilate further. The idea behind coronary steal is that coronary blood flow would be preferentially
directed to healthy tissue. This is an example of the “reverse-Robin Hood” effect—by following the path of least resistance, blood
flow is preferentially directed to healthy tissue (the rich) at the expense of disased tissue (the poor).
§ Again, this just doesn’t happen in clinical practice, but if you encounter it on the NCE, you’ll have the whole story.
Pulmonary Effects: PaCO2 and Respiratory Mechanics

• The central chemoreceptor in the medulla maintains tight control of PaCO2. Every 1 mmHg increase in PaCO2 above baseline will
increase minute ventilation by 3L/min
• Volatile anesthetics cause a dose dependent depression of the central chemoreceptor and the respiratory muscles. This contributes to
hypercarbia. Mechanisms include:
o 1. Altering the respiratory pattern
o 2. Impairing the response to carbon dioxide
o 3. Impairing motor neuron output and muscle tone to upper airway and thoracic muscles
• Altering Respiratory Pattern
o Decreased tidal volume
o Increased respiratory rate partially compensates for the reduction in tidal volume, although not enough to prevent a rise in
PaCO2.

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 • Impairing the Response to Carbon Dioxide
o The slope of the CO2 response curve represents the sensitivity of the entire respiratory apparatus to PaCO2.
§ Decreased response to carbon dioxide—shifts the CO2 response curve down and to the right.
§ Increased apneic threshold—the PaCO2 at which a patient is stimulated to breathe
o Assisted ventilation does not significantly offset the rise in PaCO2. The apneic threshold is usually 3-5 mmHg below the PaCO2
maintained during spontaneous ventilation. If ventilation is assisted to below the apneic threshold, the patient simply will not
breathe. If the PaCO2 has risen to 55 mmHg, and you assist the patient you will only be able
to reduce the PaCO2 to 50-52 mmHg before they stop breathing. To reduce the PaCO2
further would require controlled ventilation.
o a right shift implies that for a given PaCO2 the minute ventilation would be less than
predicted. This creates a respiratory acidosis.
o A left shift implies that for a given PaCO2 the minute ventilation would be more than
predicted. This creates a respiratory alkalosis.
o These acid-base disturbances are effects, and not causes, of the shifted curves.

• Impairment of Motor Neuron Output and Muscle Tone to Upper Airway and Respiratory Muscles
o Impairment of airway dilator muscles such as the genioglossus or tensor palatine leads to upper airway obstruction.
o Impairment of pulmonary muscles decreases FRC and the effectiveness of ventilation.
• Airway Resistance
o the halogenated agents are bronchodilators, however, in the absence of increased airway resistance, this effect is minimal.
Pulmonary Effects: PaO2
• The peripheral chemoreceptors in the carotid bodies monitor for hypoxemia and are important in the hypoxic ventilatory response. A PaO2 < 60 mmHg is
a stimulus to increase minute ventilation in an effort to restore arterial oxygenation.
• The carotid bodies relay afferent input to the respiratory center via the glossopharyngeal nerve (CN IX) and the aortic bodies relay afferent traffic via the
vagus nerve (CN X).
• While the carotid bodies are more sensitive to change in arterial gas tensions (PaO2, PaCO2) and H+ concentration, the aortic bodies are more sensitive to
changes in blood pressure.
• It is important to note that volatile agents also depress ventilation by inhibiting muscle function in the upper airway, diaphragm, and intercostals.
• Effects of Anesthetic Agents
o Volatile anesthetics impair the peripheral chemoreceptors for up to several hours after anesthesia.
o The impaired response to acute hypoxia occurs at 0.1 MAC. By contrast, 0.1 MAC does not impair the response to PaCO2.
o The glomus type I cells in the carotid bodies provide the sensory arm of the hypoxic drive.
o It is hypothesized the volatile agents create a reactive oxygen species that impairs the glomus type I cells.
o Because anesthetic metabolism is the source of these reactive oxygen species, those agents that undergo the greatest amount
of biotransformation in the body inhibit the hypoxic drive the most (Sevo > Iso> Dex)
o For example, 40% of halothane undergoes hepatic biotransformation, so it makes sense that halothane depresses the hypoxic
drive the most.
o Only 0.02% of desflurane undergoes metabolism, and it impairs the hypoxic drive the least.
o Nitrous oxide also impairs the carotid body response to hypoxemia, but likely for a different reason.
o The physiology is especially important in the patient who relies on the hypoxic drive to breathe, such as those with emphysema
or sleep apnea. Desflurane is the best agent in this patient.
o In contrast to their effects on the ventilator response to CO2, pain and surgical stimulation do not reverse depression of the
hypoxic ventilator drive.

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Neurophysiologic Effects

• Volatile agents affect: CMRO2, CBF, cerebral blood volume, autoregulation, and CSF dynamics.
• Cerebral Metabolic Rate
o CMRO2 is dependent on:
§ 1. Electrical activity (60%)
§ 2. Cellular homeostasis (40%)
o volatile anesthetics reduce CMRO2, but only to the extent that they reduce electrical activity. Once the brain is isoelectric,
volatile agents cannot reduce CMRO2 any further.
o 1.5-2.0 MAC is required to produce an isoelectric state.
o Sevoflurane in high concentration (2.0 MAC) can produce seizure activity. this is exacerbated by hypocapnia and is more
common in pediatric inhalation induction.
• Cerebral Blood Flow
o The brain matches its blood flow with its metabolic requirement.
§ When metabolic demand increases, the blood vessels dilate (cerebrovascular resistance decreases).
§ When metabolic demand decreases, the blood vessels constrict (cerebrovascular resistance increases).
o We’ve already established that volatile anesthetics are cerebral vasodilators (they decrease CVR).
o Therefore, there are two competing factors at play: vasoconstriction from the reduction in CMRO2 and vasodilation from the
anesthetic agent. The net effect is a dose dependent increase in cerebral blood flow, cerebral blood volume, and ICP.
o Mild hyperventilation and/or concurrent administration of propofol, opioids, or barbiturates partially offset the vasodilatory
effects.
o Nitrous oxide is different. It increases CMRO2 and cerebral blood flow.
• Cerebral Autoregulation
o The cerebral vasculature continuously adjusts vessel diameter to maintain a constant cerebral blood flow between cerebral
perfusion pressure of 50-150 mmHg.
o Volatile anesthetics disrupt autoregulation in a dose-dependent fashion. Cerebral blood flow becomes increasingly dependent
on blood pressure as the concentration of the volatile agent is increased.
• Cerebrospinal Fluid Volume

o The tendency of the volatile anesthetics to affect CSF dynamics is

greatly overshadowed by their ability to increase CBF.
• Evoked Potential Monitoring
o Evoked potentials are used to monitor the integrity of a neural pathway. There
are 4 types of evoked potentials:
§ 1. Somatosensory (SSEP)
§ 2. Motor (MEP)
§ 3. Visual (VEP)
§ 4. Brainstem auditory (BAEP)
o evoked potentials are produced by applying current to a neural pathway. For example, SSEPs are produced by applying current to a peripheral
nerve—most commonly the ulnar n. or tibial n. The electrical current travels from the peripheral nerve to the contralateral side of the cerebral
cortex.
§ SSEPs monitor the integrity of the dorsal column (medial lemniscus). It is perfused by the posterior spinal arteries.
§ MEPs monitor the integrity of the corticospinal tract. This region of the cord is perfused by the anterior spinal artery.
§ SSEPs do not monitor the anterior cord, and therefore aren’t interchangeable with MEPs.
o We are most concerned with two components of the evoked potential waveform:
§ 1. Amplitude (strength of the nerve response)
§ 2. Latency (speed of nerve conduction)
§ Hypoxia, hypercarbia, and hypothermia also disrupt amplitude and
latency.
§ Nerve ischemia also decreases amplitude and increases latency. So we
don’t confuse the issue, we either omit or reduce our use of volatile
agents in favor of an intravenous technique.
• Effects of Volatile Agents
o Desflurane, isoflurane, and sevoflurane produce a dose-dependent effect
on evoked potentials. They:
§ Decrease amplitude
§ Increase latency
o The addition of nitrous oxide to a halogenated anesthetic agent can lead to a more profound amplitude reduction. Therefore,
N2O should not be sued during evoked potential monitoring.
• Sensitivity of Each Modality to Volatile Agents
o Visual evoke potentials are the most sensitive to volatile anesthetics
o Brainstem evoked potentials are the most resistant to volatile anesthetics
o SSEPs and MEPs are somewhere in between.

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Intravenous Drugs

Propofol

• Propofol Kinetics
o At time= 0, all of the injected propofol is in the blood
o The blood concentration (Cp) declines over time.
o There is rapid distribution from the blood to the vessel rich group.
o The brain concentration peaks at ~ 1 min.
o Next, there is redistribution from the VRG to the muscle and fat.
o Awakening is due to redistribution out of the brain.
• Cardiovascular Effects
o Decreased BP (due to decreased SNS tone and vasodilation)
o Decreased SVR
o Decreased venous toneàdecreased preload
o Decreased myocardial contractility
• Respiratory Effects
o Shifts CO2 response curve down and to the right (less sensitive to CO2)àrespiratory depression and/or apnea
o Inhibits hypoxic ventilatory drive
• CNS Effects
o Decreased
§ Cerebral metabolic rate of oxygen
§ Cerebral blood flow
§ Intracranial pressure
§ Intraocular pressure
o No analgesia
o Anticonvulsant properties
§ Myoclonus may occur
§ There are a few reported cases of propofol inducing seizures, but these are very rare exceptions.
• Other
o Propofol infusions can change the color of the urine:
§ Green urine= phenol excretion
§ Cloudy urine = increased uric acid excretion (does not suggest renal impairment or infection)
o Antioxidant properties-free radical scavenging properties
• Allergic Reaction
o Despite concerns that propofol might precipitate anaphylaxis in patients allergic to egg, soy,and/or peanuts, there is a gross lack of evidence to justify these
fears. This can be a confusing subject, so listen up!
o The problem begins with lecithin, an emulsifier derived from eggs, soy, and peanuts.
o Egg:
§ Most people with egg allergy alre allergic to the albumin in egg whites. Egg lecithin is derived from the yolk.
§ There is no good evidence to support cross-sensitivity in egg allergic patients.
§ Propofol is probably safe to administer to patients with egg allergies.
o Soy:
§ Any soy proteins that are capable of producing an immune response are removed during the refining process.
§ Propofol is safe to use in patients with soy allergy.
o Peanut:
§ Like soy, peanuts are a type of legume. Some have speculated the potential of cross-sensitivity between peanuts and soy (and thus propofol),
although there is no evidence to support this.
§ Propofol is safe to use in patient with a peanut allergy.
o The bottom line is that propofol may be safely administered to patients allergic to soy, peanuts and probably egg.

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• Propofol Infusion Syndrome
o Propofol contains long chain triglycerides, and an increased LCT load impairs oxidative phosphorylation and fatty acid metabolism. This starves cells
of oxygen, particularly in cardiac and skeletal muscle. Propofol infusion syndrome is associated with a high mortality rate.
o Risk Factors:
§ Propofol dose > 4 mg/kg/hr (67 mcg/kg/min)
§ Propofol infusion duration >48 hours
§ Children > adults
§ Inadequate oxygen delivery
§ Sepsis
§ Significant cerebral injury
o Clinical presentation includes acute refractory bradycardia àasystole + at least one of the following:
§ Metabolic acidosis (base deficit > 10 mmol/L)
§ Rhabdomyolysis
§ Enlarged or fatty liver
§ Renal failure
§ Hyperlipidemia
§ Lipemia (cloudy plasma or blood) may be an early sign
o Treatment: discontinue propofol, maximize gas exchange, cardiac pacing, PDE inhibitors, glucagon, ECMO, and/or renal replacement therapy.
• Contamination
o Propofol supports bacterial and fungal growth, therefore strict attention to asepsis must be observed while withdrawing the drug from the vial.
Additionally, the vial and rubber stopper must be cleansed with 70% isopropyl alcohol before removing the drug.
o You must know how long propofol lasts in a syringe as well as an infusion after the rubber stopper has been violated:
§ Syringe (drug removed from vial)=must be discarded within 6 hours
§ Infusion (drug remains in vial)=must be discarded with 12 hours (this includes the tubing)
• Preservatives
o Branded propofol (Diprivan), contains EDTA (disodium ethylenediamine tetraacetic acid) as a preservative. It does not cause bronchial irritation.
o Generic propofol formulations contain different preservatives, and these can cause unique problems of their own.
§ Metabisulfite can precipitate bronchospasm in asthmatic patients
§ Benzyl alcohol should be avoided in infants.
• Pain on Injection
o Propofol injection pain can be minimized or eliminated by:
§ Injecting into a larger and more proximal vein
§ Lidocaine (before propofol injection or mixed with propofol)
§ Giving an opioid prior to the propofol
• Antipruritic Effect
o Propofol (10mg IV) can reduce itching caused by spinal opioids and cholestasis.
• Antiemetic Effect
o Propofol (10 – 20 mg IV) can be used to treat PONV. An infusion of 10mcg/kg/min can also be used.
Fospropofol

• Genital and anal burning are nasty side effects of fospropofol. No joke!

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Ketamine

• Cardiovascular Effects
o Increased
§ SNS tone (useful if the patient is hemodynamically unstable, but harmful if severe CAD)
§ Cardiac output
§ Heart rate
§ Systemic vascular resistance
§ Pulmonary vascular resistance (caution if severe RV failure)
o Subhypnotic doses (<0.5 mg/kg) usually don’t activate the SNS
o It’s important to understand the ketamine is actually a myocardial depressant. The cardiovascular effects discussed above require an intact SNS. The
myocardial depressant effects will be unmasked in patients with depleted catecholamine stores (sepsis) or sympathectomy.
• Respiratory Effects
o Bronchodilation (great choice if the patient is actively wheezing)
o Upper airway muscle tone and airway reflexes remain intact
o Maintains respiratory drive, although a brief period of apnea may occur following induction
o Does not significantly shift the CO2 response curve
o Increased oral and pulmonary secretions (glycopyrrolate helps) Other
• CNS Effects
o Increased • Subhypnotic dosing is gaining traction in the
§ Cerebral metabolic rate of oxygen treatment of severe depression (off-label use)
§ Cerebral blood flow • Chronic ketamine use can cause ulcerative cystitis
§ Intracranial pressure • When compared to the other induction agents,
§ Intraocular pressure ketamine undergoes the smallest amount of plasma
§ EEG activity (caution if hx of seizure) protein binding (12%)
o Nystagmus (caution during ocular surgery that requires a still eye) • While we’re at it, here’s the plasma protein binding
o Emergence delirium: numbers for the rest of the IV anesthetics:
§ Presents as nightmares and hallucinations (risk persists for up to 24 hours) o Propofol=98%
§ Benzodiazepines are the most effective way to prevent emergence o Diazepam=98%
delirium (midazolam is better than diazepam) o Midazolam=94%
§ Risk factors: age > 15 years, female gender, ketamine dose > 2mg/kg, hx of o Dexmedetomidine=94%
personality disorder o Lorazepam=90%
• Analgesia o Etomidate=75%
o Provides good analgesia & opioid-sparing effect (the only induction agent that does o Ketamine=12%
this).
o Relieves somatic pain > visceral pain
o Blocks central sensitization and wind-up in the dorsal horn of the spinal cord
o Prevents opioid induced hyperalgesia (after remifentanil infusion)
o Analgesic properties make it good for burn patients (frequent dressing changes) and those with pre-existing chronic pain syndromes.

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Etomidate

• Cardiovascular Effects
o Etomidate’s key benefit is hemodynamic stability. (minimal change in HR, SV, or CO).
o SVR is decreased, which accounts for a small reduction in BP.
o It does not block the SNS response to laryngoscopy. An opioid or esmolol will help.
• Respiratory Effects
o Mild respiratory depression (less than propofol and barbiturates)
• CNS Effects
o Decreased
§ Cerebral metabolic rate for oxygen
§ Cerebral blood flow (cerebral vasoconstriction)
§ Intracranial pressure
o Cerebral perfusion pressure remains stable
o No analgesia
• Myoclonus
o Myoclonus is described as involuntary skeletal muscle contractions, dystonia, or tremor.
o Although the exact mechanism of myoclonus is unclear, it is likely due to an imbalance between excitatory and inhibitory pathways
in the thalamocortical tract. It is NOT a seizure.
o What’s the relationship between myoclonus and seizures?
§ If the patient does not have a history of seizures, then etomidate does not increase the risk of seizures.
§ If the patient has a history of seizures, then etomidate can increase epileptiform (seizure like) activity and possibly increase
the risk of seizures.
• This property can make it useful for mapping seizures foci
• Adrenocortical Suppression
o Cortisol and aldosterone synthesis are dependent on the enzyme 11-beta-hydroxylase (located in the adrenal medulla). Some texts
also add 17-alpha-hydroxylase.
§ Etomidate is a known inhibitor of 11-beta-hydroxylase and 17-alpha-hydroxylase.
§ A single dose of etomidate suppresses adrenocortical function 5-8 hours (some books say up to 24 hours)
§ For this reason, etomidate should be avoided in patients reliant on the intrinsic stress response (sepsis or acute adrenal failure). These
patients need all of the cortisol they can muster.
§ This is also why etomidate is not used as a long-term continuous infusion in the ICU
§ Mortality may be increased by etomidate, particularly in patients with sepsis
§ The benefits of a stable induction should be weighted against the possibility for increased mortaility.
• Nausea and vomiting
o PONV is more common with etomidate then with any other induction agent (incidence may be as high as 30-40%)
• Acute Intermittent Porphyria
o ALA synthase is a key enzyme in porphyrin metabolism. This is covered in great detail on the next page.
§ Etomidate should be avoided in patients with a history of acute intermittent porphyria.

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Barbiturates

• Medicinal Chemistry
o Although you may never administer a barbiturate in your career, their historical relevance makes them fair game for the NCE.
o Barbiturates are derived from barbituric acid. Substitutions on the ring can modify the PK/PD profile for each drug.
o Thiobarbiturates:
§ There is a sulfur molecule in the second position (increases lipid solubility and potency)
§ Examples: thiopental, thiamylal
o Oxybarbiturates
§ There is an oxygen molecule in the second position
§ Example: methohexital, pentobarbital
o Other Substitutions:
§ Adding a methyl group on the nitrogen lowers the seizure threshold and increases potency (methohexital)
§ Adding a phenyl group at the 5 carbon increases the anticonvulsant effect (phenobarbital)
o We are going to focus our discussion on thiopental, and then we’ll highlight key facts about the others at the end.
Thiopental

Active metabolite

• After normal dose: none

• After high dose: pentobarbital
Respiratory Effects

• Respiratory depression (shifts the CO2

response curve to the right)
• Histamine release can cause
bronchoconstriction (caution with asthma)

o Cardiovascular Effects
§ Hypotension is primarily the result of venodilation and decreased preload; myocardial depression is a secondary cause
§ Thiopental causes non-immunogenic histamine release. This can also contribute to hypotension, however the effect is short-lived.
§ The baroreceptor reflex is preserved, so a reflex tachycardia helps restore cardiac output.
§ Compared to propofol, thiopental produces less hypotension.
o CNS Effects
§ Decreased
• CMO2
• CBF (cerebral vasoconstriction)
• ICP (used in the treatment of intracranial HTN)
Other Barbiturates
• EEG activity (can cause burst suppression and/or isoelectric EEG)
§ No analgesia ( low dose may increase the perception of pain) • Methohexital is the gold-standard for electroconvulsive
§ Neuroprotection: therapy. It decreases the seizure threshold and produces a
• Focal ischemia: Yes (examples: CEA, temporary occlusion of cerebral better quality seizure.
arteries) • Methohexital induction dose = 1-1.5mg/kg
• Global ischemia: No (example: cardiac arrest)
• Phenobarbital is excreted unchanged in the urine (all of the
o Acute Intermittent Porphyria
others are metabolized by hepatic P450 enzymes).
§ The porphyrias can be classified as acute or cutaneous.
• Acute intermittent porphyria is the most common (and dangerous) type.
• Porphyria is caused by a defect in heme synthesis that promotes the accumulation of heme precursors.
• Heme is a key component of hemoglovin, myoglovin, and the cytochrome P45- enzymes.
Succinyl-CoA + GlycineàALA synthaseàprecursorsàHeme
§ Any drug or condition that induces ALA synthase will accelerate the production of heme precursors and thereore must be avoided in the patient with
acute intermittent porphyria.
• Drugs to avoid: barbiturates, etomidate, glucocorticoids, and hydralazine
§ Acute intermittent porphyria presents as abdominal pain, psychiatric symptoms, delirium, seizures, neuropathy, and coma.
§ Anesthetic Management
• Liberal hydration
• Glucose supplementation (reduces ALA synthase activity)
• Heme arginate (reduces ALA synthase activity)
• Prevention of hypotehermia
• Acute intermittent porphyria is made worse by stimulation of ALA synthase, emotional stress, prolonged NPO status, and CYP450 induction.
o Intra-arterial Injection
§ Intra-arterial injection à intense vasoconstriction + crystal formation (occludes blood flow) + inflammation àtissue necrosis
§ Treatment
• Injection of vasodilator: phentolamine or phenoxybenzamine
• Sympathectomy: stellate ganglion block or brachial plexus block

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Dexmedetomidine

• Cardiovascular Effects
o The most common side effects are bradycardia and hypotension.
o Rapid administration of dexmedetomidine can cause hypertension (alpha-2 stimulation in the vasculature àvasoconstriction).
This direct effect occurs before the centrally mediated reduction in SNS tone. Once the CNS effect kicks in, the central alpha-2
effect will overpower the peripheral alpha-2 effect. This explains why hypertension (if it occurs at all) is usually short-lived.
• Respiratory Effects
o Dexmedetomidine does not cause respiratory depression, and this makes it attractive for procedural sedation and sedation
during difficult airway management.
§ No change in oxygenation
§ No change in blood pH
§ No change in the slope of the CO2 resposne curve
• CNS Effects
o Decreased CBF
o No change in CMRO2 (there is uncoupling between CMRO2 and CBF)
o No change in ICP
• Dexmedetomidine is unique, because it produces sedation that resembles natural sleep.
o Sedation is the result of decreased SNS tone and decreased level of arousal.
o Patients are easily aroused.
o It does not provide reliable amnesia.
• Other Effects
o Dexmedetomidine impairs the thermoregulatory response, so it produces an antishivering effect (patients who should shiver
don’t ).
o It reduces the incidence of emergence delirium in children.
o Analgesia is produced by alpha-2 stimulation in the dorsal horn of the spinal cord ( decreased substance P and decreased
glutamate release)
o It does not impair evoked potentials
o It is useful for a “wake-up” test (scoliosis surgery)
o The nasal and buccal routes have a high degree of bioavailability. This makes it useful for preoperative sedation in children (3-4
mcg/kg 1 hour prior to surgery).

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Benzodiazepines

• We are going to focus discussion on midazolam, and then we’ll highlight key facts about the others at the end.

• Cardiovascular Effects
o Sedation dose: minimal effects
o Induction dose: decreased BP and decreased SVR
• Respiratory Effects
o Sedation dose: minimal effects
o Induction dose: respiratory depression
o Opioids potentiate the respiratory depressant effects, even at doses used for sedation
o Patients with COPD are more sensitive to the respiratory depressant effects
• CNS Effects
o Sedation dose: minimal effects on CMRO2 and CBF
o Induction dose: decreased CMRO2 and CBF
o Cannot produce isoelectric EEG (propofol and barbiturates can)
o Anterograde amnesia
o Anticonvulsant
o Anxiolysis
o Spinally mediated skeletal muscle relaxation (antispasmodic—useful for the patient with cerebral palsy)
• Diazepam
o Diazepam undergoes enterohepatic recirculation, which explains why it remains in the body for such a long time (elimination t1/2 = 43 hrs)
o It can be used as an anticonvulsant and also as a preventative measure against emergence delirium following ketamine.
o It’s useful as an antispasmodic agent (it treats skeletal muscle spasticity).
o It reduces skeletal muscle tone at the level of the spinal neurons (it does not affect the physiology of the neuromuscular junction).
• Lorazepam
o Lorazepam’s amnestic action can persist for up to 6 hours
o It has a slow onset, which limits its usefulness as an anticonvulsant
• Other Key Facts
o Relative potency (greatest to least): lorazepam > midazolam > diazepam
o Benzodiazepines provide anterograde amnesia (they impair memory after the drug was administered)
o They do NOT provide retrograde amnesia ( they do NOT impair memories created before the drug was administered). In fact, non of our anesthetic drugs
provide retrograde amnesia.
o Propylene glycol is added to diazepam and lorazepam to enhance water solubility. This additive causes venous irritation (diazepam > lorazepam).
o Midazolam does not require propylene glycol, because it contains an imidazole ring (the imidazole ring makes it water soluble inside the vial and lipid
soluble in the bloodstream).
Flumazenil

• Flumazenil is a competitive antagonist of the GABA-A receptor

o It has a very high affinity, but it has a short duration of action (30-60 min)
o For this reason, repeat dosing may be necessary to prevent resedation.
o The initial dose 0.2 mg IV and titrated in 0.1 mg increments q 1 min.
• Side Effects:
o Unlike post-operative opioid reversal with naloxone (which can cause a profound increase in SNS tone), post-operative benzodiazepine reversal with
flumazenil does NOT increase SNS tone, anxiety, or neuroendocrine evidence of stress.
o In benzodiazepine dependent patients (chronic use), flumazenil reversal can precipitate signs of withdraw, including seizures.
o Flumazenil tends to reverse the sedative effects more than the amnestic effects of benzodiazepines.

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Pharm Notes

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EQUIPMENT & MONITORING

ANESTHESIA MACHINE

• The Anesthesia Machine as Three Pressure Systems

o Before we delve into the anesthesia machine, let’s acknowledge a few truths. With the diversity of anesthesia machines in
practice (both ancient and modern), it is impossible to know the idiosyncrasies of them all. What’s important, however, is that
you must be able to use any of them to provide a safe anesthetic. So with this in mind, you’ll find that the safe use of the
anesthesia machine is the prevailing theme of this tutorial. As we discuss points related to safety, we’ll also review the relevant
components of the anesthesia machine.
o The anesthesia machine can be divided into the high, intermediate, and low pressure systems. You must know everything on
this chart!

• Leak Tests—What are you Testing?

o Low Pressure Leak Test (Negative Pressure Test)
§ The low pressure leak test (negative pressure test) assesses the integrity of the low pressure circuit from the flowmeter valves to the
common gas outlet. This test is performed by attaching a bulb to the common gas outlet and creating negative pressure. The low
pressure system fails the test if the bulb inflates within 10 seconds.
• The fresh gas flow must be off.
• If there is a minimum FGF when the machine is turned on, then the machine must be turned off.
• The ventilator should be off.
• The vaporizers should be off at first, but then the test should be repeated as each vaporizer is turned on.
Indeed, the negative pressure test is the best way of detecting a vaporizer leak.
o High Pressure Leak Test
§ The high pressure leak test is conducted by closing the APL valve, pressurizing the circuit to 30cm/H2O, and observing the airway
pressure gauge (the pressure should remain constant).
§ The presence or absence of a check valve determines which components of the low pressure system are tested. If a check valve is
present (in many Ohmeda machines), it’s usually downstream from the vaporizer and upstream from the O2 flush valve. The check
valve is open in the absence of back pressure and closed when back pressure is applied (ex: pressing the O2 flush).
• If the machine does NOT have a check valve, this test assesses the breathing circuit and the entire low pressure system.
• If the machine has a check valve, this test assesses the breathing circuit and the low pressure system up to the check
valve. It does NOT assess for a leak between the check valve and the rest of the low pressure system.
• The SPDD Model: Supply, Processing, Delivery & Disposal
o The SPDD model is an alternative way to describe the architecture of the anesthesia machine. It details the path gases flow as they enter the OR
suite, travel through the anesthesia machine and breathing circuit, and finally exit the operating room.
o This nomenclature is not based on pressure, but rather it describes the location of each gas handling component.
o Components of the SPDD Model
§ Supply
• How the gases enter the anesthesia machine
• Location- Pipeline to the back of the anesthesia machine
§ Processing
• How the anesthesia machine prepares the gases before they are delivered to the patient
• Location – inside the machine up to the common gas outlet
§ Delivery
• Hot the prepared gases are brought to the patient
• Location – breathing circuit
§ Disposal
• How the gases are removed from the operating room
• Location – Scavenging system

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• We color coded the diagram to give you a clear understanding of the 5 tasks of oxygen.
• Keep in mind that this is only a generalization, and some anesthesia machines may not use oxygen for all 5 tasks. For example, a piston driven gas.
• Preventing Gas Connection Errors on the Anesthesia Machine: DISS & PISS
o You need to be sure that the gases you attach to the anesthesia machine are the correct ones in the correct locations. Mistakes
are life threatening! But the old saying “if there is a will there is a way” holds true even in this seemingly simple situation. For
this reason, each gas connection has its own unique identifier that codes for a each gas.
o Pin Index Safety System
§ The PISS prevents inadvertent misconnections of gas cylinders. The pin configuration on each hanger yoke assembly is
different for each gas, making unintended connections of the wrong gas unlikely, but not impossible. The presence of
more than one washer between the hanger yoke assembly and the stem of the tank
may allow the PISS to be bypassed.
§ PISS configurations:
• Air=1, 5
• Oxygen = 2,5
• Nitrous oxide = 3, 5
§ Diameter Index Safety System
• The DISS prevents inadvertent misconnections of gas hoses. Each gas hose
and connector are sized and threaded for each individual gas.
• Gas Cylinders: Must Know Information
o Chances are that many of you will face a question like this during boards.
o The oxygen cylinder on the back of the anesthesia machine must be turned OFF when not in use.
The only time it should be turned on is when you are NOT using the oxygen from the pipeline. If
you lose pipeline pressure and the oxygen cylinder was left open, you would use the cylinder
oxygen without knowing it. By the time the failsafe alarms, your backup oxygen supply would be
empty!

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• World Health Organization (international) Colors
o Air=black and white
o Oxygen = white
o Nitrous oxide = blue
• How Many Minutes are left in the tank?
o Know this 2-step calculation!

o In this example, we told you that the pressure gauge reads 500 psi with an oxygen flow rate of 2L /min. it is assumed that we
know that a full oxygen E cylinder contains 660 L at a pressure of 1900 psi. Therefore, it is so critical that you memorize the
entire page!
§ 1. 660 L = Contents Remaining (X) = 174 L
1900 psi 500 psi
§ 2. 174 L = 87 minutes
2 L/min
§ * if you used 2000 psi, the correct answer is 83 minutes. Indeed, some books say 1900 psi (Nagelhout) and others say
2000 psi. we would expect that the NCE would accept both answers.
• What about Nitrous Oxide?
o This calculation does not work for nitrous oxide, because N2O exists as both a liquid and a gas inside the cylinder. As long as
liquid remains in the cylinder, the partial pressure measured by the bourdon pressure gauge will read 745 psi. the pressure will
begin to decrease only after all the liquid is gone and only gas remains. At this point, approximately 250 L of N2O remains in the
tank. Therefore, it’s wise to change the tank any time the psi falls below 745 psi.
o The only reliable method to determine the volume of nitrous oxide that remains in the tank is to weigh it. We’ve never met
anyone that’s done this.

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Safe Handling of Gas Cylinders

o The gas inside a full cylinder possesses a significant amount of potential energy. If the cylinder is damaged in such a way that
allowed the gas to escape rapidly, there is a huge potential to injure yourself or the patient.
• Rules for Safe Handling of Cylinders
o Determine what is inside the cylinder by its label and NOT by its color.
o The cylinder valve is the most delicate part of the cylinder – protect it! If the cylinder is damaged, it may take off like a missile.
o Under normal circumstances, gas cylinders must be stored in the upright position AND secured. When changing the cylinder on
the anesthesia machine, however, it is appropriate to temporarily place the old cylinder on its side until it can be moved to its
appropriate storage receptacle (see point #2).
o Don’t leave an empty cylinder on the machine. This is just poor form.
o If you do not have a cylinder to use as a replacement, be sure to insert a yoke plug. This is a backup plan in case the check valve
fails. If the check valve fails and there is no cylinder or yoke plug present, gas that should be going to the patient will exit the
anesthesia machine.
o You should remove the plastic cover from the port before installing the cylinder. Failure to do so may obstruct gas flow when
the cylinder is turned on.
o Placing more than one washer between the cylinder and the hanger yoke assembly may bypass the PISS and allow the wrong
cylinder to be matched up with the wrong hanger yolk assembly.
o Never take a cylinder into the MRI scanner unless it is made of a non-magnetic material, such as aluminum. An MRI safe
cylinder will have two colors: most of the tank is silver and only the top is the color that signifies the gas it contains.
o The fire triad consists of an oxidizer, a fuel, and an igniter. Oiling the cylinder valve increases the risk of fire by combining
oxygen or nitrous with the oil. Only a heat source is needed to complete the triad.
o The cylinder should always be opened slowly. If the gas travels quickly between the valve and the yoke, its rapid re-expansion
may generate a significant source of heat; and furthermore, the heat will not be able to exit the space. This is an example of an
adiabatic process ( a situation where heat is neither gained nor lost from the environment). Dust or debris between the tank
and the yoke can fuel a fire or an explosion.
• Prevention of Cylinder Explosion
o Gas cylinders should never be exposed to temperatures higher than 130 F or 57 C. Temperatures higher than this may lead to a
fire or explosion. In the event of an environmental fire, there is a safety relief device built into the cylinder that allows the
cylinder to empty its contents in a slow and controlled way. Examples of safety relief devices include:
§ A fusible plug that melts at elevated temperatures. It is typically made from Wood’s metal: bismuth, lead, tin, and
cadmium (remember BLT with cheese)
§ A valve that opens at elevated pressures
§ A frangible disk that ruptures under pressure
o If the yoke-retaining screw punctures the safety relief valve, it may damage the cylinder causing it to leak.

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• Oxygen Pressure Failure Device: Failsafe Device
o The main purpose of the oxygen pressure failure device is to monitor for and protect against low oxygen pressure in the anesthesia machine.
This feature will alert you about a depleted oxygen tank a drop in pipeline pressure, or a disconnected oxygen hose.
o The term “failsafe” is a misnomer, as a pipeline crossover can still produce a hypoxic mixture. Again, it is the pressure in the oxygen supply line
(not oxygen concentration) that is responsible for maintaining the fail-safe valve in
the open position.
o The failsafe device resides in the intermediate pressure system and consists of two
components:
§ 1. A threshold alarm that sounds wen the oxygen pipeline pressure falls
below 28-30 psi.
§ 2. A pneumatic device that reduces and/or stops the flow of nitrous
oxide when pressure in the oxygen pipeline falls below 20 psi.
o oxygen is the only gas that passes directly from its source to its flow valve at the
flowmeter. All the other gases must first encounter a fail-safe valve before it enters
its flowmeter. For sake of completeness, we should mention that there are some
newer machines that do not require air to pass through a failsafe valve this allows
the patient to be ventilated with air if an oxygen supply is not available.
o Two Types of Oxygen Pressure Failure Devices
§ Oxygen Failsafe Device (GE Datex-Ohmeda)
• An oxygen pressure <20 psi will completely stop the flow of
nitrous oxide.
• This is an “all or nothing” response.
• If oxygen pressure >20 psi, nitrous oxide flow is allowed.
• If oxygen pressure < 20 psi, nitrous oxide flow is stopped.
• Some newer GE Datex-Ohmeda machines, such as the Aestiva/5, allow variable flow based on pipeline oxygen pressure.
§ Oxygen Failure Protection Device (Drager)
• As pipeline oxygen pressure decreases, there is a proportionate reduction of nitrous oxide flow.
• The flow of nitrous oxide is stopped only when oxygen pressure is extremely low.
§ How can you tell the oxygen failure pressure failure safety device is working?
§ Turn ON the oxygen and nitrous oxide flow. Next, make sure the backup oxygen cylinder is closed, and then remove the source of
oxygen pressure by disconnecting the oxygen pipeline. As you remove the oxygen source, be sure to observe the flowmeters. The
nitrous oxide flow should stop just before the oxygen flow stops. Reintroducing the oxygen supply to the anesthesia machine should
result in both gases restored to their previous flow rates.
• Hypoxia Prevention Safety Device: Proportioning Device
o Let’s clear up any confusion once and for all—the oxygen pressure failure device and the hypoxia prevention safety device are
NOT the same thing.
Oxygen Pressure Failure Device Hypoxia Prevention Safety Device
What It Is Fail-safe device Proportioning device
How It Works Shuts off and/or proportionately reduces N2O Prevents you from setting a hypoxic mixture with the
flow if O2 pressure is < 30 psi flow control valves

Limits the N2O flow to 3 times O2 flow

o The hypoxia prevention safety device prevents you from setting a hypoxic mixture with the flow control valves. When you are administering
nitrous oxide, the proportioning device ensures that FiO2 never drops below 25%. If at any point you are administering nitrous oxide with
oxygen and you increase the oxygen flow, one of two things will happen: some machines will automatically increase nitrous oxide to preserve
the same gas concentrations, while others will leave the nitrous oxide flow unchanged and require you to increase the nitrous oxide flow
manually.
o Two Types of Proportioning Devices
§ Link 25 System (GE Datex-Ohmeda)
• The oxygen and nitrous oxide flowmeter valves are mechanically linked by a chain (mechanical component).
• It incorporates a second stage regulator for oxygen and nitrous oxide (pneumatic component)
• If you adjust the flow control valves in such a way that it would create a hypoxic mixture, a gear engages and oxygen flow
is automatically increased.
§ Oxygen Ratio Monitor Controller (Drager)
• Oxygen and nitrous oxide flow are connected pneumatically
• If you adjust the flow control valves in such a way that it would create a hypoxic mixture, the supply pressure of nitrous
oxide going to the flowmeter will be reduced to maintain the 3:1 ratio.
o When Proportioning Devices Can’t Prevent a Hypoxic Mixture
§ Oxygen pipeline crossover
§ Leaks distal to the flowmeter valves
§ Administration of a third gas (helium)
§ Defective mechanic or pneumatic components
o With the wide variety of anesthesia machines currently in use, you must be aware we have cited broad generalizations from the textbooks. It is
up to you to become familiar with the specific anesthesia machines in your practice.

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• Flowmeters & Reynolds Number
o Opening the flowmeter valve (flow control valve) allows fresh gas to enter the flowmeter. The traditional flowmeter, otherwise
known as a Thorpe tube, is the beginning of the low pressure system. It controls and measures the fresh gas flow that travels
towards the vaporizers and common gas outlet.
o Important Architecture
§ There are several things you must know about flowmeter design.
• Annular space=area between float and side wall of the flowmeter
• Internal diameter=narrowest at base and widest along it ascent
• A “variable orifice” architecture provides a constant gas pressure
throughout a wide range of flow rates.
§ The position of the indicator float is determined by two opposing forces:
• The fresh gas flow pushes the indicator float up.
• Gravity pulls the indicator float down.
§ There are 4 types of floats: skirted, plumb bob, nonrotating, and ball. The flow measurement is taken at the widest
part of the float.
• Read at the top: skirted, plumb bob, and nonrotating
• Read in the middle: ball
o Flowmeter Leak
§ A flowmeter leak can create a hypoxic mixture. This is
problematic, because the flowmeters are distal to all the safety
devices except the oxygen analyzer.
§ The position of the flowmeters is important. Here’s why…
§ Top Images:
• O2 can escape through a leak, but N2O does not.
§ Middle Images:
• N2O can escape through a leak, but O2 does not.
• N2O flow prevents O2 from going “backwards.”
§ Bottom Images:
• A leak in the O2 flowmeter can create a hypoxic mixture
§ The key point is that the O2 flowmeter should be positioned all the way to the
right (closest to the common gas outlet). This minimizes, but does not eliminate,
the risk of a hypoxic mixture in the event of a flowmeter leak.
§
o Laminar Flow, Turbulent Flow & Reynolds Number
§ The flow rate through the tube determines whether the gas flow is laminar or turbulent, and this can be predicted by
Reynolds number.
§ Re<2.000 àlaminar flow (dependent on gas viscosity—Poiseuille equation)
§ Re > 4,000 àturbulent flow (dependent on gas density – Graham’s law)
§ Re 2,000-4,000 àtransitional flow
o In the context of Thorpe tube flow dynamics, a low fresh gas flow will favor a laminar flow pattern. At a higher fresh gas flow,
the annular space acts like an orifice, creating a turbulent flow pattern.
• Flowmeter FiO2 Calculation
o Don’t miss the opportunity to answer easy questions! Here is how to calculate FiO2.

1. Question: You are administering air 1 L/min and oxygen 3L/min. calculate the fraction of inspired oxygen. (enter your number as a
percentage)
o In this question, you are delivering air 1L/min and oxygen 3L/min.
§ FiO2 = (1 x 21) + (3 x 100) = 80.25 = 80%
4
o Key Points
§ Flowmeters are usually made of glass, making them the most delicate part of the anesthesia machine. A leak will
allow oxygen to escape the low pressure system, which could result in the delivery of a hypoxic mixture.
§ The order of flowmeters is important. The oxygen flowmeter should be positioned closest to the manifold outlet (on
the right in the United States). If a leak develops in any of the OTHER flowmeters, it should not reduce the FiO2
delivered to the patient. If, however, a leak develops inside the oxygen flowmeter, then all bets are off.
§ If any component of the flowmeter is damaged, the entire unit must be replaced.
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• Fresh Gas Coupling
o Just about all the modern anesthesia machines separate fresh gas flow form tidal volume—the tidal volume you enter on the
ventilator is what the patient receives. The problem is that many older anesthesia machines couple fresh gas flow to the tidal
volume set on the ventilator, and this may lead to errors in predicted Vt and minute ventilation. It is critical to understand the
implications of this.
o With fresh gas coupling, the total tidal volume delivered to the patient equals:
§ Vt set on ventilator + FGF during inspiration – volume lost to compliance
§ 1. Convert fresh gas flow from L/ min to mL/min
• 4L/min= 4000mL/min
§ 2. The i:E ratio is 1:2. Over the course of 1 min, the patient will spend 20 seconds in inspiration and 40 seconds in
expiration. Said another way, the patient will spend 1/3 of the minute inspiring and 2/3 of the minute expiring. Since
only fresh gas flow during inspiration will be added to the tidal volume set on the ventilator, we multiply the total
fresh gas flow by 1/3 or 33.33%.
• 4000mL/min x (1/3)= 1333mL/min
§ 3. We have established that over the course of a minute 1333mL will be added to the tidal volume. We need to
calculate the tidal volume per breath, so we divide 1333mL by the respiratory rate.
• 1333 mL/ 10 breaths per min = 133 mL
§ 4. Add the volume set on the ventilator to the FGF during inspiration
• 500+ 133 mL = 633 mL tidal volume
§ The entire calculation looks like this:
• [4000 mL/min x (1/3)] = 133 mL
10 breaths/min
• 133 mL + 500 mL = 633 mL tidal volume
§ if you were asked to factor in the volume lost to circuit compliance, you would subtract it from 633 mL. we will
address how to calculate circuit compliance in the next question.
o Relationship between Vt, RR, I:E and FGF
§ As a rule, assuming the other 3 Vt Increases with: Vt Decreases with:
variables are held constant: Decreased respiratory rate Increased respiratory rate
§ Any change in the FGF, bellows, RR< Increased I:E ratio (ex 1:2 to 1:1) Decreased I:E ratio (ex 1:2 to 1:3)
or I:E ratio will impact the total tidal Increased FGF Decreased FGF
volume delivered to the patient. Increased bellows height Decreased bellows height
§ Increasing the FGF will increase tidal volume, minute ventilation, and peak inspiratory pressure. In this situation, we
would expect the end-tidal CO2 to decrease.
§ Decreasing the FGF will decrease tidal volum3, minute ventilation, and peak inspiratory pressure. In this situation, we
would expect the end-tidal CO2 to increase.
§ Remember, that this only holds true for machines that couple fresh gas to tidal volume. You don’t have to worry
about any of this with machines that decouple FGF from tidal volume.
• Circuit Compliance
o Compliance is a change in volume for a given change in pressure – it is a measure of distensibility.
Compliance = Change Volume / Change Pressure
o When the ventilator produces positive pressure inside the breathing circuit, some of this gas causes the circuit to expand. This
quantity of gas does not reach the patient, and therefore does not contribute to the tidal volume that the patient receives.
o You were told that the circuit compliance is 5 mL/cm H2O and the peak pressure is 25 cm H2O in the example. You would
multiply these numbers to arrive at the volume lost to the circuit.
§ 5 mL/cm H2O x 25 cm H2O = 125 mL
o you were told that the ventilator is set to deliver 600 cc, so you would subtract 125 mL from the tidal volume.
§ 600 mL – 125 mL = 475 mL
o Many modern ventilators will automatically compensate for fresh gas lost to circuit compliance.
• Variable Bypass Vaporizer Overview
o When you think about the variable bypass vaporizer, the following concepts should come to mind: variable bypass, flow-over,
temperature compensated, out-of-circuit, and agent specific. Let’s explore each one of these concepts in greater detail.
o To fully comprehend the concept of variable bypass, you must understand the splitting ratio. When fresh gas enters the
vaporizer, some of it encounters liquid anesthetic, while the rest of it bypasses the anesthetic liquid. Before leaving the
vaporizer, these two fractions mix and determine the final anesthetic concentration.

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o By setting the concentration on the dial, you determine the splitting ratio. Setting a higher concentration directs more fresh gas
towards the volatile agent, while setting a lower concentration directs less fresh gas towards the liquid anesthetic.
o Fresh gas enters the vaporizing chamber and flows-over a series of baffles and wicks. These increase surface area and
turbulence, ensuring the fresh gas inside the vaporizing chamber becomes 100% saturated with agent. Full saturation is
required to guarantee a consistent vaporizer output. Flows less than 200 mL/min or greater than 15 L/min can lead to reduced
vaporizer output.
o If the vaporizer is tipped over, it’s possible that some of the liquid anesthetic will enter the bypass chamber (this can increase
vaporizer output). Indeed, 1 mL of liquid anesthetic produces ~ 200 mL of anesthetic vapor (assumes 20 C and 1 atm). If the
vaporizer is tipped, then you should run a high FGF through it for 20 -30 minutes before it can be used for a patient.
o The latent heat of vaporization is the number of calories needed to convert 1 g of liquid into vapor without a change in
temperature. This value is similar for all the halogenated anesthetics. You should know that heat is carried away by the
vaporized molecules and this causes the anesthetic liquid to cool. Cooling decreases vapor pressure and ultimately vaporizer
output. The temperature compensating valve adjusts the ratio of vaporizing chamber flow to bypass flow and guarantees a
constant vaporizer output over a wide range of temperatures. This device is either a bimetallic strip or an expansion element.
o The vaporizer is out-of-circuit.
o Vaporizers are agent specific. Filling a vaporizer with the incorrect anesthetic can lead to catastrophic errors in output.
o Pumping Effect
§ The pumping effect can increase vaporizer output. Anything that causes gas that has already left the vaporizer to re-
enter the vaporizing chamber can cause the pumping effect. This is generally due to positive pressure ventilation or
use of the oxygen flush valve. It is enhanced by low fresh gas flows, low concentration dial setting, and low levels of
liquid anesthetic in the vaporizing chamber. The pumping effect is minimized by modern vaporizer design.
o Vaporizer Leak
§ A loose filler cap is the most common cause of a vaporizer leak.
§ An internal leak in the vaporizer is the most common location for a leak to occur in the low pressure system.
§ A leak can only be detected when the vaporizer is turned on. The vaporizer is functionally removed from the low
pressure system when it is turned off.
o How to Calculate How Much Liquid Anesthetic is Used
§ You can predict how long your agent will last with this equation.
• mL of liquid anesthetic used per hour = Vol% x FGF (L/min) x 3

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• The Tec 6 Desflurane Vaporizer
o The GE-Datex-Ohmeda Tec 6 and the Drager D-Vapor are the only vaporizers approved for the use of desflurane. Although the
principles of operation are similar, our discussion specifically addresses the Tec 6.
o Unlike a variable bypass vaporizer that directs a certain amount of fresh gas towards the liquid anesthetic, the Tec 6 injects a
precise amount of vaporized desflurane directly into the fresh gas flow.
o Requirement for a Specialized Vaporizer
§ Desflurane has a unique physiochemical profile; it is significantly less potent than its peers, and it has a vapor
pressure close to atmospheric pressure.
o Low Potency and the Cooling Effect
§ The latent heat of vaporization is the number of calories needed to convert 1 g of liquid into vapor without a change
in temperature. This value is similar for all the halogenated anesthetics. Because desflurane (MAC 6.6) is much less
potent than isoflurane (MAC 1.2) or sevoflurane (MAC 2.0), this presents a problem. To achieve the same depth of
anesthesia, the absolute volume of desflurane that must be vaporized is higher. Furthermore, heat is carried away by
the vaporized molecules and this leads to excessive cooling of the anesthetic liquid as well as a reduction in vaporizer
output. Heating and pressurizing the TEC 6 to 39 C and 2 atmospheres respectively solves this issue.
o High Vapor Pressure and the Requirement for a High Fresh Gas Flow
§ Desflurane’s vapor pressure is 3-4 times higher than those of the other agents; its boils just above room temperature
(22 C). for this reason, using a variable bypass vaporizer for desflurane would lead to a very inefficient design. Recall
that the fresh gas that passes through a variable bypass vaporizer is split. Some fresh gas enters the vaporizing
chamber and becomes saturated with anesthetic, while the remainder is bypass flow that dilutes the final
concentration leaving the vaporizer. Because desflurane has such a high vapor pressure, it would require a bypass
flow well beyond the limits of the anesthesia machine to dilute the desflurane to a clinically useful concentration. An
injector design solves this issue.
o Delivery of Desflurane at Elevation
§ For all intents and purposes, the output from a conventional variable bypass vaporizer is not affected by a change in
elevation—it compensates on its own. The Tec 6 vaporizer is a different story—it does not compensate for changes in
elevation.
§ Why is this important?
• The partial pressure of volatile anesthetic in the brain (not the concentration) is what determines depth of
anesthesia.
• At a higher elevation, the concentration exiting the vaporizer will be whatever you set the dial; however,
since atmospheric pressure is lower at elevation, the partial pressure in the breathing circuit will also be
lower, at a lower elevation or hyperbaric chamber, the concentration will be whatever you set the dial,
however the partial pressure in the breathing circuit will be higher than expected.
§ How to Calculate Vaporizer Output at Elevation
• Required dial setting = Normal dial setting (% x 760 mmHg)
Ambient pressure mmHg
o A lower ambient pressure (higher altitude) requires a higher setting on the dial.
o A higher ambient pressure (hyperbaric oxygen tank) requires a lower setting on the dial.

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• Oxygen Analyzer
o Types of Oxygen Analyzers
§ Galvanic Fuel-Cell
• Increasing oxygen tension generates a current across two electrodes.
• It must be calibrated daily.
• The components are consumable, so they must be replaced over time.
§ Paramagnetic Device
• Increasing oxygen tension creates an increased magnetic attraction.
• It is self-calibrating.
• There are no consumable components.
• Compared to the galvanic fuel-cell, the paramagnetic device has a faster response time.
o Key Points:
§ The oxygen analyzer resides in the inspiratory limb (galvanic fuel-cell), or it is a component of a multigas monitor (the
one that measures CO2 and anesthetic vapor).
• It monitors oxygen concentration (not pressure)
• It can detect an oxygen pipeline crossover (the oxygen pressure failure decvice and proportioning system
can’t)
• It can detect a leak in the breathing circuit.
o Most common site = circuit disconnect (usually the y-piece)
o Second most common site=CO2 canister
o Closed Circuit Anesthesia
§ During closed circuit anesthesia, the anesthesia provider attempts to match oxygen delivery to the patient’s oxygen
consumption. If consumption increases, but delivery remains constant, it’s possible to create a hypoxic mixture. Only
the oxygen analyzer will detect it.
• A likely question related to this concept might ask about causes of reduced FiO2 during low flow anesthesia.
Recall that oxygen consumption for the average adult is 250 mL/min. think about situations that might
cause this to increase. Examples might include sepsis, pain, sympathetic stimulation, thyrotoxicosis, fever,
etc.
§ When you are learning about a topic, always ask yourself how you can draw connections to other areas of your
studies. The more you actively engage your study material, the more you’ll gain from it!
• Oxygen Pipeline Supply Failure
o When the oxygen analyzer alarms, it is best to assume that a pipeline crossover has occurred until other causes can be ruled
out. You should carry out the following actions.
§ 1. Trust the oxygen analyzer and do not attempt to fix it. This could waste precious time.
§ 2. Turn ON the oxygen cylinder, then disconnect the pipeline oxygen supply. This is a key step! If a crossover occurred,
simply turning on the oxygen tank would not fix the problem. If an adequate oxygen pipeline pressure is present
(regardless of the gas inside), it will prevent the oxygen tank from releasing its contents. The take home is whenever
you switch to the oxygen cylinder, you must also disconnect the pipeline.
§ 3. Verify that the oxygen concentration in the breathing circuit is increasing. If not, you should assume a machine
malfunction and you should ventilate the patient with an Ambu. Be sure to use a different oxygen tank or room air.
The auxiliary oxygen flowmeter on the anesthesia machine is supplied by the pipeline. If an oxygen crossover
occurred, it would supply the wrong gas to the patient.
§ 4. Conserve tank oxygen by using low flows. On many anesthesia machines, oxygen is the driving pressure to
compress the bellows. If you are using this type of machine, you should hand ventilate the patient to conserve
oxygen. If your machine uses air to power the ventilator or is piston drive, then the patient may remain on the
ventilator.
§ 5. Call for help and additional oxygen tanks if needed. Calculate how long the oxygen supply will last.
§ 6. Determine how long the problem will persist.
§ 7. Only reconnect to pipeline oxygen after the supply has been tested.
§ 8. If you are not able to use the circle system, ventilate the patient with an Ambu, and convert to a total intravenous
anesthetic (TIVA).

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• Oxygen Flush Valve & Ventilator Spill Valve
o The oxygen flush valve provides a path for oxygen to travel from the intermediate pressure system to the breathing circuit. It
bypasses the low pressure system.
o Pressing the oxygen flush button exposes the breathing circuit to:
§ 1. Oxygen flow of ~35-75 L/min
§ 2. Oxygen pressure of ~50 psi (pipeline pressure)
o pressing the oxygen flush during the inspiratory cycle can lead to barotrauma. Since the ventilator spill valve is closed during
inspiration, pressing the oxygen flush would expose the breathing circuit and the patient to 50 psi and an oxygen flow rate of
35-75 L/min. therefore, it is critical that you do not press the oxygen flush during inspiration when the patient is on the
ventilator.
o To make sense of this, we need to review the function of the ventilator drive gas and the ventilator spill valve.
o The Drive Gas on a Pneumatic Ventilator Serves 2 Functions:
§ 1. The drive gas compresses the bellows
• The bellows separates the drive gas circuit from the patient breathing circuit. The drive gas circuit is located
outside the bellows and the patient breathing circuit is inside the bellows. During inspiration, the drive gas
flow increases the pressure inside the ventilator chamber. This creates a pressure gradient that pushes
fresh gas into the patient’s lungs. During exhalation, the drive gas flow stops and the pressure gradient
reverses—the pressure in the chest is higher than inside the bellows, which allows the patient to exhale the
tidal volume.
§ 2. The drive gas opens and closes the ventilator spill valve
• During inspiration, the drive gas closes the spill valve. This ensures that the tidal volume goes to the patient
and not to the scavenger. During exhalation, the flow of the drive gas stops. The exhaled tidal volume first
refills the bellows and after the circuit pressure exceeds ~3 cm H2O, the spill valve opens and excess gas
goes out the scavenger. This explains the intrinsic PEEP in pneumatic ventilators. Remember that fresh gas
is continuously added to the breathing circuit. The amount of air going to the bellows is the sum of the tidal
volume + flowmeter flow during expiration.

o Methods to Reduce Risk of Barotrauma

§ 1. Anesthesia machines can minimize the risk of barotrauma by isolating the tidal volume delivered by the ventilator
from the flowmeters and oxygen flush valve. This is called fresh gas decoupling. In these machines, what is set on the
ventilator is what is actually delivered to the patient.
§ 2. The inspiratory pressure limiter can limit the breathing circuit pressure during inspiration. When the breathing
circuit pressure rises above the set point, the excess gas is vented out the scavenger. You can think of the inspiratory
pressure limiter as an APL valve that affects the ventilator.
o Other Complications Associated with the O2 Flush Valve
§ Because the gas from the oxygen flush does not pass through the vaporizers, excessive use of the oxygen flush valve
adds gas to the breathing circuit that does not contain volatile anesthetic. As a result, it dilutes the partial pressure of
volatile agent and may lead to patient awareness.
§ Most manufactures do not recommend using the oxygen flush valve for jet ventilation. Its use in this context is
considered “off label.”
§ A stuck open flush valve will result in barotrauma.

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o Pneumatic Bellows
§ The bellows is classified by its movement during expiration. Ascending and
descending have the letter “e” in them, which should help you remember
that they fill during “expiration.”
§ Ascending Bellows
• An ascending bellows rises during expiration.
• An ascending bellows will not fill if there is a disconnect. If there is a
leak, it will only partially fill.
• For this reason, the ascending bellows is generally regarded as safer
than a descending bellows design.
§ Descending (Hanging) Bellows
• The descending bellows is upside down, so it falls with expiration.
• The classic problem with the descending bellows it that it may continue to rise and fall if there is a circuit disconnect. In
this situation, gravity will cause it to fall during expiration. As it falls, it will entrain room air. This may trick the low volume
and low pressure alarms, so you would be unaware if the bellows was filling with the patient’s exhaled tidal volume or
entraining room air. Newer designs incorporate safety mechanisms to make detection easier. For example, they include
CO2 monitors and/or the anesthesia machine decouples fresh gas flow from the ventilator.
§ Bellows Leak
• A leak in the bellows may transmit the high gas pressure to the breathing circuit.
• Increased breathing circuit pressure may cause barotrauma.
• If there is a bellows leak and oxygen is used as the ventilator drive gas, the FiO2 in the breathing circuit may increase.
• Alternatively, if the ventilator drive gas uses air or an air-oxygen mixture and you are running a high FiO2, then a hole in
the bellows may cause FiO2 to decrease.
• Piston Ventilator
o The ventilator on the anesthesia machine comes in 3 varieties:
§ 1. Ascending pneumatic bellows
§ 2. Descending or hanging pneumatic bellows
§ 3. Piston
o we will review the must know details of the piston ventilator and contrast it with the pneumatic bellows where appropriate.
o Mechanism
§ Piston operated ventilators utilize an electric motor to compress the piston to generate positive pressure. It will not
consume tank oxygen in the event of oxygen pipeline failure. Some machines with a piston-driven ventilator include:
Apollo, Fabius, and Narkomed 6000. A pneumatic bellows requires oxygen to compress the bellows during mechanical
ventilation. In the event of oxygen pipeline failure, the oxygen in the tank may be used to provide fresh gas to the
patient as well as compress the bellows, quickly draining the tank oxygen supply. Some machines will use 100%
oxygen, while others may use a mixture of oxygen and air if available. Obviously, this isn’t an issue if only air is used to
compress the bellows.
o Pressure Relief Valves
§ There are 2 pressure relief valves in the piston ventilator: positive pressure and negative pressure. The positive
pressure relief valve will open at 75 +/- 5 cm H2O. this prevents excessive pressure build up in the anesthesia circuit.
The negative pressure relief valve opens at -8cmH20. When circuit pressure falls below this value, the negative
pressure relief valve opens and entrains room air. This protects the patient against negative end-expiratory pressure
(NEEP). In this instance, mixing of room air with fresh gas will cause a dilution of oxygen and anesthetic agents.
o Fresh Gas Decoupling
§ Piston ventilators decouple fresh gas flow from the ventilator. They deliver a consistent tidal volume regardless of
changes made in fresh gas flow, respiratory rate, or the I:E ratio. Many gas-driven bellows ventilators couple tidal
volume to fresh gas flow. Changes in fresh gas flow, respiratory rate, or the I:E ratio will affect the total tidal volume
delivered to the patient.
o PEEP
§ Although a gas-driven bellows automatically adds 2-3cm H2O peep due to the design of the ventilator spill valve, the
piston ventilator does not add PEEP in this way.
o Breathing Bag
§ The breathing bag is incorporated into the ventilator circuit during mechanical ventilation. The bag inflates during
inspiration and deflates during expiration (this may seem counter intuitive). If the breathing bag rapidly deflates, you
should suspect a circuit disconnect. The piston will not move when a patient initiates spontaneous breaths while on
the ventilator.

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• Mechanical Ventilation: Pressure Control vs Volume Control
o Operating room ventilators cycle between inspiration and expiration over a set amount of time. During inspiration, the inspiratory flow
continues until a specified tidal volume or airway pressure is achieved. If the tidal volume is set, you are using a volume controlled mode, and if
the airway pressure is set, you are using a pressure controlled mode. Some newer ventilation modes blend these approaches.
o Volume Controlled Ventilation (VCV)
§ VCV delivers a preset tidal volume over a predetermined time. Since the tidal volume is fixed, the inspiratory pressure will vary as
the patient’s compliance changes. The inspiratory flow is held constant during inspiration.
o Pressure Controlled Ventilation (PCV)
§ In contrast to VCV, pressure control ventilation delivers a preset inspiratory pressure over a predetermined time. Since the pressure
and time are fixed, the tidal volume and inspiratory flow will be variable and dependent on the patient’s lung mechanics. If airway
resistance rises or lung compliance decreases, then tidal volume will suffer and a higher inspiratory flow will be required to achieve
the preset airway pressure.
Volume Controlled Pressure Controlled
Fixed Tidal volume Peak inspiratory pressure
Inspiratory flow rate Inspiratory time
Inspiratory time
Variable Peak inspiratory pressure Tidal volume
Inspiratory flow

o Advantages of PCV
§ It delivers a larger tidal volume for a given inspiratory airway pressure.
§ The inspiratory flow pattern may improve gas exchange.
§ It reduces the risk of ventilator associated lung injury (VALI).
§ It is useful if the patient has low compliance, high PIP is dangerous, or to compensate for leaks. See examples below.
Low Compliance High PIP is Dangerous Compensate for Leaks
Pregnancy LMA LMA
Obesity Neonate Uncuffed ett in children
Laparoscopy Emphysema
ARDS
o Disadvantages of PCV
§ Increased airway resistance and/or decreased lung compliance reduce tidal volume.
§ Requires extra attention with circumstances that can alter pulmonary resistance or compliance, as they will cause the
tidal volume to change.
Vt Decreased with: Vt Increased with:
Decreased Compliance Increased Compliance
• Pneumoperitoneum • Release pneumoperitoneum
• Trendelenburg position • Going from Trendelenburg to supine
Increased Resistance Decreased resistance
• Bronchospasm • Bronchodilator therapy
• Kinked ett • Removing airway secretions
o Spontaneous vs Machine Breaths
§ No matter what mode of ventilation is used, a negative deflection just before the breath indicates a spontaneous
breath. By contrast, a machine initiated breath will only have a positive deflection. Some monitors also differentiate
patient vs machine initiated breaths with different colors.
§ Depending on the mode of ventilation, the ventilator will either synchronize with and/or augment the spontaneous
breath or it may ignore it completely.

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• Mechanical Ventilation
o Controlled Mandatory Ventilation (CMV)
§ Machine initiated breath delivers a preset Vt and RR on a fixed schedule.
§ Does not compensate for patient initiated breaths (risk of patient-ventilator asynchrony).
§ Best for apneic patients.
o Assist Control (AC)
§ Machine initiated breath delivers a preset Vt and RR.
§ Spontaneous breaths receive the full preset tidal volume. Said another way, the tidal volume will be the same if the
machine or the patient initiates the breath.
§ A patient that overbreathes the ventilator is at risk for hyperventilation and respiratory alkalosis.
o Synchronized Intermittent Mandatory Ventilation (SIMV)
§ Machine initiated breath delivers a pereset Vt and RR, but this mode allows the patient to breath spontaneously
between machine initiated breaths.
§ If the patient draws a breath before a machine breath is due, the timing of the machine breath will adjust to
coordinate with the patient’s spontaneous breath.
§ This mode promotes better synchrony between the patient and the ventilator.
§ Spontaneous breaths can be augmented with pressure support.
§ Guarantees a minimum minute ventilation – the more the patient works, the less assistance the ventilator provides
and vice versa.
§ Useful for weaning or with an LMA.
o Pressure-Control Ventilation with Volume Guarantee (PCV-VG)
§ How many times have you used PCV only to realize that your patient’s tidal volume changed drastically? This is
usually the result of compliance changes, which are common during laparoscopic surgery or in response to surgical
positioning.
§ PCV-VG gives you the benefits of pressure control ventilation, but it also guarantees a predetermined tidal volume
while applying the minimum pressure required to achieve it.
o Pressure-Support Ventilation (PSV)
§ Augments spontaneous breaths with a pre-set amount of pressure support.
§ There are no machine initiated breaths, unless the ventilator provides a back-up rate if apnea is detected (PSV-Pro).
§ Useful for weaning or with an LMA.
o Continuous Positive Airway Pressure (CPAP)
§ A continuous amount of pressure is applied to the breathing circuit throughout the respiratory cycle.
§ This has two benefits: :it augments the patient’s spontaneous breath, and it reduces airway collapse during
expiration.
§ By comparison, PSV only applies pressure to the circuit when the patient initiates a breath (there is nothing during
expiration).
o Biphasic Positive Airway Pressure (BiPAP)
§ Two levels of pressure are set.
§ P1= Inspiratory positive airway pressure (think pressure support for a spontaneous breath)
§ P2= Expiratory positive airway pressure (think CPAP during exhalation).
§ This means the patient receives one pressure during inhalation and a different pressure during exhalation.
§ Useful for the patient with COPD or when CPAP isn’t quite enough.
o Airway Pressure Release Ventilation (APRV)
§ Used for spontaneous ventilation.
§ Like BiPAP, but there is a high level of CPAP throughout most of the respiratory cycle.
§ The high level of pressure is released at preset intervals to facilitate exhalation.
§ Useful in the patient with ARDs.
o Inverse Ratio Ventilation (IRV)
§ The respiratory cycle is divided into inhalation and exhalation, and the I:E ratio determines how much time is spent in
each part.
§ For most modes of ventilation, exhalation time is usually longer than inhalation time.
§ IRV reverses this ratio by allocating more time to inspiration.
§ Requires a paralyzed and sedated patient (no spontaneous ventilation).
§ Useful in patients with a small FRC or in the patient with ARDs.
§ Risk of dynamic hyperinflation (auto-peep or breath stacking).
o High-Frequency Ventilation
§ Conventional modes of ventilation deliver a tidal volume that exceeds anatomical dead space. Gas transport occurs by convection
(large airways) and convection + molecular diffusion (small airways and alveoli).
§ By comparison, high-frequency ventilation delivers a tidal volume below anatomic dead space in conjunction with a very high
respiratory rate. Gas transport occurs by a combination of molecular diffusion, coaxial flow, and high velocity flow.
§ Types of high-frequency ventilation include high-frequency oscillation, high-frequency jet ventilation, and high-frequency percussive
ventilation.

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• Soda Lime
o Carbon dioxide absorbents remove exhaled carbon dioxide from the breathing circuit – a base neutralizes an acid. Without
carbon dioxide absorption, closed and semi-closed anesthesia circuits would not be possible. CO2 absorbents also allow for
conservation of anesthetic gases as well as humidity within the respiratory tract and the anesthesia circuit. You should be able
to write the soda lime reaction from memory and understand the processes that occur.

o Mesh Size
§ The size of the granule must strike a balance between surface area (absorptive capacity) and airflow resistance (work
of breathing).
• Small granule = high surface area with high resistance
• Large granule = low surface area with low resistance
§ The best balance is achieved when 4-8 mesh granules are used. Each granule is between 1/8 to ¼ inch in diameter and
will pass through a mesh screen with 4-8 holes per square inch. This size provides the best combination of absorptive
capacity and airflow resistance.
o Problems with Soda Lime
§ There are 2 major problems that can occur with carbon dioxide absorbent:
• 1. The absorbent is exhausted—it is no longer able to neutralize carbon dioxide
• 2. The absorbent is desiccated—it is too dry
§ Exhaustion
• The sodium hydroxide present in soda lime makes it a strong base. As Co2 consumes the basic substrates, the pH of the
absorbent decreases. As the pH falls below 10.3, an indicator dye such as ethyl violet will change to a blue-purple color.
When the Co2 absorbent changes color, the absorbent is no longer able to effectively neutralize carbon dioxide, and it is
time to change the canister. Soda lime does not regenerate.
• Ethyl violet may revert to a colorless state when the anesthesia machine is not in use, however this does not indicate that
the soda lime has regenerated. If the CO2 absorbent is exhausted, the color will quickly return to blue-purple in the
presence of carbon dioxide.
• In the presence of exhausted soda lime, the anesthetist may be tempted to increase the minute ventilation. While this
action will remove a greater amount of carbon dioxide from the body, it does not prevent the patient from rebreathing
carbon dioxide and may lead to hypercarbia. Instead, if the anesthetist is unable to replace the CO2 absorbent, the
appropriate action is to increase the fresh gas flow to convert the circle system into a semi-open system. This will prevent
rebreathing and the baseline on the capnography should return to zero.
§ Desiccation
• Water is required to facilitate the reaction of carbon dioxide with CO2 absorbent. The granules are hydrated to 13-20%
by weight. In addition, some water is created during the soda lime reaction. Ethyl violet does NOT provide information
regarding the water content of the CO2 absorbent. When the absorbent is devoid of water, it is said to be dessicated.
• Desiccated soda lime increases the production of carbon monoxide in the presence of halogenated anesthetics
(desflurane>isoflurane>>>sevoflurane) and compound A in the presence of sevoflurane. Carbon monoxide can cause
carboxyhemoglobinemia and compound A may cause renal dysfunction. Sevoflurane is the most unstable halogenated
anesthetic in the presence of soda lime.
• Methods to minimize the risk of carbon monoxide and compound A:
o Utilize low fresh gas flow to preserve the water content of the soda lime.
o Turn off fresh gas flow in between cases.
o Change all the absorbent at one time (not a single canister in a dual canister setup).
o Change canisters when the ethyl violet signifies exhaustion.
o Change canisters if you are unsure about the level of hydration (if FGF was left on overnight or over the
weekend).
§ Silica
• Sodium hydroxide is a strongly alkaline compound that is irritating to skin and mucous membranes. The addition of silica
provides hardness and minimizes the creation of dust. Less dust means less bronchial irritation and less risk of
bronchospasm. Additionally, the addition of silica has the added benefit of decreasing flow resistance. On the flip side,
silica reduces the efficacy of the granules. Since only a small amount of silica is needed, this isn’t a significant issue.

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• Calcium Hydroxide Lime (Amsorb Plus)
o Calcium hydroxide lime (Amsorb Plus) does not contain strong bases, such as sodium hydroxide or potassium hydroxide. Instead, it uses calcium
hydroxide to neutralize carbonic acid. Calcium chloride is an additive that acts as a humectant (think opposite of desiccant). This keeps the
absorbent moist, lessening the chance of desiccation. Instead of silica, calcium sulfate and polyvinylpyrrolidone increase hardness.
CO2 + H2O à H2CO3
H2CO3 + Ca(OH)2 àCaCO3 + 2H2O + energy (heat)
o Benefits
§ There is no carbon monoxide production.
§ There is very little or no compound A production.
§ There may be a lower risk of fire when compared to soda lime.
o Drawbacks
§ Soda lime can absorb 26L of Co2 per 100g of absorbent, while calcium hydroxide lime can only absorb 10.6 L of CO2 per 100g of
absorbent.
§ The absorptive capacity is less than soda lime, so it will require more frequent replacement. It is also more expensive.
• Equipment Related Causes of Low Pressure in the Breathing Circuit
o Circuit disconnection is the most common source of preventable equipment related complications. It can be partial or complete.
Disconnect most commonly occurs at the y-piece between the endotracheal tube and the breathing circuit.
o Problems with the breathing circuit are typically due to too much or too little pressure. We will cover too little pressure here.
o Sources of Low Pressure in the Breathing Circuit
§ Circuit disconnect
§ Defective carbon dioxide absorbent canister
§ Leaks around the carbon dioxide absorbent—common after the granules have been changed
§ Malfunction of the bag/ventilator selector switch
§ Incompentent ventilator spill valve (tidal volume is directed to the scavenger)
§ Leaks in the breathing circuit
§ Leaks in the anesthesia machine (most common in the low pressure system)
§ Moisture buildup in flow sensors preventing proper function of the ventilator
o Monitors for Circuit Disconnect
§ There are 4 ways to monitor for circuit disconnect: pressure, volume, ETCO2, and your own vigilance
• Precordial stethoscope
• Visual inspection of chest rise
• Capnography
• Respiratory volume monitors
• Low expired volume alarm
• Low peak pressure alarm
• Failure of bellows to rise with an ascending bellows (not with descending bellows or piston).
§ *The oxygen analyzer monitors the concentration of oxygen in the breathing circuit. It is NOT a disconnect monitor.
§ If you are unable to ventilate due to low pressure, do not withhold ventilation or waste valuable time attempting to diagnose
the machine. The correct course of action is to ventilate the patient with an Ambu and oxygen tank while providing TIVA.
§ You may be asked about which monitor will detect a circuit disconnect first. While the correct answer will only emerge in the
context of the distractors, you will need to ask two questions:
• 1. Will the monitor alert you in real time or is there a delay? Anything that is electronic will have a delay.
• 2. If all the monitors have some degree of delay, which one is the shortest?
• Equipment Related Causes of High Pressure in the Breathing Circuit
o Consequences of Elevated Breathing Circuit Pressure
§ Barotrauma § High PEEP
§ Decreased venous return § Pneumothorax
§ Decreased cardiac output § Subcutaneous emphysema
§ Hypotension § Death
§ Cardiovascular collapse
o In our scenario, the peak inspiratory pressure rose enough to trigger the high peak inspiratory pressure alarm. Patient related causes
should first be ruled out. Chief among these concerns is bronchospasm. As you rule out patient related causes, attempt to manually
ventilate the patient. Since the PIP improved immediately upon removing the patient from the ventilator, bronchospasm was unlikely.
o If you remove the patient from the ventilator and the peak pressure returns to baseline, the most likely explanation is that the
ventilator spill valve failed. The function of the spill valve is to vent excess fresh gas from the flowmeter to the scavenger. If the valve
malfunctions, the fresh gas will have nowhere to go and high circuit pressure may result.
o If you removed the patient form the ventilator and the circuit pressure remains elevated, the most likely cause is that the scavenger is
occluded or that the positive pressure relief valve on the scavenger has failed. For either cause, it is appropriate to remove the
scavenger transfer tubing from the APL valve. If you are unable to do this, or this does not relieve the high pressure, remove the
patient from the breathing circuit and ventilate with an Ambu bag and begin TIVA.
o Other Equipment Related Causes of High Pressure
§ Failure to remove plastic wrap from the carbon dioxide absorbent
§ Failure to remove plastic from the anesthesia mask
§ Occlusion of the lumen of the breathing circuit by plastic or other materials
§ A malfunctioning PEEP valve
§ Malfunctioning expiratory unidirectional valve in the breathing circuit or scavenger.

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• Scavenger System
o The function of the scavenger is to remove excess gas from the anesthesia circuit and minimize environmental exposure to
waste anesthetic gas. To maintain a constant pressure inside the breathing circuit, the scavenger must only remove an amount
of gas equal to fresh gas flow minus the volume of gas lost due to the patient’s oxygen consumption.
o The most critical component of the scavenger is the interface. Removal of too much gas would create a negative pressure in the
circuit, while removal of too little gas could increase the risk of barotrauma.
o Control of Fresh Gas Going to the Scavenger
§ Spontaneous ventilation – the APL valve controls the
amount of gas that remains in the circuit and the
amount that is released to the scavenger.
§ Mechanical ventilation—the ventilator’s spill valve
determines the amount of gas that remains in the circuit and
the amount that is release to the scavenger.
o 5 Components of the Scavenger System
§ 1. Gas collecting assembly
• collects waste gas from the breathing circuit
• located at the APL valve and the ventilator spill valve
§ 2. Transfer tubing
• directs collected gas to the interface
§ 3. Interface (open or Closed system)
• Open system:
o is open to the atmosphere.
o No need for positive or negative pressure relief valves.
o Removes risk of barotrauma or removal of fresh gas from breathing circuit.
o Too much suction entrains room air into the scavenger.
o Too little suction vents scavenged gas into the operating room.
o Contains a reservoir
o Can only be used with active systems
o Higher risk of exposing OR personnel to waste gas
• Closed system:
o Communication to the atmosphere with pressure valves
o If passive system used—it must have positive pressure relief
o Since there is no suction with a passive system, it will not remove excess fresh gas from the breathing circuit.
o If active system used—it must have positive and negative pressure relief.
o Contains a reservoir.
§ 4. Gas disposal tubing
• removes gas from the interface
§ 5. Gas disposal system
• directs gas from the scavenger to the hospital suction and ultimately earth’s atmosphere.
• Passive disposal does not use suction to remove waste gas, but instead relies on the positive pressure of
fresh gas leaving the interface
• Action disposal uses suction to remove waste gas
• OSHA Recommendations Regarding Inhalation Anesthetic Exposure
o The Occupational Safety and Health Administration (OSHA) developed guidelines that detail the maximum exposure to
inhalation anesthetics for health care workers in the operating room.
§ Halogenated alone should be < 2 ppm
§ Nitrous oxide alone should be < 25 ppm
§ Halogenated agents + nitrous oxide should be < 0.5 ppm and 25 ppm respectively
o The health hazards related to occupational exposure to halogenated anesthetics are unclear and unproven.
o Determinants of Exposure to Waste Gases
§ 1. Amount of OR ventilation and air turnover
§ 2. Functional status of anesthesia equipment
§ 3. Your practice as a CRNA:
• good mask fit
• turn on anesthetic gas only after achieving a good mask fit
• prevent fresh gas from entering the atmosphere
• turn off anesthetic gas before suctioning patient
• evacuate anesthetic gases into the scavenger at the end of the case
• use cuffed endotracheal tubes
• monitor the anesthesia machine for leaks
• do not spill anesthetic agent
• use TIVA
avoid nitrous oxide
• use low fresh gas flows

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• Classification of Breathing Circuits
o The primary function of the breathing circuit is to deliver oxygen and anesthetic agent to the patient, while eliminating carbon dioxide to
prevent rebreathing. Carbon dioxide is removed from the breathing circuit by washout with a high fresh gas flow or through a chemical reaction
with a CO2 absorbent.
o There are 4 classifications of breathing circuits: open, semi-open, semi-closed, and closed. Although some texts no longer recognize this
classficiation schema, others do. This makes it fair game for the NCE.
o Open
§ A noncontained system where the patient exchanges gas with the atmosphere.
o Semi-open
§ Does not allow rebreathing of exhaled gas
§ FGF is greater than minute ventilation
o Semi-Closed
§ Allows rebreathing of exhaled gas.
§ FGF is less than minute ventilation
§ Unidirectional valves increase airway resistance
o Closed
§ There is complete rebreathing of exhaled gas
§ Uses very low FGF
§ The amount of gas that needs to be replaced is the sum
of the patient’s oxygen consumption plus the amount of anesthetic agent that is absorbed by the patient.
§ Since the volumes of inspired and expired gases are equally matched, gas does not exit the scavenger.
§ The APL valve is closed
§ The change in gas concentration is very slow as a result of a very low FGF
o Note that the circle system can take on 3 different configurations
• Circle System
o The circle system prevents rebreathing of exhaled carbon dioxide, but it does allow the patient to rebreathe oxygen and
anesthetic agent.

o There are 2 common conditions that increased inspired carbon dioxide:

§ 1. CO2 Absorbent Exhaustion
• if the CO2 absorbent exhausts during a procedure and you
cannot change the granules, a closed or semi-closed circuit
should be converted to a semi-open circuit by increasing the
FGF to 5-8 L/min.
• if increasing the FGF does not fix the problem, it is likely that a
unidirectional valve is incompetent.
• Increasing minute volume is NOT the correct choice in this
situation, as the patient will continue to rebreathe exhaled
carbon dioxide.
§ 2. Incompetent Unidirectional Valve
• the purpose of the unidirectional valves is to ensure that gas moves in one direction.
• Checking the valves is part of the FDA preanesthetic checkout. They should be tested in bag and vent mode.
• If a valve becomes incompetent, then the patient will rebreathe exhaled gas.
• The definitive fix its to correct the valve.
• If this cannot be done, then a closed or semi-closed system should be converted to a semi-open system.

§ You might think these things never happen. Ha! Do this long enough, and you’ll see quite a bit. Here is an image I took of an
expiratory valve that failed in the middle of a procedure. You should notice two things about this waveform:
• 1. The beta angle becomes wider during the inspiratory phase.
• 2. The baseline does not return to zero
§ I took apart the valve assembly and flipped the disc over. Worked like a
charm.

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• Mapelson Circuits
o There are 6 different configurations of the Mapelson circuit (A-F).
o All of these are classified as semi-open or non-rebreathing circuits. Since inhaled and exhaled gases travel through the same
tubing, there is a risk of rebreathing.
o How do they work?
§ 1. During expiration, gas containing carbon dioxide enters the corrugated tubing and travels away from the patient.
§ 2. After expiration but before the next inspiration, the FGF continue to washout exhaled gas left inside the corrugated
tubing.
§ 3. During inhalation, the patient breathes in fresh gas. If the FGF is inadequate, the patient will also breathe in
exhaled gas leftover in the corrugated tubing.
o Rebreathing is minimized with a higher FGF, a smaller tidal volume, and a longer expiratory time.
o End-tidal CO2 monitoring is the best method of determining the amount of fresh gas flow required to prevent rebreathing (look
at the baseline of the capnograph).

o Which is the Best?

§ Well, that depends if the circuit will be used for spontaneous or controlled ventilation. You should know which are
the best and worst for each mode of ventilation.
§ Spontaneous Ventilation:
• Best: Mapleson A (A>DFE>DB)
• Worst: Mapleson B
§ Controlled Ventilation:
• Best: Mapleson D (DFE>BC>A)
• Worst: Mapleson A
§ If you really want tp get picky, the amount of rebreathing is a function of many things. These include fresh gas flow,
minute ventilation, mode of ventilation, respiratory rate, tidal volume, inspiratory flow rate, I:E ratio, volume of the
reservoir bag, volume of corrugated tubing, and the use of a mask, LMA, or endotracheal tube.
§ It’s impossible to predict exactly how much FGF is required to prevent rebreathing. As a general rule ~2.5 times the
patient’s minute ventilation should be enough in most cases. There are exceptions, however. A Mapleson A requires a
FGF of ~20 L/min during
controlled ventilation!
o When to Use a Mapleson Circuit?
§ By knowing the advantages and
disadvantages of the Mapleson
designs, you can easily
determine when to use them.

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 • Bain System

o Key Facts
§ The Bain system is a modified Mapleson D.
§ Fresh gas enters the circuit through the thin inner tubing and exhaled gas exits via the corrugated tubing.
§ The outer corrugated tubing should be transparent, so you can assess the integrity fo the inner tubing.
§ Exhaled gas warms and humidifies the incoming fresh gas.
§ The Bain circuit is useful for spontaneous and controlled ventilation.
§ To prevent rebreathing, the FGF should be 2.5x minute ventilation.
o Pitfalls of the Bain Circuit
§ It is possible that the inner tubing can become kinked or disconnected. This situation converts all of the corrugated
tubing to dead space, putting the patient at risk for hypercarbia.
§ The Pethick test should be done as part of the pre-anesthetic checkout. Steps include:
• 1. Occlude the elbow at the patient end of the circuit
• 2. Close the APL valve
• 3. Use the oxygen flush valve to fill the circuit
• 4. Remove the occlusion at the elbow while flushing the circuit.
§ Interpretation of Results:
• If the inner tubing is patient, the Venturi effect will cause the reservoir bag to collapse. The circuit is safe to
use.
• If the inner tubing is occluded, the reservoir bag will remain inflated. The circuit is not safe to use.
Monitoring

• Assessment of Pulmonary Resistance & Compliance

o Resistance= [P (airway)- P (alveolar)] / Gas Flow Rate
§ Is the force that acts opposite to the relative motion of an object
o Compliance = DV/DP
§ Is a change in volume for a given change in pressure
§ It measures the elastic properties of the lungs and chest wall
§ It is influenced by:
• Muscle tone
• Degree of lung inflation
• Alveolar surface tension
• Amount of interstitial lung water
• Pulmonary fibrosis
o Dynamic Compliance
§ Dynamic means “movement”
§ Dynamic compliance is the compliance of the lung/chest wall during air movement.
§ The pressure required to inflate the lung to a given volume is a function of airway resistance AND the tendency of the lung/chest to
collapse.
o Static Compliance
§ Stasis means “not moving”
§ Static compliance measures lung compliance when there is no airflow.
§ The pressure required to keep the lung inflated to a given volume is a function of the tendency of the lung/chest to collapse. Since
there is no airflow during this measurement, there is no resistance to overcome.
o The Significance of Peak Inspiratory Pressure and Plateau Pressure
§ The peak inspiratory and plateau pressures provide key insight to a key insight to a patient’s airway resistance and lung-thoracic
compliance.
§ Peak Inspiratory Pressure (PIP)
• The PIP is the maximum pressure in the patient’s airway during inspiration.
• Because air is flowing into the airway during inspiration, PIP is affected by airway resistance as well as chest/lung
compliance.
• There is controversy whether or not an increased PIP in isolation increases the risk of barotrauma.
o Dynamic Compliance = Tidal Volume
Peak Pressure –PEEP

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 § Plateau Pressure (PP)
• Plateau pressure is the pressure in the small airways and alveoli after the target tidal volume is delivered.
• Since there is no airflow at this time, airway resistance does not affet plateau pressure.
• Therefore, plateau pressure reflects the elastic recoil of the lungs and thorax during the inspiratory pause ( no gas is
moving in or out of the lungs).
• Barotrauma risk increases when plateau pressure exceeds 35 cm/H2O.
• Complications of an elevated plateau pressure include: ventilator-associated lung injury, pneumothorax,
pneumomediastinum, and subcutaneous emphysema.
• If barotrauma exists, you should aim to reduce plateau pressure by reducing tidal volume, inspiratory flow, and PEEP.
Sedation is also helpful.
o Static Compliance = Tidal Volume
Plateau Pressure –PEEP

• In the adult, the normal static compliance is 35-100 mL/cmH2O

• In the child, the normal static compliance is > 15 mL/cmH2O
o Assessment of Dynamic & Static Compliance
§ For the information provided by the PIP and PP to be most
useful, we need to determine what is happening with
each.

• Capnography: Normal Waveform

o Capnography measures end-tidal CO2 concentration over time. It permits continuous assessment of metabolism, circulation, and ventilation.
Additionally, it can inform you of a large variety of equipment related problems.
o CO2 Concentration Gradient: From the Tissues to the Breathing Circuit
§ Carbon dioxide is the final product of aerobic metabolism. It diffuses away from the tissue and
enters the venous circulation. From here, the cardiac output determines the rate of transfer
towards the lungs. In the lungs, CO2 follows a concentration gradient as it diffuses across the
alveolocapillary membrane. Once CO2 is in the alveolus, ventilation is the process by which CO2 is
removed from the body.
o Components of the Capnograph
§ You will see the components of the capnography described in two ways—letters or numbers. We
have included them both here.
§ Point D is where end-tidal CO2 is measured. This is normally 35-40mmHg. Occasionally you may
see a small peak just before inspiration. This reflects emptying of alveoli with longer time constants and higher CO2 concentrations.
o Alpha Angle: Airflow Obstruction
§ The alpha angel is measured at point C.
§ Normally this is 100-110 degrees.
§ An increased alpha angle signifies an expiratory airflow obstruction, such as COPD, bronchospasm, or a kinked endotracheal tube.
o Beta Angle: Rebreathing
§ The beta angle is measured at point D.
§ Fresh gas does not contain carbon dioxide, so when the patient inspires, the capnography should immediately return to zero. This
creates a 90 degree angle at point D.
§ The beta angle is increased in some (but not all) etiologies of rebreathing. It is specific to rebreathing caused by a faulty
unidirectional valve, but it will appear normal in other instances of rebreathing (exhausted CO2 absorbent). In the case of CO2
absorbent exhaustion, the baseline increases but the beta angle is normal.
o You might think these never happen. Ha! Do this long enough, and you’ll see quite a bit. Here’s an image of an expiratory valve that failed in the middle of a
procedure. You should notice two things about this waveform:
§ 1. The beta angle becomes wider during the inspiratory phase.
§ 2. The baseline does not return to zero.
o I took apart the valve assembly and flipped the disc over. Worked like a charm.
o Methods of CO2 Analysis
§ Mainstream (In-Line)
• The device is attached to ETT.
• It provides a faster response time, and doesn’t require a water trap or pumping mechanism.
• Because it’s attached to the ETT, it does increase apparatus dead space as well as adds extra weight.
§ Sidestream (Diverting)
• The device is located outside of the airway.
• A pumping mechanism continuously aspirates the gas sample from the breathing circuit, and for this reason, the response time is
slower.
• Additionally, this arrangement requires a water trap to prevent contamination of the device.

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• Capnography: Abnormal Waveforms
o Airflow Obstruction
§ Prolonged upstroke with increased alpha angle.
§ Examples: COPD, bronchospasm, kinked ett.
o Cardiac Oscillations
§ Result from the heart beating against the lungs.
§ More common in children (close proximity of heart to the lungs).
o Curare Cleft
§ Spontaneous breaths during mechanical ventilation.
§ If present during spontaneous ventilation, the presence of a curare cleft suggest
inadequate muscle relaxant reversal (lack of synchronization between intercostal
muscles and diaphragm).
o Low EtCO2
§ The plateau phase is well below normal. Look for a scale or a reference wave.
§ Occurs with hyperventilation, decreased CO2 production, or increased alveolar dead
space.
§ Examples: hyperventilation: light anesthesia, metabolic acidosis.
§ Examples: decreased CO2 production: hypothermia.
§ Examples: Increased alveolar dead space: hypotension, pulmonary embolism.
o Elevated EtCO2 with Normal Plateau
§ Look at the baseline. It returns to zero. This is not rebreathing.
§ Occurs with increased CO2 production or decreased alveolar ventilation.
§ Examples: increased CO2 production: MH, sepsis, fever, hyperthyroidism.
§ Examples: decreased alveolar ventilation: hypoventilation, narcotics.
o Inspired CO2
§ Look at the baseline. It does not return to zero. This is rebreathing.
§ Causes include: exhausted CO2 absorbent, incompetent expiratory valve, hole in the
inner tube of a Bain system, inadequate FGF with Mapleson circuit.
o Incompetent Expiratory Unidirectional Valve
§ Decreased slope during inspiratory phase with widened beta angle.
§ There is CO2 in the limb with the faulty unidirectional valve.
§ The waveform may or may not reach zero depending on the FGF.
o Leak in Sample Line During Positive Pressure Ventilation
§ The beginning of the plateau is low because of dilution of alveolar gas as atmospheric
air is aspirated into the sample line.
§ Positive pressure during inspiration pushes the CO2 rich gas through the sample line,
which results in the peak at the end of the plateau.
§ Not seen with spontaneous ventilation, because there is no positive pressure.
§ This pattern may also occur in obese and pregnant patients.
o Patient with Single Lung Transplant
§ Alveolar gas from the transplanted lung and the diseased lung have different time
constants.
§ The first peak is alveolar gas from the transplanted lung. It has a normal time constant.
§ The second peak is alveolar gas from the diseased lung. Because air is trapped in the sick lung, there is a longer time
constant during exhalation.
• Causes of High & Low End-Tidal CO2
o For EtCO2 to be detected, the following requirements must be met:
§ 1. Carbon dioxide must be produced during metabolism.
§ 2. There must be an adequate pulmonary blood flow to deliver CO2 to the lungs for elimination.
§ 3. There must be an adequate ventilation to transport CO2 to the breathing circuit.
§ 4. There must be an intact sampling system.
o When answering a question about changes in end-tidal CO2, you’ll need to answer two things:
§ 1. What is the cause?
• Causes can be divided into changes in CO2 production, impaired pulmonary perfusion, and/or impaired
ventilation. Equipment malfunction can also affect EtCO2.
§ 2. Does this affect the PaCO2 to EtCO2 gradient?
• PaCO2 is higher than EtCO2. Carbon dioxide follows a concentration gradient from the cells moving towards
the breathing circuit.
• The normal gradient is 2-5 mmHg.
• A wide gradient suggests a V/Q mismatch or that the equipment has malfunctioned.
• The first thing that should come to mind is increased dead space (hypotension, reduced CO, PE, etc).

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• Pulse Oximetry: How it Works
o The pulse oximeter is based on the Beer-Lambert law, which relates the intensity of light transmitted through a solution and
the concentration of the solute within the solution. In this instance, the solution is blood and the solute is hemoglobin.
o The oxygen saturation determines the color of the blood. Since the optical characteristics of hemoglobin change at different
degrees of oxygen saturation , we can compare the ratio of light absorption in arterial and venous blood.
o The pulse oximeter emits 2 wavelengths of light at a constant intensity. This light is sensed by 2 sensors opposite the tissue
sample.
§ 1. Red light (660 nm) is preferentially absorbed by deoxyhemoglobin (higher in venous blood).
§ 2. Near-infrared light (940 nm) is preferentially absorbed by oxyhemoglobin (higher in arterial blood).

o The amount of light absorbed changes throughout the pulse cycle.

§ At the trough of the pulse waveform, there is a greater amount of venous blood in the tissue sample.
§ At the peak of the waveform, there is a greater amount of arterial blood in the tissue sample.
§ The pulse oximeter calculates the absorption ratio on a continuous basis to determine SpO2.

o SpO2 Response Time

§ As a general rule, the closer the monitoring site is to the central circulation, the faster it will respond to arterial desaturation.
Additionally, central monitoring sites are less resistant to the vasoconstrictive effects of SNS stimulation and hypothermia.
§ These sites are ordered from most to least responsive:
• Fast = Ear, nose, tongue, esophagus, forehead
• Middle = finger
• Slow = toe
§ When SpO2 is monitored on the head or esophagus, the Trendelenburg position can cause venous engorgement resulting in a falsely
decreased SpO2 measurement.

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• Pulse Oximetry: Relationship to the Oxyhemoglobin Dissociation Curve
o SpO2 monitoring is most useful when the patient’s PaO2 aligns with the steep
portion of the oxyhemoglobin dissociation curve. On the steep portion of the
curve, you can reasonably predict the PaO2 for a given SpO2.
o While we covered the oxyhemoglobin dissociation curve in great detail in the
respiratory unit, it never hurts to see it again. You will see this on the NCE in some
way, shape, or form!
o Once the SpO2 reaches 100% on the plateau portion of the curve, you are no
longer able to extrapolate the PaO2; it could be 100 or 500 mmHg. Either way, the
SpO2 will read 100%.
o How does SpO2 Relate to PaO2?
§ Under normal conditions, you can roughly estimate the PaO2 based on
the SaO2 (what you see on the pulse oximeter). Having said this,
anything that shifts the oxyhemoglobin dissociation curve to the left or right alters this relationship.
o Methods to Improve the SpO2 Signal:
§ Performance of digital block SpO2% PaO2 mmHg
§ Warming the extremity 90 60
§ Protecting the extremity from ambient light 80 50
§ Vasodilating cream 70 40
§ Administer an arterial vasodilator
• Pulse Oximetry: What it Does & Does Not Do
o The pulse oximeter is a noninvasive monitor of:
§ 1. Hemoglobin saturation
§ 2. Heart Rate
§ 3. Fluid responsiveness (pulse pressure variation)
o The pulse oximeter is also a useful tool to assess perfusion. For example, the brachiocephalic
(innominate) artery may be compressed during mediastinoscopy. In this procedure, the
medastinoscope is placed behind the thoracic aorta and in front of the trachea. If the pulse
oximeter is placed on the right extremity, the perfusion index and the quality of the
waveform will be affected if the brachiocephalic artery is compressed by the scope.
o Remember the innominate artery supplies blood to the right arm, head and neck. It is the
first branch off the aortic arch, but is the third branch off the aorta – the left and right
coronary arteries are the first two branches off the aorta.
o Other examples of how the pulse oximeter can monitor for decreased perfusion include:
§ Placement on the toe to monitor foot perfusion in the lithotomy position
§ Limb perfusion following a fracture
§ Brachial artery compression during shoulder arthroscopy
o The Pulse Oximeter is Not a Monitor of Anemia
§ SpO2 monitors the percentage of hemoglobin bound with oxygen. It does not
quantify the amount of hemoglobin nor does it account for dissolved oxygen in
the blood. While the amount of hemoglobin is reduced during anemia, if the hemoglobin is fully saturated with oxygen, then the
SpO2 will continue to read 100%.
§ Since oxygen carrying capacity (CaO2) and oxygen delivery (DO2) are highly dependent on the amount of hemoglobin (not just
saturation), SpO2 is not a monitor of oxygen carrying capacity or oxygen delivery.
§ The pulse oximeter may overestimate SpO2 with severe anemia.
o The Pulse Oximeter is NOT a Monitor of Ventilation
§ According to the alveolar gas equation, a patient who is hypoventilating while breathing room air will have an
increased alveolar PCO2 and decreased alveolar PO2. As alveolar PO2 falls, so will PaO2 and SpO2.
Alveolar oxygen = FiO2 x (Pb – PH2O) – PaCO2
RQ
§ If the patient is receiving supplemental oxygen, the PaO2 and SpO2 may be “normal” in the presence of hypercarbia.
This patient can be hypercarbic, but still have a SpO2 of 100%. Therefore, the pulse oximeter is not a monitor of
ventilation.
§ Prove it to yourself by doing this calculation with a PaCO2 of 70 mmHg at a FiO2 of 21% and then again at 40%.
o The Pulse Oximeter is NOT a Monitor of Bronchial Intubation
§ Well…not always. The pulse oximeter is not a reliable method for detection of bronchial intubation. If a high inspired oxygen
concentration is used, it’s possible that the SpO2 reading will be minimally affected. Indeed, just because a patient does not
desaturate does not mean the endotracheal tube is not positioned in the left or right bronchus.
§ Assessment of bronchial intubation is better accomplished by the presence of bilateral breath sounds, chest x-ray, and/or visualizing
the carina through a fiber optic bronchoscope. It can also be detected by observing an acute reduction in lung compliance.
Additionally, an acute rise in peak inspiratory pressure during volume controlled ventilation may signal a bronchial intubation. As
you withdraw the endotracheal tube, the peak inspiratory pressure and the pressure and flow volume loops should return to
baseline.

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• Pulse Oximetry: Common Problems & Limitations
o The pulse oximeter has a margin of error of +/-2-3% when the SpO2 is between 70-100%, and when SpO2 is between 50-70%,
there is a margin of error of 3%.
o Despite the high degree of accuracy afforded by this technology, there are a variety of circumstances that defeat the usefulness
of the pulse oximeter.
o Dysfunctional Hemoglobin
§ The pulse oximeter can only see oxygenated Hgb and deoxygenated Hgb, and it gets confused by some dysfunctional
hemoglobin species. You’ll need a co-oximter to measure these.
§ Methemoglobin
• Absorbs 660 nm and 940 nm equally
• The 1:1 absorption ratio is read as 85%
• Falsely underestimates SpO2 if O2 sat >85%
• Falsely overestimates SpO2 if O2 sat <85%
§ Carboxyhemoglobin
• Absorbs 660nm to the same degree as O2-Hgb
• Co-Hgb and O2-Hgb look the same to the pulse
oximeter
• Reads the sum of O2-Hgb + CO-Hgb
(overestimates SpO2)
o Decreased Perfusion
§ Vasoconstriction
§ Hypothermia
§ Hypoperfusion
§ Reynaud’s syndrome
o Altered Optical Characteristics
§ Dyes such as methylene blue, indocyanine green, and indigo
carmine
§ Nail polish especially black, blue and green
§ External light
o Non-Pulsatile Flow
§ Cardiopulmonary bypass
§ Left ventricular assist device
o Motion Artifact Factors that Do NOT Affect the
§ Shivering Reliability of the Pulse Oximeter
§ Patient movement
§ Patient positioning • Hemoglobin S
o Other • Hemoglobin F
§ Electrocautery • Jaundice
§ Venous pulsation (tricuspid regurgitation) falsely decreases SpO2 • Fluorescein
• Measurement of Exhaled Gases • Polycythemia
o Infrared Absorption Spectrophotometry • Acrylic finger nails
§ Infrared absorption spectrophotometry has replaced all of the other methods of
exhaled gas analysis. Each gas absorbs a different wavelength of infrared light, each having a signature “fingerprint.”
§ The greater the partial pressure of a gas inside the breathing circuit, the greater the partial pressure of that gas that is delivered to
the gas analyzer. In turn, this higher concentration of the gas absorbs more infrared light and diminishes the intensity of light that
reaches the sensor. Infrared absorption spectrophotometry determines the concentrations and identities of all the sample gases
simultaneously. It is portable and more energy efficient than previous methods of gas analysis.
§ Oxygen does not absorb infrared light, so its concentration must be measured by electrochemical analysis (galvanic cell or Clark
electrode) or paramagnetic analysis.
o Mass Spectrometry
§ Mass spectrometry bombards a gas sample with electrons creating ion fragments. Because all of the particles become charged, they
can be separated and identified based on their mass. The mass spectrometry system is large and may be utilized for more than one
patient at a time.
o Raman Scatter Spectrometry
§ A spectrometry employing Raman scatter uses a high power argon laser to produce photons, which in turn collide with the gas
molecules. The scattered photons are measured in a spectrum that can identify each gas and its concentration.
o Piezoelectric Crystals
§ An analyzer using piezoelectric crystals is a new tool that can detect inspired, expired, and breath to breath changes of a particular
gas by incorporating a lipid layer on the crystal. This lipid layer responds to individual gases as they make contact and get absorbed.
Unfortunately, this technology is unable to identify multiple gases at once, making it impractical to use in the clinical setting.

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Monitoring II: Hemodynamics

• Blood Pressure Measurement

o Auscultation Method
§ The auscultation method relies on the Korotkoff sounds. These sounds represent turbulent flow in an artery that was
previously occluded by the BP cuff. There are 5 sounds, but only two are worth mentioning here.
• SBP is measured at the first sound.
• DBP is measured when the last sound disappears.
o Oscillatory Method
§ Automated NIBP machines utilize the oscillometric method to measure BP. An inflatable cuff occludes arterial blood
flow, and as the cuff pressure is released, the monitor measures the pressure fluctuations that occur in response to
arterial pulsations.
• SBP is measured when oscillations first appear (the reappearance of flow after occlusion by the cuff).
• MAP is measured when the amplitude of the oscillations is greatest.
• DBP is measured at the minimum pressure where oscillations can still be registered. The diastolic reading is
most susceptible to error.
§ The oscillatory method requires pulsatile flow, so a NIBP cuff won’t function in the patient on cardiopulmonary
bypass or with a left ventricular assist device. As long as the heart isn’t ejecting blood, these patients have continuous
flow and require an arterial line to monitor mean arterial blood pressure.
o Factors that Affect the Accuracy of the Oscillatory Method
§ Bladder Size:
• Ideal length = 80% of the extremity circumference
• Ideal width = 40% of the extremity circumference
o A cuff that is too small overestimates SBP. The cuff
pressure required to occlude the artery is higher with a cuff
that’s too small.
o A cuff that is too large underestimates SBP. The cuff pressure required to occlude the artery is
lower with a cuff that’s too large.
§ Cuff Location
• As the pulse moves from the aortic root towards the periphery, the systolic pressure increases, diastolic
pressure decreases, and the pulse pressure widens. Mean arterial blood pressure remains constant through
the arterial tree.
o At the aortic root, the SBP is the lowest, DBP is the highest, and PP is the narrowest.
o At the dorsalis pedis, the SBP is highest, the DBP is the lowest, and the PP is the widest.
§ Arm Positioning
• Blood in the circulation behaves like a column of fluid and follows the rules of hydrostatic pressure. Let’s examine how
the real blood pressure differs from what you see on the monitor when the patient’s heart and BP cuff are at different
heights.
o If the BP cuff location is above the heart, the BP reading will be falsely decreased (there is less hydrostatic
pressure).
o If the BP cuff location is below the heart, the BP reading will be falsely increased (there is more hydrostatic
pressure).
o For every 10 cm change, the BP changes by 7.4 mmHg.
o For every inch change, the BP changes by 2 mmHg.
• Example: the BP cuff is 10 inches below the level of the heart. What is the true BP at the level of the heart?
o 10 in x 2 mmHg/in = 20 mmHg
§ The BP on the monitor falsely increases, therefore the BP at the heart is 20 mmHg less than what
you see on the monitor.
• Keep this concept in mind when the patient is in the sitting or reverse Trendelenburg position. Furthermore, never
measure blood pressure in the calf when in these positions! Cerebral ischemia can occur even with a “normal” blood
pressure reading on the monitor.
o Complications of NIBP Measurement
• Pain
• Neuropathy (radial, ulnar or median)
• Measurement errors
• Limb ischemia
• Compartment syndrome
• Bruising
• Petechiae
• Interference with IV medications if IV is distal to the cuff
§ Do not place the BP cuff over a PICC line, over a bone fracture, or on a limb with an AV fistula. It should probably be avoided on
patients who have has a previous axillary lymph node dissection, as this may impair lymphatic drainage and cause limb edema,
although this point is considered controversial by some.

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 o Arterial Blood Pressure Waveform
§ You can gain a great deal of information by assessing the morphology of the arterial waveform. Here are a few
general rules:
• Systolic BP = Peak of waveform
• Diastolic BP = Trough of waveform
• Pulse pressure = Peak – trough
• Contractility = Upstroke
• Stroke Volume = Area under the curve
• Closure of aortic valve = dicrotic notch
§ *Stoelting says that the height of the dicrotic notch is not a
reliable estimate of SVR.
o Factors that Affect the Accuracy of the invasive Method
§ Optimal waveform morphology balances the amount of
damping with the amount distortion from the transducer system. The high pressure flush test helps us determine this
when we flush the system and observe the oscillations that result (if any).
• Optimally damped system: Baseline is re-established after 1 oscillation.
• Under-damped system: Baseline re-established after several oscillations (SBP is overestimated, DBP is
underestimated, and MAP is accurate).
• Over-damped system: Baseline is re-established with no oscillations (SBP is underestimated, DBP is
overestimated, and MAP is accurate). Causes include an air bubble or clot in the pressure tubing or low
flush bag pressure.
§ Invasive blood pressure monitors measure BP at the level of the transducer –not the site of insertion. As long as the
transducer is at the level of the right atrium, changes in body or extremity position will not affect the accuracy of the
arterial BP measurement.
• Central Venous Catheter: Placement
o How Far to Thread the Catheter?
§ To accurately interpret hemodynamic data, you should have a solid understanding of normal distances, pressures, and waveforms. We will
cover distances here.
• The tip of the CVP catheter should rest just above the junction of the vena cava and the right atrium. It should not be placed
inside the right atrium, as this will increase the risk of dysrhythmias, thrombus formation, and cardiac perforation.
• The tip of the PA catheter should reside in the pulmonary artery, distal to the pulmonic valve (25-35 cm from the VC junction).
§ There is an easy way to do this calculation.
• 1. You must know the distance from the site of entry to the vena cava junction.
• 2. You must know the distance from the vena cava junction to where the tip of the catheter should be placed.
• 3. Add these two numbers to determine the distance from the site of insertion to the tip of the catheter.

§ If you think you’ve advanced the catheter too far, you

probably have. If you advanced 10 cm beyond the
calculated distance and still don’t see the expected
waveform, assume that the catheter is coiled. In this
case, deflate the balloon, withdraw the catheter to the junction of the vena cava and right atrium, and try again. If you encounter
resistance while pulling back, the catheter is probably knotted or entangled with the chordae tendineae. Obtain a chest x-ray to rule
out these complications.
o Complications of Central Lines
§ Complications are related to placement of the line, catheter residence, or floating a pulmonary catheter.
§ Obtaining access via the left IJ has the added risk of puncturing the thoracic duct. This can cause chylothorax (lymph in the chest).
§ Dysrhythmias are the most common complication while obtaining access. The best way to treat PACs and PVCs is to withdraw the catheter
and start over.
§ The incidence of catheter related infection increases after 3 days.
§ Don’t float a PAC in the patient with a left bundle branch block. Advancing the catheter into the RV can cause a right bundle branch block,
and this can put the patient in complete heart block.
§ Hemoptysis is the classic presentation of pulmonary artery rupture.
§ The risk of pulmonary artery rupture is increased by:
• Patient factors: anticoagulation, hypothermia, and advanced age.
• Provider factors: inserting the catheter too far, prolonged balloon inflation, chronic irritation of vessel wall, unrecognized
wedging, and filling the balloon with liquid instead of air.

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• CVP Waveform
o The CVP waveform is a reflection of the pressure inside the right atrium. It has 3 peaks (a,c,v) and 2 trough (x,y). Each of these
represents pressure changes as blood moves into and out of the right atrium.
o When reviewing the CVP waveform you should understand how it correlates with the:
§ 1. Pressure in the right atrium.
§ 2. Mechanical events in the right atrium.
§ 3. Electrical activity of the heart.
o We’re going to break this down piece by piece.
o CVP Waveform and Mechanical Events

o CVP Waveform and Electrical Events

§ With this image, try to quiz yourself by reciting the components of the CVP waveform and then relate them to the
electrical events on the EKG and the cardiac cycle.

• CVP: Interpretation
o Measurement
§ CVP should be zeroed at the phlebostatic axis.
§ This is the fourth intercostal space mid anteroposterior level.
• A transducer placed above the zero point underestimates CVP.
• A transducer placed below the zero point overestimates CVP.
§ CVP should be measured at end-expiration. During this phase of the ventilatory cycle, extravascular pressure equals atmospheric
pressure, and this allows us to measure CVP relative to atmospheric pressure. Said another way, the CVP measurement is not
affected by intrathoracic pressure if the reading is recorded at end-expiration.
o Physiology
§ The normal CVP in the adult = 1-10 mmHg.
§ CVP is a function of:
• 1. Intravascular volume
• 2. Venous tone
• 3. Right ventricular compliance
§ in a perfect world, we assume the right ventricular output equals left ventricular output and that RAP reflects LVEDP.
§ Unfortunately, things are seldom this easy. We just said that CVP is a function of 3 things (intravascular volume is only on of them),
and a change in any of these variables can alter CVP. Therefore, evaluating CVP as a surrogate measure of volume status
oversimplifies the evaluation of intravascular volume and may lead to false conclusions.

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 o Interpretation
§ A low CVP usually means low intravascular
volume.
§ A high CVP indicates at one or more of the
following:
• 1. Hypervolemia
• 2. Reduced ventricular compliance
• 3. Increased intrathoracic pressure.
o Causes of Altered Central Venous Pressure
• CVP Waveform: Abnormal
o A good understanding of the underlying events of the
normal CVP waveform make interpretation of abnormal waveforms much easier. We’ll go over a few general ideas, then we’ll
give you a bunch of examples. We strongly encourage you to work through these examples in your mind. If you’re still shaky on
the normal CVP waveform morphology, review that page before moving on.
o Loss of a Wave:
§ This occurs when synchronized contraction of the right atrium is lost.
§ Examples:
• Atrial fibrillation
• V-pacing if the underlying rhythm is asystole.
o Large a Wave:
§
T'd amplitude
The atria contracts and empties against a high resistance (either at the valve or non-compliant ventricle).
§ Examples:
• Tricuspid stenosis
• Diastolic dysfunction
• Myocardial ischemia
• Chronic lung disease leading to RV hypertrophy
• AV dissociation
• Junctional Rhythm
• V-pacing – asynchronous
• PVCs
o Large v Wave:
§ Tricuspid regurgitation allows a portion of the right ventricular volume to pass through the closed but incompetent
tricuspid valve during RV systole. This increases the volume and pressure in the RA and manifests as large v waves.
Also, the c and the v waves may blend into each other.
§ Examples:
• Tricuspid regurgitation
• Acute increase in intravascular volume
• RV papillary muscle ischemia
• PA Waveform

o Right Atrial Pressure

§ This was discussed in a previous page.
o Right Ventricular Pressure
§ The systolic pressure increases.
§ The diastolic pressure is equal to CVP.
o Pulmonary Artery Pressure
§ The systolic pressure remains about the same.
§ The diastolic pressure rises.
§ The dicrotic notch I formed during pulmonic
valve closure during diastole.
o Pulmonary Artery Occlusion Pressure (Pulmonary
Capillary Wedge Pressure)
§ This waveform is akin to the CVP of the left
heart.
§ The a wave is caused by left atrial systole.
§ The c wave is caused by mitral valve elevation into the LA during LV systole (isovolumetric contraction).
§ The v wave is caused by passive left atrial filling.
o *we think Nagelhout is a little confused in its description of the c and v waves on the PAOP waveform.

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• PA Catheter Tip Placement
o Where Should the Catheter Tip Be Placed?
§ In his book, “Respiratory Physiology,” John West describes the lungs as three zones that are dependent on body
position. Each zone is defined by the relative pressure in the alveolus, arterial pulmonary capillary and venous
pulmonary capillary.

§ The tip of the PAC should be in zone III. In this region, there is a continuous column of blood between the tip of the
PAC and the left ventricle. Since LVEDP reflects back through the pulmonary circulation, a tip positioned in zone III
provides the most accurate estimation of LVEDP.
§ Zone III is defined as P arterial > P venous > P alveolus.
§ Zone III is in the dependent region of the lung.
• Sitting: At the the lung base
• Supine: Towards the back
• Prone: towards the chest
• Lateral: towards the dependent (lower) lung
o How Can You Tell the Tip is in Zone III?
§ Here are some things that suggest the tip of the PA cath is NOT in zone III:
• PAOP>pulmonary artery end-diastolic pressure
• Nonphaseic PAOP tracing
• Inability to aspirate blood from the distal port with the balloon is in the wedge position.
§ As an aside, we have several links to Dr. West discussing respiratory physiology in the links on the apex resources
page.
• PA Catheter: Abnormal
o In order to use the PAC appropriately, you must know which circumstances that can skew the data. We’ve laid out the
cardiopulmonary pressures in order from the right atrium to the left ventricle and inserted a few examples of conditions othat
can change the relationships in the circuit.

o When PAOP Does Not Accurately Predict LVEDV

§ Conditions where PAOP overestimates LVEDP (and by extension LVEDV) include:
• Impaired LV compliance (ischemia)
• Mitral valve disease (stenosis or regurgitation)
• Left-to-right cardiac shunt
• Tachycardia
• PPV
• PEEP
• COPD
Pulmonary Hypertension
• Non West Zone III Placement of PAC
§ Conditions where PAOP underestimates LVEDV include:
• Aortic insufficiency

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• Cardiac Output
o Thermodilution Method
§ The thermodilution method is the most common way we measure cardiac output. An injection of 5% dextrose or 0.9
NaCl of known quantity and temperature is bloused through the proximal port on the pulmonary artery catheter.
Each injection should occur during the same phase of the respiratory cycle and be completed in <4 seconds. It is
common practice to average 3 separate injections to arrive at the final cardiac output. This improves the accuracy of
the final value.
§ Using the modified Stewart-Hamilton equation, a computer plots temperature change vs. time. The area under the
curve (AUC) is inversely proportional to cardiac output.
• If CO is high, the injectate rapidly travels towards the distal tip of the PAC. The AUC is smaller.
• If CO is low, it takes longer for the injectate to travel past the distal tip of the PAC. The AUC is larger.

Factors that Influence Thermodilution Cardiac Output Measurements

o Continuous Cardiac Output

§ Continuous cardiac output monitoring (CCO) has the advantages of providing continuous data and avoiding the inaccuracies from
the human element.
§ There is a significant drawback to CCO monitoring. There is a 30 second delay between the time the CO is measured and when it
appears on the monitor. Furthermore, the CCO value on the monitor averages the previous 3-6 minutes of CO data. This time delay
may be unacceptable in a hemodynamically unstable patient. In this instance, it may be preferential to use the standard bolus
thermodilution method.
• Mixed Vneous Oxygen Saturation
o Mixed venous oxygen saturation is a function of 4 variables:
§ Q=Cardiac output (L/min)
§ VO2=Oxygen consumption (mL O2/min)
§ Hgb=amount of hemoglobin (g/dL)
§ SaO2=Loading of hemoglobin in arterial blood (%)
SvO2= SaO2 - VO2 Normal= 65-75%
(Q x 1.34 x Hgb x 10)
o When hgb, SaO2, and VO2 are held constant, then mixed venous oxygen saturation becomes an indirect monitor of cardiac output.
o Factors that Change SvO2
§ When oxygen consumption increases or oxygen delivery decreases, the oxygen content returning to the heart decreases. This
manifests as a decreased SvO2.
§ You can memorize a long list of things
that alter SvO2, or you can learn to apply
the equation. Once you know it, you will
always be able to rationalize your way to
the correct answer. If you prefer lists,
we’ve got you covered.
§ Other key causes of increased SvO2
include:
• Sepsis creates a high cardiac
output state with an arterial
admixture. Even though
sepsis causes end organ
hypoxia, oxygen essentially bypasses the tissues (arterial admixture) and SvO2 remains elevated.
• Impaired oxygen uptake by the tissues. Cyanide poisoning from sodium nitroprusside is the classic example.
• Left-to-right shunt. Oxygenated blood travels from the left heart to the right heart and is added to pulmonary venous
blood.
o Why Do We Need a Pulmonary Artery Catheter to Measure SvO2?
§ Since different organs extract different amounts of oxygen, a true mixed venous sample must contain blood returning form the
superior vena cava, inferior vena cava, and the coronary sinus. Mixing of blood form these 3 sources occurs in the pulmonary artery,
thus a pulmonary artery catheter is required to measure SvO2.

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Monitoring III: Cardiac Rhythms
• Cardiac Conduction System
o Conduction System Anatomy
§ The cardiac conduction system contains:
• Sinoatrial (SA) node
• Intermodal tracts
• Atrioventricular (AV) node
• Bundle of His
• Bundle branches
• Purkinje fibers
o Internodal Tracts
§ There are 3 internodal tracts that connect the SA to the AV
node.
• 1. Anterior intermodal tract (Bachmann bundle)
• 2. Middle intermodal tract (Wenckebach tract)
• 3. Posterior intermodal tract (Thorel tract)
o Conduction Velocity
§ The conduction velocity quantifies how fast an
electrochemical impulse propagates along a neural pathway.
§ Conduction velocities of the cardiac conduction pathway:
• SA and AV nodes = 0.02-0.1m/sec (slow
conduction)
• His bundle, bundle branches, and purkinje fibers =
1-4 m/sec (fast conduction)
• Myocardial muscle cells = 0.3-1 m/sec
(intermediate conduction)
§ Conduction velocity is a function of:
• 1. Resting membrane potential
• 2. Amplitude of the action potential
• 3. Rate of change in membrane potential during
phase 0
§ Conduction velocity is affected by:
• ANS tone
• Hyperkalemia induced closure of fast Na+ channels (this is reviewed in question in the local anesthetic
tutorial)
• Ischemia
• Acidosis
• Antiarrhythmic drugs
o Accessory Pathways
§ There is a band of connective tissue that electrically isolates the atria from the ventricles. While this architecture
preserves AV synchrony by preventing atrial tissue from prematurely exciting ventricular tissue, it places supreme
importance on the AV node. This is because the AV node serves as the only electrical pathway between the cardiac
chambers. We want you to think of the AV node as the “gatekeeper” of electrical transmission between the atria and
the ventricles.
§ Accessory pathways bypass the normal conduction pathways, and Accessory Pathway Connections
these can be the basis of pathologic arrhythmias. A classic James Fiber Atrium to AV node
example of this is a Wolff-Parkinson-White syndrome and Kent’s Atrio-hisian fiber Atrium to His bundle
bundle. More on this later… Kent’s Bundle Atrium to ventricle
• The EKG and the Cardiac Action Potential Mahaim bundle AV node to ventricle
o Before we can review cardiac rhythms, we must first revisit how the EKG
relates to the cardiac action potential.
o Electrocardiogram: Waves, Intervals, and Segments

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 o Ventricular Action Potential and the EKG

§ The absolute refractory period means that no stimulus (no

matter how strong) can depolarize the myocyte.
§ The relative refractory period means that a larger than normal stimulus is required to depolarize the myocyte.
o EKG and Mechanical Events
§ It is imperative that you can correlate what you observe on the EKG with:
• The electrical activity inside the heart.
• The cardiac cycle (contraction occurs just after depolarization).

• EKG: Normal Values and Abnormalities

Duration (sec) Amplitude (mm) Key Facts
st
P wave 0.08-0.12 <2.5 Prolonged with 1 degree heart block
PR Interval 0.12-0.20 PericarditisàPR interval depression
Q wave <0.04 <0.4-0.5 Consider MI if:
-amplitude is greater than 1/3 of R wave
-Duration is greater than 0.04 seconds
-Depth is greater than 1 mm
QRS Complex <0.10 Progressively increases from If increased consider:
V1àV6 -LVH, bundle branch block, ectopic beat, WPW
-Normal R wave progression
QTc interval <0.45 men X See Long QT Syndrome page
<0.47 women
ST segment X X Consider MI if:
-elevation or depression greater than 1 mm
Elevation also caused by:
-hyperkalemia or endocarditis

T wave X <10 in precordial leads Usually T wave points in same direction as QRS
<6 in limb leads T wave points in opposite direction of QRS if
repolarization is prolonged by:
-myocardial ischemia, bundle branch block
Peak T waves are caused by:
-Myocardial ischemia, increased potassium,
intracranial bleed.
U wave X Usually absent If greater than 1.5mm, then consider decreased
potassium
189
• Where Do You Measure ST Changes?
o The PR segment is an isoelectric line. Because of this, it is used as the reference point for measuring ST elevation and
depression.
o The J point is where the QRS complex ends and the ST
segment begins. By measuring this point relative to the
PR segment, we can quantify the amount of ST
elevation and depression. As a general rule, great than
+ 1.0 or less than – 1.0 are significant.
o The degree of ST changes typically parallels the
severity of the event. It’s important to consider the situation in context, as other factors can affect the ST segment (abnormal
cardiac conduction, electrolyte disturbances, digitalis, and hypothermia).
• How Do Electrolytes Affect the EKG?

• The Importance of Understanding Vectors

o Each myocyte generates an action potential, and each of these potentials can travel in
any direction.
o To make order out of chaos, the mean electrical vector is the average current flow of
all the action potentials at a given point in time. The waveform you see on the EKG is a
measure of the mean electrical vector.
o There are 2 vectors that you must understand:
§ 1. The vector of depolarization
§ 2. The vector of repolarization
• How Does the EKG Measure the Mean Electrical Vector?
o Each lead consists of one negative electrode and one positive electrode.
§ We want you to think of the positive electrode as a camera that
monitors the path of the mean electrical vector.
§ Additionally, we want you to think of the direction of the electrical
current as well as its polarity (is the current positive or negative).
o This can be tricky stuff, but understanding this material is critical to developing your understanding of
EKG abnormalities.
• Vector of Depolarization = QRS Complex
o Direction: The heart depolarizes from 1.) base àapex and 2.) endocardium àepicardium
o Polarity: The myocytes go from internally (-) to internally (+). This produces a positive electrical current.
o Looking at the image above, you can see that:
§ A positive deflection occurs when the vector of depolarization travels towards the positive electrode.
§ A negative deflection occurs when the vector of depolarization travels away from the positive electrode.
§ A biphasic deflection occurs when the vector of depolarization travels perpendicular to the positive
electrode.
• Vector of Repolarization=T Wave
o Direction: the heart repolarizes from 1.) apex àbase and 2.) epicardium àendocardium.
§ You can think of repolarization as the opposite of depolarization
o Polarity: The myocytes go from internally (+) to internally (-). This produces a negative electrical current.
§ A positive deflection occurs when the wave travels away from the positive electrode.
o All things considered, you might expect that the direction of the T wave should point in the opposite direction of the
R wave. Obviously, this isn’t what happens. Here’s why:
§ The vector of repolarization travels in the opposite direction as the vector of depolarization.
§ The vector of repolarization produces a negative current.
§ This “double negative” explains why the T wave usually points in the same direction as the R wave.

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• 12 Leads = 12 Cameras
o We commonly use 12 leads to look at the heart’s electrical activity from a variety of different angles. We can divide these leads
into 3 groups:
§ 1. Bipolar leads (3)
§ 2. Limb leads (3)
§ 3. Precordial leads (6)
o You should be able to match each lead with the region of the heart it monitors as well as its corresponding coronary artery.

• Axis Deviation
o How to determine Axis Deviation
§ The axis represents the direction of the mean electrical vector in the frontal plane.
§ There are several ways to determine axis deviation, but this is the easiest to remember. You’ll need to examine lead I
and aVF.

o How to Remember
§ If the leads are Reaching towards each other (I pointing down and aVF pointing up), then we have Right axis
deviation.
§ If the leads are Leaving each other (I pointing up and aVF pointing down), then we have Left axis deviation.
o Numbers to Know
§ Normal axis is between -30 to +90 degrees.
§ Left axis deviation is more negative than -30 degrees.
§ Right axis deviation is more positive than 90 degrees.
o Causes of Axis Deviation
§ The axis can shift as a consequence of a hypertrophy, conduction block, or a physical change in the position of the
heart.
§ The mean electrical vector tends to point:
• Towards areas of hypertrophy (there is more tissue undergoing depolarization).
• Away from areas of myocardial infarction (the vector has to move around these areas).

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• Selected Rhythm Disturbances
o Sinus Arrhythmias
§ Sinus arrhythmia occurs when the SA node’s pacing rate varies with respiration. It’s usually benign.
§ Remember the Bainbridge reflex/ this is the one where an increased venous return stretches the right atrium and SA node causing the heart rate to increase. It
should also make sense that the Bainbridge reflex cause sinus arrhythmia.
• Inhalationà decreased intrathoracic pressure à increased venous return à increased heart rate
• Exhalation à increased intrathoracic pressure à decreased venous return à decreased heart rate
o Sinus Bradycardia (HR <60 BPM)
§ Sinus bradycardia is common in athletes.
§ Increased vagal tone is often the source of bradycardia.
§ Atropine is a first-line treatment, however underdosing it (<0.5 mg IV) can cause paradoxical bradycardia. This is probably mediated by presynaptic muscarinic
receptors.
§ Severely symptomatic patients (syncope or chest pain) should receive immediate transcutaneous pacing.
§ Glucagon is useful in the setting of beta blocker or calcium channel blocker overdose. By stimulating glucagon receptors on the myocardium, glucagon effectively
increases cAMP sleading to increased heart rate, contractility, and
§ AV conduction. The initial dose is 50 -70 mcg/kg q 3-5 min. this can be followed with an infusion at 2-10 mg/hr.
o Sinus Tachycardia (HR >100 BPM)
§ Sinus tachycardia is usually caused by an increased intrinsic firing rate of the SA node or sympathetic stimulation.
§ Etiologies include hypovolemia, hypoxemia, infection, pain, thyrotoxicosis, and malignant hyperthermia.
§ Sinus tachycardia simultaneously increases myocardial oxygen demand while decreasing oxygen supply.
§ It can precipitate myocardial ischemia and congestive heart failure in patients with poor cardiac reserve.
§ In patients with CAD, this can precipitate myocardial ischemia and/or infarction.
§ Treatment includes treating the underlying cause and/or rate control with beta blockers or calcium channel blockers.
o Atrial Fibrillation
§ AF is an irregular rhythm with the absence of a P wave. Chaotic electrical activity in the atrium is conducted to the ventricle at a varied and irregular rate.
§ Loss of atrial kick reduces cardiac output.
§ Increased risk of perioperative mortality.
§ Increased risk of atrial thrombus formation (risk of stroke)
§ A rapid ventricular response reduces diastolic filling time and is associated with a severe reduction in CO (syncope, chest pain, shortness of breath).
§ Treatment includes rate control (beta blockers, calcium channel blockers, and digoxin) and anticoagulation.
§ Acute onset a-fib is treated with cardioversion (start at 100 joules).
§ If the onset is older than 48 hours (or if onset is undetermined), a TEE must be performed to rule out atrial thrombus.
§ New onset or undiagnosed atrial fibrillation is an indication to cancel surgery.
§ AF is the most common postoperative tachydysrhythmia, usually occurring between post-op day 2 and 4. It is most common in older patients after cardiothoracic
surgery.
o Atrial Flutter
§ Unlike atrial fibrillation, atrial flutter is an organized supraventricular rhythm. You should recognize it by its characteristic “saw tooth”
pattern.
• The atrial rate is usually very fast (250-350bpm).
• Each atrial depolarization produces an atrial contraction, but not all atrial depolarizations are conducted past the AV node.
• There is usually a defined ratio of atrial to ventricular contractions (ex: 3 atrial contractiosn: 1 ventricular contraction).
• The effective refractory period prevents all atrial impulses from being transmitted to the ventricles.
• If the onset is older than 48 hours (or if onset is undetermined), a TEE must be performed to rule out atrial thrombus.
• A rapid ventricular rate can lead to hemodynamic instability.
• Treatment includes rate control or cardioversion.
• Hemodynamically unstable atrial flutter should bet treated with cardioversion (start at 50 joules).
• Atrial flutter is an indication to cancel surgery.
o Premature Ventricular Contractions
§ Premature ventricular contractions originate from foci below the AV node. As such, the QRS complex is wide.
• PVCs that arise from a single location are unifocal (the morphology is the same on the EKG).
• PVCs that arise from multiple locations are multifocal (there are different QRS morphologies on the EKG).
§ There are many conditions that are associated with the development of PVCs. Examples Include:
• SNS stimulation (hypoxia, • Hypomagnesemia
hypercarbia, acidosis, light • Digitalis toxicity
anesthesia) • Caffeine
• Myocardial ischemia and/or • Cocaine
infarction • Alcohol
• Valvular heart disease • Mechanical irritation (central line
• Cardiomyopathy insertion)
• Prolonged QT interval
• Hypokalemia
§ A PVC that lands on the second half of the T wave (during the relative refractory period) can precipitate the R on T phenomenon.
§ PVC’s should be treated when they are frequent (>6/min), polymorphic, or when they occur in runs of 3 or more. Treatment includes:
• Reverse underlying cause: reversal of hypoxia/hypercarbia, correction of electrolyte imbalances, discontinuation of QT prolonging
drugs, and repositioning a central line that’s tickling the atrium.
• Symptomatic PVCs are treated with lidocaine 1.0-1.5 mg/kg. if PVCs continue, follow with an infusion of 1-4 mg/min.
o Brugada Syndrome
§ Brugada syndomre is a sodium ion channelopathy in the heart.
§ It is a common cause of sudden nocturnal death due to ventricular tachycardia or fibrillation.
§ It is more common in males from Southeast Asia.
§ Diagnostic EKG findings include a right bundle branch block and ST-segment elevation in the precordial leads (V1-V3).
§ Patient may require ICD or pad placement during surgery.

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• Heart Block
o First Degree Heart Block
§ If “R”is far from “P” then you have a First Degree.
§ The PR interval is >0.20 sec.
§ Affected region:
• AV node or His bundle
§ Etiology:
• Age related degenerative changes, CAD, digoxin, amiodarone
§ Treatment:
• Monitor (usually asymptomatic)
o Second Degree Heart Block (Mobitz Type I)
§ Longer, longer, longer, drop then you have a Wenckebach.
§ The PR interval becomes progressively longer with each cycle, but the last Pwave does not conduct to the ventricles.
Then, the cycle repeats.
§ Why does this happen? Each successive depolarization increases the duration of the refractory period in the AV node.
The last P in the cycle is dropped, because it arrives at the AV node while it’s in the absolute refractory period. This
beat is not conducted, but the pause that follows provides enough time for the AV node to reset. Then, the cycle
repeats.
§ Affect Region:
• AV node
§ Etiology:
• Structural conduction defect, myocardial
injury/infarction, beta-blockers, CCBs,
digoxin, sympatholytic agents
§ Treatment:
• If the patient is asymptomatic, the it is safe just to monitor
• If the patient is symptomatic, then give atropine
o Second Degree Heart Block (Mobitz Type II)
§ If some “P”s don’t get rhoguh then you have a Mobitz II.
§ Some P’s conduct to the ventricles, while others don’t
(there is usually a set ratio 2:1 or 3:1). After the
dropped QRS, the next P arrives right on time.
§ Affected region: His bundle or bundle branches
§ Etiology: Structural conduction defect or infarction
§ Treatment:
• Often symptomatic (palpitations and syncope)
• Pacemaker (transcutaneous, transvenous, or implantable)
• Atropine often not effective
§ Key Point:
• There is a high risk of progressing to complete heart block
o Third Degree Heart Block
§ If “P”s and “Q”s don’t agree then you have a Third Degree
§ The atria and ventricles each have their own rates (AV dissociation)
• Block in the AV node has a narrow QRS (rate 45-55 bpm)
• Block below the AV node has a wide QRS (rate 30-40 bpm)
§ Etiology:
• Fibrotic degeneration of the atrial conduction system, Lenegre’s disease
§ Treatment:
• Often symptomatic (dyspnea, syncope, weakness, vertigo)
• Pacemaker (Transcutaneous, transvenous, or implantable)
• Isoproterenol (chemical pacemaker)
§ Key Points:
• Can lead to CHF to due decreased HR and Co.
• Stokes-Adams attack = decreased CO à decreased cerebral perfusion à syncope
o The Heart Block Rhyme
§ If “R “ is far from “P” then you have a First Degree
§ Longer, longer, longer, drop then you have a Wenckebach.
§ If some “P”s don’t get through then you have a Mobitz II.
§ If “P”s and “Q”s don’t agree then you have a Third Degree

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• Antidysrhythmic Medications
o Antiarrhythmic drugs are classified according to their ability to block specific ion channels and currents of the cardiac action
potential.
§ It’s easy to get caught up in the minutiae. For this reason, we’re going to limit our review to the most important
antidysrhythmic qualities of these drugs.
§ Notice the effects on each phase of the action potential as well as which types of action potentials are affected
(SA/AV or ventricular).

o Adenosine
§ Adenosine is an endogenous nucleoside that slows conduction through the AV node. By stimulating the cardiac
adenosine-1 receptor, adenosine inhibits K+ currents, which hyperpolarizes membranes and reduces action potential
duration.
• It is rapidly metabolized in the plasma (t1/2=5 seconds).
• It is useful for supraventricular tachycardia as well as WPW with a narrow QRS.
• It is not useful for atrial fibrillation, atrial flutter, or ventricular tachycardia.
• It can cause bronchospasm in asthmatic patients.
§ How to Dose Adenosine
First Dose Second Dose (if required)
Peripheral (AC preferred) 6 mg 12 mg
Central 3 mg 6 mg
• Reentry Pathways
o Reentry pathways are the most common cause of tachyarrhythmias. Understanding this physiology aids in your understanding
of a variety of fast heart rhythms.
o Impulse Conduction Through the Normal Pathway
§ The cardiac impulse moves in one direction: SA nodeàAV nodeàHis bundleàbundle branchesàpurkinje fibers
§ The cardiac impulse cannot move backwards, because all the tissues behind the impulse remain in the absolute
refractory period.
§ There is a 1:1 ratio of SA node depolarization and cardiac contraction.
o See It In Action
§ As the cardiac impulse propagates, it may encounter an area where it can create
an electrical circuit.
§ At this point, the impulse propagates along both pathways.
§ The impulses travel along the left and right pathways at the same speed.
§ The impulses meet along connecting pathways, but they cancel each other out.
§ Since the impulses cancel each other out, there is no opportunity for reentry to
occur.

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• Impulse Conduction Through a Reentry Pathway
o Reentry describes the process where a single cardiac impulse can move backwards and excite the same part of the myocardium
over and over.
o Since the ratio of SA node discharge and cardiac contraction can exceed a 1:1 ratio, there is a risk that an impulse that circles
around the reentry pathway will precipitate a reentry tachyarrhthmia.
o See It In Action

o 1. In the circuit, one pathway is normal and the other has a unidirectional block. The impulse in the normal pathway continues
through the circuit, while the impulse that encounters the unidirectional block does not.
o 2. The impulse in the normal pathway splits (lower left corner of the triangle). It continues along the distal conduction pathway
(arrow pointing down), but it also continues through the circuit (arrow pointing right).
o 3. The impulse inside the circuit encounters the unidirectional block. Because it’s approaching this region from the other
direction, it is allowed to pass through. This occurs because the impulse took a longer amount of time to arrive at this location
and these cells have recovered (i.e. they are past the refractory period and can be depolarized again).
o 4. The reentry circuit is complete. The impulse goes around the loop, and each time it circles it gives off an additional impulse
that continues throught the rest of the normal conduction pathway (arrows pointing down). Each of these impulses will
ultimately stimulate the myocardium.
• How to Break the Circuit
o The circuit can be broken by 1.) slowing conduction velocity through the circuit or 2.) increasing the refractory period of the
cells at the location of the unidirectional block. More about this on the next page.
• When is a Reentry Pathway Likely to Develop?
o There are several situations when a reentry pathway is likely to develop.

• Wolff-Parkinson-White Syndrome
o Wolff-Parkinson White is the most common pre-excitation syndrome.
o Its defining feature consists of an accessory conduction pathway (Kent’s bundle) that bypasses the AV node.
§ The accessory pathway forms a direct line of communication between the atrium and the ventricle.
§ In the normal conduction pathway, the cardiac impulse is delayed at the AV node. Said another way, the AV node has a long
refractory period.
§ In the accessory pathway, there is no delay, so the impulse quickly moves from the atrium to the ventricle. There is no gatekeeper
function.
o What WPW Looks Like
§ WPW is usually diagnosed with a routine EKG or during the workup for a history of tachyarrhythmias.
§ Common characteristics observed on the EKG include:
• Delta wave caused by ventricular preexcitaion
• Short PR interval (<0.12 seconds)
• Wide QRS complex
• Possible T wave inversion
§ You may be wondering about the origin of the delta wave. After the SA node depolarizes, the
electrical impulse travels through the AV node and the accessory pathway at the same time.
The accessory pathway does nto delay the impulse; therefore, this impulse arrives at the
ventricle early which causes the characteristic delta wave on the EKG. When the impulse that
was delayed at the AV node catches up, you’ll see the rest of the QRS complex.

o AV Nodal Reentry Tachycardia & WPW

§ AV nodal reentry tachycardia is the most common tachydysrhythmias associated with WPW. It can be classified as orthodromic or
antidromic.

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 Orthodromic AVNRT Antidromic AVNRT
Incidence More common (~90% of case) Less common (~10% of cases)
Reentry Conduction Pathway Atrium à AV nodeàventricleà AtriumàAccessory pathwayàventricleà
accessory pathwayàatrium AV nodeàatrium

QRS Morphology Narrow Wide

--Ventricular depolarization occurs --Ventricular depolarization is slower since
normally via the His-purkinje system the His-Purkinje system is bypassed
Treatment Block Conduction at the AV node pathway Block conduction at the accessory pathway
(increase AV node refractory period) (increase accessory pathway refractory
period)
-vagal maneuvers
-amiodarone -procainamide
-adenosine -amiodarone
-beta-blockers -cardioversion
-verapamil
-cardioversion **Do NOT give agents that increase the
refractory period of the AV node. Doing so will
favor conduction through the accessory
pathway.
§ Of the two types of AVNRT, antidromic is more dangerous. This is because the gatekeeper function of the AV node is
bypassed and the heart rate can increase well beyond the heart’s pumping ability (it dramatically reduces filling time).
§ Here is where things get tricky. If you give an AV nodal blocking drug to a patient with antidromic AVRNT , then you’ll
then force conduction along the accessory pathway. This can induce ventricular fibrillation! Therefore, you must avoid
drugs that block conduction through the AV node. Drugs to avoid with antidromic AVRNT include:
• Adenosine
• Digoxin
• Calcium channel blockers (diltiazem and verapamil
• Beta-blockers
• Lidocaine
§ Amiodarone or cardioversion are safe options for orthodromic and antidromic AVNRT.
o Atrial Fibrillation & WPW
§ Because there is no delay in the accessory pathway, a rapid atrial rate can be conducted to the ventricles in a 1:1
ratio.
§ During atrial fibrillation, the atria can depolarize up to 300 times per minute. The combination of AF and WPW can
precipitate CHF, ventricular fibrillation, and death.
§ Procainamide is the treatment of choice because it increases the refractory period in the accessory pathway. If the
patient is hemodynamically unstable, then cardioversion is the best option.
§ Avoid drugs that increase the refractory period of the AV node (see list above).
o Radiofrequency Ablation
§ Definitive treatment for WPW is ablation of the accessory pathway.
§ Radiofrequency ablation of pathways involving the left atrium imposes a risk of thermal injury to the left atrium and
esophagus. For this reason, you must closely monitor an esophageal temperature during this procedure. If the
temperature rises during periods of ablation, you must inform the cardiologist immediately.

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• Torsades de Pointes
o What It Looks Like
§ Torsades de pointes is a polymorphic ventricular tachycardia that is literally translated as “twisting of the spikes.” The
underlying cause for this rhythm is a delay in ventricular repolarization (phase 3 of the action potential). This rhythm
is usually self-limiting, however it can deteriorate into ventricular fibrillation.

o What Causes It
§ Torsades de pointes is usually associated with a long QT interval.
§ Mnemonic: POINTES
• Phenothiazines
• Other meds (see chart
• Intracranial bleed
• No known cause
• Type I antiarrythmias
• Electrolyte disturbances
• Syndromes
§ The QT interval varies inversely with heart
rate, so we use the QTc (c for corrected) to
compensate for this. A prolonged QT interval
is defined as:
• Men>0.45 seconds
• Women >0.47 seconds
• Some texts say>0.40 seconds
§ An electrical stimulus, such as a PVC or
nd
poorly timed pacer discharge, during the relative refractory period (during the 2 half of the T wave) can cause
torsades de points. This is called the R-on-T phenomenon.
o Prevention and Treatment
§ Patients with long QT syndrome may require beta-blocker prophylaxis and/or ICD placement.
§ Avoid SNS stimulation.
§ Acute treatment for torsades de pointes includes reversing the underlying cause and/or shorten the QT interval.:
• Magnesium sulfate
• Cardiac pacing to increase the heart rate will reduce action potential duration and the QT interval.
• Pacemakers: Part I
o The cardiac output is dependent on the heart’s ability to generate a normal rate and rhythm. If the heart is unable to produce a
normal rate and rhythm, a pacemaker can be placed to accomplish this task.

o A pacemaker consists of a pulse generator and pacing leads the deliver electrical current to the heart.
§ Epicardial leads stimulate the surface of the heart.
§ Transvenous leads stimulate the cardiac chamber (RA and/or RV).
o Pacemaker Designation
§ Pacemakers are categorized by a 5 letter code. Each letter describes a function performed by that particular
pacemaker.
§ Mnemonic: PaSeR
• Pa=Chamber Paced
• Se = Chamber Sesed
• R=Response
o Appearance on the EKG
§ If the atrium is paced, the electrical signal travels through the AV node and the QRS maintains its normal, narrow
appearance.
§ If the ventricle is paced, the electrical signal is delivered beyond the AV node and the QRS takes on a wide
appearance.

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 Position I O=None This is the chamber that is paced.
A=Atrium
V=Ventricle
D=Dual (A+V)
Position II O= None This is the chamber that is sensed.
A=atrium
V=Ventricle
D=Dual (A+V)
Position III O=None This is the response to sensed native cardiac activity.
T=Triggered T=sensed activity tells the pacemaker to fire.
I=Inhibited I= sensed activity tells the pacemaker NOT to fire.
D=Dual (T + I) D= if native activity is sensed, then pacing is inhibited. If native activity is not sensed, then
the pacemaker fires.
Position IV O=None This indicates the programmability of the pacemaker. This describs the ability to adjust
R=Rate modulation heart rate in response to physiologic need. Sensors can measure respiration, acid-base
status, vibration, etc.
Position V O=None This indicates that the pacemaker can pace multiple sites.
A=Atrium
V=ventricle
D=Dual (A+V)

• Pacemakers: Part II
o The Role of the Magnet
§ This continues to be a confusing topic for many people. Here’s what you need to know:

o How to Minimize the Risk of Pacemaker Failure

§ Pacemaker failure has 3 causes:
• 1. Pulse generator failure
• 2. Lead failure
• 3. Failure to capture
§ Pacemaker function can be impaired because of electromagnetic interference (EMI) or conditions that make the myocardium more resistant
to depolarization.
§ The risk of EMI is greatest with the use of electrocautery and radiofrequency ablation.
§ Electrocautery:
• When the electrocautery is used, the “coagulation” setting causes more Emi than the “cutting” setting.
• A monopolar cautery causes more EMI than a bipolar cautery or ultrasonic Harmonic scalpel.
• If the surgeon insists on monopolar cautery, then you insist that s/he use short bursts (< 0.5 seconds).
• The risk of EMI is highest when the electrocautery tip is used within a 15 cm radius of the pulse generator.
• Place the electrocautery return pad far away from the pulse generator and in a location that prevents a direct line of current
through the pulse generator.
§ Conditions that make the myocardium more resistant to depolarization (the pacemaker fires but there may be failure to capture):
• Hyper- and hypokalemia
• Hypocapnia (intracellular K+ shift)
• Hypothermia
• Myocardial infarction
• Fibrotic tissue buildup around the pacing leads
• Antiarrhythmic medications
§ MRI is contraindicated in patients with a pacemaker or ICD.
§ Lithotripsy is not contraindicated. The beam should be directed away form the pulse generator.
§ Electroconvulsive therapy is not contraindicated.
§ In theory, succinylcholine could make the myocardium less resistant to depolarization (transient increase in serum K+ and skeletal muscle
contraction that could confuse the pacemaker). This doesn’t seem to ban an issue in clinical practice and is not a reason to avoid
succinylcholine in this patient population.
§ * The chart in Stoelting’s Anesthesia and Co-Existing Disease 6th ed. On p101 is not accurate.
o If the Pacemaker Fails
§ The single most important information to have preoperatively is the patient’s underlying rhythm—so you know how to adequately prepare if
the device fails.
§ Consider isoproterenol, epinephrine, and/or atropine.

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Monitoring IV: Miscellaneous
• Cerebral Oximetry
o Cerebral oximetry utilizes near infrared spectroscopy (NIRS) to measure cerebral
oxygenation.
§ It measures venous oxygen saturation.
§ It detects regional oxygenation—it is NTO a global monitor of cerebral
oxygenation.
§ It is noninvasive and provides continuous data.
§ Usually there are 2 sensors placed on the forehead. We only show 1 sensor in the image.
o Placement
§ The sensor is placed on the patient’s scalp, generally over the frontal lobe.
§ It contains a light emitting diode and two light sensors: a surface photodetector and a deep photodetector.
§ The infrared light follows an elliptical pathway from the emitting diodeàscalpàskullàbrainàskullàscalpàphotodetectors.
o How it Works
§ Arterial hemoglobin, venous hemoglobin, and tissue cytochromes absorb different frequencies of infrared light.
§ Cerebral oximetry relies on the fact that cerebral blood volume is 1 part arterial to 3 parts venous; 75% of blood in the brain is on
the venous side of circulation.
§ Since NRIS does not have the ability to detect pulsatile blood flow, it is primarily a measure of venous oxyhemoglobin saturation and
oxygen extraction.
§ Decreased cerebral oxygen delivery à increased cerebral oxygen extractionà decreased venous hemoglobin saturation.
§ A >25% change from baseline suggests a reduction in cerebral oxygenation.
§ Scalp hypoxia can contaminate the signal, NRIS may falsely interpret scalp hypoxia as brain ischemia.
• Electroencephalogram
o The EEG measures the differences between electrical potentials in multiple regions of the brain. It provides information about
the electrical activity of the cerebral cortex, but offers little information about the subcortical structures, spinal cord, and the
cranial and peripheral nerves.
o Classification of Brain Waves
o How Brain Waves Change During Anesthesia
§ Induction of general anesthesia is
associated with increased beta
wave activity.
§ Light anesthesia is also associated
with increased beta wave activity.
§ Theta and delta waves
predominate during general
anesthesia.
§ Deep anesthesia produces burst
suppression.
§ At 1.5-2.0 MAC, general
anesthetics cause complete
suppression or isoelectricity.
o How Anesthetic Agents Affect the EEG
§ Nitrous oxide alone increases beta
wave activity.
§ Sevoflurane can increase epileptiform EEG activity.
§ Etomidate can cause myoclonus, but this is not associated with epileptiform EEG activity.
§ Ketamine can increase high frequency cortical activity and may confuse EEG interpretation—the patient may be deeper than the
EEG suggests.
§ Burst suppression may occur with hypothermia, especially during cardiopulmonary bypass.
§ Unilateral burst suppression is suggestive of cerebral ischemia.
o EEG as a Monitor of Cerebral Ischemia
§ EEG provides a sensistive measure of brain tissue at risk of infarction.
• The brain requires an adequate perfusion pressure to provide a steady supply of oxygen and glucose.
• In the absence of these substrates, the brain is unable maintain its electrical function.
§ The development of new delta waves during anesthetic maintenance may signify that brain is at risk for ischemia.
§ The following circumstances mimic cerebral ischemia: deep anesthesia, hypotehermia, and hypocarbia.
§ EEG monitoring is useful during the following procedures:
• Carotid endarterectomy (cross clamping impairs cerebral perfusion)
• Cerebral aneurysm
• Arteriovenous malformations
• Cardiopulmonary bypass
• Deliberate hypotension
• Assessment of barbiturate coma
• Epilepsy diagnosis and treatment
• Coma and death

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• Modified EEG Monitors: Bispectral Index & Patient Safety Index
o Bispectral Index (BIS)
§ The bispectral index monitor (BIS) uses a
computer algorithm to translate raw EEG
data into a number between 0-100.
§ How Drugs Affect the BIS
• As the level of anesthesia becomes
deeper, the EEG waveforms exhibit
a:
o 1. Lower frequency (they
become slower)
o 2. Higher amplitude (they
become taller)
• There are 2 exceptions. These can
interfere with your interpretation of the BIS value:
o Nitrous oxide increases the amplitude of high frequency activity and reduces the amplitude of low
frequency activity. having said this, nitrous oxide (used as a sole agent) does not reduce the BIS
reading.
o Ketamine increases high frequency activity. this can produce a BIS value that is higher than the
level of sedation/anesthesia would otherwise suggest.
§ Limitations
• There is a 20-30 second lag between measuring the EEG and computing the BIS value.
• Hypothermia, electromyographic interference (increased muscle tone), and encephalopathy can impair the
accuracy of the BIS.
• The BIS is less accurate in children.
§ There is some data to suggest that a BIS value <40 for more than 5 minutes correlates with an increased 5 year
mortality. Other studies have failed to replicate these results.
o Patient Safety Index Monitor (PSI)
§ The PSI is similar to BIS, however the target range for general anesthesia is 25-50.
• Electricity in the Operating Room
o Electricity basics
§ Electricity obeys Ohm’s Law where: electromotive force (voltage) = Current x Impedance
• Voltage ~ Driving pressure
• Current ~ Flow
• Impedance ~ Resistance
o Electrical Injury
§ To receive a shock, a person must become part of and complete an electrical circuit. For current to flow, there has to
be a voltage difference (driving pressure) across an impedance. Therefore, if a closed circuit exists, then exposure to a
live electricity source provides an electromotive force (voltage) that pushes the current through an impedance. The
impedance can be you or the patient!
§ An electric current that enters the body will exit the body along the path of least resistance.
§ Consequences of electrical injury:
• Cardiac arrhythmias
• Nerve injury à muscle contractiosn and diaphragmatic paralysis
• Thermal injury (damage to internal organs may be more extensive than damage you observe on the skin)

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 o Macro vs Microshock
§ Macroshock is a comparatively larger amount of current that is applied to the external surface of the body. The
impedance of the skin offers a high resistance, so it takes a larger current to induce ventricular fibrillation.
§ Microshock is a comparatively smaller amount of current that is applied directly to the myocardium. The high
resistance of the skin is bypassed, so it takes a significantly smaller amount of current to induce ventricular
fibrillation.
• A central line, PA catheter, or pacing wires provide a direct conductive pathway to the heart, so it should
make sense that they increase the patient’s susceptibility to microshock.

§ The electrical systems in the OR are designed to Home Operating Room

reduce the risk of electric shock. This risk is Power Grounded Not grounded
minimized because: Equipment Grounded or Ungrounded Grounded
• 1. The OR power supply is NOT grounded.
• 2. The equipment is grounded.
§ While it may seem counterintuitive, the absence of grounding in the operating room provides a second layer of
protection against electrical shock. For an electric shock to occur in the OR there must be two faults in the system:
• 1. After the first fault, the OR power supply becomes grounded. There is no completed circuit and there is
no shock.
• 2. After the second fault, the circuit is complete and electric shock occurs.
§ When you are at home, an electric shock can occur with the first fault.
o Line Isolation Monitor
§ The line isolation monitor assesses the integrity of the ungrounded power system in the OR. It tells you when the OR
becomes grounded and how much current could potentially flow through you or a patient if a second fault occurs.
• The primary purpose of the LIM is to alert the OR staff of the first fault (this means the OR has become
grounded).
• The LIM does NOT (by itself) protect you or the patient from macro- or microshock.
• If the alarm sounds, the last piece of equipment that was plugged in should be unplugged.
• The LIM will alarm when 2-5 mA of leak current is detected.
• All electrical devices leak a small amount of current. If the sum of all the currents exceeds 2-5 mA, the alarm
will sound, however there is no risk of electric shock in this situation and no corrective action is required.
• Electrocautery
o The surgical electrocautery device delivers a high frequency current (500,000-1million Hz) that is used to cut, coagulate, dissect,
or destroy tissue. These higher frequencies have a low tissue penetration and do not affect excitable cells, thus ventricular
fibrillation is not a risk.
o Energy Pathway for Monopolar Electrocautery

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o To some this may seem like an issue of semantics, but the return electrode is often incorrectly referred to as the “grounding
pad.”
§ Patients in the operating room are intentionally isolated from electrical ground, so it defies logic why anyone would
want to apply a device that would ground the patient.
§ Instead, a functional return electrode serves as the exit point by providing a large, low impedance surface area for the
electrical current to exit the body and return the power generator.
o Risks of Electrocautery
§ A fault in the return electrode places the patient at risk for burns. If the return electrode malfunctions, the electrical
current will find another pathway to exit the patient, such as the EKG electrodes, temperature probe, or metal probe,
or metal components of the surgical table. The smaller the area that the electricity exists the body, the greater the
intensity of the burn.
§ Prevention
• To prevent burns at the return pad site, the entire surface of the return electrodes should be in direct
contact with the patient’s skin. It should not be placed over bony prominences or metal implants.
• The electrolyte gel on the return pad should be inspected for dryness. Indeed, the return electrodes have a
finite shelf life. If the gel dries out, the electrical current won’t have a direct path to the return electrode
and will find another way to exit the body.
§ The electrocautery can emit sparks and cause a fire, particularly in an oxygen rich environment.
o Energy Pathway for Bipolar Electrocautery
§ The tip of the bipolar electrosurgical device (forceps) contains the active electrode as well as the return electrode.
There is not return pad.
o The Patient with a Pacemaker or ICD
§ It’s critical that the current return must not pass across
the pacemaker. To learn more about pacemakers, check
out our coverage on pacemakers in Monitoring III: Cardiac
Rhythms.

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Equipment & Monitoring Notes

203
APEX: NEURO

CNS I: BRAIN

Cells of the Central Nervous System

• Neurons
o The neuron is the functional unit of the nervous system. Its primary role is to receive and send information.
§ The cell bodies form the grey matter.
§ The axons form the white matter.
o There are 3 types found in the CNS:
§ 1. Multipolar
• most of the CNS neurons
§ 2. Pseudounipolar
• dorsal root ganglion
• cranial ganglion
§ 3. Bipolar
• retina
• ear
• Glial Cells
o The glial cells (nerve glue) support neuronal function by:
§ Creating a healthy ionic environment.
§ Modulating nerve conduction.
§ Controlling reuptake of neurotransmitters.
§ Repairing neurons following neuronal injury.
o Most tumors arise from the glia.
Gross Structures of the Brain
o The Brain can be divided into 4 areas:
§ 1. Cerebral hemispheres
§ 2. Diencephalon
§ 3. Brainstem
§ 4. Cerebellum
• Cerebral Hemispheres
o The corpus callosum connects the hemispheres. It is located deep in the longitudinal fissure.
o Each cerebral hemisphere is divided into 4 lobes.
§ 1. Frontal—contains the motor cortex
§ 2. Parietal—contains somatic sensory cortex
§ 3. Occipital—contains vision cortex
§ 4. Temporal—contains auditory cortex and speech centers
• Wernicke’s area= understanding speech
• Broca’s area=motor control of speech
§ The cerebral hemisphere contain the following structures:
• Cerebral cortex –cognition, sensation, and movement.
• Hippocampus—memory and learning
• Amygdala—emotion, appetite, responds to pain and stressors
• Basal ganglia—fine control of movement
• Diencephalon
o Thalamus—acts as a relay station that directs information to various cortical structures
o Hypothalamus—primary neurohumoral organ
• Brainstem
o Midbrain—auditory and visual tracts
o Pons—autonomic integration
o Medulla—autonomic integration
o Reticular activating system—controls consciousness, arousal, and sleep
• Cerebellum
o Archeocerebellum—maintains equilibrium
o Paleocerebellum—regulates muscle tone
o Neocerebellum—coordinates voluntary muscle movement

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Cranial Nerves

• In contrast to spinal nerves that arise from the spine, the cranial
nerves arise from the brain and brainstem. There are 12 cranial
nerve pairs.
• There are two mnemonics to learn. The first one is to remember
the order of the nerves, and the second is to remember whether
each nerve is sensory, motor, or both.
• Nerve Names: On Occasion Our Trusty Truck Acts Funny Very Good
Vehicle Any How
• Functions: Some Say Marry Money But My Brother Says Bad
Business to Marry Money

• Key Facts
o With the exception of the optic n. (CN II), all of the cranial nerves are part of the peripheral nervous system. This means that
the optic n is the only cranial nerve that is surrounded by the dura.
o Mnemonic for 5 branches of the facial n (CN VII): Two Zebras Bit My Car.
o Bell’s palsy results from injury to the facial n. (CN VII). This causes ipsilateral facial paralysis.
o Tic douloureux (trigeminal neuralgia CN V) generates excrutiating neuropathic pain in the face.
o Eye movement is controlled by CN III, IV, and VI.
o Parasympathetic output is carried by CN III, VIII, IX and X. (Nagelhout p 692 incorrectly states II instead of III)
o The Vagus (CN X) is responsible for 75% of all parasympathetic activity.

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• CSF Dynamics & the Blood Brain Barrier
o Overview
§ The cerebrospinal fluid cushions the brain, provides buoyancy, and delivers optimal conditions for neurologic
function. It is located in the:
• Ventricles (left lateral, right lateral, third and fourth)
• Cisterns around the brain
• Subarachnoid space in brain and spinal cord
o Blood Brain Barrier
§ The blood brain barrier separates the CSF from the plasma. The BBB:
• Has tight junctions that restrict passage of large molecules and ions.
• Becomes dysfunctional at sites of tumor, injury, infection, or ischemia.
• Is not present at the chemoreceptor trigger zone, posterior pituitary gland, pineal gland, choroid plexus,
and parts of the hypothalamus.
• Does not have carrier proteins.
• Is poorly developed in the neonate.
§ Regarding cerebrospinal fluid, you must be aware of its production, circulation, reabsorption, and composition.
o CSF Production
§ CSF volume is ~150 mL
§ Specific gravity = 1.002-1.009
§ It is produced by the ependymal cells of the choroid plexus at a rate of 30 mL/hr.
§ The choroid plexus is located in all 4 cerebral ventricles.
§ CSF pressure is 5-15 mmHg.
o CSF Circulation

o Mnemonic for CSF flow in the brain: Love My 3 Silly 4 Lorn Magpies
§ Lateral ventricles
§ Monro (foramen)
rd
§ 3 ventricle
§ Sylvius (aqueduct)
th
§ 4 ventricle
§ Luschka
§ Magendie
o CSF Reabsorption
§ CSF is reabsorbed into the venous circulation via
the arachnoid villi in the superior sagittal sinus.
§ Reabsorption is dependent on the pressure
gradient between the CSF and venous circulation.
o CSF Composition
§ Although CSF is isotonic with plasma, it is not an
ultrafiltrate of the plasma. Indeed, it has its own
chemical composition that provides optimal
conditions for the brain. Don’t memorize the
specific number, but do try to get a general idea of
the differences between the composition of the
CSF and the plasma.

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Cerebral Blood Flow
o There is a lot to take in on this page, but all of it is important! Take your time, and refer to it often. Maybe
print several of the corresponding workbook pages to test yourself?
o Cerebral blood flow is continuously adjusted to ensure that a constant supply of oxygen and glucose is
delivered to the brain.
Cerebral Blood Flow = Cerebral Perfusion Pressure
Cerebral Vascular Resistance
o Critical Thresholds
§ CBF ~20 mL/100g tissue/min àevidence of ischemia
§ CBF ~15 mL/100g tissue/min à complete cortical suppression
§ CBF < 15 mL/100g tissue/min à membrane failure & cell death
o There are 5 Determinants of Cerebral Blood Flow
§ 1. Cerebral metabolic rate for oxygen
§ 2. Cerebral perfusion pressure
§ 3. Venous pressure
§ 4. PaCO2
§ 5. PaO2
• 1. Cerebral Metabolic Rate for Oxygen
o CMRO2=3.0—3.8 mL/O2/100g brain tissue/min. cerebral blood flow is coupled to CMRo2—the
higher the need for oxygen, the more blood flow there will be satisfy this need.
o Breakdown of oxygen utilization:
§ 60% is used for electrical activity
§ 40% is used for cellular integrity
§ even if the brain is electrically silenced, it still has to consume oxygen to support
cellular integrity.
o Decreasing CMRO2:
§ CMRO2 decreases by 7% for every 1 degree C decrease in temperature, EEG
suppression occurs at 18-20 degrees C.
§ CMRO2 is decreased by hypothermia, halogenated anesthetics, propofol, etomidate, and barbiturates.
§ We can improve outcomes in the patient who suffers anoxic brain injury by reducing CMRO2. Indeed, patients have an improved neurologic
outcome following resuscitation from out-of-hospital ventricular fibrillation when there are treated with mild hypothermia (32-34 degrees C)
for 12-24 hours after hospital admission.
o Increasing CMRO2:
§ CMRO2 is increased by hyperthermia, seizures, ketamine, and nitrous oxide.
§ Hyperthermia beyond 42 degrees C denatures proteins and destroys neurons. At this point, cerebral blood flow decreases.
• 2. Cerebral Perfusion Pressure
§ The cerebral vasculature autoregulates its resistance to provide a constant cerebral perfusion pressure of 50-150mmHg.
• This ensures a relatively stable blood flow and confers protection against swings in blood pressure.
• Autoregulation is influenced by products of local metabolism, myogenic mechanism, and autonomic innervation.
Cerebral Perfusion Pressure = MAP – ICP (or CVP) whichever is higher
o Notice that 50-150 is cerebral perfusion pressure and NOT mean arterial pressure. This is an important point. To ensure a CPP of 50 mmHg. MAP
must be 60-65 mmHg if ICP is in the normal range of 10-15 mmhg. If ICP is elevated, cerebral perfusion requires a higher mean arterial pressure.
o When autoregulation is impaired, CPP becomes dependent on blood pressure. Autoregulation is abolished by:
§ Intracranial tumor
§ Head trauma
§ Volatile anesthetics
o The textbooks will tell you that chronic hypertension shifts the entire curve to the right—the brain becomes more tolerant of hypertension, but it
also becomes less tolerant of hypotension. In reality, the plateau of the curve narrows and CBF becomes more closely dependent on CPP.
• 3. Venous Pressure
o A high venous pressure decreases cerebral venous drainage and increase cerebral volume. This creates a backpressure to the brain that reduces the
arterial/venous pressure gradient (MAP –CVP).
o Conditions that impair venous drainage include:
§ Jugular compression secondary to improper head positioning
§ Increased intrathoracic pressure secondary to coughing or PEEP
§ Vena cava thrombosis
§ Vena cava syndrome
• 4. PaCO2
o There is a linear relationship between PaCO2 and CBF.
o The pH of the CSF around the arterioles controls cerebral vascular resistance.
o At a PaCO2 of 40 mmHg, CBF is 50 mL/100g brain tissue/min.
o For every 1 mmHg increase in PaCO2, CBF will increase by 1-2 mL/100g brain tissue/min.
o For every 1 mmHg decrease in PaCO2, CBF will decrease by 1-2 mL/100g brain tissue/min.
o Maximal vasodilation occurs at a PaCO2 of 80-100 mmHg.
o Maximal vasoconstriction occurs at a PaCO2 of 25 mmHg.
o Respiratory acidosis increases CBF.
o Respiratory alkalosis decreases CBF.
o Metabolic acidosis does not affect cerebral blood flow. This is because H+ does not pass through the blood brain barrier.
• 5. PaO2
o A PaO2 below 50-60mmHg causes cerebral vasodilation and increases CBF.
o When PaO2 is above 60 mmHg, it does not affect cerebral blood flow.

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Intracranial Pressure: Overview

• Overview
o Intracranial pressure is the supratentorial CSF pressure.
§ Normal ICP (opening pressure ) is 5-15 mmHg.
§ Cerebral hypertension occurs if ICP >20 mmHg
§ The gold standard of ICP measurement is an intraventricular catheter.
§ ICP can also be measured with a subdural bolt or a catheter placed over
the convexity of the cerebral cortex.
§ ICP measurement is indicated with a Glasgow Coma Scale score < 7.
• Determinants of Intracranial Pressure
o The brain lives in a rigid, bony box. Within this box, there are 3 components: brain,
blood, and cerebrospinal fluid.
o The Monro-Kellie hypothesis (or doctrine) describes the pressure-volume equilibrium between the brain, blood, and CSF within
the confines of the cranium. It says that an increase in one of the components must be countered with a decrease in one or
both of the others. If not, then pressure inside the cranium will rise.

o At lower intracranial pressures, CSF is shunted into the spinal canal. This is represented by the horizontal portion of the ICP
curve. As intracranial volume rises beyond the inflection point on the graph, cerebral perfusion pressure begins to suffer
(CPP=MAP – ICP).
o Intracranial hypertension reduces oxygen delivery to the brain. This sets off a vicious circle of cerebral ischemia à cerebral
swelling àdecreased CPP àmore ischemia.
• Cushing’s Triad
o Cushing’s triad is a sign of intracranial hypertension.
§ 1. Hypertension
§ 2. Bradycardia
§ 3. Irregular respirations
o increased ICP reduces CPP. In an effort to preserve cerebral perfusion, blood pressure increases. Hypertension activates the
baroreceptor reflex, leading to bradycardia. Compression of the medulla causes irregular respirations.
• Herniation
o Brain herniation tends to occur at 4 different locations:
§ 1. Herniation of the cingulate gyrus under the falx.
§ 2. Herniation of contents over the tentorium cerebelli (transtentorial herniation).
§ 3. Herniation of the cerebellar tonsils through the foramen magnum.
§ 4. Herniation of contents through a site of surgery or trauma.
o The most common site of transtentorial herniation is at the temporal uncus. As ICP rises, the temporal uncus is forced from the
supratentorial space into the infratentorial space. This increases pressure on the midbrain.
§ The oculomotor nerve (CN III) originates from the midbrain and crosses near the tentorium.
§ Herniation applies pressure to the nerve, making it ischemic. Clinically this manifests as a fixed and dilated pupil.

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Intracranial Hypertension: Treatment

o Methods to Reduce ICP can be divided into 3 areas:

§ 1. CBV reduction
§ 2. CSF reduction
§ 3. Cerebral edema reduction
§ 4. Cerebral mass reduction
o It’ll be helpful to refer to this chart as you review
the treatments for intracranial hypertension.
• 1. Cerebral Blood Volume Reduction
o Decrease Cerebral Blood Flow
§ Hyperventilation
• CO2 dilates the cerebral vessels à
decreased cerebral vascular
resistance à increased
CBFàincreased ICP
• Hyperventilation (PaCO2 30-35
mmHg) constricts the cerebral
vessels à increased cerebral
vascular resistance à decreased CBFàdecreased ICP.
• Lowering PaO2<30 mmHg increases the risk of cerebral ischemia due to vasoconstriction and shifting the oxyhemoglobin
dissociation curve to the left (this reduces oxygen offloading).
• The effect of hyperventilation only lasts 6-20 hours.
• Even in the traumatized brain, CO2 reactivity is usually preserved.
§ Avoid Hypoxemia
• PaO2<50-60 mmHg greatly increases CBF and ICP.
§ Drugs
• Avoid cerebral vasodilators (nitroglycerine and nitroprusside).
• Drugs that reduce CMRO2 are thought of as cerebral vasoconstrictors (thiopental, propofol).
§ Hemodynamis
• Avoid extreme hypertension –BP beyond the upper limit of autoregulation contributes to cerebral edema.
o Increase Venous Outflow
§ Position
• Head elevation > 30 degrees facilitates venous drainage from the brain.
• Neck flexion or extension can compress the jugular veins, reduce venous outflow, increase CBV, and increase ICP.
• Head down increases CBV and ICP.
§ Reduce Intrathoracic Pressure
• PEEP increases intrathoracic pressure and reduces venous drainage from the brain.
• Bucking, coughin, and straining have the same effect.
• 2. Cerebrospinal Fluid Reduction
o CSF Drainage
§ Draining CSF is most useful when there is an obstruction to CSF flow such as hydrocephalus.
§ Acute treatment: a drain placed in the lateral ventricles or intrathecal space improves ICP by reducing CSF volume.
§ Chronic treatment: a shunt drains CSF to the peritoneal cavity (ventriculoperitoneal shunt) or the right atrium (ventriculoatrial
shunt).
o Drugs
§ Acetazolamide and furosemide reduce CSF production.
• 3. Cerebral Edema Reduction
o Diuretics
§ Loop diuretics reduce cerebral edema by inducing diuresis and decreasing the rate of CSF production.
§ Osmotic diuretics (mannitol 0.25-1.0g/kg) increases serum osmolarity and “pull” water across the blood brain barrier.
§ If the blood brain barrier is disrupted, mannitol enters the brain and increases cerebral edema!
§ Mannitol transiently increases blood volume, which can increase ICP and stress the failing heart.
§ While not a diuretic, the high tonicity of 3% sodium chloride also reduces ICP by “pulling” water across the blood brain barrier.
o Corticosteroids
§ Dexamethasone and methylprednisolone reduce cerebral edema caused by mass lesions.
§ Corticosteroids cause hyperglycemia. Remember that hyperglycemia in the setting of cerebral ischemia is associated with worse
outcomes.
§ Steroids are also used for spinal cord injury.
§ Steroids should NOT be used for traumatic brain injury.
• 4. Cerebral Mass Reduction
o Tumor debulking or evacuation of hematoma.
o By reducing cerebral edema, diuretics (such as mannitol) reduce intracerebral mass (water mass – not cellular mass).

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Cerebrovascular Anatomy

• The arterial cerebral circulation can be divided into 2 separate circulations: anterior and posterior. They converge at the circle of Willis.
• Anterior Circulation
o The internal carotid arteries supply the anterior circulation. They enter the skull through the foramen lacerum.
§ Aortaàcarotid a. àinternal carotid a. àcircle of willisàcerebral hemispheres
• Posterior Circulation
o The vertebral arteries supply the posterior circulation. They enter the skull through the foramen magnum.
§ AortaàSubclavian a. à Vertebral a. à Basilar a. à Posterior fossa structures and cervical spinal cord
• Circle of Willis
o The anterior and posterior circulations converge at the circle of
Willis. The primary function of the circle of Willis is to provide
redundancy of blood flow in the brain. If one side of the circle
becomes occluded, then the other side should theoretically be able
to perfuse the affected areas of the brain. While the only holds true
in 42-52% of the population, there are usually additional collateral
networks that provide circulatory redundancy.
o Venous Circulation
§ The venous cerebral circulation can also be divided into 22
separate circulations.
• Venous blood from the cerebral cortex and
cerebellum drain via the Superior sagittal sinus
and the dural sinuses.
• Venous blood from the basal brain structures
drain via the inferior sagittal sinus, vein of Galen and the straight sinuses.
• Both venous pathways converge at the confluence of sinuses
• All venous blood exits the brain via the paired jugular veins.
• Ischemic Stroke
o Overview
§ A person who exhibits a sudden change in neurologic function or a progressive change in neurologic status is most
likely experiencing a cerebrovascular accident (CVA). We can classify the type of CVA as either ischemic or
hemorrhagic. Ischemic strokes are more common and most likely stem from a cardio-embolic event, such as an atrial
fibrillation.
§ A transient ischemic attack (TIA) or “mini stroke” is a focal neurologic deficit that spontaneously resolves within 24
hours. It’s a warning sign of cerebrovascular disease and impending stroke.
o Risk Factors
§ Hypertension (most important)
§ Smoking
§ Diabetes mellitus
§ Hyperlipidemia
§ Excessive alcohol intake
§ Elevated homocysteine level
o Acute Management
§ The type of CVA must be determined prior to treatment, because a thrombolytic should NOT be given to be given to a
patient with hemorrhagic stroke.
§ Since the etiology of CVA cannot be determined by clinical criteria alone, the patient should receive an emergent non-
contrast CT>
§ In the first few hours after the precipitating event, CT will reliably detect intracerebral hemorrhage. If bleeding is
ruled out, the patient most likely suffers an ischemic stroke.
§ If treatment can being < 3 hours after the onset of symptoms, the patient with an ischemic CVA should receive an
intravenous thrombolytic such as recombinant tissue plasminogen activator (tPA).
§ Aspirin is an alternative if tPA cannot be administered.
§ Immediate assessment of airway reflexes and ventilatory drive is indicated after an acute CVA, however the majority
of patients can protect their airways and only require supplemental oxygen.
§ Hypertension is common after ischemic CVA. An elevated BP supports CPP and cerebral oxygenation.
§ Hypotension reduces CPP, which worsens ischemia.
§ The target pressure should be maintained under 185/110.
§ Fluid replacement supports blood pressure, cardiac output, and CPP. It also improves CBF by decreasing viscosity.
§ During cerebral hypoxia, glucose is converted to lactic acid. Cerebral acidosis destroys brain tissue and is associated
with worse outcomes. Monitor serum glucose and treat hyperglycemia with insulin.
§ Hyperthermia increases CMRO2 and cerebral oxygen consumption. Controlled hypothermia reduces CMRO2.

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Cerebral Aneurysm
• The most common cause of subarachnoid bleeding is aneurysm rupture. Most aneurysms arise
in the circle of Willis.
o Arterial bleeding usually occurs in the subarachnoid space (between the arachnoid
and pia).
o Venous bleeding usually occurs in the subdural space (between the dura and
arachnoid).
• Aneurysm Rupture
o An increased transmural pressure predisposes the aneurysm to rupture. As the
vessel bursts, blood flows into the subarachnoid space.
o We like to think of MAP as the pressure pushing outwards against the aneurysmal
sac and ICP as the counter pressure that pushes against it. In essence, ICP creates a
tamponade effect. Using this model, it’s easy to see that the risk of rupture is
increased by hypertension and/or an acute reduction in ICP.
o The most common sign of SAH is an intense headache that is often described as the “worst one in my life.” Consciousness is lost about 50% of
the time, and other s/sx include focal neurologic deficits, N/V, photophobia, and fever. Meningismus (signs of meningitis) occurs as blood
spreads throughout and irritates the subarachnoid space. Furthermore, blood can block CSF flow, causing obstructive hydrocephalus and
increasing ICP.
o Morbidity is usually the result of:
§ 1. Obstructive hydrocephalus
§ 2. Rebleeding
§ 3. Vasospasm
• Vasospasm
o Cerebral vasospasm is a delayed contraction of the cerebral arteries. It can lead to cerebral infarction and is the most significant source of
morbidity and mortality in the patient with SAH.
o Free hemoglobin that is in contact with the outer surface of the cerebral arteries increases the risk of vasospasm. Indeed, there is a positive
correlation between the amount of blood observed on CT and the incidence of vasospasm.
o It occurs in about 1:4 patients and is most likely 4-9 days following SAH.
o Treatment is aimed at maintaining cerebral perfusion pressure (CPP=MAP – ICP or CVP whichever is higher).
o The idea is that ischemic areas of the brain are already maximally vasodilated, so perfusion to these regions is pressure dependent.
o Frequent neurologic checks and transcranial Doppler exams monitor for the development vasospasm.
o If vasospasm occurs, triple H therapy (hypervolemia, hypertension and hemodilution to Hct 27-32%) is the standard of care. It should be noted
that there is little evidence for this.
o Liberal hydration supports blood pressure and CPP. It also creates a state of hemodilution, which reduces blood viscosity and cerebrovascular
resistance. Together these improve cerebral blood flow.
o Nimodipine is the only calcium channel blocker shown to reduce morbidity and mortality associated with vasospasm. Interestingly, it does not
actually relieve the spasm, but instead it increases collateral blood flow.
o It should be noted that triple H therapy and nimodipine are only used if the aneurysm has ruptured.
• Surgical Options
o Surgical options include aneurysm clipping or endovascular coiling. The goals of anesthetic management are similar for both types of
procedures.
o Back in the day, surgery was delayed until 2 weeks after the blood. A more modern approach focuses on minimizing the risk of rebleeding and
vasospasm. To reduce the risk of rebleeding, surgical repair should take place 24-48 hours following the initial bleed. Intervention at this time
makes triple H therapy safer (hypertension can cause rebleeding if the aneurysm isn’t clipped).
o If an endovascular coil is placed, the patient will require heparinization. If the aneurysm ruptures during the procedure, you should immediately
reverse heparin with 1 mg of protamine for every 100 U of heparin administered. MAP should be lowered into the low/normal range. While it
wasn’t cited in our references, adenosine can be given to temporarily arrest the heart, so the interventional radiologist can control the
bleeding.
• Intraoperative BP Control
o As a general rule, intraoperative SBP should be between 120-150 mmHg. If the patient undergoes an open repair, a clamp is commonly placed
on a proximal feeder vessel. This reduces transmural pressure and the risk of intraoperative rupture, while also circumventing the need for
controlled hypotension. A high/normal BP is required to perfuse the collateral circulation. Some surgeons won’t use a clamp and may request
controlled hypotension. The most significant drawback of this technique is a reduction in CPP.
§ If BP is too high, transmural pressure rises and increases the likelihood of rebleeding.
§ If BP is too low, CPP may be inadequate, as autoregulation is usually impaired following SAH.
o Meticulous BP control during induction and intubation is critical! If rupture occurs during this time, the focus of anesthetic management is on
reducing ICP and utilizing methods of cerebral protection.
• Cerebral Salt-Wasting Syndrome
o Hyponatremia is most commonly the result of cerebral salt-wasting syndrome (not SIADH). The brain releases natriuretic peptide (just like the
overfilled heart), and this leads to volume contraction, hyponatremia, and sodium wasting by the kidney. Cerebral salt-wasting syndrome is
treated with isotonic crystalloids. As a point of comparison, SIADH causes euvolemia or slight hypervolemia and is treated with fluid restriction.

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Traumatic Brain Injury
• Head trauma can be blunt or penetrating. Initial considerations include stabilization of the cervical spine, airway protection, optimization of
hemodynamics, and cerebral protection.
• Head CT rapidly determines the presence of intracranial bleeding. If a patient with minor head trauma satisfies the following criteria, a head CT probably
isn’t required:
o No physical evidence of trauma above the clavicles
o No headache
o No N/V
o No neurologic deficit
o No impairment of short term memory
o No intoxication
o No seizures
o Age < 60 years
• Glasgow Coma Scale
o The GCS provides an objective assessment of neurologic status. A GCS <8 is
consistent with traumatic brain injury.
• The Anticoagulated Patient with a Head Injury
o No doubt that this presents a challenge without clear and consistent
guidelines.
§ Warfarin can be reversed with FFP, prothrombin complex
concentrate, and/or recombinant factor VIIa.
§ Clopidogrel, aspirin, or both can be reversed with platelet transfusion. There is also evidence of reversal with recombinant factor
VIIa.
• Anesthetic Management
o KEEP CPP>70 mmHg.
o You’ll want to reduce ICP with all of the techniques we described a few pages back, but there are 2 things you should specifically avoid in the
patient with TBI.
§ Barash and Hines state that hyperventilation can worsen cerebral ischemia in patients with TBI. Hyperventilation is only indicated as
a temporary measure to acutely reduce ICP.
§ Steroids worsen neurologic outcome.
o Fluid Selection
§ Hypertonic saline restores intravascular volume and decreases brain water.
§ Hypotonic solutions are avoided, as they increase cerebral edema.
§ Glucose containing solutions worsen neurologic outcome in the setting of cerebral ischemia. Glucose is only indicated in the
hypoglycemic patient.
§ Albumin has been linked to a poorer outcome.
o Nitrous Oxide
§ Other injuries, such as pneumothorax, may only become evident after anesthetic induction and positive pressure ventilation. Nitrous
oxide can rapidly expand a pneumothorax or cause pneumocephalus. Do not use it in the patient with TBI.
Seizure Disorders

• Seizures are the result of an abnormal electrical discharge in the brain. A partial (focal) seizure results when this activity is localized to a
particular cortical region. A generalized seizure occurs when the activity affects both hemispheres. A partial seizure can progress to a
generalized seizure. This is called a Jacksonian march.
Key Concepts
Grand Mal Generalized tonic-clonic activity
§ Tonic phase whole body rigidity
§ Clonic phase=repetitive jerking motions
Respiratory arrest à hypoxia
§ Increased oxygen consumption d/t increased brain activity and muscle contraction
Acute treatment: propofol, diazepam, and thiopental
Surgical treatment: Vagal nerve stimulator or resection of foci
Focal cortical Localized to a particular cortical region
§ Can be motor or sensory
§ Usually no LOC
Absence (petit mal) Temporary loss of awareness
More common in children
Akinetic Temporary LOC and postural tone
§ Can result in fallàhead injury
More common in children
Status epilepticus Seizure activity that lasts >30 min or
2 grand mal seizures without regaining consciousness in-between
Respiratory arrestàhypoxia
§ Increased oxygen consumption d/t increased brain activity and muscle contraction
Acute treatment: phenobarbital, thiopental, phenytoin, benzos, propofol, and even GA

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• Etiology
o Epilepsy is characterized by idiopathic seizures. It is diagnosed in childhood.
o In the adult, new onset seizures are usually the result of a:
§ 1. Structural brain lesion: tumor, head trauma, or cerebrovascular event
§ 2. Metabolic cause: hypoglycemia, drug toxicity, withdrawal, or infection
• Effects of Anesthetic Agents
o Inhalational Agents
§ Although all of the inhalational agents have been implicated in producing seizure activity, these drugs tend to reduce
EEG activity in a dose dependent fashion.
§ Seizures can occur under general anesthesia. Signs include tachycardia, hypertension, and increased EtCO2 as a result
of increased oxygen consumption.
o IV Agents
§ Ketamine can induce seizure activity and should be avoided in the patient with a history of seizures.
§ Etomidate commonly causes myoclonus. This is not associated with increased EEG activity in patients that do not
have epilepsy.
§ In patients with seizure disorders, methohexital, etomidate, and alfentanil increases EEG activity and can be used to
help determine the location of the seizure foci during cortical mapping.
§ There are several case reports of propofol induced seizures and opisthotonos (rigid posture with arched back). Keep
in mind that propofol is a first line agent for control for acute seizure activity.
§ Atracurium metabolism yields laudanosine, a proconvulsant. This is only a potential issue with long-term infusions in
the ICU.
§ Cisatracurium also produces laudanosine, but in a much smaller quantity.
§ Normeperidine is a metabolite o fmeperidine. It is capable of producing seizure activity.
§ Local anesthetics reduce the seizure threshold, but a properly executed regional anesthetic does not increase the risk
of seizures.
• Anticonvulsants

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• Alzheimer’s Disease
o Alzheimer’s disease is a chronic degenerative condition of the CNS. It is the most common cause of dementia in patients 65
years and older. There is no cure for Alzheimer’s.
o S/sx include memory loss, apraxia, aphasia, and agnosia.
o Pathophysiology
§ Key findings include the development of diffuse beta amyloid rich plaques and neurofibrillary tangles in the brain.
§ Consequences of plaque formation include:
• Dysfunctional synaptic transmission. This is most noticeable in nicotinic Ach neurons.
• Apoptosis (programmed cell death)
o Treatment
§ Treatment is palliative and aims to restore the concentration of Ach.
§ This is accomplished with cholinesterase inhibitors such as tacrine, donepezil, rivastigmine, and galantamine.
o Anesthetic Management
§ Patients are often confused, scared, and uncooperative, thus making them poor candidates for MAC and/or regional
anesthesia with or without sedation.
§ When a general is planned, shorter acting drugs are best. In theory, this allows the patient to return to his or her
baseline cognition as soon as possible.
§ Preoperative sedation can worsen confusion, so it should be avoided if possible.
§ Cholinesterase inhibitors increase the duration of action of succinylcholine, although the clinical significance of this is
debatable.
§ These drugs increase PNS tone, so s/sx of parasympathetic excess can develop: bradycardia, syncope, and n/v.
§ If an anticholinergic is required, glycopyrrolate is the best option since it does not cross the blood brain barrier.
o Current Controversies
§ Some studies suggest that NMDA receptor antagonists and GABA agonists increase the rate of apoptosis
(programmed cell death) in the brains of the very young and the very old. Obviously, this encompasses nearly all of
the sedatives hypnotics.
§ Other investigations claims there is an increased risk of Alzheimer’s if the patient has undergone multiple general
anesthetics prior to age 50.
§ Some of the halogenated anesthetics (halothane and isoflurane) increase beta amyloid production—the protein that
is implicated in the genesis of Alzheimer’s disease.
• Parkinson’s Disease
o Pathophysiology
§ Parkinson’s disease is a chronic neurodegenerative disorder of the basal ganglia.
§ As you’ll learn in the spinal cord tutorial, “normal” muscle coordination requires a complicated feedback loop. The
motor cortex sends instructions to the basal ganglia and the cerebellum. Next, the basal ganglia and cerebellum send
information back to the cortex by way of the thalamus. This feedback loop is dependent on the relative concentration
of dopamine and acetylcholine in the basal ganglia.
§ In the patient with Parkinson’s disease, the dopaminergic neurons in the basal ganglia are destroyed.
• 1. This favors a relative increase in cholinergic activity.
• 2. Increased Ach in the basal ganglia increases GABA activity in the thalamus. Recall that GABA is an
inhibitor neurotransmitter, so increased GABA suppresses the thalamus.
• 3. Thalamic inhibition suppresses the cortical motor system and motor areas in the brainstem. The end
result is an over activity of the extrapyramidal system.
o Diagnosis
§ Diagnosis requires two of the four cardinal signs:
• 1. Resting “pill rolling” tremor
• 2. Skeletal muscle rigidity
• 3. Postural instability—loss of balance with
altered gait
• 4. Bradykinesia—very slow movement and
reflexes
§ Secondary signs include: psychosis, depression,
dementia, lack of facial expression, diaphragmatic
spasm, and oculogyric crisis. Patients may be unable
to handle oral secretions.
§ The greatest risk factor is old age. Other risk factors
include exposure to manganese in welders as well as
herbicides, pesticides, and possibly genetics.

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 o Treatment
§ Treatment seeks to increase dopamine or decrease acetylcholine in the basal ganglia.
§ Levodopa & Carbidopa
• When given together, these drugs increase the concentration of dopamine in the basal ganglia.
• Levodopa is a precursor to dopamine.
• In the circulation, levodopa is metabolized to dopamine, and DA in the blood does not penetrate the CNS.
• Carbidopa is a decarboxylase inhibitor. By preventing levodopa metabolism in the blood, more levodopa can enter the
CNS>
• Cardiovascular side effects include increased inotropy, tachycardia, and orthostatic hypotension.
• Other side effects include dyskinesia, nausea, and vomiting.
§ Selegiline
• MAO-B inhibitors restore dopamine concentration by reducing dopamine metabolism in the CNS>
• Unlike non-selective MAOIs, selegiline does not increase the risk of tyramine induced hypertensive crisis.
§ Other Treatments
• Dopamine agonists
• Anticholinergics
• Catechol-o-methyltransferase inhibitors
• Amantadine
• Hormone replacement
o Anesthetic Management
§ Patients are at risk for autonomic instability, orthostatic hypotension, arrhythmia, and aspiration.
§ Levodopa has half-life of 6-12 hours. It must be given the morning of surgery to prevent worsening of symptoms such as rigidity, which can
impact ventilation. For longer procedures, levodopa may be administered via an orogastric tube.
§ Antidopaminergic drugs such as metoclopramide, utyrophenones (haloperidol & droperidol), and phenothizaines (promethaxzine) may
exacerbate extrapyramidal s/sx. These drugs are contraindicated.
§ Anticholinergics may be used to treat acute exacerbation of Parkinsonian symptoms.
§ Diphenhydramine has anticholinergic properties and is useful for seation and reduction of tremor.
§ Hypotension should be treated with intravascular volume expansion and direct-acting agents, such as phenylephrine.
§ Alfentanil may cause an acute dystonic reaction due to interruption of central dopaminergic neurotransmission.
§ Ketamine is controversial due to its effects on the SNS>
§ There is no contraindication to succinylcholine or nondepolarizers.
§ Monitor for postoperative ventilatory failure.
o Deep Brain Stimulation
§ If deep brain stimulation is planned, it may be helpful to withhold levodopa. Holding levodopa causes symptoms to worsen, which facilitates
optimal electrode placement.
§ Deep brain stimulation requires a burr hole to insert electrodes into the subthalamic nucleus, globus palllidus, and ventralis intermedius. This
is done under stereotactic guidance.
§ The patient’s head is placed in a rigid frame. This can complicate airway management. Avoid over sedation and respiratory depression.
§ To determine optimal electrode placement, the patient must be awake, but can be lightly sedated with opioids and/or dexmedetomidine.
§ Because of the crucial role of GABA in the thalamus, GABA agonists, such as propofol or benzodiazepines, are voided as they can interfere
with the electrophysiologic brain monitoring.
§ The sitting position increases the risk of venous air embolism. A precordial Doppler aids in diagnosis. If VAE is detected, the patient should
not take a deep breath, as this entrains more air. Instead the surgeon must flood the field with saline. The patient may need to be re-
positioned supine and hemodynamic support provided as needed.
§ To minimize the risk of intracranial hemorrhage, SBP should not exceed 140 mmHg.
§ Seizures can be treated with a small dose of propofol, barbiturate, or benzodiazepine.
Ischemic Optic Neuropathy
o In the perioperative period:
§ Corneal abrasion is the most common eye complication.
§ Ischemic optic neuropathy is the most common cause of vision loss.
o Pathophysiology
§ ION is a consequence of ischemia of the optic nerve. The most likely explanation is that venous congestion in the optic canal reduces
perfusion pressure. Increased intraabdominal and/or intrathoracic pressure can also increase intraocular pressure.
• Ocular Perfusion Pressure = MAP – Intraocular pressure
§ The central retinal and posterior ciliary arteries are at highest risk because they are “watershed” areas—they lack anastomosis with other
arteries. A rise in intraocular pressure can compress these vessels, which reduces
oxygen delivery to the retina.
o Risk Factors
§ ION is most common after spinal surgery in the prone position. It has also occurred
following cardiopulmonary bypass and radical neck dissection.
§ Because ischemic optic neuropathy is a very rare event, there aren’t enough data to
formulate clear guidelines or even pin down a definitive list of risk factors. The
anesthesia texts aren’t entirely consistent on these, so we went with Nagelhout.
§ Prevention of ION targets modifying those risk factors that we can at least partially
control in the operating room.
§ Vision loss typically occurs 24-48 hours after surgery. It is not associated with pain.

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Spinal Cord Blood Flow

• Spinal Cord Circulation

o The spinal cord’s circulation consists of:
§ 2 posterior spinal arteries
§ 1 anterior spinal artery
§ 6-8 raticular arteries
o Posterior Spinal Arteries (2)
§ Aortaàsubclavian a. àvertebral a. àposterior spinal a.
§ Aorta àsegmental a. àposterior radicular a.-->posterior spinal a.
§ Perfuses the posterior 1/3 of the spinal cord (green)
o Anterior Spinal Artery (1)
§ Aortaàsubclavian a. àvertebral a. àanterior spinal a.
§ Aortaàsegmental a. àanterior radicular a. àanterior spinal a.
§ Perfuses the anterior 2/3 of the spinal cord (yellow)
o Artery of Adamkiewicz
§ It is the most important radicular artery.
§ It perfuses the anterior spinal cord in the thoracolumbar region.
§ It most commonly originates on the left side between T11-12.
§ In 75% of the population, it originates between T8-T12, and in another 10% it arises at L1-2.
o It’s critical to understand that the spinal cord is perfused at each segment, but not necessarily along its entire length. Some regions of the cord
have only a single blood supply. These are called watershed areas, and they’re particularly vulnerable to ischemia.
o For example, the thoracolumbar region of the anterior spinal cord is highly dependent on the radicular arteries. Interruption of radicular flow
can cause ischemia or infarction to the corresponding spinal cord segments.
• Anterior Spinal Artery Syndrome
o An aortic cross clamp placed above the artery of Adamkiewicz can cause ischemia to the lower portion of the anterior spinal cord. This can
result in anterior spinal artery syndrome—otherwise known as Beck’s syndrome. Classic signs and symptoms include:
§ Flaccid paralysis of the lower extremities
§ Bowel and bladder dysfunction
§ Loss of temperature and pain sensation
§ Preserved touch and proprioception
o We tend to generalize that the anterior cord contains motor neurons and the posterior cord contains sensory neurons. While this is enough to
get you by in most situations, we need to dig deeper to help you understand the presentation of anterior spinal artery syndrome.
§ The corticospinal tract is perfused by the anterior blood supply. This explains why the patient presents with flaccid paralysis of the
lower extremities.
§ Autonomic motor fibers are perfused by the anterior blood supply. This explains why the patient experiences bowel and bladder
dysfunction.
§ The spinothalamic tract is perfused by the anterior blood supply. This explains why the patient loses pain and temperature
sensation.
§ The dorsal column is perfused by the posterior blood supply. This explains why touch and proprioception are spared in this patient.
• Anatomy Overview
o The spinal cord links the peripheral nerves to the brain. Sensory neurons from the periphery enter the spinal cord via the dorsal nerve root,
while motor and autonomic neurons exit via the ventral nerve root.
o Ganglion: A ganglion is a collection of cell bodies that reside outside of the CNS.
o Grey Matter
§ The grey matter contains the neuronal cell bodies. This is the
processing center for afferent signals that arrive from the periphery.
Notice the “H” shape. This is important for you to determine the
orientation. If this was a hotspot that was upside down, would you
be able to determine the correct orientation?
§ Laminae
• The grey matter is subdivided into 9 laminae.
• Laminae I-VI reside in the dorsal grey matter. There are sensory.
• Laminae VII-IX reside in the ventral grey matter. These are motor.
§ Regional Differences
• The grey matter is larger in two specific regions of the spinal cord.
• The region of cervical enlargement (C5-C7) houses the cell bodies for the neurons that supply the upper extremities.
• The region of lumbar enlargement (L3-S2) houses the cell bodies for the neurons that supply the lower extremities.
o White Matter
§ Contains the axons of the ascending and descending tracts.
§ Is divided in the dorsal, lateral, and ventral columns.

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 o Tracts
§ A tract is a group of fibers inside the white matter in the CNS that relay information up or down the spinal cord or to and from the
brain.

§ The name of the tract will often give you a clue about its function. Many times, the first half of the name indicates where the tract
begins and the second half of the name indicates where the tract ends.
• The corticospinal tract travels from the cortex to the spine. This is clearly a motor pathway.
• The spinothalamic tract travels from the spine to the thalamus. This is clearly a sensory pathway.
• Some of the pathways aren’t quite this easy, but thinking about them in this way should help get you started.
o Information to Know About Each Pathway
§ What is the anatomical organization of each tract?
§ What types of sensation are transmitted (pain, touch, proprioception, etc)?
§ How fast does each pathway relay information?
§ Where does the pathway cross to the contralateral side of the body?
§ What happens when the pathway is injured?
• Sensory Pathways: Dorsal Column—Medial Lemniscal System
o Overview of the Dorsal column—Medial Lemniscal System
§ Transmits mechanoreceptive sensations: fine touch, proprioception, and vibration, and pressure (fine degree of intensity).
§ Capable of two-point discrimination—a high degree of localizing the stimulus.
§ Consists of large, myelinated, rapidly conducting fibers.
§ Transmits sensory information faster than the anterolateral system.

o Peripheral Receptors

o First Order Neuron

§ Enters the spinal cord through the dorsal
root ganglion.
§ Relays sensory information from the dorsal column to the medulla.
§ Ascends the spinal cord on the ipsilateral side (the same side that it entered).
§ Synapses with the second order neuron in the medulla (cuneate and gracile nuclei)
o Second Order Neuron
§ Crosses to the contralateral side in the medulla, then ascends towards the thalamus via the medial lemniscus.
§ Second order neurons are joined by the trigeminal nerve. Recall that the trigeminal nerve provides sensation to the head.
§ Synapses with the third order neuron in the thalamic relay station—ventrobasal complex.
o Third Order Neuron
§ These fibers pass through hthe internal capsule and advance towards the somatosensory cortex in the postcentral gyrus in the
parietal lobe.

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• Sensory Pathways: Anterolateral System—Spinothalamic tract
o Overview of the Anterolateral System—Spinothalamic Tract
§ Transmits: pain, temperature, crude touch, tickle, itch, and sexual
sensation.
§ Consists of smaller, myelinated, slower conducting fibers.
§ Transmits sensory information ½ to 1/3 as fast as the dorsal column
(medial lemniscal system).
§ Two-point discrimination is not present.
o Peripheral Receptors
§ Free nerve endings
§ Nociceptive receptors
o First Order Neuron
§ Enters the spinal cord through the dorsal root ganglion.
§ Cell body is in the dorsal root ganglion.
§ May ascend or descend 1-3 levels on the ipsilateral side via the Lissauer tract before synapsing with the second order neuron.
§ Synapses with the second order neuron in the dorsal horn laminae I, IV, V, and Vi.
§ Pain neurons synapse in the substantia gelatinosa in laminae II and III.
o Second Order Neuron
§ Crosses to the contralateral side of the spinal cord, tehn ascends towards the brain via 2 pathways: the anterior spinothalamic tract
and lateral spinothalamic tract.
§ Cell bodies reside in the dorsal horn of the spinal cord.
§ Second order neurons synapse in the reticular activating system and the thalamus.
o Third Order Neuron
§ Most tactile signals are relayed to the ventrobasal complex of the thalamus. These fibers pass through the internal capsule and
advance towards the somatosensory cortex in the postcentral gyrus in the parietal lobe.
§ Most pain fibers synapse with the third order neuron in the reticular activating system. From here there are connections to the
thalamus.
• Motor Pathways: Corticospinal Tract
o The corticospinal tract is the most important motor pathway. This pathway is often referred to as the pyramidal tract. The pyramids are formed by the
corticospinal neurons as they run through the medulla.
o All the other motor pathways outside of the corticospinal (pyramidal) tract are known
collectively as the extrapyramidal tract. This is because these fibers do not pass through the
pyramids.
o Overview of the Corticospinal Tract
§ Motor neurons exit the precentral gyrus of the frontal lobe, pass through the
internal capsule, and then travel inferiorly through the pyramids of the
medulla.
§ Lateral Corticospinal Tract
• The fibers that innervate the limbs crossover to the contralateral
side in the medulla. From here, they descend the spinal cord via
the lateral corticospinal tract.
§ Ventral Corticospinal Tract
• The fibers that innervate the axial muscles remain on the
ipsilateral side as they descend via the ventral corticospinal tract.
• Most of theses fibers crossover to the contralateral side of the
spinal cord when they reach the cervical or upper thoracic area.
o Upper Motor Neuron
§ The upper motor neurons begin in the cerebral cortex and end in the ventral horn of the spinal cord.
§ Injury to Upper Motor Neuron
• The cell bodies of the upper motor neuron originate in the cerebral cortex.
• If an injury occurs above the level of decussation in the medulla, paralysis will be on the opposite side of the body.
• If an injury occurs below the level of decussation in the medulla, paralysis will be on the same side of the body.
• There is a subset of neurons in the corticospinal tract that exert and inhibitory influence on lower motor neurons. This inhibitory
action prevents the lower motor neurons from firing too frequently.
• Since inhibitory impulses from the brain are blocked at the level of the injury, there is an over activity of lower motor neurons and
manifests as hyperreflexia and spastic paralysis.
• Examples of upper motor neuron disease include: cerebral palsy and amyotrophic lateral sclerosis.
§ Babinski Sign
• The Babinski test is a method to test the integrity of the corticospinal tract.
• Normal response-a firm stimulus to the underside of the foot produces a downward motion of all the toes.
• Damage to the corticospinal tract—a firm stimulus to the underside of the foot produces an upward extension of the big toe with
fanning of the other toes.
o Lower Motor Neuron
§ The lower motor neurons begin in the ventral horn and end at the neuromuscular junction.
§ Injury to Lower Motor Neuron
• The cell bodies of the lower motor neuron originate in the ventral horn.
• These are peripheral motor fibers that link the spinal cord to a muscle.
• Injury to a lower motor neuron results in paralysis on the same side of the body as the injury.
• Lower motor neuron injury presents with impaired reflexes and flaccid paralysis.
§ Babinski Sign
• Absent with lower motor neuron injury

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• Acute Spinal Cord Injury: Neurogenic Shock
o Acute spinal cord injury (SCI) is most likely to result from a motor vehicle accident, fall, assault, or sports injury. C7 is the most common site of
SCI.
o Complete spinal cord injury damages the upper motor neurons, which initially leads to flaccid paralysis and loss of sensation below the level of
injury. Loss of bowel and bladder function occurs as well. After the acute phase, spinal reflexes return and may lead to spasticity.
o In addition to paralysis, there is a concurrent hemodynamic derangement known as neurogenic shock. Hemodynamic instability is greatest with
injuries to the cervical or upper thoracic cord. The higher the injury, the greater degree of hemodynamic instability.
o SCI with neurogenic shock is characterized by Sympathectomy below the level of injury. This manifests as the triad of hypotension, bradycardia,
and hypothermia. Neurogenic shock can last 1-3 weeks.
o Pathophysiology of Neurogenic Shock:
§ Impariment of cardioaccelarator fibers (T1-T4)àunopposed cardiac vagal toneàbradycardia & reduced inotropy
§ Decreased SNS toneàvasodilationàvenous poolingàdecreased CO and BP
§ Impairment of sympathetic pathways from hypothalamus to blood vesselsàinability to vasoconstrict or shiveràhypothermia
§ Hypothermia is the result of the inability of the cutaneous vasculature to vasoconstrict, causing a redistribution of blood flow
towards the periphery and allowing more heat to escape from the body.
o In the trauma patient, neurogenic shock may be confused with hypovolemic shock.
§ Neurogenic Shockàbradycardia, hypotension, hypothermia with pink, warm extremities
§ Hypovolemic shockàtachycardia, hypotension, and cool, clammy extremities
o Norepinephrine is a good choice to restore SVR and inotropy. Volume expansion is required as well, but keep in mind that over resuscitation
may lead to myocardial dysfunction and pulmonary edema, particularly after the Sympathectomy resolves. An arterial line will help determine
the adequacy of both of these endeavors.
o Succinylcholine should be avoided 24 hours after injury and should not be used for at least 6 months thereafter. Fasciculations may worsen
outcome with SCI. Many practitioners will forego the use of succinylcholine all together, so if given the option on the NCE, select a
nondepolarizer. If you must use succinylcholine, pay attention to the timing of administration relative to the timing of the SCI.
o The major causes of morbidity and mortality in patients with cervical and upper thoracic lesions are ineffective alveolar ventilation and inability
to clear pulmonary secretions.
• Chronic Spinal Cord Injury: Autonomic Hyperreflexia
o After the spinal shock phase ends (1-3 weeks), the body begins to mend itself in a pathologic and disorganized way. There is a return of spina
sympathetic reflexes below the level of injury, however without inhibitory influences that would normally come from above the level of injury, the
sympathetic reflexes below the level of injury exist in an overactive state. This places the patient at risk for autonomic hyperreflexia (mass reflex).
o While up to 85% of patients with injury above T6 will develop AH, it is very unlikely to occur in patients with injury below T10. The higher the level of
injury, the more intense the response.
o Common Events that Cause AH include:
§ Stimulation of the hollow organs—bladder, bowel, or uterus
§ Bladder catheterization
§ Surgery—especially cystoscopy or colonoscopy
§ Bowel movement
§ Cutaneous stimulation
§ Childbirth
o Pathophysiology
§ The classic presentation of autonomic hyperreflexia is hypertension and bradycardia.
§ Stimulation below the level of SCI triggers sympathetic reflex arc that creates a profound degree of vasoconstriction below the level
of injury.
§ Other signs and symptoms include:
• Reflex vasodilation above the level of spinal cord injuryànasal stuffiness
• Hypertensionàheadache and blurred vision
• Malignant hypertensionàstroke, seizure, left ventricular
failure, dysrhythmias, pulmonary edema, and/or myocardial
infarction.
o Anesthetic Management
§ Even though the patient does not have sensation below the level of SCI,
stimulation to the affected areas can elicit autonomic hyperreflexia—
prevention is paramount!
§ General or spinal anesthesia are the best options.
§ An epidural may be used for a laboring mother, however
when compared to a spinal anesthetic, an epidural does not
inhibit the sacral nerve roots to the same degree.
§ Hypertension is best treated with:
• Removal of the stimulus
• Deepening the anesthetic
• A rapid acting vasodilator, such as sodium
nitroprusside
§ Bradycardia can be treated with atropine or glycopyrrolate
§ Administration of positive chronotrope with
vasoconstrictive properties will worsen hypertension.
§ Adding lidocaine jelly to the cystoscope or Foley catheter
does not prevent AH.
§ Succinylcholine should be avoided for at least 6 months
following SCI.
§ AH may present in the postoperative period as the effects of anesthesia wear off; close postoperative monitoring is warranted.

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• Amyotrophic Lateral Sclerosis (ALS)
o Amyotrophic lateral sclerosis (ALS) causes progressive degeneration of motor neurons in the corticospinal tract. Astrocytic gliosis replaces the affected
motor neurons. Both the upper as well as the lower motor neurons are affected.
o The etiology is unknown.
o Signs & Symptoms
§ Upper neuron involevement presents are spasticity, hyperreflexia, and loss of coordination.
§ Lower motor neuron involvement presents as muscle weakness, fasciculations, and atrophy.
§ It often begins in the hands. Over time, weakness spreads to the rest of the body, affecting the tongue, pharynx, larynx, and chest.
§ The ocular muscles are not affected.
§ Autonomic dysfunction is evidenced by orthostatic hypotension and resting tachycardia.
§ Sensation remains intact.
§ Riluzole (a NMDA receptor antagonist) is the only drug that reduces mortality.
§ Respiratory failure is the most common cause of death.
o Anesthetic Management
§ There is no evidence that supports a clear benefit of any particular anesthetic technique.
§ Succinylcholine can cause lethal hyperkalemia. Lower motor neuron dysfunction is associated with the proliferation of postjunctional
nicotinic receptors.
§ There is increased sensitivity to nondepolarizing neuromuscular blockers.
§ Bulbar muscle dysfunction increases the risk of pulmonary aspiration.
§ Chest weakness reduces vital capacity and maximal minute ventilation.
§ Consider postoperative mechanical ventilation.
• Myasthenia Gravis
o Pathophysiology
§ Myasthenia gravis is an autoimmune disease. igG antibodies destroy post-junctioal, nicotinic, acetylcholine receptors at the neuromuscular junction.
§ Although Ach is present in sufficient quantity, there aren’t enough receptors to translate the extracellular signal into an intracellular response. This manifests as
skeletal muscle weakness.
§ A key feature of myasthenia gravis is skeletal muscle weakness that becomes worse later in the day or that develops with exercise. Periods of rest allow for
recovery of skeletal muscle function.
§ The thymus gland plays a key role, and thymectomy brings symptom relief to many patients.
o Symptoms
§ Diplopia, ptosis (earliest signs)
§ Bulbar muscle weakness (muscles of mouth and throat)àdysphagia, dysarthria, and difficulty
handling saliva
§ Dyspnea with exertion
§ Proximal muscle weakness
§ Situations that Exacerbate Symptoms
• Pregnancy Infection
• Electrolyte abnormalities Surgical and psychological stress
• Aminoglycoside antibiotics
§ *Pregnancy intensifies the symptoms of myasthenia gravis in one third of women. Anti-AchR IgG antibodies cross the placenta and cause weakenss in 15-20% of
neonates. This can persist up to 2-4 weeks, which is consistent with the half-life of the Anti-AchR IgG antibodies in the neonate’s circulation. These neonates may
require away management.
o Treatment
§ Anticholinesterases
• Oral pyridostigmine is the first line medical treatment.
• Overdose of anticholinesterases causes cholinergic crisis and muscle weakness.
• Cholinergic crisis may be difficult to differentiate from myasthenic crisis.
• The diagnosis is made by administering 1-2 mg IV edrophonium, otherwise known as the “Tensilon test.”
• If muscle weakness is made worse, then the patient has cholinergic crisis. An anticholinergic is the appropriate treatment for this patient.
• If there is an improvement in muscle strength, then the patient had an exacerbation of myasthenic symptoms.
§ Immunosuppression: Corticosteroids, cyclosporine, azathioprine, mycophenolate
§ Surgery: Thymectomy reduces circulating Anti-AchR IgG in most patients. Surgical approach may be via median sternotomy or by the transcervical approach.
§ Plasmapheresis
• Provides temporary relief during myasthenic crisis or prior to thymectomy.
o Neuromuscular Blockers
§ Because there is a reduction in the number of nicotinic receptors (type-m) at the neuromuscular junction, patients with myasthenia gravis have an increased
sensitivity to non-depolarizing NMBs and a resistance to succinylcholine.
§ When dosing neuromuscular blockers, you should keep the following principles in mind:
• Nondepolarizers—increased Sensitivity
o Potency is increased.
o Reduce dose by ½ to 2/3 monitor the response with nerve stimulator.
• Succinylcholine—increased Resistance
o If RSI is required, the dose should be increased to 1.5-2.0mg/kg.
o Pyridostigmine is the mainstay of medical management.
o It impairs the efficacy of Pseudocholinesterase. This prolongs the duration of succinylcholine.
• Remember that volatile anesthetics cause skeletal muscle relaxation by acting in the ventral horn of the spinal cord. In many cases, this eliminates the
need for neuromuscular blockers.
o Post-operative Concerns
§ 1. Patients with MG are very sensitive to the effects of residual neuromuscular blockade.
§ 2. Bulbar muscle weakness (mouth and throat) manifests as difficulty handling oral secretions. This increases the risk of pulmonary aspiration.
§ 3. Patients with myasthenia gravis should be counseled on the need for post-operative ventilation. This risk is increased with:
• disease duration > 6 years Daily pyridostigmine >750 mg/day
• Vital capacity <2.9L COPD
• Surgical approach: median sternotomy >transcervical thymectomy

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• Eaton-Lambert Syndrome
o Otherwise known as myasthenic syndrome. Eaton=Lambert syndrome is a disorder of the
neuromuscular junction that results in skeletal muscle weakness. When the NCE item writers come
up with incorrect responses to their questions, they’ll try to confuse you with things that are
similar. Do not confuse Easton-Lambert syndrome with myasthenia gravis.
o Pathophysiology
§ Eaton-Lambert syndrome is caused by IgG mediated destruction of the presynaptic
voltage-gated calcium channel at the presynaptic nerve terminal.
§ When the action potential depolarizes the nerve terminal, Ca+2 entry into the
presynaptic neuron is limited, thereby reducing the amount of Ach that is released into the synaptic cleft.
§ The postsynaptic nicotinic receptor is present in normal quantity and functions normally.
o Clinical Presentation
§ The proximal muscles are most affected, and weakness is generally worse in the morning and gets better throughout the day.
§ The respiratory musculature and
diaphragm become weak.
§ Autonomic nervous system dysfunction
causes orthostatic hypotension, slowed
gastric motility, and urinary retention.
o Treatment
§ 3,4-diaminopyridine (DAP) increases Ach
release from the presynaptic nerve
terminal and improves the strength of
contraction.
§ Anticholinesterases are not helpful and the
Tensilon test does not aid in diagnosis.
o Anesthetic Considerations
§ Patients are sensitive to succinylcholine AND nondepolarizers—the doses should be reduced.
§ Volatile anesthetics provide enough muscle relaxation for most surgical procedures.
§ Reversal with anticholinesterases may be inadequate despite proper dosing.
§ Patients are at high risk for post-operative ventilatory failure.
§ Upwards of 60% of patients with Eaton-Lambert syndrome have small-cell carcinoma of the lung (oat-cell carcinoma). Consider the
possibility of this disorder in all patients with suspected lung cancer undergoing mediastinoscopy, bronchoscopy, or thoracoscopy.
• Guillain-Barre Syndrome
o The peripheral nervous system includes all the nerves of the body outside of the brain and spinal cord. Peripheral polyneuropathies are a class
of disease processes that affect the peripheral nervous system, and with the near eradication of polio, Guillain-Barre syndrome has become the
most common cause of acute, generalized paralysis.
o Pathophysiology
§ Guillain-Barre Syndrome (acute idiopathic polyneuritis) is characterized by an immunologic assault on myelin in the peripheral
nerves.
§ The action potential can’t be conducted, so the motor endplate never receives the incoming signal.
§ It usually persists for ~2 weeks and ends with full recovery in ~ 4 weeks.
§ About 2% of those affected with GBS will develop chronic inflammatory demyelinating polyneuropathy.
o Clinical Presentation
§ A flu-like illness usually precedes paralysis by 1-3 weeks.
§ The most common culprits are Campylobacter jejuni bacteria,
Epstein-Barr virus, and cytomegalovirus. Other causes include
vaccinations, surgery, and lymphomatous disease.
o Signs & Symptoms
§ Flaccid paralysis begins in the distal extremities and ascends bilaterally towards the proximal extremities, trunk, and face.
§ Intercostal muscle weakness impairs ventilation.
§ Facial and pharyngeal weakness causes difficulty swallowing.
§ Sensory deficits include: paresthesia, numbness, and/or pain.
§ Autonomic dysfunction is common: tachycardia or bradycardia, hypertension or hypotension, diaphoresis or anhidrosis, and
orthostatic hypotension.
o Treatment
§ Medical treatment includes plasmapheresis and/or IV IgG.
§ In contrast to multiple sclerosis, steroids and interferon do not improve this condition.
o Anesthetic Considerations
§ The major anesthetic concerns are skeletal muscle denervation, impaired ventilation ,and autonomic dysfunction.
• Avoid succinylcholine. There is a risk of hyperkalemia from proliferation of extrajunctional Ach receptors.
• Increased sensitivity of nondepolarizers.
• Facial and pharyngeal weakness causes difficulty swallowing and increases the risk of aspiration.
• May require postoperative mechanical ventilation.
• Patients with autonomic dysfunction are at risk for hemodynamic instability from anesthesia, position changes, positive pressure
ventilation, and blood loss, they require intra-arterial pressure monitoring.
• There is an exaggerated response to indirect acting sympathomimetics due to upregulation of postjunctional adrenergic
receptors.
• Regional anesthesia is controversial—there is inconcolusive data.
• Steroids are not useful.
• Immobility increase the risk of DVT.

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• Familial Periodic Paralysis
o Pathophysiology
§ Familial periodic paralysis is characterized by acute episodes of skeletal muscle weakness accompanied by changes in the serum
potassium concentration. There are two variants of this disease: hypokalemic and hyperkalemic.
§ While the cause is unknown, a few things are understood:
• 1. It is a disorder of the skeletal muscle membrane (reduced excitability).
• 2. It is not a disease of the neuromuscular junction.
• 3. Hypokalemic periodic paralysis is associated with a calcium channelopathy.
• 4. Hyperkalemic periodic paralysis is associated with a sodium channelopathy.
o Diagnosis
§ Hypokalemic periodic paralysis is present if skeletal muscle weakness follows a glucose-insulin infusion. The patient became weak
after the serum K+ was reduced.
§ Hyperkalemic periodic paralysis is present if skeletal muscle weakness follows oral potassium administration. The patient became
weak after the serum K+ was increased.
o Treatment
§ Acetazolamide is the treatment for both forms of this disease. It creates a non-anion gap acidosis, which protects against
hypokalemia, and it also facilitates renal potassium excretion, which guards against hyperkalemia.
o Anesthetic Considerations
§ Hypothermia must be avoided at all costs. Indeed, it is recommended that these patients remain normothermic even when they are
placed on cardiopulmonary bypass!
§ Serial serum potassium monitoring is indicated.

§ Notice that all the drugs to avoid either affect serum glucose or potassium. If you can remember this, you’ll be able to reason out
the correct answer on the exam.
§ We would like to note that Hines states that succinylcholine is safe in patients with hypokalemic periodic paralysis, while Nagelhout
says that succinylcholine is contraindicated. Given our understanding of the pathophysiology of these conditions, we agree with
Hines.
• Malignant Hyperthermia
o MH is an inherited disease or skeletal muscle that is characterized by disordered calcium homeostasis. There are only two classes of drugs
known to trigger MH: halogenated anesthetics and depolarizing neuromuscular blockers. For this reason, it would be a waste of your time to
memorize a list of drugs that are safe for the patient at risk for MH. Just know halogenated agents and succinylcholine. That’s it.
o Pathophysiology
§ When the T-tubule is depolarized, extracellular Ca+2 enters the myocyte via the dihydropyridine receptor. This activates the
defective ryanodine receptor (RYR1), which instructs the sarcoplasmic reticulum to release way too much calcium into the cell. You
can think of the RyR1 receptor as a Ca+2 faucet that can’t be turned off. Not only is there more Ca+2 to engage with the contractile
elements, but the cell attempts to return the excess Ca+2 to the SR via the SERCA2 pump. Both processes consume a substantial
amount of ATP, increase oxygen consumption, and increase CO2 production.

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o Consequences of Increased Intracellular Calcium in the Myocyte
§ Sustained muscle contraction
§ Accelerated metabolic rate and rapid depletion of ATP
§ Increased oxygen consumption
§ Increased CO2 and heat production
§ Mixed respiratory and lactic acidosis
§ Sarcolemma breaks down
§ Potassium and myoglobin leak into the systemic circulation
§ Rigidity from sustained contraction
o Associated Conditions
§ MH is definitively linked to only three other co-existing diseases:
• 1. King-Denborough syndrome
• 2. Central core disease
• 3. Multiminicore disease
*Some texts list Evans myopathy as the third disease that is definitively linked to MH. Our list came from Nagelhout, and its also what’s
listed on the MHAUS website.

§ What about Duchenne Muscular Dystrophy?

• The patient with Duchenne muscular dystrophy does not code for dystrophin. The absence of dystrophin destabilizes the
sarcolemma during muscle contraction and increases membrane permeability.
o Extracellular Ca+2 is free to enter the cell, which can increase the rate of metabolism.
o Intracellular potassium is free to exit the cell, which can result in hyperkalemic cardiac arrest.
o Myoglobin is free to exit the cell, which can cause renal failure.
• An MH-like syndrome is associated with Duchenne muscular dystrophy, but this is due to rhabdomyolysis-not true MH. Indeed,
the patient with Duchenne muscular dystrophy has a normal RyR1 receptor. Furthermore, Dantrolene does not treat this
condition.
• It is possible that halogenated agents and succinylcholine can initiate this MH-like syndrome in the patient with DMD, so it is
prudent to avoid these agents.
• ANY patient with Duchenne muscular dystrophy or other muscular dystrophy who sustains a cardiac arrest on induction should
be assumed to have severe hyperkalemia and be immediately treated with calcium chloride.
§ Any Other Associations?
• The risk of MH is NOT increased in Becker muscular dystrophy, neuroleptic malignant syndrome, myotonia congenital, or
myotonic dystrophy. Some of you will absolutely see this on the NCE.
§ Incidence
• The overall incidence of MH varies between 1:5,000 to 1:50,000. Factors that increase risk include:
o 1. Geography-families from Wisconsin, Nebraska, West Virginia, and Michigan appear to be at higher risk.
o 2. Male sex
o 3. Youth
o Clinical Presentation
§ Signs & Symptoms
• The most sensitive indicator is an
EtCO2 that rises out of proportion to
minute ventilation. MH can occur as
late as 6 hours after exposure to a
triggering agent.
• You should know the time course of symptom progression.
§ Masseter Spasm
• Trismus and masseter muscle rigidity are two entities that exist on a continuum.
o Trismus describes a tight jaw that can still be opened.
o Masseter muscle rigidity describes a jaw that cannot be opened.
• Masseter muscle rigidity complicates airway management. Spasm is due to increased Ca+2 in the myoplasm. Since this site of
action is distal to the neuromuscular junction, a neuromuscular blocker will not relax the jaw.
• Trismus is a normal response to succinylcholine, so it’s ok to proceed with surgery if trismus occurs in isolation. Even so, it’s
probably wise to convert to a non-triggering agent.
• If the patient experiences masseter muscle rigidity, assume MH until proven otherwise.
§ Differential Diagnosis
• Although the diagnosis of MH may appear obvious here, this isn’t always the case in practice. There are several conditions that
should be considered in the differential.
o Thyroid storm
o Malignant neuroleptic syndrome
o Sepsis
o Pheochromocytoma
o Serotonergic syndrome
o Heat stroke
o Metastatic carcinoid
o Cocaine intoxication
§ Halothane Contracture Test
• Anyone who has experienced MH or masseter spasm should be referred for a halothane contracture test for diagnosis. Although
this is the definitive test for diagnosis, it only has an 80% specificity, so there is a risk of a false-negative result.

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o Treatment
§ Dantrolene
• Dantrolene has two mechanisms of action:
o 1. It halts Ca+2 release from the RyR1 receptor.
o 2. It prevents Ca+2 entry into the myocyte, which reduces the stimulus for calcium-induced calcium release.
• Each vial contains 20 mg of dantrolene + 3 g of mannitol. The vials must be reconstituted with 60 mL of preservative free
water. NaCl introduces additional solute, which prolongs the time required for dantrolene to dissolve into the diluent.
Coming from someone who has experience with this, mixing dantrolene is a chore. Enlist help early.
• You should be able to calculate the total dose of dantrolene to administer as well as the number of bottles needed to
treat a patient of a particular weight.
• Dantrolene is classified as a muscle relaxant. Its most common side effects are muscle weakness and venous irritation.
§ Treatment: Acute Phase
• It’s important to understand the steps of treating an MH episode. Nagelhout recommends the following treatment
sequence:
o 1. Discontinue the triggering agent (volatile agent and/or succinylcholine).
o 2. Call for help, and inform the surgeon to end the procedure.
o 3. Hyperventilation with 100% O2 at a minimum FGF of 10 L/min (don’t waste tie changing the soda lime).
§ Facilitates CO2 elimination
§ Enhances O2 delivery
§ Drives K+ into cells
o 4. Administer dantrolene.
§ 2.5 mg/kg IV and repeat q 5-10 min
§ stop dantrolene when symptoms of hypermetabolism subside
§ continue in the ICU at 1 mg/kg q 6 hr or 0.1-0.3 mg/kg/hr for 48-72 hours
§ venous irritation is common-used the largest vein possible
§ if the patient requires more than 20 mg/kg, reconsider the diagnosis of MH
§ have you ever tried to mix dantrolene? It’s a chore! Shortly after graduation, Kevin et. aAl.
Conducted a randomized, controlled single blinded trial examining dantrolene solubility and
proposed a simple bedside method of enhancing dantrolene solubility.
§ Ryanodex is a newer dantrolene formulation that solubilizes in ~1 minute. Each vial contains
dantrolene 250 mg (enough for a loading dose for most patients) and only requires 5 mL of sterile
water diluent.
o 5. Cool the patient until temperature drops below 38 degrees C.
§ cold IVF
§ cold fluid lavage of stomach and bladder
§ ice packs
o 6. Correct lactic acidosis.
§ Sodium bicarbonate 1-2 mEq/kg IV titrated to ABG and base deficit
o 7. Treat hyperkalemia
§ CaCl 5-10 mg/kg IV
§ Insulin 0.15 units/kg + D50 1 mL/kg
§ Hyperventilation (added here for completeness—you started this earlier)
o 8. Protect against dysrhythmias (Class I antiarrhythmics).
§ Procainamide 15 mg/kg IV
§ Lidocaine 2 mg/kg IV
§ Co-administration of a calcium channel blocker with dantrolene can precipitate life-threatening
hyperkalemia!
o 9. Maintain urine output > 2 mL/kg/hr
§ protects against renal injury from myoglobin
§ IV hydration
§ Mannitol 0.25 g/kg IV
§ Furosemide 1 mg/kg IV
o 10. Disseminated intravascular coagulation is a late complication and signals impending demise.
§ Check coagulation panels
§ Treatment: After Stabilization
• After the patient is stabilized, he should be observed in the ICU. MH may reoccur up to 36 hours.
§ Preparation for the Patient at Risk for MH
• Dantrolene prophylaxis is unwrapped.
• The anesthesia machine must be flushed wit high flow oxygen. Depending on the particular model, times range from 20
to over 100 minutes.
• All the external parts should be removed and replaced. These include: CO2 absorbent, circuit, and breathing bag.
• The vaporizers must be physically removed from the machine.
• If the patient doesn’t present with s/sx of MH within the first hour of the procedure, it’s very unlikely that it will occur
later.
• The patient should be monitored for 1-4 hours in the PACU. Discharge to home is ok.

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 • Muscular Dystrophy
o Skeletal muscle myopathy is an umbrella term for a variety of related conditions. The most common is Duchenne muscular dystrophy. DM is an
X-linked, recessive disease that results from the absence of the dystrophin protein. Although we will focus our discussion on Duchenne, you
should be aware of the other forms of skeletal muscle myopathy including Becker, Emery-Dreifuss, facioscapulohmueral, and limb-girdie
muscular dystrophy.
• Pathophysiology
o Dystrophin is a critical structural component of the cytoskeleton of skeletal and
cardiac muscle cells. It helps anchor actin and myosin to the cell membrane. The
absence of dystrophin destabilizes the sarcolemma during muscle contraction and
increases membrane permeability.
o The breakdown of the sarcolemma allows creatine phosphokinase (a marker of
skeletal muscle breakdown) and myoglobin to enter the systemic circulation. Also,
calcium freely enters the cell, which activates proteases that destroy the contractile
elements and causes inflammation, fibrosis, and cell death.
o The absence of dystrophin allows extrajuncitonal receptors to populate the
sarcolemma. This predisposes these patients to hyperkalemia following
succinylcholine administration. Indeed, succinylcholine carries a black box warning
that details the risk of cardiac arrest and sudden death secondary to hyperekalemia in children with undiagnosed skeletal muscle myopathy.
o Classic teaching suggests that DMD increases the risk of malignant hyperthermia, however a more recent meta-analysis refutes this claim.
Instead, DMD patients are at risk for an MH-like syndrome characterized by hyperkalemia and rhabdomyolysis. Best practice includes TIVA and
avoiding succinylcholine.
• Clinical Presentation of DM
o Duchenne is more common in males and presents with atrophy and painless muscle degeneration. In the first decade of life, there is a progressive
deterioration of skeletal muscle strength culminating in profound weakness. These patients often require surgical correction of scoliosis and contractures
and rarely live past 30 years. Key pathophysiologic features include:
§ Respiratory Considerations
• Kyphoscoliosis (restrictive lung disease)à decreased pulmonary reserveàincreased secretions and risk of pneumonia
• Respiratory muscle weakness
§ Cardiac Considerations
• Degeneration of cardiac [Link] contractility, papillary muscle dysfunction, mitral regurgitation, cardiomyopathy,
congestive heart failure.
• Signs of cardiomyopathy include resting tachycardia, jugular venous distension, S3/S4 gallop, and displacement of the point of
maximal impulse.
• The gold standard of cardiac evaluation is echocardiogram, however cardiac MRI shows promise.
§ EKG Changes
• Impaired conductionàsinus tachycardia and short PR interval.
• Scarring of the posterobasal aspect (back/bottom) of the left ventricle manifests as increased R wave amplitude in lead 1, and
deep Q waves in the limb leads.
§ Gastrointestinal Considerations
• Impaired airway reflexes and gastrointestinal hypomotilityàincreased risk of pulmonary aspiration
Scoliosis

o Scoliosis is a lateral and rotational curvature of the spine and ribcage. Kyphoscoliosis is a posterior curvature of the spinal column.
• Etiology
o Idiopathic (80%)
o Congenital
o Myopathic (muscular dystrophy and amyotonia congenital)
o Neuropathic (cerebral palsy, syringomyelia, Friedreich’s ataxia)
o Traumatic
• Cobb Angle
o The Cobb Angle describes the magnitude of the spinal
curvature.
§ The two most displace vertebrae are identified (top
and bottom).
§ A line is drawn parallel to each.
§ A perpendicular line is drawn from each of
these lines
§ The angle where they intersect is the Cobb angle.
o The goal of spinal fusion with instrumentation is to stop
the progression of the curvature and prevent further
deterioration of cardiopulmonary function.
• Pulmonary
o Scoliosis alters thoracic geometry, which compresses the
lungs and creates a restrictive ventilatory defect. One side
of the thorax becomes smaller than the other.
• Cardiovascular Consideration
o Cardiac complications, such as RV hypertrophy, are the
result of an increased pulmonary vascular resistance. EKG
may reveal RV strain and right atrial enlargement.
o Other co-existing conditions include: mitral valve prolapse
(most common), mitral regurgitation, and coarctation of
the aorta.

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• Complications of the Prone Position

• Anesthetic Considerations
o Assess respiratory reserve with exercise tolerance, ABG, and vital capacity. VC < 40% predicted correlates with requirement for post-op
ventilation.
o Cervical scoliosis may cause difficult intubation.
o Nitrous oxide increases PVR.
o VAE increases dead space and is observed as a reduction in EtCO2 (increased PaCO2-EtCO2 gradient). A central line aids in aspiration of
entrained air.
o Thoracic correction higher than TB may require one lung ventilation: double lumen tube or bronchial blocker.
o Prepare for significant blood loss—IV access, type & crossmatch, autologous donation, cell saver.
o Deliberate hypotension to maintain MAP 60 mmHg carries the risk of cerebral hypoperfusion and ischemic optic neuropathy. Monitor end
organ perfusion with serial ABG (metabolic acidosis) and urine output.
o Use active warming: forced air warmer, fluids, etc.
• Wake-Up Test
o Neurologic injury (paraplegia) is a feared complication of spine surgery. The “wake-up” test is a method of assessing neurologic integrity during
complex spine surgery. Although this technique has largely been abandoned in favor of SSEP/MEP monitoring, the “wake-up” test may be
required when these modalities fail to provide conclusive evidence of the patient’s neurologic function.
o The anesthetic agents are turned off, and the patient is allowed to awaken. Next, the patient is asked to move both hands and feet. Once
neurologic integrity is assured, the patient is re-anesthetized until the conclusion of surgery.
§ If the patient is unresponsive, you can wait longer or reverse reversible agents (NMB, opioids, benzos).
§ If the patient can move his hands, but not his feet, the surgeon should reduce distraction on the spinal rods.
o Risks of the wake-up test include:
§ Tracheal extubation
§ Removal of intravenous or arterial lines
§ Air embolism
§ Awareness
§ Pain
§ Damage to surgical instrumentation
• Evoked Potentials
o Evoked potential monitoring has largely replaced the need for the wake-up test. When results from these monitors are worrisome or
inconclusive, then the wake-up test may be used.
o Somatosensory Evoked Potentials (SSEP):
§ Posterior cord (dorsal column pathway)
§ Posterior spinal arteries
§ Sensory function
§ SSEPs do NOT monitor motor function
§ Neuromuscular blockers don’t interfere with the monitor, but always communicate their use with the surgical team.
o Motor Evoked Potentials (MEP):
§ Anterior cord
§ Anterior spinal artery
§ Motor function
§ Do NOT use neuromuscular blockers
o The anesthetic implications of evoke potential monitoring is covered in detail in Volatile Anesthetics II.

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Rheumatoid Arthritis: The Airway

• Rheumatoid arthritis impacts the airway in 3 places

1. Temporomandibular joint Limited mouth opening
2. Cricoarytenoid joints Decreased diameter of glottis opening
3. Cervical spine Atlanto-occipital subluxation with flexion
Limited extension
• Temperomandibular Joint
o Synovitis of the TMJ can limit mouth opening
• Cricoarytenoid Joints
o Cricoarytenoid arthritis reduces the diameter of the glottis opening.
o This presents with hoarseness, stridor, dyspnea, and may result in airway obstruction.
o Edema or erythema of the vocal cords suggests cricoarytenoid arthritis.
o A decreased glottis diameter may increase the difficulty of passing an endotracheal tube past the vocal cords.
o Use a smaller endotracheal tube to minimize laryngeal trauma.
o This patient is also at risk of psotextubation airway obstruction.
• Cervical Spine
o The most common airway complication of RA is atlantoaxial
subluxation and separation of the atlanto-odontoid articulation.
This is due to weakening of the transverse axial ligament, which
allows the odontoid to directly compress the spinal cored at the
level of the foramen magnum. The patient is at risk for
quadriparesis or paralysis.
o The diagnosis of AO subluxation is made when the distance
between the anterior arch of the atlas and the odontoid process is
greater than 3 mm. this is best assessed with a lateral x-ray of the
cervical spine.
o Subaxial subluxation can also occur-most commonly at C5-6. Neck
motion can cause spinal cord injury.
o Surgical correction entails odontoid decompression and posterior
cervical fusion.
o The thoracolumbar spine is generally not affected by RA.
• Pathophysiology
o Rheumatoid arthritis is an autoimmune disease that targets the synovial joints. There is also widespread systemic involvement due to
infiltration of immune complexes into the small and medium arteries leading to vasculitis. Cytokines (TNF and interleukin-1) also play a central
role in the pathogenesis of RA>.
o The hallmark of RA is morning stiffness that generally improves with activity. The joints are painful, swollen, and warm. Other symptoms
include weakness, fatigue, and anorexia. Lymph node enlargement in the cervical, axillary, and epitrochlear regions may be noted as well. The
condition is 2-3 times more common in women.
o RA affects the proximal interphalangeal and metacarpophalangeal joints in the hands and feet. By contrast, osteoarthritis typically affects the
weight bearing joints and does not have systemic involvement.
• Complications of Rheumatoid Arthritis

• Laboratory Testing
o Rheumatoid factor is an anti-immunoglobulin antibody that is increased in 90% of patients with RA.
o C-reactive protein is increased.
o Erythrocyte sedimentation rate is increased.
• Medical Management
o Medical management aims at reducing inflammation with antirheumatics, glucocorticoids, and NSAIDs.
o Disease-Modifying Anirheumatic Drugs
§ Antirheumatic drugs improve symptoms by inhibiting tumor necrosis (TNF), interleukin-1 and -6, and inhibit T cells and B
lymphocytes. All these drugs suppress the immune system and increase risk of infection and cancer.
§ Examples include: methotrexate, cyclosporine, and etanercept.
§ Methotrexate causes liver dysfunction and suppresses the bone marrow.
§ Cyclosporine prolongs the duration of succinylcholine.

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Systemic Lupus Erythematosus

• Systemic lupus erythemamtosus is an autoimmune disease characterized by the proliferation of antinuclear antibodies. SLE affects nearly every organ
system, and most of the consequences are the direct result of antibody induced vasculitis and tissue destruction.
• Systemic Manifestations
o SLE is a disease that targets young women (~1:1000). The most common problems of SLE and polyarthritis and dermatitis. Arthritis can affect
any joint, but it generally does not involve the spine. Only about 33-50% of these patients develop the malar “butterfly” rash.
Complications of SLE
Airway CricoarytenoiditisàHoarseness,stridor, and airway obstruction
Recurrent laryngeal nerve palsy
Pulmonary Restrictive ventilatory defect P=Pregnancy
Pulmonary hypertension
Interstitial lung disease with impaired diffusing capacity I=Infection
Pleural effusion
Recurrent pulmonary emboli S=Surgery
Cardiovascular Pericarditis (tamponade is uncommon) S=Stress
Raynaud’s phenomenon
Hypertension E=Enalapril
Conduction defects
Endocarditis D=D-penicillamine
Hematologic Antiphospholipid antibodies
Hypercoagulability
Anemia C=Captopril
Thrombocytopenia
Leukopenia H=Hydralazine
Renal Nephritis with proteinuria
I=Isoniazid
Nervous system Stroke
Psychosis/dementia M=Methyldopa
Peripheral neuropathy
• Exacerbation of SLE P=Procainamide
o Exacerbation of SLE can occur as a result of stress or drug exposure. Drug induced lupus generally *The mnemonic
persists for several weeks to months and presents with mild symptoms of arthralgia, anemia,
leukopenia, and fever. Here are the most common offenders: “Pissed Chimp” “PISSED CHIMP” will help
• Medical Treatment you remember this list.
o Medical treatment aims to suppress the immune system and reduce the inflammatory response.
§ Corticosteroids
§ NSAIDs
§ Immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil)
§ Antimalarials (hydroxychloroquine and quinacrine)
• Anesthetic Considerations
o Cricoarytenoid arthritis may present as hoarseness, stridor, and airway obstruction. There is a risk of postextbuation laryngeal swelling and
airway obstruction necessitating steroids. Consider a smaller endotracheal tube if signs of cricoarytenoiditis are present.
o Antiphospholipid antibodies may develop. Although the aPTT is prolonged, these patients are prone to a state of hypercoagulability and
thrombosis. They are at risk for stroke, DVT, and pulmonary embolism.
o Cyclophosphamide inhibits plasma cholinesterase and increases the duration of succinylcholine.
o Pregnancy, stress, infection, and surgery can exacerbate s/sx.
Selected Musculoskeletal Disease

• Marfan Syndrome
o Marfan syndrome is a connective tissue disorder with autosomal dominant inheritance (think aortic insufficiency & AAA).
§ The classic problem is a dilated aortic root that sets the stage for aortic insufficiency and aortic dissection (minimize wwall stress with beta
blockers).
§ Other risks: abdominal aneurysm, cardiac tamponade (if aortic dissection), mitral prolapse, and spontaneous pneumothorax (careful with
PIP).
§ Patients are often tall (Abe Lincoln) with pectus excavatum (sunken chest), kyphoscoliosis, and hyperflexible joints (careful with positioning).
§ Pregnancy increases the risk of cardiovascular complicaitons.
• Ehlers-Danlos Syndrome
o Ehlers-Danlos syndrome is an inherited disorder of procollagen and collagen (think spontaneous bleeding into joints & AAA).
§ The classic problem is arterial aneurysm and increased bleeding tendency. Bleeding is the result of poor vessel integrity (not coagulopathy).
§ Due to the bleeding risk, it’s prudent to avoid regional anesthesia and IM injections. Excessive bleeding can also occur during invasive line
placement or trauma during airway management.
§ Pneumothorax is a common complication.
• Osteogenesis Imperfecta
o Osteogenesis imperfecta is a connective tissue disorder with autosomal dominant inheritance (think weak bones).
§ The classic problem is brittle bones (careful with positioning). Fractures can occur during NIBP inflation or following fasciculations caused by
succinylcholine!
§ Careful with airway management (risk of c-spine fracture and reduced cervical ROM).
§ Kyphoscoliosis and pectus excavatum reduce chest wall compliance and vital capacityàV/Q mismatch àarterial hypoxemia.
§ Serum thyroxine is increased in > 50% of the patients (increased BMR and VO2àhyperthermia). The risk of MH is NOT increased.
§ Blue sclera is a unique finding in those patients. The sclera is susceptible to fracture.

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• Multiple Sclerosis
o MS is demyelinating disease of the CNS.
§ Patients experience sensory and motor deficiencies as well as autonomic instability.
§ Cranial nerve involvement causes bulbar muscle dysfunction (aspiration risk).
§ Patients are treated with corticosteroids, interferon, and azathioprine.
§ S/sx can be exacerbated by stress and increased body temperature (as small as 1 degree C).
§ Classic teaching suggests that, while epidural anesthesia is safe, spinal anesthesia may exacerbate symptoms. The supporting
evidence is weak.
§ Succinylcholine can cause life-threatening hyperkalemia.
• Myotonic Dystrophy
o Myotonic dystrophy is characterized by a prolonged contracture after a voluntary contraction. This is the result of dysfunctional calcium
sequestration by the sarcoplasmic reticulum. Contractions can be so severe that they interfere with ventilation and intubation.
o There are 3 things that increase the risk of contractures:
§ Succinylcholine (use a nondepolarizer instead)
§ NMB reversal with anticholinesterases (theoretical concern—consider sugammadex)
§ Hypothermia (shiveringàsustained contractions)
o Patients with myotonic dystrophy are also at risk for:
§ Aspiration
§ Respiratory muscle weakness
§ Cardiomyopathy & dysrhythmias
§ Sensitivity to anesthetic agents
o Patients with myotonic dystrophy may safely receive a halogenated anesthetic (this condition does not put them at risk for MH).
• Scleroderma
o Scleroderma causes excessive fibrosis in the skin and organs, particularly in the microvasculature.
§ Airway: skin fibrosisàlimits mouth opening and mandibular mobility
§ Lungs: pulmonary fibrosis and pulmonary hypertension
§ Heart: dysrhythmias and CHF
§ Blood vessels: decreased complianceàhypertension
§ Kidneys: renal failure and renal artery stenosisàHTN
§ Peripheral and cranial nervesànerve entrapment by tight connective tissueàneuropathy
§ Eyesàdryness predisposes to corneal abrasion
o CREST syndrome is a type of scleroderma: Calcinosis, Raynaud’s phenomenon, Esophageal hypomotility, Sclerodactyly, Telangiectasia.
§ Telangiectasias (spider veins) increase the risk of mucosal bleeding, and this can become problematic during airway manipulation
(particularly during nasal intubation). This is especially troublesome, as the patient with scleroderma often has limited mouth
opening, which may necessitate nasal fiberoptic intubation.
• Paget’s Disease
o Paget’s disease is associated with excess osteoblastic and osteoclastic activity that causes abnormality thick, but weak, bone deposits.
§ It’s caused by excessive parathyroid hormone or calcitonin deficiency.
§ Pain and fractures are the most common problems with Paget’s disease.
§ Peripheral nerve entrapment can occur.
§ There is no vascular involvement.

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Neuro Notes:

230
Regional Anesthesia
Neuraxial
Anatomy of the Back Bone
• Vertebrae
o The vertebral column is made up of 33 vertebrae.
o Each vertebra can be divided into an anterior and a posterior segment. The
laminae and pedicles join the anterior and posterior segments and form the
vertebral foramen. This area contains the spinal cord, nerve roots, and
epidural space.
§ This image shows the superior view of a lumbar vertebrae.
• Facet Joint
o The spinal nerves exit the vertebral column by way of the intervertebral foramina.
o The vertebral body and intervertebral disc form the anterior border of the intervertebral foramina,
while the posterior border is created by the facet joints (one left and one right).
o The facet joint is formed by the superior articular process of one vertebra and the inferior articular
process of the vertebra directly above.
o The facet joint guides and restricts movement of the vertebral column.
o Injury to the facet joint can compress the spinal nerve that exists the respective intervertebral
foramina, causing pain and muscle spasm along the associated dermatome.
• Intervertebral Disc
o Each vertebra is separated by an intervertebral disc that acts like a shock absorber.
o Disc degeneration reduces the size of intervertebral foramina and can cause nerve compression.
• Spinous & Transverse Processes
o The transverse processes project laterally, while the spinous process projects posteriorly. Muscular
attachment to these regions provides stability and support. The spinous process also serves as a
landmark to determine the midline.
o The lumbar vertebrae can be differentiated from the thoracic and cervical vertebra by the
orientation of the spinous process.
§ Cervical and thoracic spinous process angle in a caudal direction. This requires a more
cephalad approach with the needle.
§ Lumbar spinous processes project in a posterior direction. This makes access to the epidural and intrathecal
spaces easier.
• Ligaments of the Spinal Column
o The 5 Ligaments
§ You should know the 5 ligaments of the spinal column. These are ordered from closest to the skin to the furthest
from the skin (posterior to anterior).

o 1. Supraspinous Ligament
§ runs most of the length of the spine and joins the tips of the spinous processes.
o 2. Interspinous Ligament
§ Travels adjacent to and joins the spinous processes.
o 3. Ligamentum Flavum
§ There are two flava that run the length of the spinal canal.
§ They form the dorsolateral margins of the epidural space.
§ They are thickest in the lumbar region.
§ Piercing the ligamentum flavum contributes to the loss of resistance when the needle enters the epidural space.
o 4. Posterior Longitudinal Ligament
§ Travels along the posterior surface of the vertebral bodies.
o 5. Anterior Longitudinal Ligament
§ attaches to the anterior surface of the vertebral bodies and extends the entire length of the spine.
§ It also attaches to the annulus fibrosus of the intervertebral discs.

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• Piercing the Ligaments with a Needle: Midline vs Paramedian Approach
o The needle will pass through 3 ligaments during the midline approach:
§ 1. Supraspinous ligament
§ 2. Interspinous ligament
§ 3. Ligamentum flavum
o The needle will pass through 1 ligament during the paramedian approach.
§ 1. Ligamentum Flavum
o the paramedian approach bypasses the supraspinous and interspinous ligaments. The first ligament that the needle passes through
is the ligamentum flavum. With either approach, the needle should NEVER pass through the anterior or posterior longitudinal
ligaments.
o Where
The Epidural and Subarachnoid Spaces

• From Skin to Spinal Cord:

o The epidural and subarachnoid spaces are named in relation to their

location to the 3 meningeal layers of the spinal cord (from outside in):
dura, arachnoid, pia (remember this as DAP).
• Epidural Space
o This space is shallow anteriorly, but deeper posteriorly, particularly in the lumbar
region. The boundaries of the epidural space include:
o The epidural space communicates with the paravertebral space by way of the
intervertebral foramina.
o The epidural space contains nerve roots, fat pads, and blood vessels. Epidural fat
acts as a sink for lipophilic drugs, reducing their bioavailability (bupivacaine >
lidocaine and fentanyl > morphine).
o The epidural veins (Batson’s plexus) drain venous blood from the spinal cord.
These valveless veins pass through the anterior and lateral regions of the epidural
[Link] and pregnancy increase intra-abdominal pressure, causing engorgement of the plexus. This is associated with an increased risk of
needle injury or cannulation during neuraxial techniques.
o Plica mediana dorsalis: While its existence remains controversial, many speculate that a band of connective tissue courses between the ligamentum
flavum and the dura mater. If it does exist, it could conceivably create a barrier that would impact spread of medications within the epidural space.
The plica mediana dorsalis has long been considered the culprit for difficult eipdrual catheter insertion as well as unilateral epidural blocks.
o An epidural hematoma is blood that accumulates between the dura and the bone. Since the bone is hard, accumulation of blood in the epidural
space compresses the dura. This can compress the spinal cord, causing spinal cord ischemia and permanent neurological dysfunction. Surgical
decompression within 8 hours provides the best chances of recovery.
st
• Dura Mater (1 Meningeal Layer)
o After the needle advances through the epidural space, it comes into contact with the dura mater, a tough fibrous protective shield that protects the
spinal cord. The dura begins at the foramen magnum and ends at the dural sac.
• Subdural Space
o The potential space between the dura mater and the arachnoid mater is called the subdural space. Inadvertent injection of local anesthetic in this
location will cause a high spinal if using epidural dosing or a failed spinal if using spinal dosing.
nd
• Arachnoid Mater (2 Meningeal Layer)
o A thin layer of connective tissue that neighbors the dura mater.
• Subarachnoid Space
o As its name suggests, the subarachnoid space is just past the arachnoid mater. It contains CSF< nerve roots, rootlets, and the spinal cord. This is the
target when performing a spinal anesthetic. If the needle continues anteriorly, it could pass through the pia mater, spinal cord, and the posterior
longitudinal ligament before hitting bone.
o There terminal end of the subarachnoid space is called the dural sac. This coincides with S2 in the adult and S3 in the infant.
rd
• Pia Mater (3 Meningeal Layer)
o The pia is the external covering of the spinal cord. It should never be punctured during spinal anesthesia!
o The filum terminale is a continuation of the pia mater caudal to the conus medullaris. It anchors the spinal cord to the coccyx. The internal portion
extends from the conus medullaris to the dural sac, and the external potion extends from the dural sac into the sacrum.

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• Sacral Anatomy
o The sacrum consists of 5 vertebrae.
o The superior iliac spines coincide with S2. These landmarks denote the location of the
dural sac in the adult. In neonates, the dural sac ends at S3.
o Sacral hiatus
§ Coincides with S5.
§ Results from the incomplete fusion of the laminae at S5 and sometimes S4.
§ Is covered by the sacrococcygeal ligament.
§ Provides an entry point to the epidural space.
o Sacral Cornua
§ Are boney nodules that flank the sacral hiatus.
§ Result from the incomplete development of the facets.
• Dermatomes
o The spinal cord has 31 paired spinal nerves. Each spinal nerve is formed by a posterior
(dorsal) nerve root or anterior (ventral)nerve root. Posterior nerve roots carry sensory
information and anterior nerve roots carry motor and autonomic information.
o A dermatome is an area of skin that is innervated by a dorsal nerve root from
the spinal cord. Likewise, a myotome depicts the muscles innervated by the
ventral nerve root from the spinal cord. We will cover dermatomes here.
o While dermatome charts give the impression of clearly defined areas of
innervation, the reality is that there is considerable overlap. Nevertheless,
dermatome maps are quite useful for determining the spread of the neuraxial
block.

o The dermatome relates to an area of skin that is innervated by a spinal nerve—it is not necessarily the area of skin that is in the
same plane as the spinal nerve. For example, although the umbilicus is anatomically anterior to the L3 vertebrae, it is actually
innervated by the T10 nerve root.
o You probably noticed that the face isn’t innervated by a spinal nerve. Instead, sensory input is conducted by the trigeminal nerve (CN
V).
• Site of Action
o Spinal Anesthesia
§ In the subarachnoid space, the primary site of local anesthetic action is on the myelinated preganglionic fibers of the spinal
nerve roots.
§ Local anesthetics also inhibit neural transmission in the superficial layers of the spinal cord.
o Epidural Anesthesia
§ Local anesthetics in the epidural space must first diffuse through the dural cuff before they can block the nerve roots.
§ Local anesthetics also leak through the intervertebral foramen to enter the paravertebral area. Here, local anesthetics
cause multiple paravertebral blocks.

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• Spread
o Spinal Anesthesia

o Epidural Anesthesia
§ Volume is the primary determinant of spread.
• Differential Blockade
o Spinal Anesthesia
§ Different types of nerves have different sensitivities to local anesthetic blockade.
§ Autonomic fibers are blocked first, sensory fibers are blocked second, and motor neurons are blocked last.
§ Since autonomic fibers are blocked by LA concentrations that do not affect sensory or motor neurons, the level of
autonomic blockade is higher than sensory and motor block.
§ Since sensory fibers are blocked by LA concentrations that do not affect motor neurons, the level of sensory block is higher
than motor block.
§ Autonomic blockade is 2-6 dermatomes higher than sensory block.
§ Sensory block is 2 dermatomes higher than motor block.
o Epidural Anesthesia
§ There is no autonomic differential blockade with epidural anesthesia.
§ Sensory block is 2-4 dermatomes higher than motor block.
• Classification of Peripheral Nerves

**Some texts may conflict with this table, and some texts even conflict with themselves in different chapters! We looked at all of them to determine the
most common teachings.

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• Systemic Effects of Neuraxial Anesthesia
o Cardiovascular
§ Sympathectomy vasodilates the arterial and venous circulations, although it predominantly affects the venous capacitance vessels.
Consequently, there is a reduction in venous return, cardiac output, and blood pressure. Volume loading with ~ 15 mL/kg and
vasopressors will minimize hypotension.
§ Bradycardia is caused by:
• Blockade the preganglionic cardioaccelerator fibers at T1-T4àrelative increase of parasympathetic tone.
• Unloading of ventricular mechanoreceptorsàBezold-Jarisch reflex.
• Unloading of the stretch receptors in the SA node.
o Respiratory
§ In healthy patients, Neuraxial anesthesia has negligible effects on minute ventilation, tidal volume, respiratory rate, dead space, and
arterial blood gas tensions.
§ Accessory muscle function is reduced. Impairment of the intercostal muscles (inspiration and expiration) as well as the abdominal muscles
(ability to cough and clear secretions) will decrease pulmonary reserve. This is particularly important for the patient with severe COPD.
Loss of proprioceptive input from the chest may cause the patient to complain of dyspnea.
§ Apnea is usually the result of cerebral hypoperfusion.
§ Apnea is usually NOT the result of phrenic nerve paralysis or high concentrations of local anesthetic in the CSF.
o Central Nervous System
§ Spinal anesthesia reduces sensory input to the reticular activating system. This can cause drowsiness.
o Neuroendocrine
§ By inhibiting afferent traffic originating form the surgical site, Neuraxial anesthesia diminishes the surgical stress response.
§ This reduces circulating levels of catecholamines, renin, angiotensin, glucose, thyroid stimulating hormone, and growth hormone.
o GI System
§ The gut receives parasympathetic innervation from the vagus nerve (CN X ) and sympathetic innervation from the sympathetic chain
between T5-L2.
§ Inhibition of the sympathetic chain between T5-L2 allows parasympathetic output to the gut to function unopposed.
§ Inhibition of sympathetic outflow causes sphincters to relax and increases peristalsis.
o Kidneys & Liver
§ So long as systemic blood pressure is maintained, hepatic and renal blood flow and function are unchanged.
• Contraindications to Neuraxial Anesthesia
o Contraindications to Neuraxial anesthesia can be relative or absolute. The textbooks offer conflicting guidelines on which contraindications are truly
absolute, and most make the assertion that the decision to proceed with a Neuraxial technique should be determined on a case-by-case basis.
Despite this, there is one area where the texts agree; patient refusal is always an absolute contraindication. Other contraindications (relative or
absolute) include:
o Coagulopathy
§ Risk of spinal or epidural hematoma
§ Neuraxial blocks are contraindicated in significant pathologic or therapeutic coagulopathic states.
• Platelet count <100,000
• Pt, aPTT, and/or bleeding time twice the normal value.
o Increased Intracranial Pressure
§ Increase chance of brain herniation with sudden change in CSF pressure.
o Sepsis
§ Introduction of contaminated blood beyond the BBB
§ Worsening of hypotension due to Neuraxial Sympathectomy.
o Infection at the Puncture Site
§ Needle introduces pathogen beyond the BBB.
o Hypovolemia
§ Worsening of hypotension due to Sympathectomy
o Valve lesions with fixed stroke volume
§ Examples include: severe aortic stenosis, severe mitral stenosis, or hypertrophic cardiomyopathy
o Scoliosis, Arthritis, Spinal Fusion & Osteoporosis
§ Technically more difficult
o Difficult Airway
§ Neuraxial anesthesia isn’t always the answer to the patient with a difficult airway. Block failure may require rapid conversion to general
anesthesia.
§ Depression of the reticular activating system is common, and this may contribute to sedation. Supplementation with IV sedatives may
lead to airway obstruction or collapse.
o Full Stomach
§ Hypotension related to the Sympathectomy may cause nausea and vomiting.
o Peripheral Neuropathy
§ The theory is that these patients are more susceptible to injury. They are also slower to recover from it. Although data in this area is
lacking, the legal world has a strong opinion. For this reason, many practitioners will not perform a Neuraxial block in a patient with
peripheral neuropathy.
o Multiple Sclerosis
§ Classic teaching suggests that, while epidural anesthesia is safe, an intrathecal technique may exacerbate symptoms (the NCE wants you
to know this).
§ In practice, there is no good data to support this. If a spinal anesthetic would benefit the patient with MS, then the patient should be
informed that there may be a small risk of symptom exacerbation.

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• Baricity
o CSF
§ The specific gravity of CSF is 1.002-1.009
o Local Anesthetic Solutions
§ Baricity describes the density of a local anesthetic
solution relative to the CSF.
• An isobaric solution describes a local
anesthetic solution relative to the CSF.
o An isobaric solution describes a local anesthetic solution whose baricity is similar to CSF.
o A higher density solution is hyperbaric, and a lesser density solution is hypobaric.
o These are important concepts because a hyperbaric solution will sink, a hypobaric solution will rise,
and an isobaric solution will remain in place.
o Dextrose is added to increase baricity or water is added to reduce baricity.
o As a general rule, solutions in dextrose are hyperbaric, in saline are isobaric, and in water are
hypobaric. Procaine 10% in water is an exception. A 10% solution contains a lot of molecules, which
explains why it’s hyperbaric.

• Clinical Examples of SAB at the L4 Interspace

o Hyperbaric Solution
§ A hyperbaric solution will settle to the lowest point
of the spinal canal. If we keep the patient in the
sitting position after the block, a hyperbaric solution
will sink and anesthetize the sacral nerve roots –this
is a saddle block. If we lay the patient supine after
the block, a hyperbaric solution will slide down the lumbar
lordosis and eventually pool in the sacrum and the
thoracic kyphosis.
§ You can see by the example that a spinal anesthetic tends
to level off at T4. If the patient becomes hypotensive
immediately following the SAB, you may be tempted to
place her in the Trendelenburg position. This shifts the
highest point of kyphosis to T1 and creates the real
possibility of a high spinal. Once the block is “set,” then
position changes are safe.
o Hypobaric Solution
§ A hypobaric solution will settle to the highest point of the
spinal canal. If we keep the patient in the sitting position
after the block, a hypobaric solution will rise towards the brain—this isn’t a good idea. If we inject a hypobaric solution and
then place the patient supine, the solution will float toward the lower lumbar region. It does not float towards the cervical
region, because this would first require the local anesthetic to sink into the thoracic kyphosis.

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• Spinal & Epidural Needles
o Spinal Needles
§ There are 2 classifications of spinal needles: cutting-point tip and pencil-point tip.

§ If using a spinal needle that is 22g or smaller, the risk of needle deflection is minimized by
placing an introducer needle in the interspinous ligament.
o Epidural Needles
§ Epidural needles differ by the amount of curvature at the needle tip.
§ Notice that the needle angle increases in alphabetical order:
• Crawford=0 degrees
• Hustead=15 degrees
• Tuohy=30 degrees
§ The 30 degree curvature + the blunt tip of the Tuohy needle minimizes the risk of dural puncture.
o How far to advance the Epidural Catheter?
§ The optimal depth of catheter insertion is 3-5 cm inside the epidural space. Contraindications
• Too shallowàhigher incidence of inadequate analgesia (epidural failure)
• Absolute
• Too deepàcatheter may enter an epidural vein or exit through an o Spina bifida
intervertebral foramen o Meningomyelocele of the sacrum
§ Never withdraw the catheter through the needle, as this can shear the catheter o Meningitis
leaving fragments inside the patient! • Relative
• Caudal Anesthesia o Pilonidal cyst
o The caudal approach to the epidural space allows us to block the sacral, lumbar, and lower o Abnormal superficial landmarks
thoracic dermatomes. It is useful for procedures requiring up to a T10 sensory block. o Hydrocephalus
o While this approach is commonly used in pediatric anesthesia, it is infrequently used in o Intracranial tumor
adolescence and adulthood because: o Progressive degenerative neuropathy
§ Sacral anatomy is more difficult to identify.
§ A lumbar approach to the epidural space is easier to perform and equally effective.
o Technique
§ The caudal approach to the epidural space is performed in the lateral or prone position.
§ In the lateral position, flex the hips and make sure the top leg is flexed more than the bottom leg (Simm’s position).
§ In the prone position, a small roll should be placed under the iliac crests and the legs in the frog position.
§ Using the superior iliac spine and the sacral hiatus as landmarks, envision an equilateral triangle with the apex of the triangle at the sacral
hiatus.
§ After sterile preparation, place a 22 or 25 gauge needle or 20 gauge IV catheter bevel up through the sacral hiatus at a 45 degree angle
aiming cephalad.
§ Advance until you feel a pop. This signifies entry into the epidural space. From here, drop the angel and advance into the epidural space.
§ Placing the needle tip beyond S2-S3 increases the risk of dural puncture. This is why the superior iliac spines are useful landmarks.
§ Before injection, aspirate for blood or CSF.
§ In children, air should not be used for loss of resistance. This can cause air embolism.
§ Palpate the skin during injection to rule out subcutaneous infiltration.
§ Resistance to injection suggests the needle tip is in the subperiosteal area.
§ Epinephrine 1:200,000 (5mcg/mL) will reduce vascular uptake of of the local anesthetic. This extends block duration.
§ Clonidine 1 mcg/kg provides analgesia that is equal to epidural opioids.
§ The patient may experience a feeling of fullness in the sacrum before the
block sets up. This is a normal response.
o Dosing
§ Just like an epidural, the volume determines the height of a caudal block.
§ Pediatric:
• Any concentration of bupivacaine, levobupivacaine, or
ropivacaine may be used so long as the total dose does not
exceed 2.5 mg/kg (Nagelhout) or 3mg/kg (Davis).
§ Adult:
• Follow standard dose maximums.

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• Neuraxial Opioids
o Neuraxial opioids have different PK/PD relationships when compared to IV, IM, or PO administration.
o Mechanism of Action
§ Neuraxial opioids inhibit afferent pain transmission in the substantia gelatinosa in lamina II of the dorsal horn.
§ Neurotransmission is reduced by: decreased cAMP, decreased Ca+ conductance, and increased K+ conductance.
§ When combined with local anesthetics, Neuraxial opioids create a denser block.
§ Opioids also diffuse into the systemic circulation, where the blood delivers them to opioid receptors throughout the body.
§ Neuraxial opioids do NOT cause:
• Sympathectomy
o Skeletal muscle weakness
o Changes in proprioception
o Intrathecal vs Epidural Administration
§ An opioid deposited into the intrathecal space can easily diffuse into the spinal cord.
§ An opioid deposited into the epidural space will diffuse within the epidural tissue. From the epidural space, it diffuses
across the dural cuff and into the CSF to reach the spinal cord. It also diffuses into the bloodstream. since only a fraction of
the dose reaches the subarachnoid space, a higher dose is required.

o Hydrophilic vs Lipophilic Drugs

§ Opioids are lipophilic drugs. Within this drug class, it is useful
to categorize them as being relatively more hydrophilic or
more lipophilic. Knowing where a drug falls on this
continuum allows us to make several predictions about that
drug’s PK/PD profile.

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Neuraxial Opioids: Side Effects
o There are 4 key side effects of Neuraxial opioids that you should understand: pruritus, respiratory depression, urinary retention, and nausea and
vomiting.
o Pruritus
§ Is the most common side effect of Neuraxial opioids. It is more common in obstetric patients.
§ Is caused by stimulation of opioid receptors in the trigeminal nucleus and not by mast cell degranulation. Indeed, non-histamine releasing
drugs, such as fentanyl and sufentanil, cause pruritus.
§ Can be treated with an opioid antagonist, such as naloxone. Diphenhydramine doesn’t fix the cause, but its sedative effects may be
beneficial.
o Respiratory Depression
• Hydrophilic drugs cause a biphasic respiratory depression. The early phase results from systemic absorption. Late phase
respiratory depression results from the tendency of hydrophilic opioids to ascend towards the brain where they can inhibit the
respiratory center. The early phase is <6 hours, and the late phase occurs between 6 and 12 hours.
• Lipophilic drugs are more quickly absorbed by the spinal tissue, which limits the amount of spread. In the epidural space,
diluting a lipophilic drug in 10 cc of preservative free sodium chloride will enhance spread. Early phase respiratory depression
results from systemic absorption. There sis no late phase of respiratory depression with these drugs.
• Respiratory depression is more common with:
o High opioid doses
o Co-administered sedatives
o Low lipid solubility
o Advanced age
o Opioid naivety
o Increased intrathoracic pressure
o Urinary Retention
§ Is most common in young males
§ Is more common with Neuraxial opioids when compared to IV or IM administration.
§ Results from inhibition of sacral parasympathetic tone. This causes bladder detrusor muscle relaxation and urinary sphincter contraction.
§ Can be reversed with naloxone.
o Nausea and Vomiting
§ Is caused by activation of opioid receptors in the:
• Area postrema of the medulla
• Vestibular apparatus
o Miscellaneous Effects
§ 2-chloroprocaine reduces the efficacy of epidural opioids.
§ Epidural morphine may reactivate herpes simplex labialis. This is best explained by cephalad spread of morphine to the trigeminal
nucleus. It usually presents 2-5 days after epidural morphine administration.
§ Sedation is dose dependent, but it is most common with sufentanil.
§ Peristalsis slows, increasing gastric transit time.
§ Opioids have an antidiuretic effect by increasing vasopressin release.
§ Any opioid that enters the systemic circulation becomes available to cross the placenta and enter the fetus.
§ Transfer of opioids from the epidural space to the breast milk is minimal.
• Postdural Puncture Headache & Meningitis
o Puncturing the dura causes CSF to leak form the subarachnoid space. As CSF pressure is lost, the cerebral vessels dilate. In addition, the brainstem
sags into the foramen magnum, which stretches the meninges and pulls on the tentorium. These factors contribute to PDPH.
o The classic presentation includes a fronto-occipital headache, which may be accompanied by nausea, emesis, photophobia, diplopia, and tinnitus. In
the upright position, gravity makes the headache worse, while the supine position brings relief.

Treatment
• Bed rest
• Hydration
• NSAIDs
• Caffeine (cerebral vasoconstriction)
• Epidural blood patch
• Sphenopalatine ganglion block

o Epidural Blood Patch

§ An epidural blood patch is the definitive treatment for PDPH, and each patch is associated with a 90% success rate. If the headache does
not improve after 2 blood patches, other etiologies should be sought.
§ Using sterile technique, 10-20mL of venous blood is withdrawn from the patient and then reintroduced into the epidural space. When the
patient senses pressure in her legs, buttocks, or back, the injection is complete. A blood patch is useful for 2 reasons. First, it compresses
the epidural and subarachnoid spaces, which increases CSF pressure. Second, it acts as a plug that prevents further leaks.
§ The most common side effects are backache and radicular pain.

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 o Sphenopalatine Ganglion Block
§ The SPG block is an alternative to the epidural blood patch in the treatment of PDPH. It’s simple to perform with a very low risk of side
effects.
• 1. Soak a long cotton-tipped applicator in a local anesthetic solution (1-2 % lidocaine or 0.5% bupivacaine).
• 2. Place the patient in the sniffing position.
• 3. Insert the applicator into each nare towards the middle turbinate.
• 4. Continue insertion until you encounter the posterior wall of the nasopharynx. This is in the vicinity of the sphenopalatine
ganglion.
• 5. Leave the applicator in place for 5-10 minutes.
• 6. The patient should notice symptom improvement at this time.
o Post-Spinal Bacterial Meningitis
§ When placing a Neuraxial block, there are 2 routes by which an infectious organism can reach the CSF.
• Failure of aseptic technique
• Bacteria in the patient’s blood at the time of SAB
§ Streptococcus viridans is one of the most common culprits responsible for post-spinal bacterial meningitis. It is commonly found in the
mouth, and this is why it’s so critical to wear a mask while performing a Neuraxial block. It’s also found on the hands and forearms, so
hand washing is essential.
§ How do we prepare the patient’s’ back?
• You have several prep options:
o Iodine
o Alcohol
o Chlorhexidine (is neurotoxic, so it must be allowed to dry before puncturing the skin with the needle)
• Miller says that a combination of alcohol and chlorhexidine is most effective.
• Antiplatelets & Anticoagulants
o The risk of epidural hematoma is similar during block placement and catheter removal.
o Epidural hematoma can cause paralysis. Presenting symptoms include lower extremity weakness, numbness, low back pain, and bowel and bladder
dysfunction. Surgical decompression within 8 hours offers the best chance of recovery.
o Patients with cardiac stents present a difficult situation. Discontinuation of anticoagulants and antiplatelet drugs can increase the risk of stent
thrombosis, while failure to discontinue many of these drugs puts the patient at risk for epidural hematoma.
o We’ve summarized the Consensus Statement from the American Society for Regional Anesthesia and Pain Medicine. Because the NCE relies on
textbooks, the guidelines published within the texts may be somewhat outdated. We encourage you to keep abreast of changes to these guidelines
as they occur.

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• Cauda Equina Syndrome & Transient Neurologic Symptoms
o Relevant Anatomy
§ Conus Medullaris:
• The spinal cord ends in a taper as the conus medullaris.
• In the adult: L1-L2
• In the infant: L3
§ Cauda Equina:
• Bundle of spinal nerves extending form conus medullaris to dural sac.
§ Dural Sac:
• The subarachnoid space terminates at the dural sac.
• In the adult: S2
• IN the infant: S3
§ Filum Terminale:
• This extends from the conus medullaris to the coccyx.
o Cauda Equina Syndrome
§ Cause:
• Neurotoxicity is the result of exposure to high concentrations of local anesthetic.
§ Factors that Increase Risk:
• 5% lidocaine and spinal micro catheters.
• Micro catheters focus local anesthetic on a small area of the cord, exposing this region to a high concentration of LA.
§ Signs & Symptoms:
• Bowel and bladder dysfunction, sensory deficits, weakness, and/or paralysis.
§ Treatment:
• Supportive
o Transient Neurologic Symptoms
§ Cause:
• Patient positioning, stretching of the sciatic nerve, myofascial strain, and muscle spasm. It is highly unlikely that neurotoxicity
causes TNS.
§ Factors that Increase Risk:
• Lidocaine, lithotomy position, ambulatory surgery, and knee arthroscopy.
§ Factors that do NOT Increase Risk:
• Early ambulation, local anesthetic concentration, baricity, or glucose concentration
§ Signs & Symptoms:
• Severe back and butt pain that radiates to both legs
• It generally develops within 6-36 hours and persists for 1-7 days.
§ Treatment
• NSAIDs, opioid analgesics, and trigger point injections.

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Regional Anesthesia: UPPER EXTREMITY
• Brachial Plexus Anatomy
o The brachial plexus consists of 5 consecutive nerve roots: C5-T1.
§ It is divided into 5 components: roots, trunks, divisions, cords, and branches.
§ Learning this will make some of you want to reach to drink cold beer. And yes, there’s a mnemonic buried in there.
Components of Brachial Plexus Mnemonic
Roots Reach
Trunks To
Divisions Drink
Cords Cold
Branches Beer
o Become a Master of the Brachial Plexus
§ To successfully answer questions about the brachial plexus, you’re going to have to learn to draw it. We’ve prepared a
clean, quick, and easy method for you. It would probably help if you grab a pen, crayon, napkins, or whatever you
have handy and follow along.

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• Sensory Distribution of the Upper Extremity
o Knowledge of sensory dermatomes will help you select the most appropriate block for a specific surgical procedure.
Furthermore, it is useful for determining which (if any) nerves were spared during the block. These may require
supplementation.
o As a general rule:
§ The ventral portion is supplied by the median, ulnar, and musculocutaneous nerves (lateral and medial cords).
§ The dorsal portion is supplied by the radial and axillary nerves (posterior cord).
§ The hand is the exception.

o Here’s a useful mnemonic: Push’er, Pull’em, Pinch me, Pinch u

§ Radial: tell patient to extend forearm against resistance (triceps contraction)
§ Musculocutaneous: tell patient to flex forearm against resistance (biceps contraction)
§ Median: Pinch index finger (or palmar surface of the hand)
§ Ulnar: Pinch pinky finger (or the hypothenar aspect of the hand)
o A Few Words About the Intercostobrachial Nerve
§ It arises from T2
§ It is not anesthetized with any aporoach to the brachial plexus
§ A field block is required to block this nerve. With the arm abducted and externally rotated,
begin at the deltoid prominence and move inferiorly towards the triceps. A total of 5 mL of
local anesthetic is sufficient.
§ Intercostobrachial blockade may foster tolerance for an upper arm tourniquet in an awake
patient.

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Interscalene Block: Technique
• An interscalene block is a root level block. It is the most proximal block of the brachial plexus.
o Targets: C5-C7 (upper and middle trunks)
o Indications: shoulder, arm, and elbow surgery (often spares lower trunk, so not ideal for procedures below the elbow).
o Landmarks: clavicular head of the sternocleidomastoid, clavicle, and cricoid cartilage
• Landmark Technique
o Landmark technique using nerve stimulation is accomplished by placing the patient supine with the head slightly elevated,
facing the non0operative side.
o The main landmark for this procedure is the sternocleidomastoid muscle, which can be accentuated by having the patient
slightly raise their head at the start of the procedure.
o Once it is identified, a line is drawn from the cricoid cartilage laterally to the lateral border of the clavicular head of the sternocleidomastoid muscle.
o The interscalene groove is palpated by rolling the fingers posteriorly off the lateral border. Often the transverse process of C6 (chassaignac’s tubercle)
can be felt.
o The injection site is cleansed with an aseptic solution and a small skin wheal is raised in the interscalene groove at the level of C6.
o A 22-gauge, 5cm, insulated, B-bevel needle is passed perpendicularly through the skin wheal, in a slightly caudal and posterior direction. This caudal tilt
decreases the possibility of entering the neural foramen or injecting into a dural nerve sheath.
o The needle is advanced until a motor response is elicited (see chart Acceptable Responses Unacceptable Responses
below). Deltoid (shoulder abduction) Trapezius
o Nerve stimulator current is then decreased from 1 to 0.5 mA to Pectoralis major (arm internal rotation) Diaphragm
ensure proper needle placement. Biceps (forearm flexion) (phrenic n stimulationà hiccups)
o Trapezius or diaphragmatic twitches are not acceptable endpoints. Triceps (forearm extension)
Twitching of the trapezius or diaphragm is indicative of cervical plexus Any twitch of hand or forearm
of phrenic nerve stimulation.
o Following negative aspiration, incremental injections of 5 mL of local anesthetic, each followed by negative aspiration, are administered for a volume of
25-30mL
• Ultrasound-Guided Technique
o The ultrasound-guided technique for this block is best obtained with the patient in the supine position, arms relaxed by the side, and the head slightly elevated and
turned to the non-operative side.
o Because of the shallow depth of the brachial plexus at this level, a high frequency transducer (>7MHz) should be used.
o The area is cleansed with an aseptic solution, prepped and draped in a sterile manner, and a sterile sheath is placed over the ultrasound transducer to maintain
sterility. It is important that conduction gel is placed inside the sheath to ensure optimal transmission of the sound beam.
o The transducer is then placed in the mid-clavicular fossa, directly slightly caudal.
o The division of the brachial plexus are located lateral to the hypoechoic pulsating subclavian artery, just superior to the first rib.
o The transducer is then moved cephalad until the roots of the plexus are visualized as a series of small hypoechoic circles located between the anterior and middle
scalene muscles.
o A small skin wheal is raised a the lateral edge of the transducer.
o Using an in-plane approach, a 22-gauge, 5 cm, B-bevel insulated needle is placed through the skin wheal, lateral to medial, and in a slightly caudal direction, passing
through the middle scalene muscle into the interscalene groove.
o Following negative aspiration, increments of 5 mL of local anesthetic should be deposited so that it achieves circumferential spread under direct visualization using
ultrasound.
• Continuous Interscalene Block
o A catheter can be placed to produce a continuous block.
o This provides excellent pain control for up to several days after surgery (great for shoulder sugery). Also, it can greatly reduce
post-operative opioid consumption.
o The catheter is positioned near the trunks of the brachial plexus between the scalene muscles.
o The catheter is inserted 3-5 cm beyond the tip of the block needle.
o After the initial bolus of local anesthetic, a dose of 5 ml/hr is infused.
Interscalene Block: Complications Pneumothorax
Phrenic Nerve Paralysis o Due to the proximity of the pleura, pneumothorax is
o The phrenic nerve is nearly always blocked when performing an interscalene block, possible if the needle is directed too far in a caudal
resulting in ipsilateral hemiparesis of the diaphragm. direction.
o In healthy patients, this rarely results in respiratory compromise. o The cupola of the lung I s higher on the right side.
o In patients with respiratory disease, such as COPD, phrenic nerve paralysis may result in o Consider pneumothorax is the patient coughs or complains
severe dyspnea, hypercapnia, and hypoxemia. of chest pain during needle insertion or manipulation.
Horner’s Syndrome

o The stellate ganglion (cervicothoracic ganglion) is located at C7. Hypotensive Bradycardic Episodes
o This structure is often blocked, resulting in Horner’s syndrome (ptosis, miosis, and
anhidrosis). o The Bezold-Jarisch reflex is the proposed mechanism for
o Horner’s syndrome indicates a successful block. HBEs during shoulder arthroscopy with interscalene
Epidural/Spinal Anesthesia blockade. These patients are typically in the sitting or semi-
upright position.
o If the needle is directed too far in a medial direction, it may enter the intervertebral o This reflex slows an empty heart to allow it adequate time to
foramen. Injection of local anesthetic will cause epidural or spinal anesthesia. fill.
Seizures: As little as 1 mL of local anesthetic injected into the vertebral artery can induce a o s/sx include bradycardia, hypotension, and syncope.
seizure. o The theory is that venous pooling in the lower extremities
reduces venous return. The combined effects of an
C6 Neuropathy unloaded ventricle, SNS stimulation, and epinephrine uptake
(from the block) results in a profoundly underfilled ventricle
o Intraneural injection is a risk as the needle compresses the C6 nerve root against the
that slows its rate to increase diastolic filling time.
tubercle.
o Preoperative beta blockade lessens the risk of the BJR in this
o A “crampy” sensation indicates intraneural injection.
context.
Recurrent Laryngeal Nerve Injury

o Injection of large volumes of local anesthetics may cause recurrent laryngeal paralysis that presents as hoarseness.

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• Supraclavicular Block: Technique
o The supraclavicular block targets the trunks/divisions of the brachial plexus.
§ Area anesthetized: arm, elbow, forearm, wrist, and hand (not the shoulder)
§ Landmarks: clavicle, subclavian artery
o The nerves are most compact at this level, as they travel under the clavicle and over the first
rib, just cephaloposterior to the subclavian artery.
o Landmark Technique
§ The landmark technique with nerve stimulation is accomplished by placing the
patient in a supine position with the head turned to the non-operative side, as with
an interscalene block.
§ A slight head-up position with a pillow placed between the scapulae will accentuate
the anatomy.
§ The clavicle and surrounding areas are cleansed with an aseptic cleaning solution.
§ The subclavian artery is palpated just behind and approximately 1 cm above the clavicle, and a small skin wheal is
placed just lateral to the site.
§ A 22 gauge, 5 cm B-bevel insulated needle is placed through the skin wheal and advanced perpendicularly in an
inward and caudal direction until a motor responses is noted in the distal upper extremity (hand or wrist flexion or
extension). Hadzic says that injecting the LA near the lower trunk (finger flexion or extension) is the most important
factor in producing a successful infraclavicular block.
§ The nerve stimulator current is decreased from 1 to 0.5 mA to ensure close approximation of the needle to the nerve.
§ Following negative aspiration, incremental injections of up to 5 mL of local anesthetic are given up to the intended
volume. In adult patients, this is usually 25 to 30 mL.
Acceptable Responses Unacceptable Responses
Finger flexion or extension (suggests lower trunk) Shoulder (suggests upper trunk)
Wrist flexion or extension Biceps or triceps (suggest middle trunk)
o Ultrasound Technique
§ The ultrasound-guided supraclavicular block is best obtained with the patient in the supine position, with the head slightly elevated
and turned to the non-operative side.
§ Because of the shallow depth of the trunks/divisions at this
level, a high-frequency transducer should be used.
§ As with the landmark technique, the clavicle and surrounding
areas are cleansed with an aseptic solution, then prepped and
draped in a sterile manner.
§ A sterile sheath is placed over the ultrasound transducer to
maintain sterility. It is important that conduction gel is placed
inside the sheath to ensure optimal transmission of the sound
beam.
§ The transducer is then placed at the center of the clavicle,
directed slightly caudal.
§ The trunks/divisions of the brachial plexus are located lateral to the hypoechoic pulsating subclavian artery, just superior to the first
rib. Doppler ultrasound can be used to confirm flow through the artery.
§ Once the anatomical structures are identified, the transducer is tilted so that the first rib is aligned under the nerves and over the
pleura, creating a protective barrier during needle insertion.
§ A 22 gauge, 5 cm B-bevel insulated needle is passed in-plane from lateral to medial, immediately adjacent to the subclavian artery
and superior to the first rib.
§ Following negative aspiration, incremental injections of local anesthetic of up to 5 mL are delivered, pushing the plexus superiorly.
o Complications
§ Pneumothorax
• The greatest risk of supraclavicular approach is pneumothorax.
• The cupola of the lung is just medial to the first rib. It is higher on the right side.
• Tall, thin patients have a higher risk of this complication.
• Consider pneumothorax if the patient coughs or complains of chest pain during needle insertion or manipulation.
§ Stellate Ganglion Block/Horner’s Syndrome
• Stellate ganglion blockade, Horner’s syndrome (ptosis, miosis, and anhidrosis) frequently results from this block.
• Local anesthetic spreads proximally towards the sympathetic chain on the anterior vertebral body.
§ Subclavian Artery Injection
• Aspiration prior to injection is key to rule out possible subclavian artery puncture.

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• Infraclavicular Block
o The infraclavicular approach is a cord level block.
§ Area anesthetized: elbow, forearm, and hand (not above the elbow)
§ Landmarks: coracoid process, clavicle
o Because the nerves are distant from the neuraxial structures and phrenic nerve, diaphragmatic paralysis
rarely occurs, making this a good option for patients with known pre-existing respiratory insufficiency.
o Landmark Technique
§ When performing a landmark infraclavicular technique, the patient is supine with the head
turned to the non-operative side.
§ The patient’s arm is adducted, flexed at the elbow with the hand resting on the abdomen.
Alternatively, the arm can be abducted and flexed 90 degrees at the elbow.
§ The coracoid process is identified by palpating the clavicle, and then sliding distally into the
acromioclavicular joint and deltopectoral groove.
§ The area is cleansed with an aseptic solution and a skin wheal is placed 2 cm medial and 2 cm caudal to the coracoid process.
§ The infraclavicular block is considered one of the more painful upper extremity blocks, as the needle must pass through both the
pectoris major and pectoris minor muscles. Injecting 1-2 mL of local anesthetic below the subcutaneous tissue will reduce some of
the discomfort associated with this procedure.
§ Since the cords are typically found at a depth of 4-5 cm, a longer needle is normally needed.
§ An 18-22 gauge, 9cm, B-bevel insulated needle is inserted perpendicularly and directed slightly posterior until a motor response is
elicited.
Acceptable Responses Unacceptable Responses
§ Acceptable motor responses include finger
flexion/extension when nerve stimulation is Hand twitch Pectoralis (needle is not in infraclavicular fossa)
decreased from 1 mA to 0.5 mA. Biceps (indicates musculocutaneous stimulation)
§ The artery is easily punctured at this point, so careful deltoid
aspiration is required prior to any incremental injection of up to 30mL.
§ Elbow flexion is indicative of lateral cord stimulation, and if local anesthetic is injected at this level, an incomplete block will occur.
§ Inserting the needle deeper and injecting additional local anesthetic is warranted.
o Ultrasound Technique
§ An ultrasound-guided infraclavicular block is performed with the patient
positioned in a similar fashion to the landmark technique; supine with the head
turned to the non-operative side and the arm adducted, flexed at the elbow with
the hand resting on the abdomen.
§ The area of the distal clavicle and coracoid process is cleansed with an aseptic
technique, then prepped and draped in a sterile manner.
§ Depending on body habitus, either a high-frequency linear array transducer, or a
low-frequency curved array transducer is used.
§ After placing a sterile sheath over the ultrasound transducer to maintain sterility
(place conduction gel inside the sheath for optimal imaging), it is placed in a
parasagittal position just distal to the coracoid process.
§ The resultant picture will be a short-axis image of the cords of the brachial plexus and axillary vessels.
§ The lateral cord of the plexus is often visualized as a hyperechoic oval structure cephalad to the axillary artery.
§ The medial and posterior cords are more difficult to identify as the medical cord often lies between the axillary artery and vein and
the posterior cord lies deep to the axillary artery.
§ Unlike the interscalene and supraclavicular blocks, the nerves at this level appear hyperechoic (bright) rather than hypoechoic
(dark). This is most likely due to the increased amount of connective tissue around the nerve fascicles as they move distal into the
extremity.
§ A skin wheal is placed just proximal to the transducer.
§ An 18-22 gauge, 9cm, B-bevel insulated needles is then passed in-plane caudal and posterior.
§ Because there is higher variability in the location of the cords, nerve stimulation is also used in conjunction with ultrasound.
§ The goal is to place the needle posterior to the axillary artery.
§ Following gentle aspiration, local anesthetic is injected incrementally up to 30 mL.
§ A complete block is obtained when local anesthetic spreads from the area of the posterior cord cephalad and caudally, forming a
semi-circle around the axillary artery.
§ If spread is deemed inadequate the needle is repositioned prior to injecting further increments.
o Complications
§ Vascular Puncture
• Vascular puncture is a real complication for this block; therefore, careful aspiration should precede any incremental
injection.
§ Pneumothorax
• Insertion of the needle in a slightly lateral fashion decreases the risk of pneumothorax.
• Needle insertion too far medial increases this risk.
• This approach has a lower incidence of pneumothorax when compared to the interscalene and supraclavicular
approaches.
§ Other
• Compared to the interscalene and supraclavicular block, the risk of phrenic nerve and stellate ganglion block is much less.
• While not a complication, you should note that this block is more painful than the interscalene and supraclavicular
approaches.

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• Axillary Block
o The axillary block targets four terminal branches of the brachial plexus as they course distally
with the axillary artery and vein along the humerus from the apex of the axilla.
§ Area anesthetized: forearm and hand
§ Landmarks: axillary artery pulse
o The primary nerves are the radial, median and ulnar branches, which are contained in a neurovascular sheath around the axillary artery. The
course of the terminal nerves in relation to the axillary artery is as follows:
§ The median nerve is located anterior and medial.
§ The ulnar nerve lies posterior and medial.
§ The radial nerve lies posterior and lateral.
§ The musculocutaneous nerve lies anterior and lateral.
o Because the musculocutaneous leaves proximal to this area (via lateral cord) and travels through the coracobrachialis muscle, it must be
blocked separately.
o Axillary blockade is often desired in patients with a full stomach and those who want to avoid general anesthesia. There are few
contraindications to the axillary block. Local infection, neuropathy and bleeding risk must be considered.
o Transarterial Technique
§ The transarterial technique has fallen out of favor in recent years because the axillary artery is intentionally punctured, thereby increasing
the risk for inadvertent intravascular injection of local anesthetic.
§ The patient is placed supine, with the arm to be blocked abducted 90 degrees, the forearm flexed upward and parallel to the long axis of the
body.
§ Starting at the lateral edge of the pectoralis major muscle, the axillary artery is palpated and then followed distally in the muscular groove
between the coracobrachialis and triceps muscles.
§ The artery is marked as high in its course through the axilla as practical.
§ The area is cleansed with an aseptic cleaning solution.
§ Using the index and third finger of the non-dominant hand, the axillary artery is again palpated, and a small skin wheal is placed over top of
the axillary artery between the two fingers.
§ A 21 gauge, 1 ½ inch needle is placed through the skin wheal perpendicularly and advanced slowly until blood is aspirated.
§ The needle is then advanced along the same place until blood can no longer be aspirated, indicating the needle has passed through the
posterior wall of the artery. Care must be taken not to advance the needle too deep, causing the local anesthetic to be deposited outside the
sheath.
§ Following careful aspiration, a test dose of 3 mL is injected and the patient is observed approximately one minute for possible signs of direct
intravascular injection.
§ Following negative aspiration, incremental injections of 5mL are accomplished until 20 ml of local anesthetic is deposited.
§ The needle is then slowly withdrawn back through the artery, noting when the aspiration of blood stops, indicating that the needle is now
located in the neurovascular sheath anterior to the axillary artery.
§ Again, following gentle aspiration, a test dose of 3 ml is injected and the patient is observed for signs of direct intravascular injection.
§ Following each aspiration, 5 ml of local anesthetic is incrementally injected until a total of 40 mL is deposited.
o Landmark & Nerve Stimulation Technique
§ For the axillary block using the landmark-nerve stimulation technique, the patient is placed supine with the arm to be Acceptable Responses
blocked abducted 90 degrees, the forearm flexed upward and parallel to the long-axis of the body. Radial à finger or wrist extension
§ Starting at the lateral edge of the pectoralis major muscle, the axillary artery is palpated, and then followed distally in Ulnar à ulnar deviation
the muscular groove between the coracobrachialis and triceps muscles. Median à finger flexion
§ The artery is marked as high in its course through the axilla as practical. Musculocutenous à biceps twitch
§ The area is cleansed with an aseptic cleaning solution using the index and third finger of the non-dominant hand, the
proximal axillary artery is again palpated, and a small skin wheal is placed over the top of the axillary artery between Unacceptable Responses
the two fingers. Anything not listed above
§ A 22 gauge, 5 cm, B-bevel insulated needle is inserted slightly cephalad.
§ As viewed by the practitioner, the musculocutaneous and median nerves lie on the superior aspect of the artery, while the ulnar and
radial nerves lie posterior and behind the artery respectively.
§ When using nerve stimulation, ideally the nerves innervating the area of the proposed surgery are blocked first.
o Ultrasound Technique
§ When performing an ultrasound-guided axillary block, the patient is positioned supine with the arm to be blocked
abducted 90 degrees, the forearm flexed upward and parallel to the long axis of the body.
§ A high-frequency linear array transducer is placed in the axillar at the crease formed by the biceps muscles and
pectoralis major.
§ A short axis image of the axillary artery and terminal nerve branches are visualized.
§ Notice that the position of the nerves in the ultrasound image is different than the image above (the ultrasound image is
rotated ~90 degrees clockwise as a function of transducer placmenet).
§ The median nerve normally lies superficial to the axillary artery. It can be further identified by its close proximity to the
axillary artery as you scan distally toward the elbow.
§ The ulnar nerve also lies superficial to the axillary artery, however its course remains more superficial and medial as it
travels distally toward the cubital fossa.
§ The radial artery is located posterior to the axillary artery.
§ The musculocutaneous nerve lies lateral to the axillary artery in the fascial plane between the coarcobrachilais and biceps brachii muscles.
§ Once the location of all the terminal branches has been identified, the area is cleansed with an aseptic cleaning solution, then prepped and draped in a sterile
manner.
§ A sterile sheath is placed over the ultrasound transducer to maintain sterility. It is important that conduction gel is placed inside the sheath to ensure optimal
transmission of the sound beam.
§ A 22 gauge, 5 cm, B-bevel insulated needle is inserted anterior to the nerves using an in-plane technique until the tip of the needle is in close proximity of each
nerve.
§ Following negative aspiration, a small volume of local anesthetic (5-10 mL) is injected uneder direct visualization until circumferential spread is noted around each
branch.
o Complications
§ Hematoma (hold pressure for 3-5 minutes if using the transarterial technique)
§ Local anesthetic toxicity

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• Distal Nerve Blocks: Forearm
o The three terminal nerves of the hand can be blocked at the level of the forearm or at the wrist. Not only are these techniques
useful for surgery on the forearm or hand, but they can also be used for rescue if a nerve was missed during brachial plexus
blockade.
o Like all regional blocks, these are great hotspot questions…
o Radial Nerve
§ Derived from the posterior cord of the brachial plexus.
§ Local anesthetic is injected between the biceps tendon and brachioradialis.
§ Volume=3-5mL
o Ulnar Nerve
§ Derived from the medial cord of the brachial plexus.
§ The elbow is flexed 90 degrees and local anesthetic is injected between the
olecranon and medial epicondyle of the humerus.
§ Volume=3-5 mL
§ Using too high a volume can compress the ulnar nerve, resulting in ischemic
injury.
o Median Nerve
§ Derived from the lateral and medial cords of the brachial plexus.
§ In the antecubital fossa, local aneshtetis is injected medial to the brachial
artery.
§ The brachial artery is located medial to the biceps tendon.
§ Volume = 3-5 mL
§ Avoid this block in the patient with carpel tunnel syndrome.
• Distal Nerve Blocks: Wrist & Digital
o The wrist block is used to produce anesthesia of the hand and fingers. This technique targets 3 nerves: radial, ulnar, and median. Remember
this as, “ho ho ho and a bottle of R.U.M.”
o Radial Nerve Block
§ Anatomic landmarks:
• Radial styloid
§ Where to inject:
• Subcutaneous injection (field block) of 10mL proximal to the radial styloid.
• A field block is used, because there are several branches of the radial
nerves at this point in the wrist.
o Ulnar Nerve Block
§ Anatomic landmarks:
• Ulnar styloid
• Ulnar pulse
• Flexor carpi ulnaris tendon
§ Where to inject:
• Injection 3-5 mL medial to and below the flexor carpi ulnaris tendon.
• Confirm negative aspiration due to proximity to ulnar artery.
o Median Nerve Block
§ Anatomic landmarks:
• Flexor carpi radialis tendon
• Flexor palamaris longus tendon
§ Where to inject:
• Inject 5 mL between the flexor carpi radialis tendon and the flexor
palmaris longus tendon.
o Key Points
§ Do not use an epinephrine containing solution (risk of ischemic injury).
§ Placement of a wrist tourniquet does not require additional nerve blockade.
§ Toxicity is uncommon due to the small volume of local anesthetic injected at each
location.
o Digital Nerve Block
§ There are 4 small nerves that innervate each digit.
§ Anesthesia to the finger is provided by injecting 2-3mL of local anesthetic at the
base of both side of the finger.
§ Note the proximity of the arteries.
§ For the NCE, do not use epinephrine (risk of ischemia), however the avoidance of epinephrine is
considered dogma by some.

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• Intravenous Regional Anesthesia (Bier Block)
o Intravenous regional anesthesia can be used for procedures on the extremities (upper or lower). We will discuss IVRA in the
context of the upper extremity, and then we’ll follow with what’s different about using IVRA on the lower extremity.
o Because the local anesthetic is washed out following tourniquet release, the Bier block is best suited for procedures that
produce minimal postoperative pain.
o Procedure
§ Order for Initial tourniquet Inflation
• Place a double cuff tourniquet on the
patient. Do not inflate it.
• Place a 22g PIV in a distal peripheral vein
of the operative extremity (placement in
the hand is best for hand and wrist
procedures).
• Elevate the extremity for 1-2 minutes to
allow for passive exsanguination.
• Wrap the Esmarch bandage around the
extremity to further exsanguinate it.
Begin at the distal limb and move proximally until you reach the distal tourniquet cuff.
• Inflate the DISTAL cuff (this helps further exsanguinate the arm and tests the distal cuff on the patient).
• Inflate the PROXIMAL cuff.
• Deflate the DISTAL cuff.
• Remove Esmarch bandage.
• Inject the local anesthetic. Use a large volume of dilute anesthetic, such as 50mL of 0.5% lidocaine. Since the distal cuff is
deflated, local anesthetic will anesthetize the region of the arm under this cuff. This is useful if you need to change cuffs
during the surgical procedure.
• Tourniquet inflation pressure should be ~250 mmHg (or at least 100 mmHg over SBP).
• Bupivacaine is avoided due to difficult resuscitation should cardiac arrest occur.
• Do not use a solution that contains epinephrine (risk of ischemia) or a preservative (risk of thrombophlebitis).
• Ketorolac (15-30 mg) may be added to the LA solution. This assists with postoperative analgesia and does not increase
the risk of bleeding.
• The PIV may be removed or left in situ if it’s outside of the surgical field and redosing is anticipated (after 90 min).
o Tourniquet Pain
§ Tourniquet pain typically begins at ~45-60 minutes after inflation, and this is the most common reason why a patient would be
unable to tolerate a procedure lasting more than 1 hour (remember 2 hours is the max inflation time –not procedure time).
§ At this point, the proximal tourniquet has been inflated since the beginning of surgery, so we need to switch cuffs without letting the
confined local anesthetic wash out into the systemic circulation.
§ How to Change Cuffs During the Operation
• Proximal cuff is currently inflated.
• Inflated distal cuff (the tissue under this cuff is already anesthetized).
• Deflate proximal cuff.

o Toxicity
§ Toxicity is the most significant risk of the IVRA. The tourniquet must remain inflated for a minimum of 20 minutes
following local anesthetic injection. This allows enough time for the LA to absorb into the tissues. If the cuff is
deflated too soon (or if it fails), then the local anesthetic is washed into the systemic circulation where it can produce
seizures or cardiovascular collapse. Make sure you have the equipment necessary to quickly handle this complication.
o When Can You Deflate the Tourniquet at the End of the Surgical Procedure?
Time Since LA Injection Action
Less than 20 min Do NOT deflate—wait until 20 min have elapsed then deflate
20-40 min Deflate, immediately reinflate, then deflate again at 1 min
More than 40 min deflate
o IVRA On the Lower Extremity
§ If the tourniquet is placed on the upper leg:
• You must give a larger volume of LA, which can increase the risk of systemic toxicity.
• The tourniquet inflation pressure must be higher (350-400 mmHg).
§ If the tourniquet is placed on the calf:
• The LA volume is the same as upper extremity procedures.
• The tourniquet inflation pressure is the same as upper extremity procedures.
• Make sure the cuff does not compress the peroneal nerve near the head of the fibula.

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Regional Anesthesia: Lower Extremities
• How to Draw the Lumbar Plexus
o The lumbar plexus arises from the anterior rami of L1-L4, with an occasional contribution from T12. Just like we did the brachial plexus, we’re going to
show you an easy way to remember the lumbar plexus. We’ll make this as painless as possible.
o There are 6 nerves that arise from the lumbar plexus. Remember these with this mnemonic.

Next, you’ll need to remember:

• 2 nerves arise from 1 nerve root (2 from 1)

• 2 nerves arise from 2 nerve roots (2 from 2)
• 2 nerves arise from 3 nerve roots (2 from 3)

Nerve Mnemonic
Iliohypogastric I
Ilioinguinal Invariably
Genitofemoral Get
Lateral femoral cutaneous Lazy
Obturator On
Femoral Fridays

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• Lumbosacral Plexus Anatomy
o A sound working knowledge of the lumbosacral plexus is a prerequisite for understanding lower extremity nerve blocks.
Additionally, you must appreciate the relationships between the plexus and the surrounding anatomic structures (vascular,
muscular, etc). in this tutorial, we will focus only on the nerves that are essential to your understanding of regional anesthesia
of the lower extremity.
o The Big Picture

o Lumbar Plexus
§ The lumbar plexus arises from the ventral rami of L1-4, with occasional contribution from T12.
• It forms posterior to the psoas muscle and anterior to the quadratus lumborum muscle.
• While there are 6 nerves that arise from this plexus, you really only need to know 3 of these:
o 1. Lateral femoral cutaneous (L2-3)
o 2. Obturator (L2-L4)
o 3. Femoral (L2-L4)
• these nerves provide motor and sensory innervation to the anterior thigh and sensory innervation to the medial aspect of
the lower extremity below the knee.

§ Lateral Femoral Cutaneous (L2-L3)

• The lateral femoral cutaneous nerve is the first nerve to leave the plexus. It emerges at the midpoint of the psoas muscle,
travels laterally along the anterior iliac spine, and then passes under the lateral border of the inguinal ligament.
• Motor: none
• Sensory: Lateral thigh
§ Femoral (L2-L4)
• The femoral nerves is the largest of these three nerves.
• It forms near the middle and lower third of the posas muscle.
• It courses distally in a groove created by the psoas major and iliac muscle, continuing under the inguinal ligament where
it lies anterior to the iliopsoas muscle and lateral to the femoral artery.
• It splits into an anterior and posterior branch, and the posterior branch gives rise to the saphenous nerve near the knee.
• Motor-anterior branch: Sartorius
• Motor-posterior branch: quadriceps
• Sensory: anterior thigh
§ Obturator (L2-L4)
• The obturator nerve arises from the medial border of the psoas muscle at the level of the sacroiliac joint.
• It travels distally into the pelvis minor throught the obturator canal, and is often injured in patients who undergo
extensive pelvic surgery.
• Motor: Hip adductors
• Sensory: distal inner thigh and part of the hip
o Sacral Plexus
§ The sacral plexus originates from L4-5 and S1-4.
§ Sciatic Nerve (L4-S3)
• The sciatic nerve is the largest nerve in the body, and provides motor innervation of the posterior thigh as well as motor
and sensory innervation of the vast majority of the lower leg and foot via its branches (tibial and common peroneal
nerves).
§ Posterior Femoral Cutaneous (S1-S3)
• The posterior femoral cutaneous nerve (S1-3), not the sciatic, supplies sensory innervation to the posterior aspect of the
thigh. It courses distally with the sciatic before taking a superficial course as it emerges through the piriformis muscle.

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• Sensory Distribution of the Lower Extremity

• Psoas Compartment Block (Lumbar Plexus Block)

o The lumbar plexus is contained within a sheath inside the psoas compartment. At this point, the plexus is:
§ Lateral to the vertebral column
§ Anterior to the quadratus lumborum muscle
§ Posterior to the psoas muscle
o The psoas compartment block targets three majors nerves of the lumbar plexus:
§ 1. Lateral femoral cutaneous n.
§ 2. Femoral n.
§ 3. Obturator n.
o This block is useful when neuraxial anesthesia is contraindicated and/or anesthesia to one lower extremity is preferred.
o Landmark Technique
§ The patient is placed in the lateral decubitus position with the side to be blocked in the non-dependent position. You must be able to easily
visualize the quadriceps muscle.
§ Identify the midline by palpating the spinous processes. Draw a horizontal line that connects the spinous processes.
§ Identify the iliac crests, and draw a vertical line to connect them. This marks the intercristal line (L4-5 interspace).
§ Identify the posterior superior iliac spine, and draw a second horizontal line that is parallel to the midline.
§ The point of needle entry is 3 cm caudad from L4 and 5 cm lateral from the midline.
§ The injection site is cleansed with an aseptic solution, and a small skin wheal is raised at the needle insertion point.
§ A 20-gauge, 10-15 cm insulated, B-bevel insulated needle is passed anterior and perpendicular on all planes until quadriceps contraction is
elicited.
§ Nerve stimulator current is decreased from 1 to 0.5 mA to ensure proper needle location.
§ If the needle contacts the transverse process, it is walked off caudally.
§ The needle should never be inserted more than 2 cm past the level at which the transverse process was contacted.
§ The mean skin to plexus depth is approximately 8 cm.
§ Following negative aspiration, incremental injections of 5 mL of local anesthetic, each followed by negative aspiration, are administered for a
volume of 20-30mL.
§ *Nagelhout says to use a 120cm needle. Good luck finding one.
o Complications
§ Blockade of the lumbar plexus creates a Sympathectomy of the ipsilateral extremity.
§ Local anesthetic volumes greater than 20 mL increase the risk of bilateral spread and contralateral limb involvement. This creates a bilateral
Sympathectomy.
§ Of all lower extremity peripheral nerve blocks, the lumbar plexus block has one of the highest complication rates including retroperitoneal
hematoma and renal capsular injection. For this reason, coagulopathy is a contraindication to the psoas compartment block.
§ Like all other regional techniques, intravascular injection of local anesthetic is always a risk.

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• Femoral Nerve Block & It’s Variations
o The femoral block is the most common lower extremity block. When used alone, it does not provide
sufficient coverage for surgical anesthesia, but it’s useful as part of a multi-modal approach for procedures
involving the thigh, knee, and medial aspect of the lower extremity. When combined with a sciatic nerve
block, it provides almost complete surgical coverage to the lower extremity.
o Relevant Anatomy
o The femoral nerve arises from the posterior divisions of L2-L4. After these nerve roots exit the spinal
column, they give rise to the femoral nerve within the psoas major. The femoral nerve stays in the groove
between the psoas major and iliac muscles before entering the femoral triangle.
o Inside the triangle, the femoral nerve runs:
§ Deep to the inguinal ligament
§ Anterior to the iliopsoas muscle
§ Inferior to the fascia lata and fascia iliaca
o The triangle is shaped like the “SAIL” of a ship, so we can use this as a mnemonic to remember its borders:
§ S=Sartorius muscle
§ A=Adductor longus muscle
§ IL=inguinal ligament
o Use “VAN” for the structures inside the triangle (medialàlateral):
§ V=Vein
§ A=Artery
§ N=Nerve
o The femoral nerve divides into anterior and posterior branches. This occurs either just before or just after the nerve passes under the inguinal ligament.
§ The anterior branch innervates the ventral surface of the thigh and the Sartorius muscle.
§ The posterior branch innervates quadriceps muscles, knee joint and its medial ligament.
§ The posterior branch gives rise to the saphenous nerve.
• Landmark Technique
o The patient is placed supine with slight external rotation of the leg.
o The inguinal ligament runs between the anterior superior iliac spine and the pubic tubercle.
o The femoral artery is palpated at the level of the inguinal ligament.
o An “X” is placed 1 cm lateral to the femoral artery and 1 cm inferior to the inguinal ligament.
o The injection site is cleansed with an aseptic solution, and a small skin wheal is raised at the needle insertion point.
o A 22-gauge, 5 cm insulated, B-bevel insulated needle is passed in a slightly cephalad direction (~45 degrees) until you observe
quadriceps contraction. This is also called a patellar snap.
o Two “pops” should be felt as the needle passes through the fascia lata and fascia iliaca.
o Nerve stimulation is decreased from 1 to 0.5 mA to ensure proper needle location.
o Following negative aspiration, incremental injections of 5 mL of local anesthetic (each followed by negative aspiration) are administered for a total
volume of 20-40 mL.
o Stimulation of the Sartorius muscle, exhibited as inner thigh twitches, can occur if the needle is inserted too superficial and/or medial to the femoral
nerve proper. The needle should be withdrawn and advanced in a slightly lateral direction, away from the femoral artery until proper stimulation is
achieved.
o Ultrasound-Guided Technique
§ The patient is placed in the supine position, with the operative leg in a neutral position, or with slight external rotation.
§ A high-frequency transducer is usually sufficient to perform this block; even in patients with a large body habitus, a low-frequency transducer is rarely required.
§ The area is cleansed with an aseptic solution, prepped, and draped in a sterile manner.
§ A sterile sheath is placed over the ultrasound transducer to maintain sterility. It is important that conduction gel is placed inside the sheath to ensure optimal
transmission of the sound beam.
§ The transducer is placed at the inguinal crease and the major anatomical landmarks are identified.

§ If two arteries are noted (superficial femoral and profunda femoris), the transducer is moved cephalad until a single artery (common femoral) is identified.
§ The posterior division of the femoral nerve innervates the quadriceps muscles. It is generally found on the lateral aspect of the “femoral triangle,” and the block needle
should be directed there.
§ A small skin wheal is raised a the needle insertion point.
§ Most commonly, the needle is passed using an in-plane approach, from lateral to medial, through both the fascia lata and fascia iliaca, just lateral to the femoral artery.
§ The out-of-plane approach is a more difficult technique to master, as only the tip of the needle or a small portion of the needle shaft can be observed at any one time.
§ For new practitioners, nerve stimulation can be used in conjuction with ultrasound to verify proper needle placement prior to injection of local anesthetic. Following
negative aspiration, incremental injections of 5 mL of local anesthetic (each followed by negative aspiration) are administered until a total volume f 20 mL is injected.
• Continuous Femoral Nerve Block
o A catheter may be placed to provide analgesia for up to 48 hours. After the bolus injection, 8-10 mL/hr of local anesthetic should be infused. Common drugs include: 0.2%
ropivacaine and 0.25% bupivacaine.
• 3-in-1 Block (3 Nerves with 1 injection)
o the 3-1-in-1 block is a different approach to a femoral nerve block. It is designed to anesthetize 3 nerves with 1 injection:
§ femoral n.
§ lateral femorcutaneous n.
§ obturator n. (most commonly missed)
o These nerves arise from the lumbar plexus and are contained within a facial sheath as they leave the plexus. The idea is that if you can force the local anesthetic to spread
proximally during a femoral nerve block, then the other two nerves can also be blocked. This is accomplished by holding digital pressure behind the needle, so the local
anesthetic is forced in a proximal direction. A greater volume of local anesthetic is required (30mL).
• Adductor Canal Block
o The adductor canal block can be thought of as a femoral nerve block lower in the thigh (the femoral nerve is beneath the Sartorius muscle at this location). Many of the motor
nerves of the femoral n. branch above the level of the adductor canal, which means that you can provide analgesia for knee surgery without affecting quadriceps function. This
helps patients ambulate faster after surgery.

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• Fascia Iliaca Block
o The fascia iliaca block is similar to the femoral nerve block, however the approach is slightly different. The needle insertion point is more lateral and
distant from the femoral neurovascular bundle.
o This patient has been used for analgesia following hip fractures, as well as surgical procedures of the hip, femur, and knee in adult and pediatric patients.
o Nerve stimulation or ultrasound is not required when performing this block, and reliable anesthesia can be accomplished with a sound understanding of
the anatomical landmarks and tactile sensation. A successful block is more dependent on the needle passing through both fascia layers (fascia lata and
fascia iliaca), so that the local anesthetic is deposited inferior to the fascia iliaca but superior to the iliopsoas muscle.
o Landmark Technique
§ The patient is placed supine, and a line is drawn from the pubic tubercle to the anterior superior iliac spine. This line marks the inguinal
ligament.
§ The line is divided into thirds, with the needle insertion point marked 1 cm caudal to where the lateral third meets the middle third of the
inguinal ligemant line.
§ The injection site is cleansed with an aseptic solution, and a small skin wheal is raised at the needle insertion point.
§ A 22-gauge, 5 cm insulated, B-bevel insulated needle is passed perpendicular to the skin until two “pops” are felt as the needle passes
through the fascia lata and fascia iliaca.
§ Following negative aspiration, incremental injection of 5 mL of local anesthetic (each followed by negative aspiration) are administered until
a total volume of 30-40 mL is injected.
§ This volume usually covers both the lateral femoral cutaneous and femoral nerve as they travel in the same plane between the fascia and
underlying muscle.
• Saphenous Nerve Block
o The saphenous nerve is the terminal branch of the posterior division of the femoral nerve.
§ It provides sensory innervation from the medial aspect of the knee to the medial malleolus.
§ There is no motor component.
o This block is useful when combined with a popliteal or ankle block, as these don’t capture the saphenous distribution.
o Landmark Technique
§ Using the proximal saphenous landmark technique, a 22 gauge, 5 cm insulated, B-bevel needle is inserted 2 cm
distal to the tibial tuberosity and directed medially.
§ 5-10 mL of local anesthetic is infiltrated as the needle is directed toward the posterior aspect of the leg.
o Ultrasound-Guided Technique
§ The saphenous nerve may be blocked proximal to the knee just deep to the Sartorius muscle.
§ A high-frequency linear array transducer is used to identify the point where the Sartorius, adductor longus and vastus medialis meet distal to
Hunter’s canal.
§ The area is cleansed with an aseptic solution, prepped and draped in a sterile manner, and a sterile sheath is placed over the ultrasound
transducer to maintain sterility.
§ It is important that conduction gel is placed inside the sheath to ensure optimal transmission of the sound beam.
§ The transducer is placed at the distal thigh and the femur is located as a point of reference.
§ The transducer is moved slightly lateral until the proper anatomy is identified.
§ A small skin wheal is raised at the needle insertion point, and the needle is passed using an in-plane approach, medial to lateral, with 5-10 mL
deposited within the fascial plane between the muscles.
• Sciatic Nerve Block
o Relevant Anatomy
§ The sciatic nerve arises from L4-5 and S1-3.
• The sciatic nerve is actually two nerves contained within a sheath (tibial n. and
peroneal n.)
• It exits the pelvis inferior to the piriformis muscle via the great sacrosciatic
foramen.
• As it continues caudally, it passes between the major trochanter and the
tuberosity of the ischium into the lower third of the thigh. This is where the sciatic
nerve divides into tibial and common peroneal nerve.
§ By itself, the sciatic nerve block is useful for procedures on the back of the thigh, lower leg,
ankle, and foot. Combining the sciatic nerve block with a lumbar plexus block provides
complete anesthesia to the lower extremity and may be useful in the patient who may not
tolerate Sympathectomy from a neuraxial block.
o Landmark Technique
§ The posterior landmark approach, also known as the classic or Labat approach, is often used
in conjuction with a femoral nerve block to provide complete coverage for knee arthroplasty.
§ The patient is placed in the Sims position with the operative leg in the non-dependent position and slightly flexed.
§ A first line is drawn from the greater trochanter to the posterior supine iliac spine.
§ A second line is drawn from the sacral hiatus to the greater trochanter.
§ At the midpoint of the first line, a third line is drawn perpendicular to the first and second line in a caudal direction.
§ The needle insertion point is the intersection between the second and third lines.
§ The injection site is cleansed with an aseptic solution, and a small skin wheal is raised at the needle insertion point.
§ A 22-gauge, 10 cm insulated, B-Bevel insulated needle is inserted perpendicular on all planes of the skin. As the needle is advanced through
the gluteal muscles, a motor response may be encountered.
§ Continue advancing the needle until plantar or dorsiflexion is elicited.
§ For surgical anesthesia, plantar flexion (foot inversion) is preferred. (tibial n. component- plantar flexion – foot inversion).
§ (common peroneal nerve- dorsiflexion-foot eversion).
§ If bone is contacted, redirect the needle medially.
§ If blood is aspirated (superior gluteal artery), redirect the needle laterally.
§ Nerve stimulation is decreased from 1 to 0.5 mA to ensure proper needle location.
§ Following negative aspiration, incremental injections of 5 mL of local anesthetic (each followed by negative aspiration) are administered for a
total volume of 25 mL.

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• Popliteal Nerve Block
o Relevant Anatomy
§ The popliteal block targets the sciatic nerve in the proximal popliteal fossa.
• At this location, the sciatic nerve is posterior and lateral to the popliteal artery and vein, and is bordered medially by the
semitendinosus and semimembranosus muscles and laterally by the biceps femoris muscle.
• A “triangle” is formed in the posterior knee with the base being the popliteal crease at the knee, and the apex formed by
the convergence of the biceps femoris and semitendinosus muscles.

o Landmark Technique
§ When using a landmark technique with nerve sitmulation, the optimal position for performing a popliteal block
is having the patient in the prone position.
§ A line is drawn along the popliteal crease from the medial border of the biceps femoris muscle, to the lateral
border of the semitendinosus muscle.
§ At the midpoint, a second line is a drawn perpendicular and cephalad 7-10 cm to the apex of the triangle
formed by the biceps femoris and semiteninosus muscles.
§ These structures are more identifiable if you have the patient flex at the knee.
§ The needle insertion point is 1 cm lateral to the apex.
§ The injection site is cleansed with an aseptic solution, and a small skin wheal is raised at the needle insertion
point.
§ A 22-gauge, 5-10 cm insulated, B-bevel needle is inserted perpendicular on all planes of the skin.
§ The needle is slowly advanced until plantar or dorsiflexion is obtained.
§ As with the classic sciatic block, plantar flexion (foot inversion) is preferred.
§ Nerve stimulation is decreased from 1 to 0.5 mA to ensure proper needle injection.
§ Following negative aspiration, incremental injections of 5 mL of local anesthesic (each followed by negative
aspiration) are administered to r a toal of 30-40 mL.
o Ultrasouund-Guided Nerve block
§ ultrasound-guided blocks in the popliteal fossa can be performed using the prong, lateral,
supine approach. Because the sciatic nerve bifurcates in the tibial and common peronal
nerves at varying location along the posliteal fossa. It is important to scanthe region
proximally and distally to determine the area that offers the greateropputy for success. A
high-frequency transduce is placed in the popliteal crease and moved cephalad to
evaluate the anatomy, taking o t th enajor landmarks such sa= frmoral and popliteal
crease and move cephalad to evulate taking not of major. High-frequency transducer.
§ It is important to note that the US image will be inverted if you perform the block with
the patient in the supine position. The transducer should be reversed to produce the
proper orientation.
§ The practitioner should make note the point at which the sciatic nerve begins to divide,
as this is the desired location for local anesthetic placement.
§ Once the correct position is determined, the needle is aimed slightly to one side of the
sciatic, rather than directly at the nerve itself.
§ If an out-of-plane approach is used, hydrolocation can assist the anesthetic in determining the position of the needle tip.
§ Practitioners often use nerve stimulation in conjuction with ultrasound.
§ Once the optimal injection site is identified, it is cleansed with an aseptic solution.
§ A small skin wheal is raised at the needle insertion point.
§ A 22 gauge, 5 cm insulated, B-bevel needle is passed in plane from lateral to medial until the tip of the needle adjacent to the nerve.
Following negative aspiration of blood, 5 mL of local anesthetic is incrementally injected (each following a negative aspiration) until a total
volume of 20-30 mL is injected.
§ Circumferential spread of local anesthetic around the nerve usually results in a complete block. The needle may need to be redirected to
accomplish this.

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• Ankle Block:
o An ankle block anesthetizes 5 nerves.
o The 3 nerves that begin with an “S” are purely sensory, while the other 2 are sensory and motor.
§ Superficial peroneal
§ Sural
§ Saphenous
§ Tibial (inversion + plantar flexion)
§ Deep peroneal (eversion + dorsiflexion)
o Mnemonic:
§ TIPPED (Tibial Inversion Plantar Flexion + Peroneal Eversion Dorsiflexion)

o Technique
§ Ankle blocks can be used for surgery involving the foot below the ankle. All 5 nerves can be anesthetized or individual blocks may be selectively administered to
accommodate the needs of surgery. As you review these blocks, coordinate the anatomy in the images with your right ankle.
• Tibial Nerve
o Anatomy
§ The tibial nerve is the larger of the two branches of the sciatic nerve. As it courses distally along the lower extremity, it takes a posterior and medial path to the
ankle.
§ At the level of the ankle, it sits behind the posterior tibial artery and vein, and between the tendons of the long flexor muscles of the toes and the long flexor
muscles of the great toe.
§ Several branches leave the nerve at the level of the medial mallelus, most notably the medial and lateral plantar nerves, which provide innervation to the sole of
the foot.
o Nerve Blockade
§ Draw a line connecting the superior portion of the medial malleolus and the Achilles tendon.
§ The posterior tibial artery is palpated and the needle is inserted perpendicular to the skin lateral to the artery.
§ If the artery cannot be identified, the needle is inserted lateral to the Achilles tendon at the level of the superior medial malleolus and advanced lateral toward the
position of the posterior tibial artery.
§ If paresthesia is elicited, 5 mL of local anesthetic is injected. As the needle is slowly withdrawn, inject an additional 3mL of local anesthetic.
§ If paraesthesia is not elicited, the needle is advanced until it contacts the medial malleolus. Then, it is withdrawn 2-3 mm and following negative aspiration, up to 5-
8 mL of local anesthetic is injected as the needle is slowly withdrawn.
• Sural Nerve
o Anatomy
§ The sural nerves is formed from branches of the tibial and common peroneal nerves.
§ If travels superficially as it courses distally behind the lateral malleolus of the ankle, providing sensation to the posterior portion of the heel and sole of the foot, as
well as part of the Achilles tendon above the ankle.
o Nerve Blockade
§ A horizontal line is drawn from the Achilles tendon to the superior lateral malleolus.
§ The needle is inserted in the plane of the line between the Achilles and lateral malleolus, and advanced toward the edge of the lateral condyle.
§ The needle is slowly withdrawn as 5-8 mL of local anesthetic is injected.
• Superficial Peroneal Nerve
o Anatomy: The superficial peroneal nerve, also a branch of the common peroneal nerve, becomes superficial in the lower two-thirds of the leg. It courses subcutaneously anterior
to the lateral malleolus, providing several branches to the dorsum of the foot.
o Nerve Blockade:An infiltration block with 5-8 ml of local anesthetic is accomplished creating a ring starting from the midpoint of the distal tibia toward the inferior border of the
lateral malleolus.
• Deep Peroneal Nerve
o Anatomy
§ The deep peroneal nerve is a branch of the common peroneal nerve.
§ It travels distally below the knee between the anterior tibial muscle and the long extensor muscle of the great toe into the ankle.
§ At the level of the ankle, it lies lateral to the anterior tibial artery and medial to the long extensor muscle of the great toe.
§ It is responsible for innervating the short extensors of the toes, and provides sensory innervation to the skin on the lateral side of the hallux and medial side of the
second digit.
o Nerve Blockade
§ Ask the patient to flex his foot against resistance this makes the tendons of the anterior tibial muscle and the long muscles of the great toe more visible.
§ The needle is inserted perpendicular to the sin toward the distal tibia at the midpoint of these two structures.
§ The needle is advanced until paresthesia is elicited.
§ If there is no paresthesia, the needle is advanced until bone is contacted. The needle is slightly withdrawn, and following negative aspiration, 5 mL of local
anesthetic is injected.
• Saphenous Nerve
o Anatomy
§ The saphenous nerve is the terminal branch of the femoral nerve and courses subcutaneously along the medial aspect of the knee.
§ It follows the greater saphenous vein distally along the anterior aspect of the medial malleolus.
§ It provides sensory innervation to the medial aspect of the lower extremity below the knee.
§ At the level of the ankle the saphenous nerve is located in the subcutaneous tissue, superficial to the vein.
o Nerve Blockade: An infiltration block with 5-8 mL of local anesthetic is accomplished creating a ring starting from the midpoint of the distal tibia toward the inferior border of the
medial malleolus.
• Complications
o The ankle block, usually performed by infiltration technique, can be challenging, as it requires identification and injection of local anesthetic at multiple sites.
o Four of these nerves are located close to either arteries or veins, increasing the potential for vascular injection.
o Additionally, because the nerves of the ankle are confined within tight space between ligaments and tendons, excessive local anesthetic volumes and vasoconstrictors such as
epinephrine should be avoided to minimize the risk of ischemic complications.

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Regional Notes

257
FLUIDS & BLOOD
Fluid Compartments
• Body Water Distribution: 60/40/20 (15/5)
o In the textbook 70 kg male, water represents 60% of the total body weight. This equals 42L.
o The total body water (TBW) can be divided into:
§ 1. Intracellular volume = 40% of total body weight or 28 L (Major ions = K+, Mg+2, PO4-2)
§ 2. Extracellular volume = 20% of total body weight or 14 L (Major ions= Na+, Ca+2, HCO3-)
o The ECV can be further divided into:
§ 1. Interstitial fluid = 16% of total body weight or 11L *if it’s easier to remember 15% and 5%, that’s ok
§ 2. Plasma fluid = 4% of total body weight or 3 L
§ Population with higher TBW & by weight: Neonates
§ Populations with lower TBW % by weight: Females,
obese and elderly.
o Plasma Volume
§ Plasma is the non-cellular fraction of circulating blood
volume.
§ The plasma is in direct contact with the interstitial fluid by
way of pores in the capillaries. The movement of fluid
between the intravascular space and the interstitial space
is determined by Starling forces and the glycocalyx.
§ Starling Forces
• 1. Forces that move fluid from the capillary to
the interstitium:
o Pc=Capillary hydrostatic pressure
(pushes fluid out of capillary)
o p if = interstitial oncotic pressure
(pulls fluid out of capillary)
• 2. Forces that move fluid from the interstitium into the capillary.
o Pif=interstitial hydrostatic pressure (pushes fluid into capillary)
o p c= capillary oncotic pressure (pulls fluid into capillary
• As fluid enters the capillary, it tends to be pushed out by capillary
hydrostatic pressure. Towards the end of the capillary, fluid tends to be
pulled back into the capillary by capillary oncotic pressure (this assumes
normal physiology).
§ Glycocalyx
• The endothelial glycocalyx forms a protective layer on the interior wall of
the blood vessel. It can be viewed as the gatekeeper that determines
what can pass from the vessel into the interstitial space. It also contains
anticoagulant properties.
• Disruption of the glycocalyx contributes to capillary leak. Accumulation of
fluid and debris in the interstitial space reduces tissue oxygenation.
Conditions that impair the integrity of the glycocalyx include:
o Sepsis
o Ischemia
o Diabetes mellitus
o Major vascular surgery
o Blood Volume
§ Erythrocytes are filled with fluid, but because they are contained by a membrane they are considered part of the intracellular compartment.
Therefore, blood volume is the sum of plasma volume and blood cell volume (60% plasma and 40% blood).
§ The hematocrit is the fraction of blood volume that is occupied by erythrocytes.
• Hct is increased by an increased number of RBCs (polycythemia) or a decreased plasma volume (hypovolemia).
• Hct is decreased by a decreased number of RBCs (anemia) or increased plasma volume (hemodilution).
o Interstitial Fluid
§ The interstitium is the space between the cells.
§ Nearly all the interstitial “fluid” is a gel consisting of fluid and proteoglycan filaments. Less than 1% of the interstitial volume is free floating
fluid. There is very little free flow of fluid throughout the interstitial space. Instead, fluid movement is a function of diffusion.
o Lymphatic System
§ You can think of the lymphatic system as a fluid scavenger. It removes fluid, protein, bacteria, and debris that has entered the interstitium. It
accomplishes this goal with a pumping mechanism that propels lymph through a vessel network lined with one-way valves. This creates a net
negative pressure in the interstitial space.
§ Lymph is returned to the venous circulation by way of the thoracic duct at the juncture of the internal jugular and subclavian vein. You can
injure the thoracic duct during venous cannulation. Since the thoracic duct is larger on the left side, there is a greater risk of chylothorax
during left sided IJ insertion.
§ For completeness, you should know that there is a much smaller thoracic duct at the junction of the right IJ and SC veins. It drains lymph from
the right upper extremity, right thorax, and right side of the head and neck. Again, this duct is much smaller and is often omitted from the
textbooks.
§ Edema occurs when the rate of interstitial fluid accumulation exceeds the rate of removal by the lymphatic system.
§ Fluid that accumulates in a potential space is called an effusion.

258
• The 4 O’s: Osmosis, Osmotic Pressure, Osmolarity and Osmolality
o This can be a tricky subject. It helps if you can accept a few truths before moving forward.
§ 1. Semipermeable membranes separate the body’s compartments.
§ 2. Most solutes (ions, proteins, glucose) don’t diffuse across these semipermeable membranes. Instead, carrier proteins transport
them from one side to another.
§ 3. Water freely passes through these membranes. Since water likes to follow solute, it travels from areas of lower solute
concentration to areas of higher solute concentration.
o Now that we have this down, let’s dig into some concepts.
o Osmosis
§ Osmosis is the net movement of water across a semipermeable membrane.
• The direction of water movement is driven by the difference in solute concentration on either side of the membrane.
• Water tends to move from areas of lower solute
concentration to areas of higher solute concentration.
• Example: when we administer an IV fluid, the water in the
fluid diffuses across the blood vessel walls and equilibrates
with the extracellular volume.
o Osmotic Pressure
§ Osmotic pressure is the pressure of a solution against a semipermeable
membrane that prevents water from diffusing across that membrane.
• Osmotic pressure is a function of the number of osmotically active particles in solution (amount of ionization).
• It is NOT a function of their molecular weights.
o Osmolarity & Osmolality
§ These are measures of concentration.
• Osmolarity measures the number of osmoles per liter of solvent.
• Osmolality measures the number of osmoles per kilogram of solvent.
§ For our purposes, the differences between osmolarity and osmolality are so miniscule that we’re going to pretend they’re the same
thing. But for those of you wondering, it’s easier to think about bodily fluids using volume (liters and osmolarity than it is to think of
them in terms of weight (kilograms and osmolality). Since the body’s fluid compartments are pretty dilute, it makes little difference
which one we choose. And knowing is half the battle.
• Plasma Osmolarity
o Plasma Osmolarity
§ Plasma osmolarity is normally 280-290 mOsm/L. we can calculate this value with the following equation:
Plasma Osmolarity = 2 [Na+] Glucose + BUN
18 2.8
§ from this equation, you can see that sodium is the most important determinant of plasma osmolarity.
§ You should also notice that hyperglycemia or uremia can increase plasma osmolarity.
• Tonicity
o Tonicity compares the osmolarity of a solution relative to the osmolarity
of the plasma. Remember the plasma is the reference point we use to
make the comparison.
o Since plasma is isotonic to cells, we can think about tonicity another way.
We can use it to compare the tonicity of a solution to the tonicity of the
cells.
o Hypotonic Solutions
§ Hypotonic solutions have a lower osmolarity than the plasma (or
cells).
§ These fluids are the same as giving free water, and this free water
distributes throughout the body compartments.
§ This explains why hypotonic solutions are poor expanders of
intravascular volume and why you should never give a
hypotonic solution to a patient with increased ICP!
§ Some of you are probably thinking that glucose in D5W
should be osmotically active. Well…you’re half right.
You’re right because the glucose contributes osmotically
active molecules to the plasma. The other side of the
story is that this glucose is metabolized to carbon
dioxide and water. What’s left over? Water, and this
water is, you guessed it..hypotonic.
o Isotonic Solutions
§ Isotonic solutions have an osmolarity that is very close to the plasma (or cells). These solutions expand the plasma volume and the ECV.
§ Crystalloids tend to remain in the intravascular space for ~30 min.
§ Sodium chloride can caused hyperchloremic metabolic acidosis if it is given in large amounts.
§ The lactate in LR functions as a buffer. It is converted to bicarbonate by the liver and kidneys.
o Hypertonic Solutions
§ Hypertonic solutions have an osmolarity that exceeds the plasma (or cells).
§ These solutions expand the intravascular volume by pulling fluid from the ICF into the ECV.
§ Hypertonic saline is useful for treating cerebral edema as well as correcting hyponatremia.
§ Myelinolysis can result if sodium is replaced too quickly. More on this in the CNS I: Brain Tutorial.

259
• The Great Debate: Colloids vs Crystalloids

o Albumin is the only colloid that is derived from human blood products. It does not contain antibodies nor does it increase the
risk of infectious disease transmission.

260
• Electrolyte Balance

261
• Acid-Base Disturbances: Overview
o Overview
§ Cellular and enzymatic function are highly sensitive to pH. Therefore, any condition that alters pH can affect
homeostasis.
§ The body attempts to regulate blood pH to 7.40.
• Normal pH=7.35-7.45
• Acidosis pH<7.35
• Alkalosis pH>7.45
§ The Henderson-Hasselbalch equation says that a solution’s pH is a function of the ratio of dissociated anion [A-] to the
non-dissociated acid [HA].
pH= pK + log [A-]/ [HA] or pH=pK + log [ HCO3-]/[CO2]
o Buffer Systems
§ Buffer systems help to mitigate pH changes. These systems include:
• Blood
o Bicarbonate buffer (most important)
o Hemoglobin (second most important)
• Respiratory compensation
o Altering ventilation to change PaCO2 (a volatile acid)
• Renal compensation
o Reabsorption of filtered bicarbonate
o Removal of titratable acids (non-volatile acids)
o Formation of ammonia
o How to Evaluate Acid-Base Balance On ABG
§ Questions to ask when evaluating pH:
• 1. Is the pH normal? (7.35-7.45)
• 2. Is the PaCO2 normal? (35-45 mmHg)
• 3. Is the HCO3- normal? (22-26 mEq/L)
• 4. Apply ROME (see below)
• 5. Has compensation occurred?

§ Mnemonic: Rome
• Respiratory Opposite (PaCO2 moves pH in the opposite direction)
• Metabolic Equal (HCO3- moves pH in the same direction)
§ Compensation:
• Full compensation restores pH to normal.
• Partial compensation moves pH towards normal, but the pH is still abnormal.
§ Mixed disorders are possible. For example, a patient with sepsis who received excessive sedation could have a mixed
metabolic respiratory acidosis.
o Consequences of Acid-Base Imbalance

262
• Acid-Base Disturbances: Respiratory
o Respiratory Acidosis
§ Respiratory acidosis occurs when alveolar ventilation is unable to keep up with
CO2 production. There are 3 etiologies: increased CO2 production, decreased
CO2 elimination, and rebreathing. Treatment is aimed at reversing the
underlying cause, and a pH < 7.20 is an indication for mechanical ventilation.
§ PaCO2= CO2 Production
Alveolar Ventilation
• Hypercapnia= PaCO2 > 45 mmHg
• Hypocapnia = PaCO2 < 35 mmHg
§ How Does a Change in PaCO2 Affect pH?

§ Consequences of Respiratory Acidosis

• *Hypercarbia has the opposite effect on pulmonary blood vessels than in the peripheral circulation. In the lungs, CO2 is a direct
acting vasoconstrictor, where it can cause pulmonary hypertension and increase the right ventricular workload.
• Do not correct PaCO2 in the patient with chronic respiratory acidosis (think COPD). These patients normally retain bicarbonate,
and if you return their CO2 to normal then you’ve created a metabolic alkalosis.
o Respiratory Alkalosis
§ Respiratory alkalosis occurs when alveolar ventilation exceeds CO2 production. Physiologically, it has the opposite effects as respiratory
acidosis.
• Causes:
o Iatrogenic (mechanical ventilation). This is the most
common cause.
o Hypoxia (high altitude, low FiO2, profound anemia)
o Pain
o Anxiety
o Pregnancy
o Drugs (progesterone, salicylates, aspirin)
o Pulmonary embolism
o Reduced mechanical dead space with the same
alveolar ventilation (removing an HME, changing from
mask to ETT).
§ Metabolic Compensation:
• The kidneys excrete HCO3- to return pH to normal. This may take several days.
§ Consequences of Respiratory Alkalosis
§ Treatment
• The best treatment is to reverse the underlying cause.
• In the spontaneously ventilating patient, respiratory alkalosis can be treated with sedation ( a concern when pH>7.60).
• In the mechanically ventilated patient, respiratory alkalosis is treated by reducing minute ventilation on the ventilator.

263
• Acid Base Disturbances: Metabolic
o Metabolic Acidosis
§ Metabolic acidosis is characterized by a pH<7.35 as the result of accumulation of nonvolatile acids, loss of
bicarbonate, and/or large volume resuscitation with a NaCl solution.
§ The anion gap helps us determine that cause of the acidosis.
• Anion ion gap= major cations – major anions or [Na+] – ([Cl0] + [HCO3-]) = 8-12 mEq/L
§ Accumulation of acidàgap acidosis
§ Loss of bicarbonate or ECF dilutionànon-gap acidosis

§ Respiratory Compensation:
• PaCO2 decreases as a function of increased minute ventilation.
o PaCO2 decreases by 1-1.5 mmHg for every HCO3- decrease of 1 mEq/L
§ Treatment:
• Anion gap acidosis – treat underlying cause:
o Lactic acidosis (IVF, oxygen, cardiopulmonary support)
o Diabetic ketoacidosis (IVF, insulin)
o Uremia or drug induced (dialysis)
o NaHCO3 used for anion gap acidosis is controversial. It’s best used as a temporary measure if pH is
<7.2 and the patient is hemodynamically unstable (enzymes in the body don’t work well in an
acidic environment). Also, NaHCO3 can cause intracellular acidosis in the setting of inadequate
ventilation or perfusion.
• Non-gap acidosis – treat the underlying cause:
o NaHCO3 is useful, because most of the etiologies produce bicarbonate loss.
o Metabolic Alkalosis
§ Metabolic alkalosis is characterized by a pH>7.45. it is caused by increased bicarbonate and/or a loss of nonvolatile
acids.

§ Respiratory Compensation:
• PaCO2 increases as a function of decreased minute ventilation.
o PaCO2 increases by 0.5-1 mmHg for every HCO3- increase by 1 mEq/L.
• Treatment
o Correction of underlying cause
o Acetazolamide (carbonic anhydrase inhibitor) increases renal excretion of HCO3-)
o Spironolactone is a mineralocorticoid antagonist
o Dialysis

264
Blood | Coagulation
• The Big Picture
o This is among the most confusing subjects you’ll encounter when preparing for the NCE. Before we begin, we’re going to give you a bird’s eye
view of the process. Then, we’ll break down everything into smaller pieces. We like to think of this approach as learning in layers. It may be
helpful to revisit this page as you progress though this tutorial.
o Blood exists as a viscous liquid. When there is no injury, blood remains a liquid because:
§ 1. Coagulation proteins circulate in an inactive form.
§ 2. The endothelium is smooth and the glycocalyx repels clotting factors.
§ 3. Undamaged endothelium does not express tissue factor or collagen. This prevents activation of platelets and the coagulation
cascade.
§ 4. Activated factors are removed by brisk blood flow through the vessels as well as anticoagulants in circulation.
o When there is a vascular injury, the blood plugs the damaged vessel by forming a clot (it solidifies). Over the next several days, the vessel
repairs itself and the clot is reabsorbed.
• The 4 Steps of Hemostasis
o 1. Vascular spasm
o 2. Formation of the platelet plug (primary hemostasis)
o 3. Coagulation and the formation of fibrin (secondary hemostasis)
o 4. Fibrinolysis when the clot is no longer needed
• Clotting to Death vs. Bleeding to Death
o There is a delicate balance between factors that create clot and those that prevent clot. In
the absence of injury or pathology, these counterbalance each other. Disruption to this
delicate balance leads to a relative overabundance of the opposing factors.
o Clotting to Death
§ If the procoagulation predominate, then the blood tends to clot. This increases
the risk of stroke, myocardial infarction, or thrombosis elsewhere in the body.
o Bleeding to Death
§ If the anticoagulants predominate, then the blood has a tendency not to clot.
This increases the risk of bleeding.
o *Nagelhout says that protein C and S are procoagulants. We believe this is an error.
• Platelets
o Overview
§ Platelets are formed by megakaryocytes in the bone marrow.
§ Normal value is 150,000—300,000/mm3.
§ Lifespan is 8-12 days (1-2 weeks).
§ Cleared by marcophages in the reticuloendothelial system and the spleen.
§ The spleen can also sequester up to 1/3 of all circulating platelets for later use.
§ Because of their smaller size, platelets are pushed towards the vessel wall,
which strategically places them close to their site of action.
o Platelet Components
§ In addition to being a structural component of the clot, platelets are key delivery vehicles that provide many of the substrates
required for clot formation.

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• Natural Platelet Inhibition
o In the absence of vascular injury, the endothelium inhibits platelet function by secreting:
§ Prostaglandin I2-inhibits vWF adherence, TxA2 activation, and release of storage granules.
§ Nitric oxide-inhibits TxA2 receptor
• Platelet Receptors
o Platelets contain several receptors that are critical for the formation of the platelet plug. These receptors are key targets for
antiplatelet therapy. We’ll get there soon, but for now, just familiarize yourself with the receptors.
• The Platelet Plug: Adhesion, Activation, Aggregation
o On the “Big Picture” slide, we said that there are 4 steps in the hemostatic mechanism: vascular spasm, formation of the
platelet plug, formation of the fibrin clot, and fibrinolysis.
o Vascular Spasm
§ Intact vascular endothelium inhibits clot formation, and injury to the blood cells or endothelial layer of the blood
vessel initiates the hemostatic mechanism. Common sources of injury include:
• surgery
• trauma
• plaque dislodgement
• spontaneous micro injury (these occur daily)
§ immediately following vascular injury, the vessel (tunica media) contracts to reduce blood flow to the area.
Contraction is a result of SNS reflexes, the myogenic response, and release of vasoactive substances, such as
thromboxane A2.
§ Vascular spasm serves 2 functions:
• 1. It reduces blood loss.
• 2. It helps procoagulants remain in the affected area, so they can do their jobs.
§ The next step is primary hemostasis.
o Primary Hemostasis: Formation of the Platelet Plug
§ Once vascular injury occurs, platelets evolve into a platelet plug via a 3 step process:
• 1. Adhesion
• 2. Activation
• 3. Aggregation
§ The platelet plug is formed in ~5 minutes.

§ Step 1:Adhesion
• Endothelial injury exposes collagen and, within seconds, platelets adhere to collagen via the Gp Ia/IIa and
Gp VI receptors.
• von Willebrand factor (vWF) is synthesized and released from the endothelium. It binds to the GpIb
receptor on the platelet and anchors the platelet to the subendotehlium.
• Von Willebrand diseases is a disorder of platelet adhesion. We’ll get to this shortly.
§ Step 2: Activation
• Collagen at the site of vascular injury activates platelets. Thrombin also plays a key role in platelet activation.
• Activated platelets release ADP and thromboxane A2.
• ADP and TxA2 activate nearby platelets. They also facilitate aggregation.
• TxA2 has an additional role of acting as a vasoconstrictor.
• Activated platelets contract and extrude the contents of their alpha granules (fibrinogen, fibronectin, vWF, platelet factor
IV, and platelet growth factor). This process calls other platelets to the site of injury and promotes clotting.
• The activated platelet becomes a swollen, irregularly shaped, “stick” mass. This helps the platelet adhere to the site of
injury as well as to other platelets.
• Activated platelets express two glycoproteins on their surface: GpIIb and GpIIIa.
§ Step 3: Aggregation
• The GpIIb/IIIa receptor complex links activated platelets together to form the platelet plug.
• TxA2 and ADP are required to configure GpIIb/IIIa to accept fibrinogen.
• For micro injuries, a platelet plug is all that is needed to mesh the wound. In other words, activation of the coagulation
cascade is not required to stop the bleeding.
• For significant vascular injury, the platelet plug creates a loose, fragile, and temporary fix that requires the coagulation
process to form fibrin threads to strengthen the clot.

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• Coagulation Cascade in a Single Page
o For those of you eager to memorize all the intricacies of the coagulation cascade, we’ve got you covered in the next few questions. For the rest
of you, we’ve put together some tricks to help you get by.
o First we’re going to learn all the factors, then we’re going to give you a diagram that puts it all together.
o Know the Factors with this Mnemonic
§ “Foolish People Try Climbing Long Slopes After Christmas, Some People Have Fallen”

o Drawing the Coagulation Cascade in 6 Steps

§ 1.) Count backwards from 12.
§ 2.) 3, 4, and 6 don’t exist*.
§ 3.) 10 is the front man in the band—it’s the only one out of order.
§ 4.) 5 and 8 are co-factors, so they go above the line.
§ 5.) 7 is lucky, so it goes in your pocket (below the line).
§ 6.) 2 is prothrombin and 1 is fibrinogen.
§ *3 and 4 don’t exist as blood proteins and 6 doesn’t exist anywhere.
o Other Key Insights from the Diagram
§ The top row is IN-line so it is Intrinsic pathway.
§ The pathway that begins with factor 7 enters from the outside, so it is the Extrinsic pathway.
§ The Intrinsic pathway is longer, so it’s measured by PTT (more letters).
§ The Extrinsic pathway is shorter, so it’s measured by the PT(fewer letters).
§ The extrinsic pathway looks like a gun and guns are used in war. Therefore, WARfarin inhibits the Extrinsic pathway (PT).
§ The gun of the extrinsic pathway is fired with your Trigger Finger (TF=tissue factor), so the extrinsic pathway is activated by tissue factor (TF).
§ 10 is the front man in the band. The factors around the front man are the other band members. Their group is dependent on vitamin k.
(2,7,9,10).
§ For the final common pathway, just think of dollar denominations: $10, $5, $2, $1
• Classical Extrinsic Pathway
o The science of coagulation is ever evolving. The older model of coagulation consists of two distinct pathways, and each arrives at the same
endpoint—the final common pathway (thrombin activation).
§ The extrinsic pathway is activated when coagulation is initiated outside of the intravascular space.
§ The intrinsic pathway is initiated when coagulation is initiated inside the intravascular space.
o Our current understanding is a hybrid of these pathways, and is known as the cell-based model of coagulation. In this model, coagulation is
initiated by the extrinsic pathway, as injured endothelium releases tissue factor (factor III). The intrinsic pathway serves to amplify the thrombin
generating effect of the extrinsic pathway.
o The classical pathways are still important to know for the NCE, so let’s review these now.

§ The extrinsic pathway is fast, requiring only ~15 seconds.

§ Prothrombin activator is simply another name for the collective of the coagulation factors that lead to thrombin activation.
o How should you remember which factors belong to which pathway? We have a mnemonic that ties all of this together, but for now we’re just
going to give you part of it. Isn’t the anticipation painful? *For 37 cents you can purchase the extrinsic pathway.”

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• Classical Intrinsic Pathway
o The classical intrinsic pathway is also called the contact activation pathway.
o Mnemonic
§ “If you can’t buy the intrinsic pathway for $12, you can buy it for $11.98.”

o the intrinsic pathway is slower, requiring up to 6 minutes to form a clot.

• Classical Final Common Pathway & Summary of Classical Coagulation Cascade
o 1. Injury activates the coagulation cascade by activating the extrinsic and intrinsic
pathway. The primary goal of both pathways is to produce prothrombin activator.
o 2. The final common pathway begins where prothrombin activator changes prothrombin
(II) to thrombin (IIa).
o 3. Thrombin (IIa) is a proteolytic enzyme that changes fibrinogen to fibrinogen monomer.
In the presence of Ca+2 (IV), fibrin fibers are created.
o 4. After the platelets aggregate, fibrin is incorporated into the platelet plug. Activated
fibrin-stabilizing factor (XIIIa) facilitates cross-linkage of the fibrin fibers, and this
completes the clot.
o 5. The clot stays in place until the underlying vascular tissue has repaired itself.
o Mnemonic:

th
“The final common pathway can be purchased at the five (V) and dime (X) for 1 (I) or 2(II) dollars on the 13 (XIII) of the month.”

o Putting it All Together

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• Fibrinolysis
o Mechanisms that Limit the Size of the Clot
§ After the clot is formed, the body must have a built-in mechanism to stop the clot from increasing indefinitely. This is accomplished
by a system that counterbalances clot formation. These processes include:
• Vasodilation washing out ADP and TxA2.
• Antithrombin inactivating thrombin.
• Tissue factor pathway inhibitor neutralizing tissue factor.
• Protein C and S, inhibiting factors III, V, and VIII.
o Mechanisms that Breakdown the Clot (Fibrinolysis)
§ Since the clot is only a temporary fix while the vessel repairs itself, the
body must have a way to breakdown the clot after it is no longer needed.
This process is called fibrinolysis.
• Plasminogen is a proenzyme that is synthesized in the liver. It is incorporated into the clot as it’s being formed, but it lays
dormant until it is activated.
• Plasmin is a proteolytic enzyme that degrades fibrin into fibrin degradation products.
§ Plasmin Activation
• Tissue plasminogen activator (tPA) is released by the injured tissue over a period of days (major mechanism).
• Urokinase is produced by the kidneys and released into the circulation (minor mechanism).
• Streptococci secrete streptokinase (situation specific).
• Plasmin activators are used therapeutically to dissolve thrombi and restore blood flow.
o Mechanisms that Turn Off Fibrinolysis When it is No Longer Needed
§ Once the clot is degraded, the body needs a way to turn off the fibrinolytic process.
• tPA inhibitor (TPAi) inhibits the conversion of plasminogen to plasmin.
• Alpha-2 antiplasmin inhibits the action of plasmin on fibrin.
§ *Nagelhout p. 884 shows plasmin changing fibrinogen to fibrin. This is an error.
• The Contemporary Cell-Based Coagulation Cascade
o Most of you are probably asking yourselves whether you need to learn the classical coagulation cascade, the contemporary cell-based cascade
or both. Unfortunately, we’re asking that same question as well. The reality is that the textbooks are inconsistent on the intricacies of the cell-
based model, and if the books don’t have it straight, there is no way the NBCRNA expects you to know this information for the NCE. At a
minimum, you should know the basics that we are present here.
o Furthermore, studying the finer points of the classical coagulation cascade (beyond what we’ve already given you) is
a low-yield approach. You should be able to apply the physiology we’ve given you to questions related to
pharmacology and hematologic disorders.
o The contemporary cell-based coagulation cascade attempts to explain how platelets, the extrinsic pathway, and the
intrinsic pathway function in an interdependent manner. The idea is that the coagulation takes place on the surface
of a cell that expresses tissue factor.
o The cascade consists of 3 phases:
§ 1. Initiation
§ 2. Amplification
§ 3. Propagation
o 1. Initiation Phase
§ The intrinsic components of the old system are not represented in the initiation phase of
the new coagulation cascade (remember, the extrinsic pathway (37 cents) is much faster
than the intrinsic pathway, so it makes sense that the initial phase leads off with factors
associated with the extrinsic pathway). Sure enough, you should note that tissue factor (III)
and VII begin the initiation phase.
• The TF/VIIa reaction activates factor X (common pathway). This step makes a
small amount of thrombin (IIa).
• Thrombin levels remain low during this phase, because tissue factor pathway
inhibitor (TFPI) limits the amount of tissue factor released.
• The quantity of thrombin produced during the initiation phase is insufficient to
activate fibrin.

o 2. Amplification Phase
§ The small amount of thrombin produced on the TF-bearing cells amplifies the
coagulation response by activating platelets, factor V, and factor XI.
§ *Nagelhout states IX is activated instead of Xi. We believe this is an error.
o 3. Propagation Phase
§ The large burst of thrombin required to produce hemostasis is produced during the
propagation phase.
• The propagation phase begins when factor X is activated by factors IV
(Ca+2), VIII, and IX on the surface of the platelet.
• This phase produces a positive feedback mechanism that produces enough
thrombin to activate fibrin.

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• Test of Coagulation
o aPTT: Activated Partial Thromboplastin Time
§ Assesses the intrinsic and common pathways.
§ Measures the time it takes to form a clot using phospholipid, calcium, and an activator.
§ Monitors the therapeutic response to unfractionated heparin, but not LMWH.
§ Normal is 25-32 seconds.
§ Remember the intrinsic pathway is slower than the extrinsic pathway, so the normal aPTT will be longer than the normal PT.
§ Factors must be reduced by more than 30% before a change in aPTT is observed.
o PT/INR: International Normalized Ratio
§ Assesses the extrinsic and common pathways.
§ Measures the time it takes to form a clot using tissue factor and calcium
§ Monitors the therapeutic response to warfarin.
§ Normal value is 12-14 secons.
§ Factors must be reduced by more than 30% before a change in PT is observed.
§ INR
• The internation normalized ratio is a calculation that standardizes PT results. It is based on the ratio between the
patient’s PT and the standard mean PT. without standardization, different labs might report different PT results, so it
would b eimpossible to compare results from different labs.
• Normal value is 1.5-2.5 times control.
o Platelet Count
§ Monitors the number of platelets, but not how well the platelets function. A normal count does not signify normal function.
§ Normal is 150,000-300,000 mm3.
§ <50,000 mm3 increases surgical bleeding risk.
§ <20,000 mm3 increases spontaneous bleeding risk.
o Bleeding Time
§ Monitors platelet function.
§ Evaluates the ability to form a platelet plug.
§ Normal value is 2-10 minutes.
§ Aspirin and NSAIDs prolong bleeding time.
§ Not commonly used in clinical practice.
o ACT: Activated Clotting Time
§ Guides heparin dosing
§ Normal ACT is 90-120 seconds
§ ACT should be >400 seconds before going on cardiopulmonary bypass.
§ ACT is measured before heparin administration, 3 minutes after it’s
given, and every 30 minutes thereafter.
o *Many of the numbers on this page vary slightly from book to book.
• Thromboelastogram (TEG)
o The TEG provides a “real time” visual representation of disorders of coagulation
and fibrinolysis. While an in-depth understanding of the TEG is beyond the
scope of the board exam, you must be ready to answer basic questions about it.
o We’ll tell you everything you need to know to correctly answer the 3 most likely
questions you’ll encounter.
§ 1. What does each segment on the TEG represent?
§ 2. Select the TEG that’s consistent with a particular diagnosis.
§ 3. How should you treat the results of a particular TEG?
o Normal TEG and its Components

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• Heparin
o Endogenous heparin is produced by basophils, mast cells, and the liver.
o Exogenous heparin is derived from bovine lung and porcine GI mucosa.
o Mechanism of Action
§ Heparin inhibits the intrinsic and final common pathways.
§ Antithrombin III is a naturally occurring anticoagulant that circulates in the plasma.
§ Heparin binds to antithrombin (AT) and greatly accelerates its anticoagulant ability 1000-fold.
§ The heparin-AT complex neutralizes thrombin and activated factors X, XII, XI, and IX.
§ It also inhibits platelet function.
§ Failed heparinization should prompt consideration of AT deficiency.
o Pharmacokinetics
§ Unfractionated heparin ranges from 3000-30,000 Daltons.
§ It is a large, negatively charged, water soluble compound with a small volume of distribution.
§ Heparin is metabolized by heparinase.
§ There are two pathways for elimination: degradation by macrophages and renal excretion.
§ It does not cross the placenta and is safe in pregnancy.
o Dose
§ 1 unit of heparin is defined as the volume of heparin-containing solution that prevents 1 mL of citrated sheep blood
from clotting for 1 hour following the addition of 0.2 mL of 1:100 CaCl.
§ The standard cardiac surgery dose is 300-400 U/kg.
§ VTE prophylaxis 5,000 U SC bid or tid.
§ Active VTE 5,000 U IV then infusion of ~1,250 U/hr to maintain aPTT 1.5-2.5 times normal.
§ Unstable angina and acute MI 5,000 U IV then infusion of 1,000 U/hr.
o Lab Evaluation
§ aPTT (Activated Plasma Thromboplastin Time)
• Therapeutic heparinization occurs when aPTT is 1.5-2.5 times normal (25-35 seconds).
§ ACT (Activated Coagulation Time)
• Normal ACT is 90-120 seconds.
• ACT should be >400 seconds before going on cardiopulmonary bypass.
• ACT is measured before heparin administration, 3 minutes after it’s given, and every 30 minutes thereafter.
• ACT is affected by:
o Hypothermia
o Thrombocytopenia
o Deficiency of fibrinogen, factor VII or factor XII
o Side Effects
§ Hemorrhage
§ Heparin Induced Thrombocytopenia (HIT)
§ Allergic reaction
§ Hypotension
§ Decreased ATIII Concentration
o Contraindications
§ Neurosurgical procedures
§ Heparin induced thrombocytopenia
§ Regional anesthesia (see guidelines in neuraxial anesthesia tutorial)
o Heparin Reversal
§ Protamine is derived from salmon sperm.
§ It is a highly alkaline compound with a strong positive charge.
§ The positive charge of protamine and the negative charge of heparin create a neutralization reaction and stop
heparin’s anticoagulant activity.
§ Dose=1 mg of protamine for every 100 U of heparin predicted to be in the circulation.
§ The heparin-protamine complex is cleared by the reticuloendothelial system.
§ When given alone, protamine is an anticoagulant.
Cause and Considerations
Side Effect
Hypotension Histamine release
Administer>5 minutes
Pulmonary Hypertension TxA2 and serotonin release
Allergic reaction Previous sensitization to NPH insulin
Fish allergy

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• Warfarin & Vitamin K Deficiency
o Warfarin
§ Inhibits the enzyme vitamin K epoxide reductase complex 1 (VKOR c1), which is responsible for converting inactive vitamin K to
active vitamin K.
§ Indirectly blocks the manufacturing of the vitamin K dependent factors. These include: II, VII, IX, X and protein C and S.
§ Is highly protein bound.
§ Requires several days to achieve a therapeutic concentration. The body stop producing vitamin K dependent factors, but it has to
use the factors that are already in the circulation. This explains why warfarin requires 36-82 hours to achieve a therapeutic
concentration.
§ Is monitored with PT/INR. The therapeutic concentration is 2-3 times normal.
§ Vitamin K and FFP are the antidotes for warfarin.
§ Vitamin K (10-20 mg) may be used to reverse warfarin for non-emergent, minor surgical procedures, however for emergent or high-
risk procedures, such as intracranial procedures, warfarin should be reversed with FFP (1-2 units), recombinant factor VIIa, or
prothrombin complex concentrate.
o Vitamin K
§ Vitamin K is a fat soluble vitamin that requires the presence of fat and bile for absorption.
§ It also manufactured by bacteria in the gut.
§ Malabsorptive diseases and decreased bile production can impair fat absorption and therefore create vitamin K deficiency.
§ A deficiency of vitamin K leads to coagulopathy.
o Risk Factors for Vitamin K Deficiency
§ Poor dietary intake.
§ Antibiotic therapy kills off the GI flora and reduces bacterial synthesis of vitamin K.
§ Malabsorption due to obstructive biliary tract disease.
§ Hepatocellular disease.
§ Neonates do not have the intestinal flora that synthesizes vitamin K (0.5-1.0 mg IM after delivery is common).
o Anesthetic Implications
§ Phytonadione is another name for exogenously administered vitamin K.
§ Vitamin K supplementation requires a functional liver; it is ineffective with a profound impairment of hepatocellular function.
§ It requires 4-8 hours to restore the concentration of vitamin K dependent clotting factors in the blood.
§ Vitamin K is the antidote for warfarin. It does not revers heparin.
§ Dose is 10-20 mg PO, IM or IV.
§ IV administration is associated with life-threatening anaphylaxis. IV administration is best avoided, however if given by this route,
the rate should not exceed 1 mg/min.
• Drugs That Affect Bleeding
o Drugs that Increases Bleeding Drugs that Decrease Bleeding

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• Von Willebrand Disease
o Von Willebrand disease is the most common inherited disorder of platelet function. As a qualitative platelet disorder, the
platelet count is normal, but the platelets do not function properly.
o vWF is synthesized by the vascular endothelium and megakaryocytes. It serves 2 key functions:
§ 1. It anchors the platelet to the vessel wall at the site of vascular injury (platelet adhesion).
§ 2. It carries inactivated factor VIII in the plasma.
o Classification
§ Type I: Mild-moderate reduction in the amount of vWF produced.
§ Type II: the vWF that is produced doesn’t work well.
§ Type III: Severe reduction in the amount of vWF produced.
o Laboratory Findings

o Anesthetic Implications
§ Desmopressin
• Desmopressin is a syntehetic analogue of antidiuretic hormone.
• It stimulates the release of endogenous vWf and increases factor VIII activity.
• Patients with type I disease respond best to desmopressin.
• Patients with type III disease do not responds to desmopressin because they do no produce vWF.
• Dose=0.3-0.5 mcg/kg IV.
§ Blood Products
• Cryoprecipitate contains factors VIII, XIII, fibrinogen, and vWF. It can be used for type I, II, or III disease.
• FFP contains all the clotting factors, so it too can be used for this patient, although there are more suitable alternatives.
• Purified VIII-vWF concentrate reduces the risk of transfusion related infection. It is the first line agent for the patient with
type III disease.
• Hemophilia A and B
o Hemophilia A: Factor 8 Deficiency
§ Hemophilia A is an X-linked chromosomal disorder (more common in males) that causes factor VIII deficiency.
§ Severe disease (factor VIIi activity<1%) is associated with spontaneous bleeding into the joints, muscle, and vital organs. These patients often
require orthopedic surgery.
§ Mild disease (factor VIII activity 6-30% normal) does not cause spontaneous bleeding, however it is associated with increased surgical
bleeding.
§ Hemophilia A is usually more severe than hemophilia B.
§ Anesthetic Implications
§ Factor VIII is part of the intrinsic pathway. Therefore, the PTT will be
greatly prolonged with severe disease and only slightly prolonged
with mild disease.
§ Since the extrinsic pathway is not affected, the PT will be normal.
§ The patient should receive factor VIII concentrate prior to surgery.
§ The half life of factor VIII is 8-12 hours, so redosing may be required. Therapy should be continued 2-6 weeks after surgery.
§ FFP and cryoprecipitate can also be sued to replace factor VIII. Their use increases the risk of transfusion related disease transmission.
§ Patients with mild-moderate disease may benefit from DDAVP.
§ Antifibrinolytics (transexamic acid or aminocaproic acid) can be used to minimize bleeding during dental procedures.
§ A type and crossmatch is required for any surgical procedure.
o Hemophilia B: Factor 9 Deficiency
§ Severe disease (IX activity <1% normal) is associated with severe bleeding.
§ Mild disease (IX activity>5% normal) may not be diagnosed until unexplained bleeding occurs during surgery.
§ Anesthetic Implications
§ Anesthetic considerations are the same as with hemophilia A.
§ Patients will have a prolonged PTT and a normal PT.
§ Factor IX-prothrombin complex concentrate can be used to replace factor IX, however its use is associated with thromboembolic
complications. Its use must be balanced against this risk.
§ Factor IX has a half-life of 18-24 hours.
o Recombinant factor 7: An Emerging Treatment for Hemophilia A & B
§ Sometimes patients with hemophilia A or B develop inhibitors that prevent exogenous factor 8 or 9 from achieving their therapeutic goals.
§ For a clot to form, the missing coagulation factor must be replaced or “bypassed”. Recombinant factor 7 is a “bypass” agent, because it skips
over factor 8 or 9 in patients with inhibitors, ultimately allowing the patient to form clot. The dose is 90-120 mcg/kg.
§ Although the exact mechanism is unclear, both the classic and contemporary cell-based theories of coagulation suggest that factor 8
contributes to thrombin generation by facilitating tissue factor at the site of vascular injury and on the surface of the platelet.
§ Recombinant factor 7 can increase the risk of arterial thrombosis (MI and embolic stroke) as well as venous thrombosis (DVT or pulmonary
embolism), so the risk/benefit ratio must be considered in patients at risk for these complications.
§ Recombinant factor 7 is also used as a “last-ditch” treatment for bleeding without an identifiable cause (this is off label). The dose is 20-40
mcg/kg.

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• Disseminated Intravascular Coagulation
o DiC is characterized by disorganized clotting and fibrinolysis that lead to the simultaneous occurrence of hemorrhage and
systemic thrombosis.

o Pathophysiology
§ The Big Picture:
• Generalized thrombin formation creates microvascular clots that impair tissue perfusion, resulting in tissue
hypoxia and acidosis. The body attempts to break down these clots by activating its anticoagulant system,
however this leads to the widespread consumption of its coagulation factors, fibrinogen, and platelets.
§ A Deeper Dive:
• In normal physiology, antithrombin and tissue factor pathway inhibitor (TFPI) keep the procoagulants at
bay.
• In the patient with DIC, tissue factor (III) is release in the absence of vascular injury.
• This activates the extrinsic coagulation cascade throughout the entire body.
• Clots in the microvasculature (thrombotic microangiopathy) impair tissue perfusion. This culminates as
tissue necrosis and end-stage organ failure.
• Widespread fibrin deposition consumes the body’s supply of fibrinogen, coagulation factors, and platelets.
This explains hemorrhage.
• Release of tPA and urokinase-type activator occurs in DIC> increased D-dimer levels are the result of
increased fibrinolytic activity. Clot is forming and broken down simultaneously.
o Signs of DIC
§ Ecchymosis
§ Petechiae
§ Mucosal bleeding
§ Bleeding at IV puncture sites
§ Prolonged PT and PTT
increased D-dimer and fibrin split products
§ Decreased fibrinogen and antithrombin
o Patients at Risk
§ There are 3 conditions that you should associate with a high risk of developing DIC:
• Sepsis: (highest risk = gram-negative bacilli)
• Obstetric complications: (highest risk=preeclampsia, placental abruption, and amniotic fluid embolism)
• Malignancy: (highest risk = adenocarcinoma, leukemia, and lymphoma)
o Treatment
§ DIC is always a manifestation of some other underlying problem. Indeed, the definitive treatment for DIC is reversing
the underlying cause. Otherwise, treatment is supportive.:
• Hypovolemia: Treat with IV fluids.
• Coagulopathy: Replace consumed blood components with FFP, platelets, and cryoprecipitate (it’s ok to
“feed the breast”)
• Severe microvascular thrombosis: IV heparin or LMWH

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• Thrombotic Disorders
o The risk of thrombosis is increased by pathologies that impair the body’s natural anticoagulant systems. We will cover the 4 conditions that you
should know for the NCE>
§ 1. Antithrombin deficiency
§ 2. Heparin-Induced thrombocytopenia
§ 3. Protein C and S deficiency
§ 4. Factor V Leiden mutation
o Antithrombin Deficiency
§ Antithrombin captures factors XII, XI, X, and IX, which ultimately leads to thrombin (factor IIa) inhibition.
§ Heparin works by increasing the anticoagulant effect of AT by 1000-fold.
§ Patients with antithrombin deficiency are unresponsive to heparin.
§ Repeated heparin administration can consume the body’s supply of AT and produce an acquired form of AT deficiency.
§ Patients with congenital disease are at risk for venous thromboembolism throughout the lifespan.
§ Treatment:
• AT concentrate
• FFP
o Heparin-Induced Thrombocytopenia (HIT)
§ Let’s get something straight – heparin-induced thrombocytopenia causes clot formation throughout the body!
§ HIT occurs when the body mounts an immune response against heparin after it binds to platelet factor 4 (PF4). IgG antibodies
activate platelets, which ultimately results in uncontrolled clot formation. The platelet count falls because platelets are consumed
faster than they are produced.

o Protein C and S Deficiency

§ Protein C produces an anticoagulant effect by inhibiting factors Va and VIIIa. This creates a feedback mechanism that prevents
unnecessary clot formation.
§ Protein S is a co-factor of protein C. said another way, protein S helps protein C do its job.
§ A deficiency of protein C or S can produce a hypercoagulable state, increasing the risk of thrombosis.
§ Treatment:
• A thromboembolism is treated with heparin that is transitioned to warfarin.
• Patients may or may not require life-long anticoagulation with warfarin.
o Factor V Leiden Mutation
§ Factor V Leiden causes a resistance to the anticoagulant effect of protein C.
§ Treatment:
• Only patients with thromboembolism require anticoagulation.
• Lifelong anticoagulation is unwarranted unless the patient experiences recurrent thrombotic events.

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• Sickle Cell Anemia
o Sickle Cell Disease
§ Sickle cell disease is an inherited disorder that affects erythrocytes. Amino acid substitution (valine is substituted for
glutamic acid) on the beta globulin chain alters RBC geometry. This affects RBC function in several ways:
• Deoxygenation of HgbS leads to sickling (a conformational change that alters the erythrocyte’s geometry).
• In severe cases, sickling causes the RBCs to clump together, which causes mechanical obstruction of the
microvasculature in the vital organs and joints. This impairs tissue perfusion and causes intense pain
(particularly in the bones and joints).
• Sickled cells are more prone to hemolysis and removal by the spleen (lifespan=12-17 days vs normal
RBC=120 days).
§ Triggers
• Anesthetic management focuses on avoiding these triggers:
o Pain
o Hypothermia
o Hypoxemia
o Acidosis
o Dehydration
§ Complications
• Vaso-Occlusive Crisis
o Sickled cellsàimpaired tissue perfusionàischemic injury
o The most common manifestation of sickle cell disease
o Treatment: analgesics (oral or IV) and hydration.
o Hydroxyurea reduces the incidence and severity of vaso-occlusive crisis.
• Acute Chest Syndrome
o ACS is a significant source of mortality (1-20%).
o It is caused by thrombosis, embolism, and infection.
o It is more common in children.
o Diagnosis requires new lung infiltrates on CXR and at least one of the following: chest pain, cough,
dyspnea, and wheezing.
o It is common during the postoperative period.
o Potential causes include: hypoventilation, narcotics, splinting, and pain.
• Sequestration Crisis:
o Occurs when the spleen removes RBCs from the circulation at a faster rate than they are
produced by the bone marrow.
o Leads to anemia and hemodynamic instability.
• Aplastic Crisis:
o RBCs with HgbS have a short half-life, so even a small amount of bone marrow suppression can
cause anemia.
o Usually caused by viral infection (parovirus B19).
• Pneumococcal Disease:
o Children are at higher risk.
o Prophylaxis includes pneumococcal vaccination and daily penicillin (up to 5 years of age).
• Other Complications:
o Asthmas occurs in 50% of patients.
o Pulmonary hypertension occurs in 10% of patients.
§ What is Sickle Cell Trait?
• Heterozygous sickle cell disease is also referred to as sickle cell trait.
o While homozygous SCD affects 0.5-1.0% of the African-American population, nearly 10%
demonstrates sickle cell trait.
o As a general rule, patients with sickle cell trait do not advance to crisis. Severe hypoxemia is a key
exception of this rule.

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Blood Transfusion
• Blood Groups
o Erythrocytes contain antigenic glycoproteins on their cell membranes (determines blood type), and the plasma contains the
opposite antibodies. A successful transfusion requires there is no antigen-antibody reaction.
§ If an antigen is expressed on the erythrocyte, then there will NOT be an antibody against that specific antigen in the
plasma.
§ If an antigen is NOT expressed on the erythrocyte, then there will be an antibody against that specific antigen in the
plasma.
§ The most clinically important antigens are the ABO and Rh systems.
o The ABO System

o The Rh System

§ A person who is Rh-negative can be sensitized by exposure to Rh-positive blood during transfusion or pregnancy.
• A Rh-negative mother can be sensitized by her Rh-positive fetus. Transfer occurs across the placenta,
usually several days after delivery.
• The mother receives Rhogam to prevent sensitization.
• If the mother becomes sensitized and develops antibodies, a subsequent pregnancy with a Rh-positive fetus
may result in erythroblastosis fetalis.
o Other RBC Antigen Systems
§ Other blood antigens include Duffy, Lewis, Kell, M, N, and P. these are less antigenic.

• Compatibility Testing & Emergency Transfusion

o Type, Screen & Crossmatch

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 o Emergency Transfusion of PRBCs
§ In the setting of acute hemorrhage, there may not be time to complete a full crossmatch. Here is the recommended
order of administering uncrossmatched blood (most to least favorable options):
• 1. Type-Specific Partially Crossmatched Blood
o tests for ABO compatibility as well as a few antibodies.
• 2. Type-Specific Uncrossmatched Blood
o tests for Abo compatibility only.
• 3. Type O Negative Uncrossmatched Blood
o this blood does not contain A, B, or Rh antigens and is considered the universal donor for PRBCs.
o Because 85% of the population is Rh-D positive, O positive can be used for emergency transfusion
if the patient is not a woman of child bearing age and has not received a previous transfusion.
• Blood Product Components

o Specific factor replacements are covered in Blood I: Coagulation.

• Maximum Allowable Blood Loss
o Blood loss should be replaced with crystalloid and/or colloid solutions until the risk of anemia is greater than the risk of transfusion.
o The 2006 ASA Task Force guidelines state that transfusions are “usually unnecessary” if hgb is greater than 10 g/dL, but blood should “usually
be administered” if the hgb is less than 6 g/dL. The decision to transfuse when hgb is between 6-10 g/dL should be based on the patient’s
response to anemia. Patients with significant coronary artery disease should be transfused when hematocrit falls below 28-30%.
o We know there are practitioners out there pushing these boundaries with great success, but that isn’t what’s tested on the NCE.
o In a world of goal directed therapy, EBL, and hgb alone should not dictate transfusion. Instead, we should also consider indicators of tissue
perfusion such as DO2, SvO2, acid-base status, lactate, hemodynamic instability, myocardial ischemia, and oliguria. In light of this, you must
know this calculation for the NCE>
o Hemoglobin Concentration with Acute Blood Loss Before Resuscitation
§ If a 70 kg patient has a hgb of 12 g/dL and acutely loses 1 L of blood, what is the new hgb value?
th
§ The answer is 12 g/dL. Why? Even though the patient has lost 1/5 of his blood volume, the amount of hgb per deciliter of blood has
not changed.
o Hemoglobin Concentration with Acute Blood Loss After Resuscitation
§ If you resuscitate the patient with a crystalloid and/or colloid solution and return him to a euvolemic state, his hemoglobin will drop
as a result of dilution. It is important to realize that MABL calculation assumes that the patient is euvolemic.
§ If we estimate the patient’s blood volume and we know his starting hgb or hct, we can predict the amount of blood that can be lost
before transfusion should be considered when a predetermined transfusion trigger is selected.

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 o MABL Part I: Determine the Estimated Blood Volume

o MABL Part II: Calculate the Blood Loss Required to Reduce Hgb to a Predetermined Value

§ *If you were given the hematocrit value, just replace hgb with hct and the calculation is the same.
§ ** some texts will place average hgb in the denominator, however we recommend the calculation presented above.
• Blood Storage and Preservation
o Overview
§ One unit of packed red blood cells contains ~ 300 mL with a hematocrit of 70%.
§ Transfusion of one unit of PRBCs raises hemoglobin by 1 g/dL and hematocrit by 2-3%.
§ Erythrocytes do not contain mitochondria, so they rely on anaerobic metabolism to convert glucose to ATP.
§ This is beneficial, so the RBC does not consume the oxygen that it is supposed to deliver to the tissues.
§ Blood is stored at 1-6 degrees C to extend its lifespan by slowing the rate of glycolysis.
o Additives that Increase Shelf Life (CPDA)
§ Citrate is an anticoagulant that inhibits calcium (factor IV). After transfusion of multiple units, the citrate load can
cause hypocalcemia.
§ Phosphate is a buffer that combats acidosis.
§ Dextrose is the primary substrate for glycolysis.
§ Adenine is a substrate that helps RBC’s re-synthesize ATP. It extends storage time from 21 to 35 days.
§ Newer preservatives (adsol, Nutricel, and Optisol) extend storage time to 42 days.
o Consequences of Preservation-RBC Storage Lesion
§ Although the CDPA preservative extends the life of banked blood, there are several important physiochemical
changes that occur during storage. This is known as the red blood cell storage lesion.
• Decreased 2,3 DPGàshifts oxyhemoglobin dissociation curve to the left (left = love àdecreased O2 release)
• Decreased ATPàshift to anaerobic metabolism
• Decreased pH (increased lactic acid)
• Increased potassium (caution in neonates and renal failure)
• Impaired ability to change shape (important for capillary flow)
• Hemolysis
• Increased production of proinflammatory mediators
o Components
§ Leukoreduction
• Removes WBCs from RBCs and platelets.
• Since leukocytes are responsible for HLA alloimmunization, febrile nonhemolytic transfusion reactions, and
CMV transmission, it makes sense that removing leukocytes reduces these risks.
§ Washing
• Washing the blood products with saline removes any remaining plasma (and antigens) in the donor RBCs
(RBCs antigens are not removed).
• This process prevents anaphylaxis in IgA deficient patients.
§ Irradiation
• This process exposes units to gamma radiation, and this disrupts WBC DNA in the donor cells.
• Prevents graft vs host disease in immunocompromised patients.
• Graft-vs-host disease is a rare, yet devastating event. Donor leukocytes attack recipient bone marrow,
leading to pancytopenia, fever, hepatitis, and diarrhea. Gamma radiation destroys donor leukocytes.
Radiated blood is particularly useful in the immunocompromised patients.
• Populations who benefit from irradiated cells include: leukemia, lymphoma, hematopoietic stem cells
transplants, and DiGeorge syndrome.

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• Infectious Complications
o Patients are concerned about acquiring an infectious disease with transfusion. Although there is a plethora of devastating complications that
occur with greater regularity, the infection risk of transfusion remains one of the more common questions you’ll be asked during the
preoperative interview.
o The incidences of infectious complications that you’ll find in the textbooks are mathematical estimates, so don’t become obsessed with specific
numbers. Instead we recommend that you learn these from least frequent to most frequent. We’ve supplied the numbers from Barash to give
you a reference point. Also, we’ve included a list of key points that you must know.

o Key Points
§ 1. Cytomegalovirust is the most common infection complication of transfusion. Leukoreduction greatly reduces this risk, so
immunocompromised patients should receive leukoreduced blood.
§ 2. The risk of infection following transfusion ordered from most to least common: CMV> Hepatitis B >Hepatitis C > HIV.
§ 3. In up to 85% of infections, hepatitis C can progress to cirrhosis, hepatocellular carcinoma, liver failure, and death.
§ 4. Bacterial contamination can progress to sepsis. Platelets are stored at room temperature, which explains why bacterial
contamination is more common with platelets than with PRBCs or FFP.
• Acute Hemolytic Reaction
o A hemolytic reaction is perhaps the most devastating complication that results from transfusion. Complement is activated in the recipient’s blood, and
plasma antibodies attack the antigens present on the donor blood cell membranes. ABO incompatibility is the most lethal. Renal failure, DIC, and
hypotension are the most catastrophic complications of intravascular hemolysis.
o Signs & Symptomsàtable
o Pathophysiology
§ Renal Failure – Acute Tubular Necrosis
• Free hemoglobin in the form of acid hematin precipitates
inside the renal tubules. This causes a mechanical
obstruction.
• Acidic urine increases precipitation.
§ Disseminated Intravascular Coagulation
• Erythrocyin is released from the RBC, and it activates the intrinsic clotting cascade. This leads to uncontrolled fibrin formation and
consumes the body’s supply of platelets and factors I, II, V, and VII.
§ Hemodynamic Instability
• Free hemoglobin activates the kallikrein system. The final product of this pathway is bradykinin – a potent vasodilator.
o Treatment
§ 1. Stop the transfusion
§ 2. Maintain urine output > 75-100 mL/hr with:
• IV fluids
• Mannitol 12.5-25 g
• Furosemide 20-40 mg if IVF and mannitol fail to provide an adequate response.
§ 3. Alkalinize the urine with sodium bicarbonate.
§ 4. Send urine and plasma hemoglobin samples to blood bank
§ 5. Check platelets, PT, and fibrinogen
§ 6. Send unused blood to blood bank to double check cross match.
§ 7. Support hemodynamics with IVF and pressors as needed.

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• TRALI & TACO
o Transfusion-Related Acute Lung Injury
§ Transfusion-related acute lung injury (TRALI) is a form of non-cardiogenic pulmonary edema that occurs following transfusion. It is
the most common cause of transfusion related mortality in the United States.
§ Populations at higher risk:
• Critically ill (highest risk)
• Anyone susceptible to acute lung injury: sepsis, burns, or post-CPB
§ Pathophysiology
• TRALI is probably caused by human leukocyte antigens (HLA) and neutrophil antibodies present in the donor plasma.
o Donor antibodies àneutrophil activation in the lungsàendothelial injuryàcapillary leakàpulmonary
edemaàimpaired gas exchangeàhypoxemiaàacidosisàdeath
• FFP and platelets contain the highest concentration of these antibodies.
• Where the blood products come from also affects the risk of TRALI. These donor groups impart the highest risk:
o Multiparous women (highest risk)
o History of blood transfusion
o History of organ transplant
§ Diagnostic Criteria
• Onset < 6 hours following transfusion
• Bilateral infiltrates on frontal CXR
PaO2/FiO2<300 mmHg or SpO2 < 90% on RA
• Normal pulmonary artery occlusion pressure (no left atrial hypertension or volume overload)
§ Management
• Management is supportive and uses a lung protective strategy.
o Maximizes PEEP .
o Low tidal volume
o Avoid over hydration
o Transfusion-Associated Circulatory Overload
§ It’s easy to confuse transfusion-associated circulatory overload (TACO) with TRALI.
§ TACO is a state of volume overload caused by expanding the plasma volume beyond the patient’s compensatory ability (ex: patient
with heart failure receiving 4 units of FFP to reverse warfarin).
§ Signs & Symptoms of TACO:
• Pulmonary edema
• Hypervolemia
• Left ventricular dysfunction
• Mitral regurgitation secondary to volume overload
• Increased pulmonary artery occlusion pressure
• Increased brain natriuretic peptide
§ Treatment is supportive.
• Massive Transfusion & Trauma
o Massive Transfusion
§ Massive transfusion is associated with:
• Alkalosis from citrate metabolism to bicarbonate in the liver.
• Hypothermia from transfusion of cold blood.
• Hyperglycemia from dextrose additive to stored blood.
• Hypocalcemia from binding of calcium by citrate.
• Hyperkalemia from administration of older blood. When RBCs are stored, the cell membrane becomes dysfunctional, which
allows potassium to leak into the supernatant. Administration of PRBCs to neonates can lead to hyperkalemia and cardiac arrest.
The risk is reduced by administering washed or fresh cells that are less than 7 days old.
o Trauma
§ The “lethal triad” of trauma consists of:
• Acidosis
• Hypothermia
• Coagulopathy
§ The problem begins with hemorrhage and hypoperfusion, and this ultimately impacts coagulation and acid-base balance.
§ Hypoperfusion/acidosis:
• Hypoperfusion and hypoxemia reduce oxygen delivery, so the body converts from aerobic to anaerobic metabolism. The
net result is lactic acidosis.
§ Hypothermia
• Hemorrhage and hypoperfusion impair the body’s ability to regulate heat.
• Exposure to the elements and/or room temperature IV solutions also contribute to heat loss.
§ Coagulopathy:
• All enzymatic processes are highly dependent on temperature
• Coagulation is an enzymatic process, so it is impaired by hypothermia.
• PT and PTT are prolonged at <34 C
• Acidosis alters enzymatic structure, so acidosis also impairs the hemostatic mechanism.
• Massive volume resuscitation causes a dilution coagulopathy.

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• Intraoperative Blood Salvage
o Intraoperative blood salvage is typically used during cardiac, major vascular, trauma, liver transplant, and orthopedic surgery
when blood loss is expected to exceed 1000mL or 20% of the patient’s expected blood volume. It is also indicated for patients
with pre-existing anemia or those that refuse allogenic blood products, such as Jehovah’s witness.
o How it Works
§ The blood lost to the surgical field is collected by a dedicated suction device. After collection, the blood is:
• 1. Mixed with an anticoagulant such as heparin or citrate.
• 2. Filtered to remove debris and then centrifuged to concentrate the red blood cells.
• 3. Concentrated and washed to remove any remaining contaminants such as anticoagulant, free
hemoglobin, white blood cells, plasma, and platelets.
• 4. Diluted with saline to a final hematocrit of 60-70%.
• 5. Ready to be auto-transfused to the patient through standard blood filter tubing.
§ It is important to note that platelets and coagulation factors are not returned to the patient. If a large volume of
salvaged blood is returned to the patient, you should consider the possibility of dilutional coagulopathy.
o Differences Between Salvaged Blood and Banked Blood
§ Salvaged blood has a better oxygen carrying capacity than banked blood. Salvaged erythrocytes contain higher
concentration of 2,3-DPG and ATP and they are better able to maintain the biconcave shape.
o Risks
§ Risks of intraoperative blood salvage are rare and include:
• 1. Contamination of collected blood by urine, feces, amniotic fluid, or malignant cells
• 2. Fever
• 3. Non-immunogenic hemolysis
o Contraindications
§ Sickle cell disease
§ Thalassemia
§ Topical drugs in sterile field such as betadine, chlorhexidine, and topical antibiotics
§ Infected surgical site
§ Oncologic procedures
o Controversial uses of intraoperative blood salvage include c-section due to the theoretical risk of anaphylactoid syndrome of
pregnancy (amniotic fluid embolism). Two systematic review failed to show an increase in morbidity and mortality when cell
saver was used during c-section.
o Intraoperative blood salvage is considered safe for transplant surgery.

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Fluids & Blood Notes:

283
KIDNEY, LIVER & ENDOCRINE
KIDNEY
Gross Anatomy
• The bean shaped kidneys reside in the retroperitoneal space between the levels of T12 and L3. The right kidney is slightly more caudal to accommodate the liver.
• The hilum is the point of entry and exit for the renal artery, renal vein, nerves, lympatics, and ureters.
• When sliced and viewed in a longitudinal section, you will see 2 major areas:
o Renal Cortex
§ The outer section of the kidney (to help you remember, think about the location of the
cerebral cortex).
§ It houses the glomerulus, Bowman’s capsule, proximal tubules, and distal tubules.
o Renal Medulla
§ The inner section of the kidney
§ It houses the loops of Henle and the collecting ducts
§ The medulla is divided into pyramids, with the APEX of each pyramid directed towards
the renal pelvis.
§ The APEX of each pyramid is called the papilla. This region contains lots of collecting
ducts.
§ The papilla drain urine into the minor calyces.
§ Multiple major calyces converge to form the renal pelvis, which empties urine into the ureter.
§ The calyces, pelvis, and ureters have the capability to contract and push urine towards the bladder.
Overview: The Six Functions of the Kidney
• Before we dig into the finer points of renal physiology, we want to give you a bird’s eye view of renal function. We certainly understand that this is a perplexing topic
for many of you, as it’s easy to become distracted by the near-endless amount of minutiae that you’ll find in the textbooks. Our job is to condense this information
into a smaller volume, while still making sure you have everything you need for the NCE. if you thirst for additional detail in this area, Guyton & Hall is a great place
to start.
• 1. Maintenance of Extracellular Volume and Composition
o we want you to make several connections:
§ 1. Aldosterone controls extracellular fluid volume (Na+ and water are reabsorbed together).
§ 2. Antidiuretic hormone (vasopressin) controls plasma osmolarity (water is reabsorbed, but Na+ is not).
o The kidneys also regulate potassium, chloride, phosphate, magnesium, hydrogen, bicarbonate, glucose, and urea.
• 2. Blood Pressure Regulation: Long and Intermediate Term
o long term control of BP is carried out by the thirst mechanism (intake) and sodium and water excretion (output).
o Intermediate term control of BP is carried out by the renin-angiotensin-aldosterone system.
o Short term control of BP is carried out by the baroreceptor reflex.
• 3. Excretion of Toxins and Metabolites
o glomerular filtration and tubular secretion clear the blood of metabolic byproducts, toxins, and drugs.
o Like the liver, the kidney is capable of phase I and II biotransformations.
• 4. Maintenance of Acid-Base Balance
o the body’s pH must be kept in a narrow range to ensure proper enzymatic and cellular function.
o The key organs of acid-base balance include the lungs and the kidneys.
o The lungs excrete volatile acids (CO2) and the kidneys excrete non-volatile acids.
o The kidneys maintain acid-base balance by titrating hydrogen in the tubular fluid, which creates acidic or basic urine.
• 5. Hormone Production
o Erythropoietin
§ Inadequate oxygen delivery to the kidney causes it to release erythropoietin. Clinical example include: anemia, reduced intravascular volume,
and hypoxia (high altitude, cardiac, and/or pulmonary failure).
§ EPO stimulates stem cells in the bone marrow to produce erythrocytes.
§ Severe kidney disease reduces EPO production and leads to chronic anemia.
o Calcitriol (1,25 [OH]2 – Active Vitamin D3)
§ Calciferol is synthesized from ingested vitamin D or following exposure
to ultraviolet light.
§ In the liver, calciferol is converted to 25 [OH] vitamin D3 (inactive D3).
§ In the kidney (under control of parathyroid hormone), 25 [OH] vitamin
D3 is converted to calcitriol (1,25 [OH]2 Vitamin D3 – the active form
of vitamin D3).
§ Calcitriol has 3 functions;
• It stimulates the intestine to absorb Ca+2 from food.
• It stimulates the bone to store Ca+2.
• It stimulates the kidney to reabsorb calcium and
phosphate.
o Prostaglandins
§ PGE2 and PGI2 vasodilate the renal arteries.
§ Thromboxane A2 constricts the renal arteries.
• 6. Blood Glucose Homeostasis
o the kidneys (like the liver) are capable of synthesizing glucose from amino acids,
thereby preventing hypoglycemia during fasting.
o The kidneys rival the liver’s ability to perform gluconeogenesis.

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• Renal Blood Flow
o At any given time, there are two types of fluid moving through the kidney: blood and tubular fluid. Be careful not to confuse the
two!
§ The kidneys receive 20-25% of the cardiac output (1000-1250 mL/min)
§ Of the blood delivered to the kidney, only 20% is filtered at the glomerulus. This means that 180 liters of blood are
actually filtered in a day. The filtered volume that enters the tubules is called the ultrafiltrate. The other 80% of the
blood that isn’t filtered circulates through the peritubular capillaries.
§ After filtration, ~99% of the ultrafiltrate is reabsorbed into the peritubular capillaries.
§ The ultrafiltrate that is not reabsorbed is excreted as urine (1-1.5 L/day)
§ All of the blood in the peritubular capillaries eventually empties into the inferior vena cava by way of the renal veins.
o Distribution of Renal Blood Flow
Renal Blood Flow = (MAP – Renal Venous Pressure) / Renal Vascular Resistance
§ The renal cortex receives 90% of the renal blood flow. The PO2 in the region is 50 mmHg.
§ The renal medulla and its juxtamedullary nephrons receive 10% of the renal blood flow. The PO2 in this region is 10
mmHg.
§ A lower PO2 in the renal medulla explains why this region is more sensitive to ischemia.
§ Renal blood flow decreases 10% per decade of life after age 50.
§ In the neonate, RBF doubles in the first 2 weeks of life and achieves an adult level by 2 years of age.
o Pathway of Blood Through the Kidney

o Control of Renal Blood Flow: Autoregulation

§ The purpose of autoregulation is to ensure a constant amount of blood flow is delivered to the kidneys over a wide range of arterial
blood pressures. Glomerular filtration becomes pressure dependent when MAP is outside the range of autoregulation.
• When renal perfusion is too low, renal blood flow is increased by reducing renal vascular resistance.
• When renal perfusion is too high, renal blood flow is reduced by increasing renal vascular resistance.
§ There is little agreement about the range of RBF autoregulation, although we like 50-180 mmHg.
• 80-170 mmHg (HALL)
• 60-160 mmHg (Stoelting)
• 50-150 mmHg (Hemmings)
• 50-180 mmHg (Nagelhout)
§ *Urine output is NOT autoregulated. It is linearly related to MAP above 50 mmHg
§ Autoregulation is carried out by several processes:
• 1. Myogenic mechanism
• 2. Juxtaglomerular apparatus and tubuloglomerular feedback
• 3. Renin-angiotensin-aldosterone system
• 4. Prostaglandins
• 5. Atrial Natriuretic Peptide
• 6. Sympathetic Nervous system
§ Of these, the myogenic mechanism and tubuloglomerular feedback are the most important.
§ Myogenic Mechanism
• If the renal artery pressure is elevated, the myogenic mechanism constricts the afferent arteriole to protect the
glomerulus from excessive pressure.
• When the renal artery pressure is too low, the myogenic mechanism dilates the afferent arteriole to increase blood flow
going to the nephron.
§ Tubuloglomerular Feedback
• The juxtaglomerular apparatus is located in the distal tubule, specifically the region that passes between the afferent and
efferent arterioles.
• Tubuloglomerular feedback about the sodium and chloride composition in the distal tubule affects arteriolar tone. In
turn, this creates a negative feedback loop to maintain renal blood flow.

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 o Renal Blood Flow During the Perioperative Period
§ The kidneys receive sympathetic innervation from T8-L1.
§ The SNS innervates the afferent and efferent arterioles. Under normal
conditions, the internal autoregulatory mechanisms override the
external effects of the SNS. In times of stress or when exogenous
catecholamines are administered, the SNS can reduce renal blood flow.
The PNS is not well represented in the kidney.
§ The surgical stress response induces a transient state of
vasoconstriction and sodium retention. This persists for several days,
resulting in oliguria and edema. Vasoconstriction of the renal
vasculature during this time predisposes the kidneys to ischemic injury
and nephrotoxicity from drugs administered during the perioperative
period.
• The Renin-Angiotensin-Aldosterone System: Salt & Fluid Retention
o Juxtaglomerular Apparatus
§ The juxtaglomerular apparatus is a monitor of renal perfusion and
solute concentration. It is located in the distal tubule, specifically the
region that passes between the afferent and efferent arterioles.
§ Tubuloglomerular feedback about the sodium and chloride
composition in the distal tubule affects arteriolar tone. In turn, this
creates a negative feedback loop that adjusts renal vascular
resistance and renin secretion in an effort to maintain renal blood
flow.
o The RAAS plays an integral role in the regulation of systemic vascular resistance
and the composition of the extracellular volume. By extension, it greatly
influences cardiac output and arterial blood pressure.

o Aldosterone
§ Aldosterone is a steroid hormone that is produced in
the zona glomerulosa of the adrenal gland.
§ By stimulating the Na/K-ATPase in the principal cells of
the distal tubules and collecting ducts, aldosterone
facilitates Na+ and water reabsorption and potassium
excretion.
§ Aldosterone does not meaningfully change serum
osmolarity. This is because the water follows sodium
in direct proportion when it’s reabsorbed into the
peritubular capillaries. Antidiuretic hormone controls
serum osmolarity, because it increases reabsorption
of water but not sodium.
§ In addition to RAAS stimulation, aldosterone release is increased by:
• Hyperkalemia
• Hyponatremia
§ While the sodium retaining effect of angiotensin II is almost immediate, there is a 1-2 hour delay between aldosterone release and
its physiologic effects.
§ Disorders of Aldosterone Release
• Conn’s disease occurs with excess aldosterone production. It causes sodium retention and potassium loss.
• Inadequate aldosterone production in isolation is uncommon. Addison’s disease is usually the result of adrenocortical
insufficiency (destruction of all of the cortical zones).

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• Osmolality & Antidiuretic Hormone
o Definition of Terms
§ Osmolarity and osmolality are measures of concentration.
• Concentration is an amount per volume.
• Osmolality measures the number of osmoles per kilogram of solvent.
• Osmolarity measures the number of osmoles per liter of solvent.
• Osmoreceptors are monitors of sodium concentration in the extracellular fluid.
§ For our purposes, the difference between osmolarity and osmolality is so miniscule that we’re going to pretend
they’re the same thing. As such, we’ll use these terms interchangeably.
§ Sodium concentration is the principal determinant of osmolarity. For completeness, you should understand that it’s
also affected by glucose and blood urea nitrogen.
Serum osmolarity=2 [ Na+] + Glucose + BUN
18 2.8
Normal Osmolarity= 280-290 mOsm/L
o Antidiuretic Hormone (Vasopressin)
§ ADH is produced in the supraoptic and paraventricular nuclei of the hypothalamus. It is released from the posterior
pituitary gland.
§ There are 2 mechanisms that control ADH release:
• 1. Increased Osmolarity of the ECF:
o an increased ECF sodium concentration shrinks the osmoreceptors in the hypothalamus. This
initiates the process of transporting ADH from the hypothalamus to the posterior pituitary gland.
After this, ADH is released into the systemic circulation.
o The thirst reflex is activated and antidiuresis prevents additional water loss. As the kidneys
conserve water, the urine becomes more concentrated (osmolarity increases).
• 2. Decreased Blood Volume
o When blood volume declines, unloading of the baroreceptors in the carotid bodies, transverse
aortic arch, great veins, and right atrium stimulate ADH release.

§ How ADH Restores Blood Pressure:

• 1. ADH stimulates the V2 receptor in the collecting ducts (increased cAMP)
o under the direction of ADH, aquaporin-2 channels (water channels) are inserted into the walls of
the collecting ducts.
o This facilitates water reabsorption, reduces plasma osmolarity, and increases urine osmolarity.
o The net result is an expansion of the plasma volume.
• 2. ADH stimulates the V1 receptor, and causes vasoconstriction in the peripheral vasculature (increased IP3,
DAG, Ca+)
o the net result is an increased SVR
§ The half-life of ADH is 5-15 min
§ While anesthetic agents do not directly affect ADH homeostasis, they do impact arterial blood pressure and venous
blood volume. In turn, these changes increase ADH release. Examples include: PEEP, positive-pressure ventilation,
hypotension, hemorrhage.

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• Mechanisms of Renal Vasodilation
o There are 3 pathways that promote renal vasodilation:
§ 1. Prostaglandins
§ 2. Atrial natriuretic peptide
§ 3. Dopamine receptors
o 1. Prostaglandins
§ prostaglandins are produced in the afferent arteriole.
§ Arachidonic acid is liberated from the cell membrane in response to ischemia, norepinephrine, and angiotensin II.
§ By producing vasodilating prostaglandins, arachidonic acid antagonizes the effects of the RAAS on renal blood flow.
§ Under ischmic conditions, the pathway favors production of vasoconstrictors: thromboxane A2 and PGF2.
§ In the presence of NSAIDs, inhibition of cyclooxygenase reduces prostaglandin synthesis and contributes to renal
vasoconstriction, impairing renal blood flow.
§ Endotoxin increases leukotriene production, which leads to renal vasoconstriction.

o 2. Atrial Natriuretic Peptide

§ ANP is produced by the myocardium in response to atrial distention.
§ It stimulates sodium and water excretion in the collecting ducts.
§ ANP provides negative feedback to the RAAS; it inhibits renin release.
o 3. Dopamine Receptors
§ There are two types of dopamine receptors: DA1 and DA2.
§ DA1 receptors are present in the kidney and the splanchnic circulation.
§ DA2 receptors are present on the presynaptic adrenergic nerve terminal.
DA1 DA2
Location Renal vasculature Presynaptic SNS nerve terminal
Tubules
nd
2 Messenger Increased cAMP Decreased cAMP
Function Vasodilation Decreased norepinephrine release
Increased renal blood flow
Increased GFR
Diuresis
Sodium excretion
o Does Dopamine Improve Outcome in Acute Kidney Injury?
§ No. while dopamine increases urine output, there is no solid evidence to support the age-old notion that renal-dose
dopamine either prevents or treats AKI.
o What About Fenoldopam?
§ Fenoldopam is a selective DA1 receptor agonist that increases renal blood flow. Low dose fenoldopam (0.1-
0.2mcg/kg/min) is a renal vasodilator and increases RBF, GFR, and facilitates Na+ excretion without affecting arterial
blood pressure.
§ It may offer renal protection during aortic surgery and during cardiopulmonary bypass.
§ Fenoldopam reduces the requirement for dialysis and in-hospital mortality in cardiac surgery patients.

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• Filtration, Reabsorption, & Secretion: An Overview
o The glomerular contains Bowman’s capsule, which filters blood as it enters the proximal tubule of the nephron. Filtration is dependent on renal
blood flow and glomerular filtration pressure.
o Glomerular Filtration
§ GFR is 125 mL/min or 180 L/day
§ The filtration fraction is 20%. This means that 20% of the renal blood flow is filtered by the glomerulus and 80% is delivered to the
peritubular capillaries.
§ Water, electrolytes and glucose are freely filtered.
§ The basement membrane of the glomerulus has a negative charge.
§ Because of albumin’s negative charge, electrostatic repulsion prevents it and other proteins from entering the glomerular filtrate.
§ The glomerular filtrate is identical to plasma except that it does not contain plasma proteins, erythrocytes, or white blood cells.
§ Kidney disease results in the destruction of the basement membrane, which allows filtration of proteins into the tubules. This
presents as proteinuria.
§ The hydrostatic pressure across the glomerulus determines GFR.
Net Filtration Pressure= Glomerular Hydrostatic Pressure – Bowman’s Capsule Hydrostatic Pressure – Glomerular Oncotic Pressure

o Glomerular Hydrostatic Pressure

§ Glomerular hydrostatic pressure is the most important determinant of GFR.
§ There are 3 determinants of glomerular hydrostatic pressure:
• 1. Arterial blood pressure
• 2. Afferent arteriole resistance
• 3. Efferent arteriole resistance
§ Arterial Blood Pressure
• Increased MAP increases GFR and decreased MAP decreases GFR.
• Autoregulation safeguards against hypo- and hypertension.
§ Afferent Arteriole Resistance
• Constriction of the afferent arteriole reduces GFR.
• Dilation of the afferent arteriole increases GFR.
§ Efferent Arteriole Resistance
• Constriction of the efferent arteriole follows a biphasic pattern.
• Mild constriction reduces flow towards the peritubular capillaries and increases GFR.
• Excessive constriction reduces renal blood flow as well as GFR.
• Dilation of the efferent arteriole increases flow towards the peritubular capillaries and reduces GFR.
o Reabsorption, Secretion & Excretion
§ Since water, electrolytes, and glucose are freely filtered by the glomerulus, the body requires a mechanism to capture
these products. Indeed, 99% of all that is filtered is reabsorbed as the glomerular filtrate makes its way thorugh the
nephron.
§ We know the concept of secretion and reabsorption can be confusing. If you think of these actions as originating from
the efferent arteriole (not the tubule), all of this will make more sense.
• Reabsorption- substance is transferred from the tubule to the peritubular capillaries
• Secretion- substance is transferred from the peritubular capillaries to the tubule
• Excretion- substance is removed from the body in the urine.

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 § Urine Production
• Urine formation is the sum of glomerular filtration, tubular reabsorption, and tubular secretion.
Urinary Excretion Rate = Filtration – Reabsorption + Secretion
• Filtration, Reabsorption & Secretion: All Along the Nephron
o It is critical that you understand the physiology of the nephron. Many of you will be asked about its anatomy, handling of electrolytes or
glucose, or the site of action for diuretics. These are terrific hotspot questions. Completing the mind map in the workbook will help you
tremendously.
o Because it helps you understand diuretic therapy, you must know sodium’s fate at each point in the nephron.
o Sodium Handling in the Nephron

§ Reabsorption of electrolytes requires energy in the form of ATP, while reabsorption of water occurs by osmosis and does not require
energy.
o Proximal Tubule – Bulk Reabsorption of Solutes and Water
§ Sodium (65%) is actively transported out of the nephron (into the peritubular fluid). This consumes a large quantity of oxygen.
§ Water (65%) follows sodium by osmosis.
§ Potassium, chloride, bicarbonate follow sodium in direct proportions by the sodium co-transport mechanism. That means that 65% of these
ions are absorbed in the proximal tubule. This is pretty easy huh?
§ Organic bases, acids, and hydrogen ions are secreted into the proximal tubule by the sodium counter-transport mechanism.
§ Examples of organic acids and bases include bile salts, uric acid, catecholamines, and toxins.
o Loop of Henle (Descending) – Countercurrent Mechanism + High Permeability to H2O
§ Water (20%) is reabsorbed in the descending thin segment.
§ The countercurrent system increases the osmolarity of the peritubular fluid along the length of the descending loop. This pulls water into this
area.
§ The osmolarity is 300 mOsm/L in the cortical region and increases to 1500 mOsm/L towards the renal pelvis.
§ The vasa recta are the peritubular capillaries that run parallel to the loop of Henle. They are essential for the countercurrent mechanism.
o Loop of Henle (Ascending)- Countercurrent Mechanism + No Permeability to H2O
§ In the thick ascending segment, sodium (20%), potassium, and chloride is actively pumped into the interstitium via the sodium-potassium-(2)
chloride co-transporter.
§ This region is impermeable to water.
§ Since water cannot follow sodium, the ultrafiltrate becomes hypotonic and the interstitial space becomes hypertonic.
§ Hydrogen is excreted via the sodium countercurrent mechanism.
o Distal Tubule – Fine Tunes Solute Concentration
§ Sodium (5%) is reabsorbed, and potassium, chloride, and bicarbonate follow via the sodium co-transport mechanism.
§ The late distal tubule is impermeable to water except in the presence of aldosterone or antidiuretic hormone.
§ Aldosterone increases Na+ and water reabsorption and increases K+ and H+ secretion.
§ ADH increases water reabsorption only (no solutes).
§ Parathyroid hormone increases calcium reabsorption.
§ Is home of the juxtaglomerular apparatus.
§ Adjusts urea concentration.
o Collecting Duct – Regulates Final Concentration of Urine
§ Reabsorbs sodium (5%)
§ ADH increases water reabsorption only (not solutes).
§ Atrial natriuretic peptide inhibits water and sodium reabsorption.
§ Aldosterone works here and in the distal tubule.
§ Adjusts hydrogen concentration.

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Diuretics
o Basis of Action
§ The kidney expends most of its oxygen on the Na/K-ATPase in the basolateral membrane of the tubular cells (the side that faces the peritubular
capillaries). This pump maintains the concentration gradient for sodium, so that sodium moves from the tubule to the peritubular capillaries. This
system also powers a variety of other pumps that drive reabsorption of the rest of the electrolytes. These pumps are often the target of the diuretics.
§ By inhibiting sodium reabsorption, we’re inhibiting water reabsorption as well. Remember that water follows sodium by osmosis. Also, by inhibiting
sodium reabsorption, we’re disrupting the other systems that drive reabsorption of chloride, calcium, magnesium, and bicarbonate. There are a few
exceptions to this, which we’ve pointed out below.
o Carbonic Anhydrase Inhibitors (Acetazolamide and Dorzolamide)
§ Mechanism of Action:
• Carbonic anhydrase inhibitors noncompetitively inhibit carbonic anhydrase
in the proximal tubule. Let’s view the reaction:
• Bicarbonate accepts H+ to forma carbonic acid. In the presence of carbonic
anhydrase (an enzyme), carbonic acid dissociates into CO2 and H2O. this faovrs a concentration gradient where HCO3- flows from the lumen of the
tubule and into the cells of the proximal tubule.
• Inhibiting carbonic anhydrase disrupts this mechanism. As a result, HCO3- isn’t reabsorbed. Since H+ isn’t used to produce carbonic acid, it is
retained by the body. Chloride is retained to maintain electroneutrality. This is the mechanism for hyperchloremic metabolic acidosis (non-gap).
• There is net loss of bicarbonate and sodium with a net gain of hydrogen and chloride.
§ Dose:
• Acetazolamide 250-500mg
§ Clinical Use:
• Open-angle glaucoma – inhibition of carbonic anhydrase reduces aqueous humor production and reduces intraocular pressure.
• High altitude sickness – A mild metabolic acidosis increases respiratory drive.
• Central sleep apnea – A mild metabolic acidosis increases respiratory drive.
§ Complications:
• Metabolic acidosis
• Hypokalemia
• In patients with COPD, loss of bicarbonate ions in the urine (reduced buffer) may exacerbate CNS depression from hypercarbia.
o Osmotic Diuretics (Mannitol, Glycerin, Isosorbide)
§ Mechanism of Action:
• Osmotic diuretics are sugars that undergo filtration but nor reabsorption in the proximal tubule (primary site) as well as the loop of Henle.
Water is excreted in excess of electrolytes.
• Osmotic diuretics pull ECF volume into the intravascular space. This increases plasma osmolarity, which reduces brain water (decreases
ICP) as well as augments RBF. In the patient with poor myocardial function, expansion of the intravascular volume can precipitate heart
failure and pulmonary edema.
• Mannitol is a free radical scavenger. This effect may limit cellular edema and decrease obstruction of the renal tubules.
§ Dose:
• Mannitol 0.25-1 g/kg
§ Clinical Use:
• Prevention of acute kidney injury – there is little evidence to support the efficacy of this
• Intracranial hypertension
• Differential diagnosis of acute oliguria (mannitol increases UOP if prerenal but has no effect with intrinsic injury)
§ Complications:
• Congestive heart failure
• Pulmonary edema
• If the blood-brain barrier is disrupted, mannitol will enter the brain and cause cerebral edema.
• Potassium-Sparing Diuretics (Spironolactone, Amiloride, Triamterene)
o Mechanism of Action:
§ Amiloride and triamterene inhibit potassium secretion and sodium reabsorption in the collecting ducts. Their function is
independent of aldosterone.
§ Sprinolactone exists in a subclass of potassium-sparing diuretics called aldosterone antagonists. By blocking aldosterone at
mineralocorticoid receptors, spironolactone inhibits potassium secretion and sodium reabsorption in the collect ducts.
o Dose:
§ Sprinolactone 12.5- 100mg
§ Amiloride 5-10 mg
§ Triamterene 50-150 mg
o Clinical Use:
§ To reduce potassium loss in a patient receiving a loop or thiazide diuretic
§ Secondary hyperaldosteronism
o Complications:
§ Hyperkalemia (risk increased with concurrent use of NSAIDs, beta-blockers, and ACE inhibitors)
§ Metabolic acidosis
§ Gynecomastia
§ Libido changes (sprinolactone)
§ Nephrolithiasis (triamterene)

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• Loop Diuretics (Furosemide, Bumetanide, Ethacrynic Acid)
o Mechanism of Action:
§ The ascending limb of the loop of Henle is impermeable to water. As the ultrafiltrate flows upward, the Na-K-2Cl
transporter removes these ions from the ultrafiltrate and dilutes the urine. This region is responsible for 25% of the
sodium reabsorption in the nephron.
§ Loop diuretics poison the Na-K-2Cl transporter in the medullary region of the thick portion of the ascending loop of
Henle (primary site). The amount of sodium that remains in the tubule overwhelms the distal tubule’s reabsorption
capability. Thus, a large volume of dilute urine is excreted. Potassium, calcium, magnesium, and chloride are lost to
the urine as well.
o Dose:
§ Furosemide 20-200 mg
§ Bumetanide 0.5-2mg
§ Ethacrynic acid 25-100 mg
§ Clinical Use:
• Acute pulmonary edema
• Acute kidney injury
• Congestive heart failure
• Hypercalcemia
• Hypertension
• Anion overdose
• Intracranial hypertension (not as effective as mannitol)
• Mobilization of edema fluid
§ Complications:
• Hypokalemic, hydrochloremic metabolic alkalosis
• Hypokalemia can increase risk of dysrhythmias when combined with digitalis, skeletal muscle weakness, and
potentiate the effect of neuromuscular blockers.
• Hypocalcemia
• Hypomagnesemia
• Hypovolemia
• Ototoxicity (ethacrynic acid > furosemide)
• Reduced lithium clearance
• Thiazide Diuretics (Hydrochlorothiazide, Chlorhalidone, Metolazone, Indapamide)
o Mechanism of Action:
§ Thiazides inhibits the Na-Cl tranposrter in the distal tubule. Stoelting says their primary site of action is the cortical
region of thick ascending loop of Henle, but this book seems to be an outlier.
§ Inhibition of the Na-Cl exchanger in the distal tubule activates the Na-Ca antiporter. This increases Ca+2 reabsorption,
ultimately increasing serum calcium.
§ A unique features of thiazide diuretics is that they cause hyperglycemia. Possible mechanisms for this include reduced
insulin release from the pancreas or impaired cellular glucose utilization in the body.
o Dose:
§ Hydrochlorothiazide 12.5-50mg
§ Chlorthalidone 12.5-50mg
§ Metolazone 1.25-5mg
§ Indapamide 1.25-5mg
o Clinical Use:
§ Essential hypertension
§ Mobilize edema fluid
§ Heart failure
§ Osteoporosis (reduces Ca+ excretion)
§ And wrap your brain around this…thiazides are used to treat nephrogenic diabetes insipidus.
o Complications:
§ Hyperglycemia – caution with diabetes mellitus
§ Hypercalcemia
§ Hyperuricemia – caution with gouty arthritis
§ Hypokalemic, hypochloremic metabolic alkalosis
§ Hypovolemia
§ Hyperlipidemia
§ Sexual dysfunction

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• Renal Function Tests
o Renal function tests provide assessment of either:
§ 1. Glomerular function – measured by GFR
§ 2. Tubular Function – measured by concentrating ability

o Blood Urea Nitrogen

§ Urea is the primary metabolite of protein metabolism in the liver
(amino acids àammonia àurea)
§ Because urea undergoes filtration AND reabsorption, it is better
indicator of uremic symptoms than as a measurement of GFR.
o Serum Creatinine
§ Creatine is produced by skeletal muscle, and creatinine is a
metabolic byproduct of creatine breakdown.
§ Creatinine production is constant and is directly proportional to
muscle mass (it is lower in women and in the elderly)
§ It undergoes renal filtration but not reabsorption. This makes it a
useful indicator of GFR.
§ A 100% increase in creatinine indicates a 50% reduction in GFR.
o BUN:Creatinine Ratio
§ The normal ratio is 10:1
§ A BUN:Cr ratio of >20:1 suggests prerenal azotemia.
§ The aforementioned non-renal causes of elevated BUN can also
increase this ratio.
o Creatinine Clearance
§ Creatinine clearance is the most useful indicator of GFR.
GFR = [(140-age) x Body Weight (kg)]
[72 x serum Cr (mg/dL)]

§ * in women this value should be multiplied by 0.85 to account for a smaller muscle mass
o Fractional Excretion of Sodium
§ Fe(Na+) relates sodium clearance to creatinine clearance.
§ If Fe(Na+) <1%, then more sodium is conserved relative to the amount of creatinine cleared. This suggests prerenal azotemia.
§ If Fe(Na+) >3%, then more sodium is excreted relative to the amount of creatinine cleared. This suggests impaired tubular function.
o Urinary Sodium
§ Working kidneys are able to conserve sodium, while failing kidneys waste sodium.
o Urinalysis
§ Urine Protein
• Large amounts of protein in urine indicates glomerular injury (>750 mg/day or > +3 by urinalysis)
§ Specific Gravity
• Measures the ability of the kidneys to concentrate or dilute the urine.
• Interpretation:
o Greater than 1.024 = physiologic oliguria
o Greater than 1.015 = prerenal oliguria
o 1.010-1.015 = acute tubular necrosis
§ Urine Osmolality
• This is a better test of tubular function than specific gravity
o Differential Diagnosis of Prerenal Oliguria vs Acute Tubular Necrosis

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Acute Kidney Injury
o Acute kidney injury (AKI) is a significant source or perioperative morbidity and mortality. The most common cause of perioperative kidney injury
is ischemia-reperfusion injury.
o The following patients are at risk for acute kidney injury during the perioperative period:
§ Pre-existing kidney disease § Sepsis
§ Prolonged renal hypoperfusion § Jaundice
§ Congestive heart failure § High risk surgery (use of aortic cross clamp
§ Advanced age and liver transplant)
o Classification of Kidney Injury
o Oliguria is common during the perioperative period, and is usually prerenal in origin. The problem with using urine output as a surrogate of
renal perfusion, is that oliguria is often the result of the physiologic response to stress. It is not specific for renal injury or risk of injury. Even so
a Foley catheter is the standard monitor of urine production.
o There are 2 modern methods used to classify the severity of renal injury:
§ 1. RIFLE criteria: risk, injury,failure, loss, end-stage kidney disease
§ 2. Acute kidney injury network (AKIN)
o both systems grade renal function on serum creatinine and urinary output. Serum creatinine (not urine output) is a more sensitive indicator of
renal dysfunction. Both methods highlight that kidney injury occurs along a continuum.

o Classification Based on the Location of Insult:

o 1. Prerenal Injury – Hypoperfusion
§ there is inadequate perfusion of the kidneys, but there is no intrinsic damage.
§ Perfusion is impaired as a result of hypovolemia, decreased cardiac output, systemic vasodilation, renal vasoconstriciotn, or
increased intra-abdominal pressure.
§ Treatment:
• Restoration of renal blood flow with IVF, hemodynamic support, and/or PRBCs (if insufficient DO2) can halt the
progression to ATN.
• Renal prostaglandins mediate vasodilation in the kidney. NSAIDS reduce prostaglandin synthesis, thereby causing
constriction of the renal vasculature. Avoid NSAIDs in patients at risk for kidney injury.
• An improvement in UOP following an intravenous fluid bolus confirms the diagnosis of prerenal azotemia.
o 2. Intrinsic Injury – Parenchymal
§ While intrinsic injury can be caused by injury of the tubules, glomerulus, or the interstitial space, we will focus our discussion on acute tubular
necrosis.
§ It’s important to think of prerenal injury and acute tubular necrosis from medullary ischemia as two ends on a continuum. A prerenal cause
can progress to intrinsic injury if left untreated. The kidney expends 80% of its oxygen to fuel the ionic gradients in the nephron.
§ Intrinsic causes of acute tubular necrosis include:
• 1. Ischemia:
o the renal medulla is more susceptible to ischemic insult.
o The renal tubules use oxygen to support ionic transfer between the tubules and the peritubular fluid, and poor
oxygenation disrupts these mechanisms.
• 2. Nephrotoxic Drugs
o the risk of nephrotoxicity from IV contrast dye, nephrotoxic antibiotics and NSAIDS is magnified in those with
pre-existing renal injury.
§ Treatment:
• Restore renal perfusion. Supportive.
o 3. Postrenal Injury – Obstruction
§ Postrenal AKI is the result of an obstructive phenomena.
§ The source of the obstruction can arise anywhere between the collecting system and the urethra.
§ Treatment: Relieve the obstruction.

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 o Etiology of Acute Renal Injury
o This is a really intimidating list! We don’t recommend that you memorize the whole thing. We’ve grouped each pathology
under a general concept. Learn the concepts and you’ll be in great shape.
Prerenal Injury Intrinsic Injury Postrenal Injury
Intravascular Volume Depletion Tubular Injury Urinary Tract Obstruction
Hemorrhage Ischemia from hypoperfusion Retroperitoneal tumor/lymph nodes
Dehydration Myoglobin Hematoma
GI losses (diarrhea, NGT, vomiting) Free hemoglobin (transfusion rxn) Fibrosis
Cirrhosis Antibiotics Surgical trauma to ureter
Nephrotic syndrome Contrast agents Hematoma
Chemotherapeutics Nephrolithiasis
Decreased Cardiac Output Blood clots/debris
CHF Tubulointerstitial Injury Tumor
Sepsis Acute allergic interstitial nephritis Stricture
Cardiogenic Shock Infection Infection
Infiltration Enlarged prostate
Systemic Vasodilation Bladder obstruction
Sepsis Glomerular Injury Stones
Anaphylaxis Inflammatory disease Neurogenic bladder
Cirrhosis Hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Renal Vasoconstriction
Early sepsis Renal Vasculature
Hepatorenal syndrome Toxemia of pregnancy
Hypercalcemia Hypercalcemia
Vasoconstrictor drugs Contrast agents
NSAIDs Malignant hypertension
Iodine containing IV contrast dye Scleroderma

Increased Abdominal Pressure Large Vessels

Abdominal compartment syndrome Thrombosis
Vasculitis
Dissection
Trauma
o Fluid Management
o The risk of prerenal azotemia is reduced by maintaining MAP > 6 mmHg and providing appropriate hydration.
o While there is no clear benefit between crystalloids and colloids, the sue of hydroxyethyl starches are associated with an
increased risk of renal morbidity.
o Excessive use of 0.9% NaCl can cause a hyperchloremic metabolic acidosis.
o Attempting to convert oliguric to nonoliguric AKI with diuretics increases risk of additional renal injury as well as mortality.
o Vasopressors
o In healthy patients, alpha-1 agonists can reduce RBF.
o The septic patient will benefit from an alpha-1 agonists so long that it supports MAP. The benefits of increased renal perfusion
outweigh the renal vasoconstrictive effects.
o Vasopressin preferentially constricts the efferent arteriole. It maintains GFR and UOP better than norepinephrine or
phenylephrine.
o Renal dose dopamine does not prevent or treat AKI.
Chronic Kidney Disease

o Chronic kidney disease is a progressive and irreversible disorder that reflects the ongoing inability of the kidneys to sustain their normal
functions.
Stages of Kidney Disease
o The most common cause of CKD is diabetes mellitus. The second most common cause is
hypertension. Stage Description GFR
o Uremic Syndrome mL/min
o S/sx: anemia, fatigue, N/V, anorexia, and coagulopathy. 1 Normal >90
o The blood urea nitrogen level parallels uremic symptoms and can be used to 2 Mildly decreased 60-89
guide management.
3 Moderately 30-59
o Uremic Bleeding
decreased
o Uremic patients are at increased risk of bleeding.
o Bleeding time is a measure of platelet function. It is elevated by uremia and is the most 4 Severely decreased 15-39
accurate predictor of bleeding risk. 5 Kidney failure < 15
o The PT, pTT and platelet counts are normal. *requires dialysis
o The first line treatment is desmopressin (von Willebrand factor VIII).
o Cryoprecipitate may be used to provide VIII-vWF, however its use is associated with an
increased risk of viral transmission.
o Dialysis improves bleeding time, so it should be performed within 24 hours of surgery

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o Anemia
o Decreased production of erythropoietin leads to normochromic normocytic anemia.
o Excess parathyroid hormone also contributes to anemia by replacing bone marrow with fibrotic tissue.
o Treatment consists of exogenous EPO or darbepoetin + iron supplementation.
o EPO can cause hypertension.
o Blood transfusion is not a first line treatment because it increases the risk of HLA sensitization and future rejection of a
transplanted kidney.
o Cardiovascular
o Hypertension is the result of RAAS activation – sodium retention & fluid overload.
o Salt and water retention contributes to congestive heart failure and pulmonary edema.
o Coronary artery disease is the most common cause of death. Assume all patients with chronic kidney disease have CAD.
o Pericarditis is common with uremia. There is a risk of pericardial effusion and cardiac tamponade.
o Acid-Base Balance
o Decreased excretion of non-volatile acid contributes to a gap metabolic acidosis.
o Remember that a gap acidosis is the result of an accumulation of nonvolatile acids, while a non-gap acidosis is the result of loss
of HCO3 ions.
o Acidosis shifts the oxyhemoglobin dissociation curve to the right. This partially compensates for anemia.
o Potassium
o Hyperkalemia is the result of impaired potassium excretion.
o Dialysis is indicated when serum potassium exceeds 6 mEq/L
o Other treatments that reduce serum potassium include:
§ Glucose (25-50 g) + insulin (10-20 units)
§ Hyperventilation (for every 10 mmHg decrease in PaCO2, the serum potassium level is reduced by 0.5 mEq/L)
§ Sodium bicarbonate (50-100 mEq)
o Calcium chloride (1g) does not change serum potassium concentration. Instead, it raises threshold potential in the myocardium
and reduces the risk of lethal dysrhythmias.
o Osteodystrophy
o Renal osteodystrophy is caused by:
§ 1. Decreased vitamin D production
§ 2. Secondary hyperparathyroidism
o Pathophysiology:
§ An inadequate supply of vitamin D impairs calcium absorption in the GI tract.
§ The body responds to hypocalcemia by increasing parathyroid hormone release. This action demineralizes bone to
restore the serum calcium concentration.
§ Additionally, hyperphosphatemia contributes to low serum calcium. Phosphate clearance parallels GFR.
§ The net result is a decreased bone density and increased risk of bone fractures.
o Respiratory
o Increased intravascular volume and uremia create a restrictive ventilatory defect.
o Volume overload may lead to pulmonary edema.
o Metabolic acidosis is compensated by respiratory alkalosis (hyperventilation).
o Neurologic
o Uremia impairs nerve conduction.
o Autonomic dysfunction contributes to reduced baroreceptor responsiveness (hemodynamic instability) as well as delayed gastric emptying.
o Peripheral neuropathies are both sensory and motor. They contribute to silent myocardial ischemia.
o Central symptoms may be mild (impaired abstract thinking, insomnia) and may progress to severe (seizures, encephalopathy, coma).
o Infection
o Impaired white cell function and a low protein diet contribute to the high risk of infection.
o Frequent exposure to blood products increases the risk of viral transmission.
o Dialysis
o Dialysis is the cornerstone of AKI treatment. There are 5 indications for its use:
§ 1. Volume overload
§ 2. Hyperkalemia
§ 3. Severe metabolic acidosis
§ 4. Symptomatic uremia
§ 5. Overdose with a drug that is cleared by dialysis
o Considerations for the Patient on Dialysis
§ Hemodialysis is more efficient than peritoneal dialysis.
§ Peritoneal dialysis is favored in patients who cannot tolerate fluid shifts associated with hemodialysis (CHF or unstable angina).
§ Emergent dialysis is carried out by obtaining central access via the internal jugular or femoral vein.
§ Hypotension is the most common event during dialysis. This is due to intravascular volume depletion and osmotic shifts.
§ Anesthetic options for graft placement include brachial plexus blockade, local infiltration, or general anesthesia.
§ Infection is a leading cause of death in dialysis patients, therefore strict aseptic technique is required.

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Anesthetic Drugs and Impaired Renal Function
o Instead of giving you a huge list of drugs that are acceptable in patients with impaired renal function, we’re going to focus our discussion on the exception,
controversies, and misconceptions.
o Altered responses to anesthetic drugs are usually due to one or more of the following:
o Active metabolites
o Acidosis increases the nonionized fraction
o Decreased protein binding increases the free fraction
o Impaired elimination of active metabolites
o Uremia-induced disruption in the blood-brain barrier.
o Patients may experience exaggerated hemodynamic effects due to:
o Antihypertensive medications, specifically ACE inhibitors and angiotensin receptor blockers
o Attenuation of SNS tone
o Positive pressure ventilation
o Halogenated Anesthetics
o Although their metabolism liberates free fluoride ions, the modern halogenated anesthetics (Des, Sevo, and Iso) do not directly cause kidney
dysfunction. In the sense that they can induce hypotension and depress cardiac output, they can indirectly cuase renal injury by reducing
perfusion. Additionally, a reduction in renal perfusion coupled with renal vasoconstriction and/or nephrotoxic agents further increase the
likelihood of acute kidney injury.
o Sevoflurane
§ Compound A is produced when sevoflurane is degraded by soda lime. Although there is no human data that links AKI and compound
A, the FDA recommends that sevoflurane be administered at a rate of 1 L/min for no more than 2 MAC hours. After 2 MAC hours
have elapsed, the fresh gas flow should be increased to 2 L/min.
• Factors associated with increased Compound A production include:
o High concentration over a long period of time.
o Low fresh gas flow
o High temperature of CO2 absorbent
o Increased Co2 production
o Methoxyflurane
§ Methoxyflurane metabolism liberates a significant amount of free fluoride ions. This is directly related to a high output renal failure
that was common with its administration.
o Muscle Relaxants
o Succinylcholine
§ Opening of the nAChR at the neuromuscular junction can increase serum potassium by 0.5-1.0 mEq/L for up to 10-15 min. in
patients with upregulation of extrajunctional receptros, the potassium concentration may rise even further.
§ Renal failure does not cause upregulation of extrajunctional receptors, so succinylcholine is safe in patients with renal failure and a
normal potassium level. In the patient with hyperkalemia (K+ >5.5 mEq/L), the normal response to succinylcholine may increase
serum potassium to a dangerous level.
§ Succinylcholine should not be administered as a continuous infusion, because its primary metabolite (succinylmonocholine) is
secreted by the kidney. Succinylmonocholine is a weakly pharmacologically active, however it may prolong period of paralysis.
o Benzylisoquinolines
§ Due to their organ independent elimination, cisatracurium and atracurium are more suitable agents in this population. Atracurium
produces more laudanosine (CNS stimulant) than cisatracurium, and it also releases histamine (risk of hypotension). If given the
choice between the two, cisatracurium is the better answer.
o Aminosteroids
§ Rocuronium primarily undergoes hepatobiliary elimination, however it is associated with an unpredictably increased duration of
action. Possible causes include a reduced clearance, altered protein binding, and/or an increased potency.
§ Veuconrium is metabolized to 3-OH vecuronium. Its duration is prolonged as a function of decreased clearance and an increased
elimination half-life.
§ Pancuronium is primarily eliminated by the kidneys and has no use in this population.
o Reversal Agents
o Both anticholinesterases and anticholinergics used to reverse neuromuscular blockers undergo renal elimantion and thus share a similar
increase in duration. They do not require dosage adjustments.
o Induction Agents
o Propofol may need an upward dosage adjustment due to a hyperdynamic circulation and/or disruption of the blood-brain barrier secondary to
uremia.
o Opioid Agonists
o Morphine is metabolized to morphine-6-glucoronide. This product is more potent than morphine, and it relies on renal excretion. Accumulation can
contribute to respiratory depression.
o Meperidine is metabolized to normeperidine. Accumulation of normeperidine can cause convulsions.
o Hydromorphone is metabolized to an active metabolite, hydromorphone-3-glucuronide. This can cause prolonged respiratory depression and myoclonus.
The books are inconsistent about this (some say there is no active metabolite), so if you are asked about renally excreted metabolites, then morphine
and/or meperidine would be the best answer choices.
o Fentanyl, sufentanil, alfentanil, and remifentanil do not produce active metabolites and are better choices with renal failure.
o Dexmedetomidine
o Dexmedetomidine is biotransformed by the liver and may be used safely in this population. The duration may be prolonged.

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Nephrotoxic Agents
o Because a primary function of the kidney is to eliminate toxins form the body, it should be logical that the kidneys may succumb to the damaging effects of these
compounds. By concentrating the toxins inside the tubules, this region is at particular risk. The concentration of the toxin as well as the duration of exposure
determine the extent of its nephrotoxic effects.
o The risk of AKI related to nephrotoxic agents is increased in patients with pre-existing kidney disease as well as those with other risk factors including hypovolemia,
sepsis, and congestive heart failure.
o Radiographic Contrast Media
o There are 2 mechanisms by which radiographic contrast media causes nephrotoxicity:
§ 1. Ischemic injury due to vasoconstriction in the renal medulla
§ 2. Direct cytotoxic effects
o signs of AKI begin at 24-36 hours and peak between 3-5 days.
o Prevention of contrast induced nephropathy (CIN):
§ Use nonionic iso- or low-osmolar contrast instead of hyperosmolar contrast.
§ Use the lowest volume of contrast as the procedure will allow.
§ Withholding other drugs with known nephrotoxic effects.
§ Intravenous hydration with 0.9% NaCl prior to administration of contrast dye.
§ Sodium bicarbonate injection or infusion.
§ N-acetylcysteine is a free radical scavenger. It has fallen out of favor for lack of efficacy.
o Don’t forget – radiographic contrast media can also cause anaphylaxis.
o Myoglobin
o Myoglobin is released into the circulation during a hemolytic reaction or rhabdomyolysis. Hemolytic reactions were covered in Blood II: Transfusion, so
we’ll focus our discussion on rhabdomyolysis.
o Rhabdomyolysis and myoglobinemia are sequelae of direct muscle trauma, muscle ischemia, or prolonged immobilization. Myoglobin binds oxygen
inside of the myocyte. When it is released into the circulation, it is freely filtered at the glomerulus. In the presence of acidic urine (pH <5.6), myoglobin
precipitates in the proximal tubule. This results in tubular obstruction and acute tubular necrosis. In addition, myoglobin scavenges nitric oxide, leading
to renal vasoconstriction and ischemia.
o Creatine phosphokinase is also released during muscle injury. A level in excess of 10,000 units/L is associated with an increased risk of kidney injury.
o Preventative strategies include:
§ Maintenance of renal blood flow and tubular flow with IV hydration
§ Osmotic diuresis with mannitol
§ UOP should be kept > 100 – 150 mL/hr
§ Sodium bicarbonate and/or acetazolamide to alkalize the urine.
o Hemolysis from a hemolytic reaction is treated in the same way.
o Sevoflurane
o There are 2 ways that sevoflurane can theoretically impair renal function. Before we go any further, however, we’d like to point out that there
is no solid human data that supports these concerns.
o Compound A (Produced in the Breathing Circuit):
§ Compound A is produced when sevoflurane is exposed to soda lime.
§ The FDA says that a minimum FGF of 1 L/min is safe for up to 2 MAC hours.
§ Example: 2% x 2 hours or 1 % x 4 hours
§ After 2 MAC hours have elapsed, the minimum FGF is 2 L/min
§ The rate of compound A production is increased by: low FGF, high sevo vol%, warm soda lime, and increased CO2 prodution.
o Free Fluoride Ions (Produced in the Liver):
§ ~5% of sevoflurane is metabolized by the liver.
§ Hepatic metabolism liberates inorganic fluoride ions.
§ Inorganic fluoride ions are nephrotoxic; they impair the concentrating mechanism in the renal tubules.
§ Previous research with methyoxyflurane concluded that the risk of nephrotoxicity was increased when [Fl-] exceeded 50 µM/L. This
does not seem to be the case with sevoflurane.
o Aminoglycosides (Gentamycin, Tobramycin, and Amikacin)
o These drugs are polycationic compounds that bind to the anionic brush boarder in the proximal tubules. They are transported into the cytosol where
they induce free radical damage.
o Risk of AKI is reduced with intravenous fluids, correction of correctable risk factors, and close monitoring of serum trough levels.
o Other Antibiotics
o Amphotericin B
o Vancomycin
o Sulfonamide
o Tetracyclines
o Cephalosporins
o NSAIDs
o The nephrotoxic action of NSAIDs have been addressed previously.
o Calcineurin Inhibitors (Cyclosporins and Tacrolimus)
o These are immunosuppressant agents used to prevent rejection of transplanted organs. Side effects include hypertension and renal
vasoconstriction.
o Sirolimus is a non-calcineurin inhibitor that carries a much lower risk of nephrotoxicity.

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LIVER

o Hepatic Anatomy
o Overview
§ The liver is the largest internal organ.
th th
§ It extends from the 7 to the 11 rib at the right midaxillary line.
§ It receives SNS innervation from T3-T11.
§ It functions as a blood reservoir.
o Functional Unit
§ The liver’s functional unit is the lobule (otherwise known as the
acinus).
• The lobules contain hepatocytes that are organized as thin
plates that are circumferentially positioned around a
central vein.
• There are 50,000 to 100,000 lobules in the liver.

§ Blood from the terminal branches of the hepatic artery and portal vein enter at the periphery of the lobule. Because
of this, cells in zone 1 (near the periphery) are well oxygenated. Cells in zone 3 (near the central vein) receive the least
amount of oxygen, and are therefore most susceptible to hypoxic injury. And as luck would have it, cells in zone 3
have the highest concentration of CYP450 enzymes.
o Kupffer Cells
§ Since portal vein blood drains the intestine, the liver receives a significant bacterial load. Kupffer cells (part of the
reticuloendothelial system) remove the bacteria before the blood drains into the vena cava.
o Bile
§ Bile is produced by the hepatocytes.
§ The canaliculi drain bile into the bile duct.
§ The bile ducts converge to form the common hepatic duct.
§ The cystic duct (from the gallbladder) and the pancreatic duct join the common hepatic duct before it empties into
the duodenum. The sphincter of Oddi controls the flow of bile released from the common hepatic duct.
§ Contraction of the sphincter of Oddi (narcotics) increases biliary pressure.
o Lymphatic Drainage
§ Lymph and proteins drain into the space of Disse (between the hepatocyte and the sinusoid) before they empty into
the lymphatic duct.
§ The liver is responsible for about half of the lymph production in the body.

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o Hepatic Blood Flow
o The liver receives ~ 30% of the cardiac output (1500 mL)
o The liver is supplied by 2 vessels: portal vein & hepatic artery
§ 1. Aorta à Splanchnic organs àPortal vein àliver
§ 2. Aorta à Hepatic artery à Liver
o Portal Vein Supplies:
§ 75% of liver blood flow
§ 50% of oxygen content (lower O2 saturation)
o Hepatic Artery Supplies:
§ 25% of liver blood flow
§ 50% of oxygen content (higher O2 saturation)

o Hepatic Venous Flow

§ The portal vein receives venous blood that has passed through the
splanchnic circulation.

o Hepatic Arterial Flow

Hepatic Artery Perfusion Pressure = MAP – Hepatic Vein Pressure
§ Hepatic arterial buffer response: This is a fancy way of saying that a reduction in portal vein flow is compensated by an increased
hepatic artery flow.
• This response is mediated by adenosine.
• Severe liver disease impairs this response.
o Effects of Anesthesia
§ General anesthesia as well as neuraxial anesthesia reduce liver blood flow as a function of decreased MAP. Induction of general
anesthesia can reduce hepatic blood flow by 30-50%.
o Liver Functions
o Understanding normal function helps you predict the consequences of liver dysfunction. Just about all the liver’s physiologic
functions can be grossly divided into 2 major categories: synthesis and metabolism.
o 1. Synthetic Function
§ since the hepatocytes produce so many proteins, it’s easier to learn what they do NOT produce. We’ll list each
compound and tell you where in the body it’s produced. After this, we’ll detail a few key proteins produced by the
liver.

§ Proteins Involved in Hemostasis

• Procoagulants
o The liver produces all the protein coagulation factors not listed in the table above. Factor IV is Ca+2 and
obviously not a protein.
o Vitamin K is required to synthesize factors II, VII, IX, and X, and absorption of vitamin K is dependent on the
presence of bile in the gut.
• Anticoagulants
o Antithrombin
o Proteins S, C, Z (these are also vitamin K dependent)
• Fibrinolytics
o Plasminogen
• Thrombopoietin
o Stimulates platelet production

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 § Plasma Proteins
• The liver produces all the plasma proteins except for immunoglobins (gamma globulins).
o Albumin is a reservoir for acidic drugs.
o Alpha-1 acid glycoprotein is a reservoir for basic drugs.
o When hepatic protein synthesis is impaired, drugs that bind to these proteins will have a higher Vd.
o Impaired plasma protein synthesis reduces vascular oncotic pressure.
§ Pseudochlinesterase
• Reduced psuedocholinesterase production increases the duration of succinylcholine and possibly increases the duration
of ester-type local anesthetics. This is only a problem with severe liver disease.
o 2. Metabolic Function
§ Carbohydrates
• The liver is an important regulator of serum glucose. It also clears insulin from the circulation. Therefore, patients with
liver failure are at risk of hypoglycemia.

§ Proteins
• Amino acid deamination allows the body to convert proteins to carbohydrates and fats. Some of these are utilized in
Krebs cycle to produce ATP.
• The deamination process produces a large quantity of ammonia. The liver converts ammonia to urea, which is eliminated
by the kidney.
• Failure to clear ammonia (hepatic failure or portosystemic shunting) leads to hepatic encephalopathy.
§ Lipids
• Energy storage in the form of triglycerides (glycerol + 3 fatty acid molecules).
• Energy release by beta-oxidation of fatty acids (used in Krebs cycle).
• Synthesis of cholesterol, phospholipids, and lipoproteins.
§ Bilirubin
• The erythrocyte’s life cycle is 120 days. Aged RBCs are processed by the reticuloendothelial cells in the spleen.
• In the spleen: Hemoglobin àheme àunconjugated bilirubin (this compound is neurotoxic).
• Unconjugated bilirubin is lipophilic. It’s transported to the liver bound to albumin.
• The liver conjugates bilirubin with glucuronic acid. This increases its water solubility.
• Conjugated bilirubin is excreted into the bile, metabolized by intestinal bacteria, and eliminated in the stool.
§ Drugs
• Refer to the pharmacokinetics tutorial.
o Liver Function Tests
o Things can get confusing here in a hurry, so we’re going to reduce this to the essentials that you’ll need to reason your way
through questions on the NCE.
Liver Function Tests Normal Values Comments
Synthetic Function
PT 12-14 sec • very sensitive for acute injury (V and VII t1/2 is <24 hours)
• prolonged by vitamin K deficiency

• Not sensitive for acute injury (t1/2 is 21 days)

Albumin 3.5-5.0 g/dL
• Poor specific for liver disease
• Decreased by impaired synthesis or increased consumption/loss
• Conditions that reduce albumin include: infection, nephrotic
syndrome, malnutrition, malignancy, and burns
Hepatocellular Injury
AST 10-40 units/L • Marked elevation of both suggests hepatitis
ALT 10-55 units/L • AST/ALT ratio > 2 suggests cirrhosis or alcoholic liver disease
Hepatic Clearance
Bilirubin 0-11 units/L • Confounding factors: hemolysis or hematoma reabsorption
Biliary Duct Obstruction
Alkaline phosphatase 45-115 units/L • AP is not very specific (it’s also in bone, placenta, and tumors)
Y Glutamyl transpeptidase 0-20 units/L • GGTP is more sensitive than AP (it’s not present in bone)
5’-Nucleotidase 0-11 units/L • 5’-NT is the most specific indicator of biliary duct obstruction

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 • when there is a bile duct obstruction, these enzymes spill into the
systemic circulation.
o Now that we know the key facts about each test, we need to see how these change during liver disease. We can categorize the
primary causes of liver disease based on the location of the problem: before the liver, in the liver, or after the liver.

o Hepatitis
o Hepatitis is another way of saying liver inflammation. It is associated with hepatocellular injury with variable degrees of
necrosis.
§ Hepatitis can be acute or chronic.
§ It is the most common cause of liver cancer and the most common indication for liver transplantation.
§ Etiologies include viruses, hepatotoxins, and autoimmune response.
o Viral Hepatitis
§ In the United States, hepatitis is most commonly caused by one of the 4 hepatitis viruses: A, B, C, and D.
• Hepatitis E is very uncommon in the US.
• Other viral etiologies include herpes simplex, CMV, and Epstein-Barr
§ Viral hepatitis is usually silent for 1-2 weeks following infection. After this time, s/sx include fever, malaise, n/v, and
jaundice. These symptoms generally last 2-12 weeks. Hepatitis B and C may have a more complex and less predictable
clinical progression.

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 o Drug-Induced Hepatitis
§ Drug-induced hepatitis is usually associated with a late onset. It typically presents 2-6 weeks after the insult, however it can be as
long as 6 months. It is clinically indistinguishable from viral hepatitis, so laboratory analysis is required. While there is a long list of
hepatotoxic drugs, we want you to be familiar with 3: acetaminophen, halothane, and alcohol.
§ Acetaminophen
• Glutathione is a substrate for many phase 2 conjugation reactions. It increases a substance’s water solubility, so that the
substance can be excreted in the bile or by the kidney.
• Acetaminophen produces a toxic metabolite called N-acetyl-p-benzoquinoneimine (NAPQI).
• With normal acetaminophen dosing. NAPQI is conjugated with glutathione. The conjugated metabolite is not toxic.
• Acetaminophen overdose consumes the liver’s supply of glutathione.
• Since the conjugation substrate isn’t available, the concentration of NAPQI rises, and this leads to hepatocellular injury.
• Treatment consists of oral N-acetylcysteine within 8 hours of acetaminophen overdose.
§ Halothane
• The liver metabolizes desflurane, isoflurane, and halothane to inorganic fluoride ions and trifluoroacetic acid (TFA).
• Up to 40% of halothane is metabolized in this way, so it makes sense that halothane metabolism produces a significant quantity
of TFA>
• By comparison, 0.02% of desflurane and 0.2% of isoflurane are metabolized. These drugs produce miniscule quantities of TFA<
however there is a theoretical risk that they can cause hepatitis, particularly in sensitized patients. Sevoflurane does not produce
TFA>
• Halothane hepatitis is believed to be the result of an immune mediated reaction caused by TFA.
• Risk factors include:
o Age > 40
o Female gender
o Greater than 2 exposures
o Genetics
o Obesity
o CYP2E1 induction (alcohol, isoniazid, phenobarbital)
§ Alcohol
• Alcohol is the most common type of drug-induced hepatitis.
• It impairs fatty acid metabolism, which causes fat accumulation in the liver. This leads to hepatomegaly.
o Chronic Hepatitis
§ Hepatic inflammation that exceeds 6 months. It leads to the progressive destruction of the hepatic parenchyma, cirrhosis, and ultimately liver
failure.
• Most common cause = alcoholism
• Second most common cause = hepatitis C
• Diagnosis: increased liver enzymes and bilirubin + histologic evidence of liver inflammation
• s/sx: jaundice, fatigue, thrombocytopenia, glomerulonephritis, neuropathy, arthritis, and myocarditis.
• PT is prolonged and albumin is decreased.
o Anesthetic Considerations for Hepatitis and Alcohol Abuse
o Your primary objectives are to preserve hepatic blood flow and avoid drugs that can potentiate hepatocellular injury. Some patients may be sensitive to
the CNS effects of anesthetic drugs, while alcoholics experience a higher tolerance.
§ If acute hepatitis: Non-emergent surgery should be postponed until symptoms have resolved and liver function tests return to normal.
§ If chronic hepatitis: the patient may proceed to surgery so long as the condition is stable.
o Anesthetic Considerations for Acute Hepatitis
§ Maintain Hepatic Blood Flow
• Use isoflurane (preserves hepatic blood flow the best)
• Avoid halothane (we know you don’t have it in the OR, but know that you shouldn’t use it)
• Avoid PEEP (increases resistance to hepatic drainage)
• Ensure normocapnia
• Liberal use of IV fluids
• Regional anesthesia is ok if there are no coagulation defects
§ Avoid Hepatotoxic Drugs or those that inhibit CYP450
• Acetaminophen
• halothane
• amiodarone
• antibiotics: PCN, tetracycline, and sulfonamides
§ Carefully Monitor the Neuromuscular Junction
• Decreased Pseudocholinesterase activity (succinylcholine)
• Decreased biliary excretion (rocuronium)
• Larger volume of distribution
o Anesthetic Considerations for Alcoholism
§ Anesthetic Requirement
• MAC is decreased in the acutely intoxicated patient.
• AMC is increased in the chronic alcohol abuser that is not intoxicated.
• Alcohol potentiates GABA. There is an increased effect of benzodiazepines.
• Alcohol inhibits NMDA receptors
§ Aspiration Risk
• Alcohol impairs pharyngeal reflexes
• Acute intoxication is considered a full stomach

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o Alcohol Withdrawal Syndrome
o Alcohol abuse creates a state of dependency. Signs and symptoms of withdrawal begin 6-8 hrs after the blood alcohol
concentration returns to near normal and peaks at 24-36 hours.
§ Early s/sx: tremors and disordered perception (hallucinations, nightmares)
§ Late s/sx: increased SNS activity (tachycardia, hypertension, dysrhythmias), N/V, insomnia, confusion, agitation.
§ Treatment: alcohol, beta-blockers, alpha-2 agonists.
o Delirium tremens occurs after 2-4 days without alcohol.
§ s/sx: grand mal seizures, tachycardia, hyper- or hypotension, and combativeness
§ treatment: diazepam (or other benzo) and beta-blockers
o other considerations include:
§ alcoholics are often deficient in vitamin B1 (thiamine). Wernicke-Korsakoff syndrome is characterized by a loss of
neurons in the cerebellum, and this is brought on by thiamine deficiency.
§ Disulfiram is a treatment used for alcoholics in recovery.
• It is hepatotoxic.
• It also inhibits dopamine beta-hydroxylase (NE synthesis) à hypotension
o Cirrhosis
o While there are many etiologies that lead to cirrhosis, we think you should at least know these.

o Cirrhosis is characterized by cell death, where healthy hepatic tissue is replaced by nodules and fibrotic tissue. This reduces the
number of functional hepatocytes as well as the number of sinusoids.

§ As the number of hepatocyte dwindles, so dose the liver’s ability to perform all its essential functions.
§ The number of blood vessels, passing through the liver is reduced, which increases hepatic vascular resistance (portal
hypertension)
§ To partially offset the increased resistance, the body creates collateral vessels that bypass the liver; these are called
portosystemic shunts.
§ Since this blood bypasses the liver, drugs and toxins (ammonia) remain in the systemic circulation for a longer period
of time.
o Assessment of Perioperative Risk
§ End-stage liver disease exists when the liver is unable to carry out its synthetic, metabolic, and clearance functions.
There are two scoring systems you should understand.
§ Model of End-Stage liver Disease (MELD):
• The MELD score uses a logarithmic calculation that examines 3 factors of hepatic function: bilirubin, INR,
and serum creatinine.
o Low risk= < 10
o Intermediate risk = 10-15
o High risk = > 15
§ Child-Pugh Score:
• The modified Child-Pugh score examines 5 factors of hepatic function: albumin, PT, bilirubin, ascites, and
encephalopathy
o Class A (5-6 points) = 10% risk of perioperative mortality
o Class B (7-9 points)= 30% risk of perioperative mortality
o Class C (10-15 points) = 80% risk of perioperative mortality
• If a patient with class A or B disease is otherwise optimized, it is reasonable to proceed with surgery. A
patient with class C disease should be managed medically until hepatic function improves.

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o Pathophysiology
§ We’re going to give you a laundry list of the key physiologic changes that accompany liver dysfunction. It’s a lot of
stuff, but it’s important, so study up!

o TiPS Procedure
§ the TIPS procedure (transjugular intrahepatic portosystemic shunt) bypasses a
portion of the hepatic circulation by shunting blood from the portal vein
(hepatic inflow vessel) to the hepatic vein (hepatic outflow vessel).
§ This reduces portal pressure and minimizes back pressure on the splanchnic
organs. In turn, it reduces the likelihood of bleeding from esophageal varices
and reduces the amount of ascites. It is also temporary treatment for
hepatorenal syndrome.
§ Hemorrhage is a significant risk during the TIPS procedure.
o Anesthetic Considerations
§ In addition to understanding the implications of the table above, you may wish
to revisit the management of acute hepatitis, as they are the same.

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o Biliary Function
o Relevant Anatomy
§ Knowing how bile and pancreatic enzymes flow from their sites of
production towards the small intestine should help your understanding of
biliary disease.
o Bile is…
§ Produced by hepatocytes
§ Stored in the gallbladder
§ Released into the duodenum through the ampulla of Vater
o Bile has 3 Key Functions
§ 1. Absorption of fat and fat soluble vitamins (DAKE). How does this affect
clotting?
§ 2. Excretory pathway for bilirubin and products of metabolism
§ 3. Alkalization of the duodenum
o Bile Release
§ Cholecystokinin (CCK) stimulates gallbladder contraction, and this increases the flow of bile into the duodenum.
o Gallbladder Pathophysiology
§ The most common gallbladder diseases are the result of obstruction or inflammation.
§ Biliary stones can cause an obstructive defect that impedes the flow of bile as well as pancreatic enzymes. If these
substances can’t move into the small intestine, they backup into the liver and the pancreas.
• Obstruction of cystic ductàgallbladder distension, edema, risk of perforation, and jaundice
• Obstruction of common bile duct à cholecystitis, jaundice, pancreatitis, and peritonitis

§ The incidence of gallstones increases with obesity, aging, rapid weight loss, pregnancy, and women > men.
§ Remember the 3 F’s: fat, female, and 40.
§ Signs & Symptoms: Leukocytosis, fever, and RUQ pain. Pain is worse with inspiration (Murphy’s sign)
§ Biliary pathologyà increased alkaline phosphatase, increased conjugated bilirubin, increased amylase, increased Y
Glutamyl transpeptidase, and increased 5’nucleotidase
§ Prolonged NPO status increases the likelihood of gallstone formation (the lack of CCK release contributes to biliary
stasis).
o Anesthetic Considerations for Cholecystectomy
§ Usually laparoscopic
§ Open approach involves a right upper abdominal incision à decreased lung volumes and increased pain
§ Avoid N2O d/t bowel distension (this takes hours). N2O also supports combustion (is the surgeon using an
electrocautery?).
§ If liver dysfunction, select a Benzylisoquinolinium NMB (cisatracurium or atracurium).
§ Opioids can precipitate spasm of the sphincter of Oddi. This is a problem if it causes a false-positive during a
cholangiogram. This is one area where the texts conflict with real world practice. We’ve never withheld narcotics for
this reason.
§ You can relax the sphincter of Oddi with: glucagon, naloxone, or nitroglycerin. Glycopyrrolate and atropine may help
as well.
§ Using naloxone in a surgical patient is a poor choice.
§ Glucagon increase the risk of PONV.

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ENDOCRINE

o Overview: Structure & Function

o There are 2 major systems that maintain homeostasis: the nervous system and the endocrine system.
o These systems work in concert to optimize physiologic function.

o Just like neurotransmitters, endocrine hormones act as first messengers that bind to a receptor and instruct a specific cell type
to carry out a function. These receptors can include:
§ Ion channels
§ G-proteins
§ Enzymes
§ Gene activation
o Feedback Loops
o Feedback loops are central to your understanding of endocrine function and disease.

o Hypothalamic-Pituitary Axis
o Hypothalamus
§ The hypothalamus links the central nervous system to the endocrine system. It does this by monitoring the hormone
concentrations in the systemic circulation, and then influencing hormone output from the pituitary gland. It’s able to
do this because the hypothalamus resides outside of the blood brain barrier.
• If hormone concentration rises, the hypothalamus instructs the pituitary gland to decrease the output of
that hormone.
• If hormone concentration falls, the hypothalamus instructs the pituitary gland to increase the output of the
hormone.
§ The hypothalamus communicates with the posterior pituitary gland through a series of neural connections (we will
discuss this shortly), and it communicates with the anterior pituitary gland with a group of releasing and inhibiting
hormones.

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 § Since ADH and oxytocin are synthesized in the hypothalamus, there is no need for the hypothalamus to produce
releasing and inhibiting hormones for them.
o Pituitary Gland
§ The pituitary gland resides in the sells turcica, and it is connected to the hypothalamus by the pituitary stalk.
• The anterior pituitary gland is also called the adenohypophysis.
• The posterior pituitary gland is also called the neurohypophysis.
§ You’ll need to know what each hormone does as well as the disease that results from hyper- or hyposecretion.

• Mnemonic: the anterior pituitary gland releases 6 hormones. Remember them with FLAT PiG (ignore the
letter “I”)
§ Systemic Hormones Involved in Hypothalamic Negative Feedback Systems
• These include:
o Triiodothyronine (T3) regulates TRH release.
o Cortisol regulates CRH release
o Testosterone, estrogen, and progesterone regulates LHRH release
o Growth hormone and insulin growth factor- 1 regulate GHRH and GHIH release.
§ Hormones NOT Involved with Negative Feedback
• Oxytocin is unique in that it is part of a positive feedback loop. Uterine contraction increases oxytocin
release, which then stimulates more intense uterine contraction and additional oxytocin release.
• Prolactin output is under neural control, where increased dopamine decreases prolactin release. This
explains why DA antagonists (metoclopramide) cause hyperprolactinaemia.

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o Pituitary Disorders
o Disorders of ADH Secretion
§ Syndrome of inappropriate ADH secretion (SIADH)= too much ADH
§ Diabetes insipidus= too little ADH

o Acromegaly
§ Growth hormone (somatotropin) facilitates growth of all the tissues in the body.
• Acromegaly results form over secretion of growth hormone after adolescence.
• Nearly all cases are caused by pituitary adenoma.
• Increased GH output before puberty causes gigantism.
§ Key Points:
• Distorted facial features (difficult mask)
• Large tongue, teeth, and epiglottis (difficult laryngoscopy)
• Subglottic narrowing and vocal cord enlargement (difficult ett placement- use a smaller tube)
• Turbinate enlargement (risk of epistaxis – avoid nasal intubation if possible)
• OSA is common
• Increased risk of HTN, CAD, and rhythm disturbances
• Glucose intolerance
• Skeletal muscle weakness
• Entrapment neuropathies are common
o Thyroid Anatomy & Physiology
o Anatomy
§ The thyroid gland is made up of a left and right lobe that are joined by the
thyroid isthmus.
§ The thyroid gland resides:
• Anterior to the trachea
• Inferior to the cricoid cartilage
• Superior to the suprasternal notch
§ The recurrent laryngeal nerve courses along the lateral border of each thyroid
lobe. This explains why the RLN is susceptible to injury during thyroid surgery.
o Physiology
§ The thyroid gland stores and secretes 3 hormones:
• 1. T4=Thyroxine (a prohormone synthesized from tyrosine)
• 2. T3= Triiodothyronine (active thyroid
hormone)
• 3. Calcitonin
o Differences Between T4 and T3

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 o Production and Release of Thyroid Hormones
§ Thyroid stimulating hormone is released from the anterior pituitary gland. It affects the thyroid gland in 2 key ways:
• 1. It tells the thyroid gland to produce T3 and T4 (this requires iodine).
• 2. It tells the follicular tissue to produce thyroglobulin colloid (this does not require iodine).

o The Importance of Iodine

§ TSH stimulates the iodide pump. Iodine is a substrate that the thyroid requires a synthesize triiodothyronine (T3) and
thyroxine (T4). When iodine is not available (dietary deficiency), the thyroid is unable to produce a sufficient quantity
of T3 and T4.
§ Under normal conditions, there is a negative feedback loop where T3 and T4 suppress TSH release. In the patient with
a hypoactive thyroid, there isn’t enough thyroid hormone to suppress TSH, so TSH remains chronically elevated. This
presents a problem.
o How Does This Cause a Goiter?
§ Remember that we said TSH stimulates the follicles to make thyroglobulin colloid and that this does not require
iodine? Well since TSH is chronically elevated, the follicles continue to produce thyroglobulin colloid, and this causes
the thyroid gland to increase in size. This is the cause of endemic goiter.
o Thyroid Hormone Physiology
o You can think of thyroid hormone as an “on switch” that stimulates many metabolic functions.
o Most of these are easy to predict if you can remember: increased thyroid àincreased BMR à increased Oxygen Consumption
+ Increased CO2 Production

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 o Too Much and Too Little
§ If you understand the chart that you just read, then most of the signs and symptoms of hyper-and hypothyroidism
should make sense. The rest you’re just going to have to commit to memory.
Hyperthyroidism Hypothyroidism
Etiologies Most Common: Grave’s disease (autoimmune) Most common: Hashimoto’s thyroiditis (autoimmune)
Myasthenia gravis (autoimmune) Iodine deficiency
Multinodular goiter Hypothalamic- pituitary dysfunction
Carcinoma Neck radiation
Pregnancy thyroidectomy
Pituitary adenoma
Amiodarone
Diagnosis Low TSH + High T3 and T4 High TSH + Low T3 and T4
Cardiac Hypertension Peripheral vasoconstriction
Tachyarrhythmias Decreased heart rate
Atrial fibrillation Decreased contractility
Heart failure
Pericardial effusion
Pulmonary Increased minute ventilation Decreased minute ventilation
Reduced response to hypoxia
Reduced response to hypercarbia
Pleural effusion
General Findings Goiter Goiter
Weight loss Weight gain
Muscle weakness Muscle fatigue/lethargy
Moist and warm skin Dry and thick skin
Heat intolerance Cold intolerance
Fine hair Dry brittle hair
Diarrhea Constipation
Tremor Delayed gastric emptying
Exophthalmos (increased retrobulbar fat) Large tongue
Hypercalcemia (increased bone turnover)

o Related Conditions
§ Thyroid Storm
• A surgery in thyroid activity that can occur in hyper-and euthyroid patients, particularly during times of stress. This is
most common time for this to occur perioperatively is 6-18 hours after surgery.
§ Myxedema coma
• Occurs with end-stage hypothyroidism. Coma is a consequence (not a cause) of severely impaired thyroid function.
§ Cretinism
• Neonatal hypothyroidism that leads to physical and mental retardation.
o Hyperthyroidism: Anesthetic Considerations
o Medical Management
Drugs Mechanism of Action Key Points
Thionamides Inhibits thyroid synthesis by blocking Requires 6-7 weeks to achieve a
Propylthiouracil (PTU) iodine addition to the tyrosine residues euthyroid state.
Methimazole on thyroglobulin.
Carbimazole These drugs are only available PO. If
PTU also inhibits peripheral conversion given intraoperatively for thyroid storm,
of T4 to T3. they can be crushed and administered by
NGT.

Serious side effects:

Hepatitis
Agranulocytosis
Beta Blockers Reduces SNS sitmulation Esmolol is easier to tirate
Propranolol Inhibits peripheral conversion of T4 to
Esmolol T3.
Potassium Iodide Reduces thyroid hormone synthesis and Administer 10 days before surgery
release.
Radioactive Iodine Destroys thyroid tissue May cause hypothyroidism.
Contraindications:
Pregnancy
Breast feeding mothers

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 o Surgical Management
§ Subtotal or total thyroidectomy can be used to control hyperthyroidism. Complications include: hypothyroidism,
hemorrhage (tracheal compression), recurrent laryngeal nerve injury, and hypocalcemia.
o Anesthetic Considerations
§ Do NOT proceed to elective surgery until the patient is euthyroid. Successful medical management may require upwards of 6-8
weeks.
§ Emergency surgery warrants administration of a beta-blocker, potassium iodide, glucocorticoid, and PTU.
§ A goiter can cause tracheal deviation or tracheomalacia.
§ On the boards, goiter=awake intubation. The next best response is a technique that maintains spontaneous ventilation.
§ Avoid sympathomimetics, anticholinergics, ketamine, and pancuronium.
§ Not that you can find it in the US, but you should still know that thiopental reduces the peripheral conversion of T4 to T3.
§ Exophthalmos increases risk of corneal abrasion.
§ Titrate NMBs carefully – increased incidence of myasthenia gravis and myopathy.
§ Hypoxia and hypercarbia stimulate the SNS>
§ Careful with positioning. Increased bone turnover increases the risk of osteoporosis.
o Thyroid Storm
§ Thyroid storm is a medical emergency that can occur in hyperthyroid AND euthyroid patients.
• It is generally brought on by stressful events: infection, surgery, etc.
• It most commonly occurs 6-18 hours after surgery.
§ Management
• Remember the 4 B’s when treating the patient with thyroid storm.
• The best agents for perioperative use are bolded.
o Block synthesis (Methimazole, carbimazole, PTU, potassium
iodide)
o Block release (radioactive iodine, potassium iodide)
o Block T4 to T3 conversion (PTU, propranolol)
o Beta blocker (propranolol, esmolol)
• Other treatments:
o Cardiopulmonary support
o Glucocorticoids (hypermetabolism, consumes endogenous
steroids)
o Active cooling measures (cold IVF, ice packs)
o Acetaminophen for fever
o Don’t give aspirin, as it can dislodge T4 from plasma proteins à increased free fraction of T4
àmakes a bad situation worse
o Surgical Complications
o Recurrent Laryngeal Nerve Injury
§ The RLN innervates all the intrinsic laryngeal muscles except for the cricothyroid muscle (innervated by the SLN). Injury to the RLN
can cause airway obstruction.
• Unilateral injuryàipsilateral vocal cord is positioned midline on inspiration àhoarseness
• Bilateral injury àboth cords are positioned midline on inspiration àairway obstruction
• Have the patient say the letter “E” or “moon” to assess for nerve injury
• A NIM endotracheal tube provides the ability to assess RLN integrity intraoperatively. When the electrodes on the tube
are positioned between the vocal cords, a current can be applied to assess RLN function.
• At the end of the procedure, direct laryngoscopy can be used to assess vocal cord function as well as help identify glottis
edema.
o Hypocalcemia
§ Resection of parathyroid glands (without reimplantation)àhypocalcemia at least 6-12 hours after surgery. Most s/sx of
hypocalcemia are the result of increased nerve and muscle irritability.
• Muscle spasm àtetany
• Laryngospasm
• Mental status changes
• Hypotension
• Prolonged QT interval
• Paresthesias
• Chvostek’s and Trousseau’s signs
§ Chvostek’s Sign
• Tapping on the angle of the jaw (facial nerve/masseter muscle)àfacial contraction on ipsilateral side.
§ Trousseau’s Sign
• An upper extremity BP cuff is inflated above SBP for 3 min
• Decreased blood flow accentuates neuromuscular irritability àmuscle spasm of the hand and forearm
§ Treatment
• IV calcium
o When compared to calcium chloride, calcium gluconate provides less elemental calcium, however it carries a
lower risk of necrosis if infiltration occurs.

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o Hypothyroidism: Anesthetic Considerations
o Medical Management
§ Thyroid hormone is replaced with synthetic T4 (levothyroxine).
§ The initial response to therapy is natriuresis and decreased TSH.
o Anesthetic Management
§ Severe hypothyroidism (myxedema) is an indication to cancel surgery.
§ Mild to moderate hypothyroidism is acceptable for elective surgeries.
§ Airway obstruction due to large tongue, swollen vocal cords, and/or goiter.
§ Again, if you are asked about airway management for the patient with a goiter, the correct response will be awake
intubation. The next best response is a technique that maintains spontaneous ventilation.
§ Delayed gastric emptying à increased risk of aspiration.
§ Hypodynamic circulation à decreased HR, decreased SV, decreased contractility, decreased CO and decreased
baroreceptor responsiveness (increased risk of hypotension with anesthesia).
§ Inhalation induction is faster!
§ MAC is unchanged (just like hyperthyroidism).
§ Hemodynamic support is best provided with sympathomimetics that improve myocardial performance (not
phenylephrine).
§ Decreased adrenal function is common. Hypotension unresponsive to catecholamines can be treated with
corticosteroids.
§ Slowed hepatic metabolism and renal excretion.
§ Lethargic patients are very sensitive to the effects of anesthetic drugs.
§ Muscle weaknessà increased sensitivity to non-depolarizing NMBs
§ D5NS provides glucose and combats hyponatremia due to impaired clearance of free water.
o Adrenal Physiology
o The adrenal gland is divided into the cortex and the medulla
o Adrenal Cortex
§ The cortex has 3 zones that synthesize and release:
• 1. Mineralocorticoids (aldosterone)
• 2. Glucocorticoids (cortisol)
• 3. Androgens (dehydroepiandrosterone)
• *these are derived form a cholesterol precursor
§ Mnemonic
• Notice that the cortical layers (outside to inside)
spell GFR. Remember what each one release with :
“salt, sugar, sex”
o Adrenal Medulla
§ The medulla synthesizes and releases 2 catecholamines:
• 1. Epinephrine
• 2. Norepinephrine
§ let’s detail the key functions of mineralocorticoids and glucocorticoids. Since androgens are of little significance to
boards, we’re not going to address them. This is a long page, so hang in there…
o Aldosterone (Mineralocorticoid)
§ Here’s a brief review of the renin-angiotensin-
aldosterone system
§ Regulation of Aldosterone Secretion
• Aldosterone release is increased by:
o RAAS activation
o Hyperkalemia
o Hyponatremia
• ACTH only has minor influence on
aldosterone release
o This explains why decreased
ACTH does not cause
hypoaldosteronism.
§ Aldosterone: Physiologic Effects
• Aldosterone enhances sodium
reabsorption in exchange for potassium and hydrogen ions. The net effect is fluid retention and expansion of the
extracellular space, with a reduction in serum potassium concentration and metabolic alkalosis.
• Aldosterone regulates intravascular volume. It does NOT regulates sodium concentration or osmolarity. Here’s why:
o When sodium is reabsorbed into the peritubular capillaries, water follows in direct proportion. The sodium
concentration does not change.
o Osmolarity (and therefore sodium concentration) is controlled by antidiuretic hormone (ADH).
o ADH increases the reabsorption of water but NOT sodium. Therefore, increased water reabsorption dilutes
sodium and reduced water reabsorption concentrates sodium.

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 § Cortisol: Physiologic Effects
• Cortisol does not interact with membrane bound receptors. Instead, it diffuses through the lipid bilayer then binds with intracellular steroid
receptors. By activating or inhibiting DNA transcription, cortisol influences
protein synthesis inside the target cell. These processes require time,
which explains the relatively slow onset of steroid medications.
• Cortisol production is 15-30 mg/day, with a normal serum level of 12
mcg/dL
• Stress can increase cortisol production upwards of 100 mg/day, with a
serum level up to 30-50 mcg/dL during and after major surgery.
• Energy Mobilization
o Gluconeogenesis (amino acids are converted to glucose by the
liver) à increased blood sugar
o Protein catabolism (mainly muscle breakdown) à increased
amino acid availability to liver for gluconeogenesis
o Fatty acid mobilization à increased FFA oxidationà increased
ability to use fat for energy instead of glucose
• Anti-Inflammatory Effects
o Cortisol mitigates the inflammatory cascade by stabilizing lysosomal membranes and reducing cytokine release.
§ It decreases the number of eosinophils and lymphocytes in the blood.
§ Cortisol does NTO reduce histamine release during an antigen-antibody response
§ This is accomplished by epinephrine at the beta-2 receptor on mast cells and basophils
• Response to Catecholamines
o Cortisol improves myocardial performance by increasing the number and sensitivity of beta receptors on the myocardium. Cortisol is
also required for the vasculature to respond to the vasoconstrictive effects of catecholamines.
o Steroids: Comparative Pharmacology
o Memorizing the specific of this table is a low-yield strategy. You would be better served by learning what makes each drug unique. Note that
cortisol is the reference drug, and that it has equal glucocorticoid and mineralocorticoid effects. Also, pay attention to the equivalent doses.

o Prednisone is an analogue of cortisol. Because of this, it’s a good choice for adrenocortical insufficiency (Addison’s disease).
o Aldosterone does NOT have glucocorticoid effects.
o Dexamethasone, betamethasone, and triamcinolone do NOT have mineralocorticoid effects.
o Triamcinolone is commonly administered in the epidural space to treat lumbar disc disease. This drug is unique, because it is associated with a
higher incidence of skeletal muscle weakness. Its also more likely to cause sedation (not euphoria) and anorexia (not increased appetite).
o Mineralcorticoid Excess: Conn’s Syndrome
o Etiology
§ Primary Hyperaldosteronism
• Increased aldosterone release from adrenal gland (renin activity is normal)
• Causes: aldosteronoma, pheochromocytoma, primary hyperthyroidism
§ Secondary Hyperaldosteronism
• Increased aldosterone stimulus from extra-adrenal location (renin activity is usually increased)
• Causes: renovascular hypertension
§ Long-term licorice ingestion (glycrrhizic acid) causes a syndrome that highly resembles hyperaldosteronism
o Clinical Features
§ Hypertension (Na+ and water retention)
§ Hypokalemia (K+ wasting)
§ Metabolic alkalosis (H+ wasting)
o Treatment
§ Removal of aldosterone secreting tumor
§ Aldosterone antagonists – spironolactone or eplerenone
§ Potassium supplementation
§ Na+ restriction
o Anesthetic Implications
§ Hypokalemia
• Muscle weakness/cramping
• Increased sensitivity to non-depolarizing NMBs
• U wave on EKG
• Avoid hyperventilation (activation of H+/K+ pump)
§ Hypertension
• Caution volume overload

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 o Cushing’s Syndrome
o Cushing’s syndrome is the result of cortisol excess either from overproduction or
exogenous administration. As a point of semantics, Cushing’s disease is the result
of excess ACTH.
o Recall that cortisol has glucocorticoid, mineralocorticoid, and androgenic effects,
so you should expect the patient with Cushing’s syndrome to have signs and
symptoms reflecting all of these.

Key Points
Etiology ACTH Dependent:
• Increased ACTH stimulates cortisol release
• Causes: pituitary adenoma, acute ectopic ACTH syndrome (associated with small cell lung carcinoma)
ACTH Independent:
• Adrenocortical tumor
Clinical Features Glucocorticoid Effects:
• Hyperglycemia
• Weight gain (central obesity, buffalo hump, moon face)
• Increased risk of infection
• Osteoporosis
• Muscle weakness
• Mood disorder
Mineralocorticoid Effects:
• Hypertension
• Hypokalemia
• Metabolic alkalosis
Androgenic Effects:
• Women become masculinized (hirsutism, hair thinning, acne, amenorrhea)
• Men become feminized (gynecomastia, impotence)
Treatment Transsphenoidal resection of anterior pituitary gland
Pituitary radiation
Adrenalectomy (if adrenal tumor)
Anesthetic Implications In addition to considerations for hyperaldosteronism covered on last page:
• Special attention to aseptic technique
• Careful positioning to reduce skin and bone injury
• Consider post-op steroid supplementation
• Diabetes insipidus may develop after removal of anterior pituitary gland
Adrenal Insufficiency
Adrenal insufficiency is characterized by the destruction of all the cortical zones. This manifests as decreased production of mineralocorticoids, glucocorticoids, and androgens.
Adrenal insufficiency is a chronic state, but this can deteriorate into acute adrenal crisis if the patient is faced with additional stress (infection, illness, sepsis, or surgery).
Key Points
Etiology Primary adrenal insufficiency (Addison’s):
• Adrenal glands don’t secrete enough steroid hormone
• Cause: autoimmune destruction of both adrenal glands (most common), HIV, TB
Secondary adrenal insufficiency:
• Decreased CRH and ACTH release
• Cause: exogenous steroid administration (most common) or HPA disease due to tumor, infection, surgery,
radiation
Acute adrenal crisis:
• Medical emergency
• Cause: chronic AI faced with stress (infection, illness, sepsis, surgery)
Clinical Features Adrenal Insufficiency:
• Muscle weakness/fatigue
• Hypotension
• Hypoglycemia
• Hyponatremia, hyperkalemia, metabolic acidosis
• Anorexia/weight loss
• n/v
• hyperpigmentation of the knees, elbows, knuckles, lips, and buccal mucosa
Acute adrenal crisis:
• hemodynamic instibalility/collapse
• fever
• hypoglycemia
• impaired mental status
Treatment Adrenal Insufficiency:
• steroid replacement therapy (15-30 mg cortisol equivalent/day)
Acute adrenal crisis:
• steroid replacement therapy (hydrocortisone 100 mg + 100-200 mg q 24h)
• ECF volume expansion (D5NS best choice)
• Hemodynamic support

*catecholamine synthesis and pheochromocytoma are covered in the ANS tutorial.

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o Suppression of the Hypothalamic-Pituitary Axis:
o Exogenous steroid supplementation suppresses ACTH release from the anterior pituitary gland. Some patients on chronic
steroid therapy wont be able to increase cortisol release in response to perioperative stress. This table will help you determine
who requires coverage, and the next table will help you determine how much to administer.

o Other Drugs that Cause Adrenocortical Suppression

o By inhibiting 11-beta-hydroxylase, etomidate causes dose-
dependent adrenocortical suppression.
§ This effect lasts more than 8 hours following a single
induction dose.
§ In non-cardiac surgical patients, induction with
etomidate (rather than propofol) was associated with
an increased 30-day mortality.
§ The need for a stable induction must be balanced
against the potential risk of adrenocortical
suppression.
o Ketoconazole also inhibits cortisol synthesis.

o Pancreas Physiology
o The pancreas produces two types of hormones:
§ Exocrine hormones are secreted into the duodenum for digestion (produced by the
acini tissue)
§ Endocrine hormones are secreted into the systemic circulation for metabolism
(produced by the islets of Langerhans)
§ Insulin is an anabolic hormone that promotes energy storage. It’s eliminated by the
kidneys and liver and has an elimination t1/2 of 5 minutes.
§ When energy abounds (after a meal), insulin secretion increases and plays a significant
role in capturing and storing the energy. Insulin accomplishes this by:
• Increasing glucose permeability in skeletal muscle, liver, and fat.
• Converting carbohydrates to glycogen in the liver and skeletal muscle.
• Converting excess carbohydrates to fats. These fats can be oxidized if blood sugar becomes low.
• Promoting cellular uptake of amino acids, potassium, magnesium, and phosphate.
• Encouraging protein synthesis and discouraging protein breakdown.
• Stimulating the Na+/K+-ATPase. As an aside, this decreases
serum potassium and is why we give insulin and D50 for
hyperkalemia.
o Insulin release and the Target Cell
§ Glucose is the primary stimulator of insulin release from the pancreatic
beta cells. Therefore, anything that increases serum glucose will also
increase insulin release.
§ The insulin receptor is made up of 2 alpha and 2 beta subunits that are joined together by disulfide bonds. When insulin binds to the
receptor, the beta subunits activate tyrosine
kinase which then activates insulin-receptor
substrates (IRS). The insulin cascade turns on
the GLUT4 transporter, which increases glucose
uptake by skeletal muscle and fat.
§ The liver and brain do not require insulin for
glucose uptake. This is particularly important in
the brain, because it requires a steady supply of
glucose for optimal function. Indeed, cerebral
function generally declines when serum glucose
falls below 50 mg/dL.

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 o Glucagon
§ Glucagon is a catabolic hormone that promotes energy release from adipose
and the liver. It is:
• Secreted by alpha cells.
• A physiologic antagonist to insulin.
• Eliminated by the kidneys and liver and has a t1/2 is 3-6 minutes.
§ Other Uses for Glucagon
• Glucagon (1-5 mg IV) increases myocardial contractility, heart rate,
and AV conduction by increasing the intracellular concentration of
cAMP. It does this independently of the autonomic
nervous system, which is useful in the following
situations:
o Beta-blocker overdose
o CHF
o Low cardiac output after MI or
cardiopulmonary bypass
o Improving MAP during anaphylaxis
• Glucagon is also administered during ERCP to relax
the biliary sphincter.
• Nausea and vomiting is a key side effect of glucagon.
o Somatostatin
§ Somatostatin, also known as growth hormone-inhibiting hormone, regulates hormone output from the islet cells. It’s
released by delta cells.
• It inhibits insulin AND glucagon.
• It also inhibits splanchnic blood flow, gastric motility, and gall bladder contraction.
o Pancreatic Polypeptide
§ PP inhibits pancreatic exocrine secretion, gallbladder contraction, gastric acid secretion, and gastric motility.
o Diabetes Mellitus
o Diabetes is often described as “starvation in a sea of food.” Although glucose is present in the blood stream, it is unable to enter many of the
cells that require it. This shifts metabolism towards protein catabolism and lipid oxidation. Remember that the brain and the liver do not
require insulin for glucose uptake.
o Diagnosis Criteria
§ Fasting plasma glucose > 126 mg/dL
§ Random glucose level > 200 mg/dL + classic symptoms
§ Two hour plasma glucose > 200 mg/dL during oral glucose tolerance test
§ Hemoglobin A1C > 6.5%
o Diabetes Classification
§ Diabetes is classified as either Type I or Type II
• T1DM is characterized by the lack of insulin production
• T2DM is characterized by a relative lack of insulin + insulin resistance

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 o Metabolic Syndrome
§ The metabolic syndrome describes the group of characteristics that are common to patients with DM or to those who
are at higher risk of developing DM. diagnostic criteria include at least three of the following:
• Fasting plasma glucose > 110 mg/dL
• Abdominal obesity (waist > 40 inches in men and > 35 inches in women)
• Serum triglyceride level > 150 mg/dL
• Serum HDL < 40 mg/dL in men and < 50 mg/dL in women
• Blood pressure > 130/85 mmHg
o Diabetic Ketoacidosis (Gap Acidosis + Hyperglycemia)
§ More common with type 1 diabetes mellitus.
§ Usually caused by infection.
§ Not enough insulin àketoacidosis, hyperosmolarity (from increased glucose), and dehydration.
§ Patient is hyperglycemic (> 250 mg/dL), but cells are starved for fuel.
§ Metabolic acidosis causes Kussmaul respirations.
§ Acetone causes fruity smelling breath.
§ Treatment= volume resuscitation, insulin, K+ after acidosis subsides.
o Hyperglycemic Hyperosmolar State
§ More common with type 2 diabetes mellitus.
§ Usually caused by insulin resistance or inadequate production.
§ Enough insulin is produced to prevent ketosis by not hyperglycemia.
§ Hyperglycemia (> 600 mg/dL) significantly increases serum osmolarity (> 330 mOsm/L).
§ Compared to DKA, HSS is associated with a greater elevation in glucose and osmolarity.
§ Glycosuria leads to dehydration and hypovolemia.
§ Mild metabolic acidosis may occur (usually > 7.3 and no anion gap).
§ Treatment = volume resuscitation, insulin, correct electrolytes. Microvascular Neuropathy (sensory, motor, autonomic)
o Diabetes Mellitus: Anesthetic Management Retinopathy
o The systemic effects of diabetes mellitus can be predicted by the long term effects of Nephropathy
hyperglycemia in neural and vascular tissue. Macrovascular Coronary artery disease
o Autonomic Nervous System Dysfunction Peripheral vascular disease
§ Painless myocardial ischemia (referred pain pathways are dysfunctional). Cerebrovascular disease
§ Reduced vagal tone à tachycardia Other Stiff joint syndrome
§ Risk of dysrhythmias Poor wound healing àinfection
Cataracts
§ Orthostatic hypotension
Glaucoma
§ Impaired respiratory compensation to hypoxia and hypercarbia à
increased sensitivity to anesthetic drugs.
Other
§ Delayed gastric emptying àincreased risk of aspiration
§ Impaired thermoregulation à increased risk of o Neuropathy usually begins in a “stocking and glove” distribution
hypothermia o Peripheral neuropathy is treated with NSAIDs, antidepressants, and
§ Regional anesthesia may worsen neurologic defects in the anticonvulsants.
patient with diabetic polyneuropathy o Assess for renal dysfunction
§ Diarrhea and constipation o Osmotic diuresisàfluid and electrolyte abnormality
o Airway o Lactate in LR can be converted to glucose and may contribute to
§ Glycosylation of the jointsàstiff joints syndrome with hyperglycemia
reduced ROM of AO joint. o Schedule surgery early to prevent interruption of nutrition and
hypoglycemic therapy.
§ The prayer sign suggests joint glycosylation and an
o Hyperglycemia worsens neurologic outcome after ischemic brain
increased risk of difficult intubation.
injury.
o General anesthesia and diabetic autonomic neuropathy can mask
intraoperative hypoglycemia.
o Beta-blockers can blunt the increased SNS response that accompanies
hypoglycemia. Additionally, these drugs diminish the hyperglycemic
effects of endogenous epinephrine.

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o Oral Hypoglycemic Medications
o There is a lot of information here. At a minimum, you should learn:
§ 1. Drugs and their classes
§ 2. Mechanisms of action.
§ 3. Whether a drug increases the risk of hypoglycemia (you can predict this based on its MOA).
§ 4. Key facts for biguanides and sulfonylureas.
Oral Hypoglycemic Agents Key Facts
Biguanides: inhibit gluconeogenesis and glycogenolysis • does NOT cause hypoglycemia
in the liver and decrease peripheral insulin resistance • risk of lactic acidosis (increased anaerobic glucose metabolism)
• lactic acidosis risk increases with drug accumulation, so avoid if: liver dx, renal
Metformin dx, acute MI, CHF, or iodinated contrast media
• treat lactic acidosis with hemodialysis, NaHCO3, and CV support
• may cause vitamin B12 deficiency
• often used for polycystic ovarian disease
• discontinue > 48 hours before surgery
Sulfonylureas: stimulate insulin secretion from • risk of hypoglycemia
pancreatic beta cells • avoid if sulfa allergy
• closes KATP channelsàinhibition of myocardial preconditioning à increased
Glyburide Tolbutamide cardiac morbidity in high risk pts
Glipizide Chlorpropamide • discontinue 24-48 hours before surgery
Glimepiride Acetohexamide
Gliclazide
Meglitinides: stimulate insulin secretion from • risk of hypoglycemia
pancreatic beta cells

Repaglinide Nateglinide
Thiazolidinediones: decrease peripheral insulin • does NOT cause hypoglycemia
resistance and increase hepatic glucose utilization • contraindicated with liver failure
• expands ECF àedema
Rosiglitazone Pioglitazone • black box warning d/t increased risk CHF
a-Glucosidase Inhibitors: slow digestion and • does NOT cause hypoglycemia
abosorption of carbohydrates from the GI tract

Acarbase Miglitol
Glucagon-Like Peptide-1 Receptor Agonists: increase • risk of hypoglycemia
insulin release from pancreatic beta cells, decrease
glucagon release form alpha cells, and prolong gastric
emptying.

Exenatidie Liraglutide
Dispeptidyl-Peptidase-4 Inhibitors: increase insulin • risk of hypoglycemia
release from pancreatic beta cells, decrease glucagon
release from alpha cells

Suffix: -liptin
Amylin Agonists: inhibit glucagon release from • risk of hypoglycemia when used with insulin
pancreatic alpha cells and reduce gastric emptying • does not alter insulin levels
• may cause N/V
Pramlintide

o Insulin
o Since patients with T1DM do not produce insulin, their survival depends on an exogenous supply. Patients with T2DM may
require insulin if lifestyle modification and oral hypoglycemic agents fail.
o One unit of insulin equals the amount of insulin required to decrease the serum glucose concentration in a fasting rabbit to 45
mg/dL. We’re not making this up…really!
o Normal Insulin Secretion
§ Under normal conditions, the pancreas secretes ~ 1U/hr into the portal circulation.
§ After a meal, insulin output increases 5-10 fold.
§ Total insulin output is ~40 U/day
§ Beta-2 and PNS stimulation increases insulin secretion
§ Alpha-1 stimulation inhibits insulin secretion.

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o Insulin Preparations

§ Regular insulin is the only formation that can be given IV.

o Goals of Insulin Therapy
§ HbA1c <7%
§ Before a meal – glucose is 70-130 mg/dL
§ After a meal – glucose is <180 mg/dL
o Side Effects

§ Drug Interactions
• Drugs that counter the hypoglycemic effect of insulin:
o Epinephrine
o Glucagon
o Estrogen
o Adrenocorticotrophic hormone
• Drugs that extend and/or enhance the hypoglycemic effect of insulin:
o Monoamine oxidase inhibitors
o Salicylates
o Tetracycline
§ If you can’t get enough of this stuff, and you’re looking for an intriguing book to read, we’d like to recommend
Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and/or the Making of a Medical Miracle by Thea Cooper and
Arthur Ainsberg.

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o Carcinoid Syndrome
o Carcinoid syndrome is associated with secretion of vasoactive substances from enterochromaffin cells. It is usually associated
with tumors of the GI tract, but it can also arise form locations outside of the GI tract as well.
o Pathophysiology
§ When hepatic function is normal, carcinoid hormones are cleared by the liver. When significant liver dysfunction
occurs, these hormones aren’t cleared by the liver, so they enter the systemic circulation and cause the signs and
symptoms characteristic of carcinoid syndrome.
§ Carcinoid syndrome can also occur if:
• Hepatic function is normal, but the amount of hormone produced by the tumor exceeds the liver’s ability to
clear it.
• The tumor resides in a location where blood flow bypasses the liver, such as the lungs.
o Signs and Symptoms
§ The most common signs are flushing and diarrhea.

§ Concurrent cardiac disease is common and manifests as pulmonic stenosis and tricuspid regurgitation.
• Protect the RV by avoiding conditions that increase PVR: hypoxia, hypercarbia, acidosis, nitrous oxide, and
light anesthesia.
§ Carcinoid Crisis
• Carcinoid crisis is life-threatening and can occur in patients with carcinoid syndrome. S/sx include:
o Tachycardia
o Hyper- or hypotension
o Intese flushing
o Abdominal pain
o Diarrhea
o Anesthetic Management
§ Drugs to Give
• Somatostatin (octreotide or lanreotide) inhibits release of vasoactive substance from carcinoid tumors
• Antihistamines (H1 & H2: diphenhydramine + ranitidine or cimetidine)
• 5-HT3 antagonists
• steroids
• phenylephrine or vasopressin for hypotension
§ Drugs to Avoid
• Histamine releasing drugs; morphine, meperidine, atracurium, thiopental, and succinylcholine (if possible).
• Succinylcholine induced fasciculations can cause hormone release from the tumor.
• Exogenous catecholamines can potentiate hormone release.
• Sympathomimetic agents: ephedrine and ketamine.

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Kidney, Liver, & Endocrine Notes

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Apex Pediatric
• Epiglottitis vs Laryngotracheobronchitis (Croup)
o Before we get started, we want you to understand that this tutorial supplements the neonate tutorials. Anything covered in those tutorials
won’t be duplicated here.
o Epiglottitis vs Croup
§ It’s a smart idea to learn these side-by-side. Learn to identify the similarities and differences.

• Postintubation Laryngeal Edema

o Otherwise known as post-intubation croup, post-intubation laryngeal edema is a complication of endotracheal intubation.
§ It is more common in small children.
§ The most common cause is using an ETT that is too large.
§ Rigid bronchoscopy can also cause this complication.
o The tracheal mucosa perfusion pressure is 25 cm H2O. using an ETT that is too large or injecting an excessive amount of air into the cuff reduces tracheal
perfusionàedemaàdecreased subglottic airway diameteràincreased work of breathing.
o The patient presents with hoarseness, a barky cough, and/or stridor. It typically occurs within 30-60 minutes following extubation.
o Risk Factors
§ Age < 4 years
§ ETT is too large
§ ETT cuff volume is too high (too much air was injected or N2O was used during the procedure)
§ Traumatic or multiple intubation attempts (one reason not to use an uncuffed tube)
§ Prolonged intubation
§ Coughing (cuff rubs against the tracheal mucosa
§ Head or neck surgery
§ Head repositioning during surgery
§ History of infectious or post-intubation croup
§ Trisomy 21
§ Upper respiratory tract infection ?
o Treatment
§ The best treatment is prevention!
§ Post-intubation laryngeal edema can occur with cuffed or uncuffed endotracheal tubes, but the key point is to maintain an air leak < 25 cm
H2O. if you are using a cuffed ETT, then you should use a manometer to intermittently measure cuff pressure.
§ Treatment aims to reduce swelling and improve airflow:
• Cool and humidified oxygen
• nebulized racemic epinephrine 0.5 mL of 2.25% solution in 2.5 mL of 0.9% sodium chloride
• dexamethasone 0.25-0.5 mg/kg IV (maximum effect requires 4-6 hours)
• heliox is a helium + oxygen mixture that improves laminar airflow by reducing Reynold’s number
§ Unlike laryngotracheobronchitis (infectious croup), post-intubation croup is not infectious. Therefore, antibiotics are not indicated.
§ The patient should be observed for a minimum of 4 hours after the racemic epinephrine treatment is complete.

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• Upper Respiratory Infection
o A child with an active or recent history of respiratory tract infection is at increased risk of pulmonary complications. In addition
to increased airway reactivity (bronchospasm), these children are more likely to experience laryngospasm, mucous plugging in
the airway, atelectasis, desaturation events, and post-operative hypoxemia. Viral infection is the most common cause of URI.
o When to Postpone Elective Surgery
§ Let’s face it..kids have runny noses all of the time! We simply can’t cancel surgery every time we see a child with a
runny nose, because these kids would never be considered “well enough” for surgery. Having said this, we don’t want
to anesthetize every child without thoughtfully considering the context of each case. The other issue to consider is
that, although the risk of pulmonary complications is higher, they rarely result in long term morbidity.
§ Most clinicians wait 2-4 weeks after onset of symptoms, although the risk of pulmonary complications can persist for
up to 6-8 weeks.

o Methods to Reduce Risk

§ Avoid mechanical irritation of the airway: Facemask>LMA>>>ETT
§ Mechanical irritation (ETT use) increases the risk of bronchospasm 10-fold!
§ If an ETT must be used, then use a smaller size than normal because these children are at higher risk of post-
intubation croup.
§ Dexamethasone 0.25-0.5 mg/kg will reduce the risk of post-intubation croup.
§ Ensure a deep plane of anesthesia before instrumenting the airway.
§ Propofol attenuates airway reactivity and may reduce the risk of bronchospasm.
§ Sevoflurane is the best volatile agent, because it is non-pungent.
§ Pretreatment with an inhaled bronchodilator (albuterol or ipratropium) or glycopyrrolate does not provide a clear
benefit.
• Foreign Body Aspiration
o Small children like to put things into their mouths, and sometimes they swallow them. Most often, the GI tract takes care of this, however there
are times when the thing in the child’s mouth finds its way into the lower airway. Of course, it doesn’t have to be a non-food [Link]
body aspiration can also occur with seeds, hotdogs, or nearly anything else. Since food is radiolucent, it can be more difficult to diagnose. The
foreign body most commonly lodges in the right bronchus.
o Presentation
§ Over 60% of children with foreign body aspiration present with the classic triad of cough, wheezing, and decreased breath sounds on
the affected side (usually the right).
§ Airway obstruction significant enough to impair gas exchange can quickly progress to hypoxemia, cyanosis, altered mental status,
cardiac arrest and death.
• Supraglottic obstructionàstridor
• Infraglottic obstructionàwheezing
o Surgical Considerations
§ Rigid bronchoscopy is the “gold standard” procedure to retrieve the foreign body.
§ Other options include flexible bronchoscopy or thoracotomy.
§ Airway obstruction is the most significant concern, so weight the pros and cons of observing NPO guidelines.
o Choice of Anesthesia
§ A sevoflurane induction with spontaneous ventilation is usually best.
§ Positive pressure ventilation can push the foreign body deeper into the bronchial tree, increasing the difficulty of its retrieval.
§ The anesthesia circuit can be connected to the port on the rigid bronchoscope. It can be used to provide oxygen and volatile agent during the
procedure. It can also be used to provide gentle PPV breaths if required.
§ The problem with this approach is the leak around the bronchoscope. You can compensate for this with a high FGF and increasing the
vaporizer output. It can be difficult to maintain a sufficient level of anesthesia if a lot of the gas is escaping around the bronchoscope.
§ If the patient coughs or bucks, the foreign body can move distally. This isn’t good.
§ For these reasons, TIVA is probably the best maintenance technique.
o Complications of Rigid Bronchoscopy
§ Laryngospasm
§ Bradycardia during scope insertion
§ Post-intubation croup
§ Pneumothorax
§ Patients may not improve immediately after the foreign body is removed (due to residual lung inflammation).

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• Conditions Associated with Difficult Airway management
o You’ll need to understand how congenital impact airway management. First, we’ll group a few together, then we’ll detail the
important considerations for each condition.

o Pierre Robin
§ Small/underdeveloped mandible (micrognathia or mandibular hypoplasia-can be used interchangeably)
§ A tongue that falls back and downwards (glossoptosis)
§ Cleft palate
§ Neonate often requires intubation
o Treacher Collins
§ Small mouth
§ Small/underdeveloped mandible
§ Nasal airway is blocked by tissue (choanal atresia)
§ Ocular and auricular anomalies
o Trisomy 21 (down syndrome)
§ Small mouth
§ Large tongue
§ Atlantoaxial instability
§ Small sublglottid diameter (subglottic stenosis)
o Klippel-Feil
§ Congenital fusion of cervical vertebraeàneck rigidity
o Goldenhar
§ Small/underdeveloped mandible
§ Cervical spine abnormality
o Beckwith Syndrome
§ Large tongue
o Cri du Chat
§ Small/underdeveloped mandible
§ Laryngomalacia
§ Stridor
o Cleft Lip & Palate
§ Cleft lip and palate are commonly associated with other genetic disorders.
§ Airway specific risks include:
• Airway obstruction
• Difficult laryngoscopy
• Difficult mask ventilation if there are additional craniofacial abnormalities
• Aspiration
• Dingman-Dott mouth retractor can reduce venous drainage and cause tongue engorgement. This increases the risk of
post-extubation airway obstruction.
§ Other considerations:
• Failure to thrive (unable to generate negative pressure required for sucking)
• Cleft lip repair ~ 1 month
• Cleft palate repair ~ 12 months
• Dingman-Dott mouth retractor can reduce venous drainage and cause tongue engorgement. This increases the risk of
post-extubation airway obstruction.

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• Down Syndrome
rd
o Our genetic make-up consists of 23 chromosomal pairs. Trisomy 21 (down syndrome) results from the addition of a 3 copy of
chromosome 21.
§ It is the most common chromosomal disorder.
§ Older mothers are more likely to give birth to a child with Down syndrome.
o While Down syndrome affects nearly every organ system, we’re going to focus our discussion on the abnormalities that affect
anesthetic management.
o Airway
§ The patient with Down syndrome is at risk for difficult ventilation and intubation.
• Small mouth
• large tongue
• palate is narrow with a high arch
• midface hypoplasia
• atlantoaxial instability
o C1 &C2 subluxation
o Avoid neck flexion during laryngoscopy
o Child should receive cervical x-ray screening between 3-5 years of age
• Subglottic stenosis
o Increased risk of postintubation croup
o Use a smaller ETT
• Obstructive sleep apnea
• Chronic pulmonary infection
o Cardiovascular
§ Co-existing congenital heart disease is common
• Most common=AV septal defect (endocardial cushion defect)
• Second most common=VSD
§ Bradycardia is very common during sevoflurane induction (tx=anticholinergic)
§ Low levels of circulating catecholamines
o Other
§ Intellectual disability
§ Epilepsy
§ Strabismus
§ Low muscle tone (hypotonia)
§ Hyperflexible joints (careful with positioning)
§ GERD
§ Thyroid disease
§ Increased incidence of leukemia
• Associations & Gene Deletion Syndromes
o You should be able to identify and understand the constellation of signs and symptoms that occur in each condition listed
below.
o All of these conditions are associated with cardiovascular defects.
o VACTERL Association CHARGE Association
§ V – vertebral defects
§ A – imperforated anus • C – Coloboma (a hole in one of the eye structures)
§ C – cardiac anomalies • H –Heart defects
§ T – Tracheoesophageal fistula • A –Choanal atresia (back of nasal passage is obstructed)
§ E – esophageal atresia • R – Retardation of growth and development
§ R – renal dysplasia • G – Genitourinary problems
§ L – limb anomalies • E – Ear anomalies
o CATCH 22
§ You might also see this called DiGeorge syndrome or 22q11.2 gene deletion syndrome.
• C – Cardiac defects
• A – Abnormal face
• T – Thymic hypoplasia
• C – Cleft palate
• H – Hypocalcemia (due to hypoparathyroidism)
• 22 – 22q11.2 gene deletion (the cause of the syndrome)
o Key Facts About DiGeorge Syndrome:
§ Hypocalcemia is common (remember hyperventilation, albumin, and citrated blood products lower free Ca+2 in the
blood).
§ If the thymus is absent, the child is at high risk for infection. Treatment consists of thymus transplant or mature T cell
infusion.
§ Transfusion of leukocyte-depleted irradiated blood is best.

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Neonate

• Vital Signs Overview

o The neonatal period encompasses the first 28 days of life, and the infant period lasts from 29 days to 1 year.
o While the healthy, full term neonate is resilient, it operates at near peak performance. This is another way of saying that it has a
reduced physiologic reserve. Without a doubt, the neonate presenting for an emergent procedure will be among the most
challenging patients you’ll ever encounter. A well-executed anesthetic hinges upon a healthy respect for the physiologic and
pharmacologic differences.
o Neonatal physiology is its own entity with a variety of unique qualities that differentiates it from the adult, or even older
children. We’re sure you’ve hard more times than you can count that children aren’t small adults, but we’re here to tell this
isn’t the best way to think about this information on the NCE> instead, we want you to think of neonates and infants as a group
all their own. In reality, children older than 1 year of age bear a closer resemblance to the adult than a neonate. This is because
most of their organ systems are mature. The implication for the NCE is that most of your time spent studying pediatrics should
focus on children < 1 year old.
o Before moving forward, you absolutely must know normal vital signs. This may sound like a basic request (perhaps too basic),
but to understand how to diagnose and treat neonatal physiologic derangements, you absolutely must have a solid
understanding of what is normal.
o Although we could give you a huge chart
with upper and lower limits, we believe that
would be an inefficient use of your precious
time. Instead, we recommend that you learn
a single set of vital signs for each age group.
Of course, this is an oversimplification, but in
the end, we believe the table will serve you
well on test day.
• Explanation of Normal Vital Signs
o Central to your understanding of neonatal vital signs is the fact that they have a much higher oxygen consumption and carbon
dioxide production. The higher requirement for oxygen coupled with immature homeostatic mechanisms places the neonate at
risk with even minor physiologic perturbations.
o Let’s examine the normal vital signs once more, then we will explain why things are how they are.
o Explanation of Respiratory Vital Signs
§ Oxygen consumption and carbon dioxide production are twice those of the adult. Therefore, the neonate must increase alveolar
ventilation accordingly. It is metabolically more efficient to increase respiratory rate than it is to increase tidal volume. This explains
why newborns have a high respiratory rate, yet tidal volume is the same as the adult on a per weight basis (6mL/kg).
o Explanation of Cardiovascular Vital Signs
§ Heart rate is the primary determinant of cardiac output and systolic blood pressure. The neonatal myocardium lacks the contractile
elements to significantly adjust contractility or stroke volume; the ventricle is noncompliant. Furthermore, the Frank-Starling
relationship is underdeveloped (but not entirely absent) in the newborn. Therefore, heart rate must be maintained to ensure
adequate tissue perfusion and oxygen delivery.
Blood Pressure = Heart Rate x Stroke Volume x Systemic Vascular Resistance

Hypotension Defined

Newborn <60 mmHg

1 year <70 mmHg

older than 1 year < [70 + (child’s age in years x 2)] mmHg

§ Stroke volume is relatively fixed and SVR is low. The non-compliant left ventricle is sensitive to an increased afterload, so increasing
heart rate is the best way to support blood pressure.
§ One caveat is that you understand that everything we’ve said assumes a euvolemic state, so in the setting of hypovolemia, the
neonate will also require volume resuscitation.
§ In the setting of hypovolemia and bradycardia, epinephrine is favored over atropine. Although both medications increase heart rate,
epinephrine has the additional benefit of augmenting contractility (if only a little bit).
§ Blood pressure is relatively low in the neonate, but over time the systemic vascular resistance rises. As the left ventricle pumps
against a higher SVR, the contractile elements multiply and mature, giving the left ventricle the ability to better adjust contractility.
These changes explain why as the child ages, he becomes relatively less dependent on heart rate to support cardiac output.
§ Autonomic regulation of the heart is immature at birth, with the SNS being less mature than the PNS. Stressful situations, such as
laryngoscopy or suctioning of the airway, may cause bradycardia. Atropine may be administered prior to induction to mitigate this
response. Additionally, the baroreceptor reflex is poorly developed, and the reflex fails to increase heart rate in the setting of
hypovolemia.
§ Even though the neonate has an immature SNS, pain activates the SNS manifesting as tachycardia and hypertension. In fact, the
combination of hypertension, an immature cerebral autoregulatory response, and a fragile cerebral vasculature predispose the
neonate to intracerebral hemorrhage.

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• Airway Anatomy
o Among the most likely pediatric questions that you will encounter on the NCE is the one that asks you to compare the infant
and adult airway. You may think you already know all of this, but read on. What you encounter may surprise you. Know
everything on this chart!

• What is the Narrowest Region of the Pediatric Airway?

o It depends on the context of the question, but the narrowest region of the pediatric airway is at the level of the vocal cords or the cricoid ring.
o Why did we list two answers for the narrowest region of the pediatric airway? That’s easy…you’ll see two answers in the texts.
§ In the anesthetized child, the most current evidence suggests that the vocal cords are the narrowest region of the pediatric airway.
Having said this, the vocal cords are soft structures that will stretch as an endotracheal tube is placed between them.
§ Classic teaching suggests that the cricoid ring is the narrowest part of the airway. This is partially true, because we can displace the
vocal cords with an endotracheal tube (dynamic), however the diameter of the cricoid ring (at the base of the funnel) can’t be
increased. It can, however, be reduced by edema that results from an endotracheal tube that is too large, multiple intubation
attempts, prolonged intubation, frequent head positioning while intubated, etc.
o How are you supposed to answer a question about narrowest region of the pediatric airway?
§ Having read all of the textbooks on the NBCRNA bibiliography, we’ve found a pretty even split (some say vocal cords and others say
cricoid). Furthermore, you’ll often find conflicting answers between chapters in the same book! In our correspondence with the
NBCRNA, they told us that each question is supposed to be referenced in at least two locations. We can only hope they’ve put as
much research into this topic as we have. A well written test question about this topic should provide context to guide you to be the
best answer, and the information we presented above should help you.

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• Oxygen Demand, Supply & Reserve
o The distal saccules of the lung begin to develop alveoli between 24-48 weeks of gestation, and the number of alveoli will
continue to rise throughout childhood until 8-10 years of age.
o Because neonatal alveolar surface area is only 1/3 of the adult and oxygen consumption is twice that of the adult, the neonate
must increase alveolar ventilation to sustain normal arterial gas tensions. It is metabolically more efficient for the neonate to
increase respiratory rate than it is to increase tidal volume.

o Neonates experience oxygen desaturation much faster than adults, and there are several interrelated explanations for this. We
like to think in terms of oxygen demand, supply, and reserve.
o When compared to adults, neonates have a/an:
§ 1. Increased oxygen consumption to support metabolic demand
§ 2. Increased alveolar ventilation to increase oxygen supply
§ 3. Slightly decreased FRC reflects a reduced oxygen reserve
o The net result is that the neonate has an increased ratio of alveolar ventilation relative to the size of its FRC. This ratio is ~2-3
times higher than in the adult. Said another way, there is an increased turnover of gases in the FRC. During hypoventilation or
apnea, the neonates’ relatively higher oxygen consumption will quickly exhaust the oxygen reserve contained in the FRC,
leading to rapid oxygen desaturation.
o The increased ratio of alveolar ventilation relative to the size of the FRC also explains a quicker inhalation induction. A faster
turnover of the FRC (fewer alveoli are need to achieve steady state) allows for a speedier development of anesthetic partial
pressure inside the alveoli and consequently more rapid changes in the anesthetic partial pressure inside the brain and spinal
cord.
o We know this was a lot to take in. if it didn’t make perfect sense, re-read this explanation until you can recite it.
• Muscles of Inspiration
o The diaphragm is the primary muscle of inspiration.
o The intercostal muscles are inadequately developed, so they contribute very little to ventilation. The ribs assume a more
horizontal position, so they are less able to significantly augment thoracic volume.
o The diaphragm and intercostal muscles are composed of two types of muscle fibers:
§ Type I describes slow twitch muscle fibers that are built for endurance—they are resistant to fatigue.
§ Type II describe fast twitch muscle fibers that are built for short bursts of heavy work—they tire easily.
o the neonatal diaphragm only has 25% type I fibers (adults have 55%), and this explains the reduction in neonatal ventilatory
reserve. Preterm babies have an even lower amount of type 1 fibers ~10%.
o A smaller number of type I muscle fibers puts the neonate at risk for respiratory fatigue, distress, and failure.
• Apnea After Surgery
o Neonates are at risk of apnea following surgery and anesthesia. Patients less than 60 weeks post conceptual age should be
admitted for 24 hour observation with an apnea monitor.
§ The younger the child, the greater the risk of postoperative apnea.
§ Prophylactic caffeine (10 mg/kg IV) is the treatment of choice. Theophylline can be used, however it’s associated with
a higher risk of toxicity.
• Pulmonary Mechanics
o Lung Volumes & Capacities
§ In the adult, the chest wall tends to expand and the lungs tend to
collapse. This creates the negative pressure in the pleural space. The
lung volume at end-expiration is called FRC.
§ Compared to the adult, the newborn has a/an:
• 1. Low lung compliance
• 2. Higher chest wall compliance due to a cartilaginous ribcage
that gives less structural support –it is flimsy.
§ Taken together, these two circumstances favor chest wall collapse during inspiration (paradoxical breathing), reduced lung volumes
at expiration and an FRC of only 10-15% of total lung capacity. To prevent V/Q mismatch during tidal breathing, the newborn can
dynamically increase FRC to near normal adult values by altering its ventilatory mechanics.
§ The ability to dynamically maintain FRC is lost during general anesthesia. Closing volume overlaps with tidal volume, which creates
V/Q mismatch, increases the A-a gradient, and predisposes the newborn to hypoxemia.
o Airway Resistance
§ Work of breathing is increased as a function of increased airway resistance (particularly in the small airways). When the neonate
inspires, it has to overcome the resistance to airflow as well as the elastic properties of the chest wall and lungs. Remember that
th
resistance is inversely proportional to the radius raised to the 4 power, so even minor reductions in airway diameter (edema or
secretions) can significantly increase the work of breathing.

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• Blood Gases: Mother & Fetus

o What you should take away from this chart

§ The fetal circulation is “backwards” with the umbilical vein supplying oxygen to the fetus. This is why the pH is higher
in the umbilical vein than the umbilical artery. The umbilical artery returns deoxygenated and carbon dioxide rich
blood to the placenta.
§ Clamping of the umbilical cord stimulates the newborn to breathe rhythmically and the acute rise in PaO2 promotes
continuous breathing. Hypoxemia causes apnea.
§ The newborn comes into the world hypoxic, acidotic, and retains carbon dioxide. Its alveoli contain fluid and it takes
deep breaths to replace the fluid with air. It generates a relatively normal FRC in the first 20 minutes. Pulmonary
blood flow also increases during this time.
§ During the first hour of extrauterine life, the newborn hyperventilates. This is likely due to its poor buffering capacity
and compensation for nonvolatile acids in the blood. After this time, the pH and PaCO2 stabilize.
§ The PaO2 continues to rise towards the adult value over the next several weeks.
o How does Hypoxemia Affect the Newborn?
§ Respiratory control doesn’t mature until 42-44 weeks.
• Before maturation: hypoxemia depresses ventilation.
• After maturation: hypoxemia stimulates ventilation.
• Fetal Hemoglobin
o Fetal hemoglobin (HgbF) has a P50 of 19 mmHg.
§ HgbF shifts the curve to the left (left=love).
§ It benefits the fetus by creating an oxygen partial pressure gradient
across the uteroplacental membrane that facilitates the passage of
O2 from the mother to the fetus.
o Why Does Hgb F have a Higher Affinity for Oxygen?
§ Adult hemoglobin (Hgb A) consists of 2 alpha and 2 beta chains, while
fetal hemoglobin has 2 alpha and 2 gamma chains.
§ We know that 2,3-DPG causes a right shift in the oxyhemoglobin
dissociation curve, but you may not know that the binding site for
2,3-DPG is only on the beta chain. Since Hgb F has 2 gamma instead of 2 beta chains, it does not bind 2,3-DPG. This
shifts the curve to the left and explains why Hgb F has a higher affinity for oxygen.
o Physiologic Anemia of the Infant
§ In the first 2 months of life, erythrocytes containing Hgb F are replaced by those that produce Hgb A. after 6 months,
Hgb F has been completely replaced by Hgb A. at this time, the P50 will be the same as the adult (26.5 mmHg).

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• Blood Component Therapy & Complications
o The goal of transfusion is to increase oxygen carrying capacity. While a numeric trigger alone should not form the sole basis for
the decision to transfuse, it is a helpful tool that should be incorporated into this decision. Instead, transfusion should be
guided by ongoing blood loss, anticipated blood loss, baseline Hgb/Hct, as well as signs of inadequate oxygenation and end
organ dysfunction.
o Let’s review transfusion of erythrocytes, FFP, and platelets.
o 1-a. Erythrocyte Transfusion for Children Less than 4 Months of Age
§ as we have learned neonates and infants have a high demand for oxygen. Furthermore, Hgb F has an increased
affinity for oxygen, so it is less likely to release oxygen to metabolically active tissue. It is, therefore, reasonable to
have a higher transfusion trigger for these patients.
• Transfusion trigger<13 g/dL in the child with severe cardiopulmonary disease
• Transfusion trigger of <10 g/DL in the child presenting for major surgery or with moderate cardiopulmonary
disease
Dose=10-15 cc/kg
10mL/kg will raise Hgb by 1-2 g/dl
o 1-b. Erythrocyte Transfusion for Children Greater than 4 Months of Age
§ by this time, RBCs containing Hgb A are beginning to proliferate. These cells have a lower affinity for oxygen, and are
more willing to release oxygen to metabolically active tissue. Transfusion volume is the same as in those less than 4
months of age.
§ For patients >4 months of age without significant cardiopulmonary disease, many clinicians will follow the Transfusion
Practice Guidelines of the ASA Task Force on Blood Component Therapy..
• 1. Transfusion is rarely indicated if Hgb>10 g/dL
• 2. Transfusion is almost always indicated if Hgb < 6 g/dL
• 3. Transfusion should be considered on a needs basis if Hgb is 6-10 g/dL.
• 4. The use of a universal transfusion trigger is not recommended.
§ Some other endpoints include:
• Intraoperative blood loss > 15 % blood volume
• Acute blood loss with hypovolemia not responsive to other therapy
o 2. Fresh Frozen Plasma Transfusion
§ The indications for transfusion of FFP mirror the recommendations set forth by the ASA guidelines referenced
previously. These include:
• 1. Emergency reversal of warfarin
• 2. Correction of coagulopathic bleeding with increased PT or PTT
• 3. Correction of coagulopathic bleeding if >1 blood volume has been replaced and coagulation studies are
not easily obtained
§ FFP is not indicated for expansion of intravascular volume
§ Dose= 10-20 mL/kg
o 3. Platelet Transfusion
§ platelet transfusion is recommended for invasive procedures to maintain platelet count above 50,000.
• Dose if obtained from apheresis = 5 mL/kg
• Dose if pooled platelet concentrate = 1 pack/10kg
§ A single apheresis unit equals 6-8 pooled platelet concentrates
§ 1 pooled platelet concentrate will increase serum platelets by 50 x 10^9/L
o Complications Related to Transfusion
§ Massive transfusion is associated with:
• Alkalosis from citrate metabolism to bicarbonate in the liver.
• Hypothermia from transfusion of cold blood.
• Hyperglycemia from dextrose additive to stored blood.
• Hypocalcemia from binding of calcium by citrate
• Hyperkalemia from administration of older blood. When RBCs are stored, the cell membrane becomes
dysfunctional, which allow potassium to leak into the supernatant. Administration of PRBCs to neonates can
lead to hyperkalemia and cardiac arrest. The risk is reduced by administering washed or fresh cells that are
less than 7 days old.
§ Graft-vs-host disease is a rare, yet devastating event. Donor leukocytes attack recipient bone marrow, leading to
pancytopenia, fever, hepatitis, and diarrhea. Gamma radiation destroys donor leukocytes. Radiated blood is
particularly useful in immunocompromised patients.
§ Erythrocytes produced by the newborn poorly express ABO antigens. Some texts say that cross matched blood is not
required.

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• Transfusion
o There are many important concepts buried in this single question. Before we can do this calculation, we must first know several
key pieces of information:
§ 1. What is the normal hemoglobin and hematocrit?
§ 2. What is the estimated blood volume?
§ 3. What is the transfusion trigger?
§ 4. How much blood can be lost before the transfusion trigger is reached?
o 1. What is the Normal H&H?

o 2. Estimated Blood Volume?

o 3. What is the Transfusion Trigger?

§ This was covered in the previous question.
o 4. How Much Blood can be Lost Before the Transfusion Trigger is Reached?
Maximum Allowable Blood Loss= EBV x (Hct starting – Hct target)

Hct starting
§ now we can finally get back to the question….
§ A 3 kg term neonate requires emergency exploratory laparotomy for necrotizing enterocolitis. Her preoperative
hematocrit is 50%. What is the maximum allowable blood loss to maintain a hematocrit of 40%?
• 1. EBV = 3kg x 80 x 100 mL/kg (premature vs term neonate) = 240 to 300 mL
• 2. Hct-starting - Hct-target = 50-40=10
• 3. MABL=240 to 300 mL x [(50-40)/50] = 48-60 mL
§ You must keep in mind that this calculation does not take crystalloid or colloid volume expansion into account.
Administration of intravenous fluids in an attempt to maintain euvolemia can dilute hemoglobin and hematocrit.
• Renal Maturation
o At birth, the neonatal kidney is immature. Compared to the adult it has a decreased:
§ Perfusions pressure
§ GFR
§ Diluting and concentrating ability
o One can quickly find his way down the rabbit hole seeking the specifics of renal function, but for the NCE you should know how neonates
handle water and solutes as well as the timeline for renal maturation.
o Water
§ Neonates do a poor job conserving water, so they are intolerant of fluid restriction. On the flips side, they are unable to excrete large
volumes of water, so they do not do well with fluid overload either. Meticulous fluid management is essential!
§ To complicate the issue, neonates also have high insensible losses. They lose most of their body water through evaporation as a
direct result of a surface area to body weight ratio that is 4 times higher than the adult. Evaporation also occurs through immature
skin, which is thinner and more permeable to water.
o Solutes
§ The neonate is an obligate sodium loser in the first few days of life. After that, it is better able to retain sodium that to excrete it. It
also tends to lose glucose to the urine.
o Renal Maturation
§ A point of confusion for many students is exactly when renal function matches that of the adult. Part of this stems from the fact that
none of the books seem to agree on the issue, while the other part is that there are actually two components to this question –when
does GFR mature and when do the renal tubules mature?
• 1. GFR improves substantially in the first few weeks of life, but does not reach adult levels until 8-24 months of age.
• 2. Renal tubular function continues to improve after birth, but it does not achieve full concentrating ability until ~ 2 years
of age.

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• Body Water Distribution
o Let’s briefly review the components of body water distribution.

o Premature babies are like little water balloons. Total body water is highest in the premature newborn and decreases as it ages.
Once again, a table full or ranges is one that you won’t be able to memorize as well. If you commit the following values to
memory and understand the implications of these numbers, you’ll be in great shape.

o Key Concepts
§ In the premature and term neonate, the ECF is larger than the ICF. This is different than the rest of the age groups.
There is a diuresis after birth that reduces ECF volume.
§ Total body water as a function of weight approximates adult values by 1 year of age.
§ A higher ICF provides a volume reserve in times of intravascular volume loss: fever, fasting, and diarrhea. This also
means that the child is more capable of adjusting to these conditions when compared to the neonate.
o Signs of Dehydration
§ Sunken anterior fontanel
§ Weight loss (a 10% reduction in the first week is normal)
§ Irritability or lethargy
§ Dry mucous membranes
§ Absence of tears
§ Decreased skin turgor
§ Increased hematocrit in the absence of transfusion
• Fluid Management in Four Parts
o Part I: Hourly Maintenance
§ Use the 4:2:1 rule.
• Step 1: 0-10 kg àBegin with 4 mL/kg/hr
• Step 2: 10-20 kg àAdd 2 mL/kg/hr to the previous total
• Step 3: >20 kg àadd 1 mL/kg/hr to the previous total
§ If the patient is >20 kg, then you can use a shortcutà patient’s weight in kg + 40
o Part II: NPO Deficit Calculation
§ Multiply the patient’s hourly fluid maintenance rate by the number of hours of NPO time.
§ Replace this deficit over 3 hours:
st
• 1 hour: 50%
nd
• 2 hour: 25%
rd
• 3 hour: 25%
o Part III: Third-Space Loss Calculation
§ Replace fluid lost to third spacing and evaporation.
• Minimal surgical trauma = 3-4 mL/kg/hr
• Moderate surgical trauma= 5-6 mL/kg/hr
• Major surgical trauma= 7-10 mL/kg/hr
§ As a general rule, third-space loss is not included in the first hour of anesthesia.
o Part IV: Blood Loss
§ Replace with crystalloid at 3:1 ratio
§ Replace with colloid at 1:1 ratio
§ Replace with blood at 1:1 ratio

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• Which Type of Fluids Should I Administer?
o Common choices include 0.9% NaCl, LR, Plasma-Lyte, and 5% albumin.
o Routine use of glucose-containing solutions is not recommended. Instead, these fluids should be reserved for infants and
children at risk of developing hypoglycemia, such as:
§ Prematurity
§ Less than 48 hours of age
§ Small for gestational age
§ Newborns of diabetic mothers
§ Children with diabetes who received insulin on the day of surgery
§ Children who receive glucose-based parental nutrition
o Signs of hypoglycemia typically manifest when serum glucose falls below 30-40 mg/dL in newborns < 72 hours old and 40 mg/dL
in those older than 72 hours. A good number to keep in your head is 40 mg/dL. General anesthesia masks these signs.
o Treatment consists of IV 10% dextrose (2ml/kg). if seizures are present, then dose is doubled (4 ml/kg) in order to provide
adequate substrate to the brain. After the bolus, a D10 infusion at 8 mg/kg/min is titrated to maintain serum glucose >40
mg/dL.
• Pharmacokinetics & Pharmacodynamics
§ The pharmacokinetics of drugs can be explained by appreciating the following pharmacokinetic concepts:
o Cardiac Output
§ In the newborn, cardiac output is 200 mL/kg/min, which means that drugs are delivered to and removed from the
rest of the body at a faster rate (when compared to adult).
o Volume of Distribution
§ Neonates have a greater percentage of total body water, so they require higher doses of water soluble drugs to
achieve a given plasma concentration.
o Protein Binding
§ Remember that plasma proteins should be thought of as a storage site or “sink” for drugs in the plasma.
• A drug bound to a plasma protein cannot exert a physiologic effect.
• Before 6 months of age there are lower concentrations of albumin and alpha-1 acid glycoprotein, so for
drugs that are usually highly protein bound,the neonate will experience increased free drug levels and have
a higher risk of toxicity.
o Adipose Content
§ Neonates have a greater percentage of total body water and a lower percentage of fat and muscle mass. Drugs that
require fat for redistribution and termination of effect have a longer duration of action.
o Hepatic Metabolism
§ Drug biotransformation reactions are underdeveloped in the first month of life.
• Adult values are reached by about 1 year of age.
• The neonate cannot conjugate bilirubin due to a reduction in glucoronyl transferase. This is the same
enzyme that metabolizes acetaminophen.
o Renal Clearance
§ Normal GFR is reached at 8-24 months of age.
§ Normal tubular function is reached at 2 years of age.
o Blood Brain Barrier
§ An immature BBB allows passage of drugs that would otherwise not be able to enter the brain. This partially explains
a higher a sensitivity to sedative hypnotics.
o MAC
§ Minimum alveolar concentration (MAC) varies with age.
• Infant 1-6 months: MAC is higher than the adult
• Infant 2-3 months: MAC peaks at its highest level
• Neonate (0-30 days): MAC is lower than the infant
• Premature: MAC is lower than neonate
§ The MAC requirement pattern for sevoflurane is different.
• 0 days to 6 months: MAC is higher (3.2%)
• 6 months to 12 years: MAC is lower, but still higher than the adult (2.5%)

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• Neuromuscular Blockers
o The Big Picture
§ Neuromuscular blockers are highly water soluble. They do not easily pass through lipid membranes and are therefore
confined to the ECF. Neonates have a larger ECF volume, so we can predict that neuromuscular blockers have a larger
volume of distribution. This characteristic argues for a larger dose. There is more to this story, so hold tight.
§ The neonatal neuromuscular junction is immature. Although several theories exist, the bottom line is that when
compared to adults, the NMJ is more sensitive to nondepolarizing neuromuscular and equally sensitive to
succinylcholine.
• The combination of an increased ECF and normal sensitivity of succinylcholine necessitates an increased
dose of 2 mg/kg. the duration of action is about the same as the adult.
• The combination of and increased ECF and an increased sensitivity to nondepolarizers is assumed to be a
wash, so the dose is the same as in the adult. Immature metabolic and clearance mechanisms may prolong
the duration of action.
o Succinylcholine
§ Succinylcholine can be administered intramuscularly. The dose for neonates and infants is 5 mg/kg, while older
children should receive 4 mg/kg. when compared to administrations into peripheral skeletal muscle, intralingual
administration via the submental approach has the fastest onset.
§ The activity of Pseudocholinesterase is reduced in the neonate, however this is clinically irrelevant. The duration of
succinylcholine is similar to adults. A prolonged effect of succinylcholine should prompt investigation for
Pseudocholinesterase deficiency.
§ In children less than 5 years of age, succinylcholine may cause bradycardia or asystole. This can occur following the
first dose, but it is more likely after repeat administration. Atropine pretreatment (0.02 mg/kg IV) will mitigate this
response.
§ The black box warning on succinylcholine warns of hyperkalemia associated with undiagnosed muscular dystrophy in
children under 8 years old. Considering this succinylcholine retains a suitable option for rapid sequence intubation,
anticipated difficult airway, laryngospasm, or other airway emergencies. Anytime a child experiences cardiac arrest
following succinylcholine, hyperkalemia should be assumed the cause until proven otherwise.
o Rocuronium
§ Rocuronium is dosed 0.6-1.2 mg/kg. it is metabolized by the liver, and there are no active metabolites. It also has a
mild vagolytic property that may cause a small rise in heart rate. It is the only nondepolarizer tha can be given via the
IM route at a dose of 1 mg/kg in children < 1 year of age and 1.8 mg/kg in those over year. Onset after IM
administration is 3-4 minutes.
o Vecuronium
§ Vecornoium is dosed 0.10-0.15 mg/kg. it is also metabolized by the liver, but active metabolites may increase the
duration of action in this population. Vecuronium is considered a long acting NMB in this population.
o Pancuronium
§ Pancuronium is dosed 0.1-0.15 mg/kg. unlike rocuronium and vecuronium, it is primarily eliminated by the kidneys.
Also, it has a stronger vagolytic effect and may cause hypertension. This has the potential to increase blood loss as
well as lead to intracerebral hemorrhage in the premature neonate.
o Atracurium & Cisatracurium
§ Atracurium and cisatracurium are useful in the neonate due to their organ independent elimination.
o Antagonizing Nondepolarizing Neuromuscular Blockade
§ Neostigmine and edrophonium may be used. Neostigmine 0.05 – 0.07 mg/kg will reach peak effect in ~10 min.
edrophonium 1 mg/kg will reach peak effect in ~ 2 minutes and is associated with less muscarinic side effects.
Atropine is best paired with edrophonium and glycopyrrolate is best paired with neostigmine.
o Assessing Recovery From Neuromuscular Blockade
§ The neonate isn’t going to follow commands prior to extubation, so we must rely on other measures that doe not
require cooperation.
§ Although it doesn’t provide an objective measure, many practitioners rely on visual inspection. Grimacing, elbow and
hip flexion, and bringing to the knees to the chest seem to correlate with adequate recovery. Although a head lift > 5
seconds is appropriate for an adult, a neonate does not have the muscle strength to raise his head.
• A TOF ratio > 90% suggests a full recovery.
• A maximum inspiratory force (MIF) less than -25 cm H2O predicts adequate recovery from neuromuscular
blockade.

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EMERGENCIES

• Esophageal Atresia & Tracheoesophageal Fistula

o Esophageal atresia is the most common congenital defect of the esophagus, and most of these children also have a tracheoesophageal fistula.
o Esophageal atresia prevents the fetus from swallowing amniotic fluid, thus maternal polyhydramnios is a key diagnostic indicator for TEF. Diagnosis is
confirmed by the inability to pass a gastric tube into the stomach. Other symptoms include: choking, coughing, and cyanosis during oral feeding.
o TEF Classification
§ Type C accounts for ~90% of all TEFs.
• In this configuration, the upper esophagus ends in a blind pouch
and the lower esophagus communicates with the distal trachea.
o VACTERL Association
§ Approximately 25-50% of patients with TEF suffer from other congenital anomalies.
Collectively these are known as the VACTERL association.
§ Approximately 20% of neonates with EA have a significant cardiac defect (ASD, VSD, tetralogy
of Fallot, or aortic coarctation).
§ Pre-op echocardiography should be performed.
o Anesthetic Management
§ Head up position and frequent suctioning minimize the risk of gastric aspiration.
§ Awake intubation or inhalation induction with spontaneous ventilation.
§ Positive-pressure ventilation àgastric distensionàdecreased thoracic complianceàincreased PIP
required to ventilateàrepeat
§ Placement of g-tube allows for gastric decompression. If the patient already has a g-tube, open it to atmosphere before induction.
§ Place the endotracheal tube below the fistula but above the carina.
§ If placed too high, respiratory gas is delivered to the stomach.
§ If placed too low, endobronchial intubation is likely.
§ A precordial stethoscope placed on the left chest will immediately detect a right mainstem intubation.
§ Right lung compression during surgical repair is common. Right mainstem intubation will cause rapid
desaturation.
• Respiratory Distress Syndrome
o Surfactant
§ Type II pneumocytes begin producing surfactant between 22-26 weeks, with peak production occurring at 35-36 weeks.
§ Surfactant reduces alveolar surface tension and prevents alveolar collapse.
• Each alveolus contains the same amount of surfactant.
• Larger alveoli have a relatively smaller concentration of surfactant.
• Smaller alveoli have a relatively large concentration of surfactant.
§ As the alveolar radius decreases, so does its surface tension.
§ This prevents smaller alveoli from collapsing and emptying into larger alveoli.
§ Law of Laplace: Pressure = 2 x Tension / Radius
o Respiratory Distress Syndrome
§ Neonates who do not produce enough surfactant are at risk for respiratory distress syndrome (RDS).
§ In the absence of adequate surfactant, the alveoli remain stiff and noncompliant. Tension inside the small alveoli rises, which favors their
collapse. At the same time, larger alveoli tend to become over distended as they accept gas from collapsed alveoli. This promotes atelectasis,
reduces the surface area where gas exchange can take place, creating V/Q mismatch. Hypoxemia leads to acidosis and possibly the return to
fetal circulation (more on this later).
§ Diagnosis Risk factors for development of RDS include:
• The diagnosis is made soon after birth, as the neonate exhibits signs of • Low birth weight
respiratory distress: grunting (to keep alveoli open), tachypnea, intercostal and • Low gestational age
subcostal retractions, and nasal flaring. Blood gas analysis yields hypoxemia,
• Oxygen toxicity
hypercarbia, and a mixed acidosis. The progression to respiratory failure leads to
• Barotrauma from positive pressure
hemodynamic instability and death.
ventilation
§ Treatment
• Endotracheal intubation
• A laboring mother with preterm fetus should receive a corticosteroid
• Maternal diabetes
(betamethasone) to hasten fetal lung maturation. Steroids will begin to help the
fetus after 18 hours, with a peak effect at 48 hours.
• Amniocentesis can assist in the determination of fetal lung development. The ratio of lecithin to sphingomyelin (L/S ratio) give
advanced warming about the state of the fetal lung by providing the ratio of lecithin (surfactant) to sphingomyelin (surfactant
precursor). While we could not find it in the books, take our word for it than an L/S ratio > 2 suggests adequate lung
development.
• After delivery, neonates that fail to produce enough surfactant are first treated with CPAP, but may require mechanical
ventilation with exogenous surfactant delivered via endotracheal tube.
§ Anesthetic Implications
• SpO2 should be maintained, while keeping in mind that hyperoxia is one factor (in addition to prematurity and low birth weight)
that may contribute to retinopathy of prematurity. Patients with RDS are usually premature with low birth weight, so these
patients are already at increased risk for ROP.
• Preductal and postductal oxygen saturation monitoring should be employed. A preductal pulse oximeter is placed on the right
upper extremity, while the postductal monitor is usually placed on a lower extremity. A difference between the values suggests
pulmonary hypertension, a right to elft cardiac shunt, and the return to fetal circulation via the PDA> an arterial line is required
for frequent ABG smapling as well as hemodynamic assessment. A preductal artery is preferred for arterial sampling.
• Positive pressure ventilation in the patient with poor lung compliance increases the risk of pneumothorax. These patients often
require postoperative mechanical ventilation.

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• Congenital Diaphragmatic Hernia
o Congenital diaphragmatic hernia is a diaphragmatic defect that allows the abdominal contents to enter the thoracic cavity.
§ The foramen of Bochdalek is the most common site of herniation (usually on the left side).
§ Other sites of herniation include the foramen of Morgagni and around the esophagus.

§ CDH is usually diagnosed at birth. The newborn will be in respiratory distress and have a scaphoid abdomen (sunken in).
• Other findings include: barrel chest, cardiac displacement, and fluid filled gastrointestinal segments in the thorax.
o Pathophysiology and Anesthetic Management
§ The mass effect of abdominal contents within the chest impairs lung development, leading to pulmonary hypoplasia. One or both lungs can
be affected.
• Consequences include poor pulmonary vascular development, increased pulmonary vascular resistance, pulmonary hypertension,
impaired airway development and airway reactivity.
• Keep PIP< 25-30 cmH2O to minimize barotrauma and the risk of pneumothorax of the “good” lung. This may require permissive
hypercapnia; and while it will increase PVR, it’s the lesser of two evils in this situation.
• Avoid other conditions that increase PVR (hypoxia, acidosis, hypothermia).
• Abdominal closure may increase PIP. The surgeon can create a temporary ventral hernia to increase the abdominal volume.
• A pulse oximeter placed on a lower extremity can warn of increased intra-abdominal pressure.
§ Right-to-left shunting through the ductus arteriosus leads to hypoxemia and cyanosis, and this gives rise to a positive feedback loop where
PVR increases even further.
• Use the right upper extremity to monitor preductal SpO2 and BP
• Preductal SpO2 should be >90%
§ Surgery is delayed 5-15 days to allow for stabilization of the pulmonary, cardiac, and metabolic status.
• The procedure can be an open or thoracoscopic technique
• Thoracoscopy adds CO2 into the thorax, and this can negatively effect acid-base balance.
• May require one-lung ventilation. This is accomplished by advancing the ETT into the mainstem bronchus of the “good” lung.
There is no double lumen tube or bronchial blocker available for neonates.
• Omphalocele and Gastroschisis
o It’s best to learn these conditions side-by-side, as you will likely be asked about the differences between them.

o Anesthetic Management
§ if gastroschisis, abdominal contents are placed in a bag after delivery. This minimizes water and heat loss.
§ Monitor peak airway pressure. If PIP>25-30 cmH2O, then surgical closure of the abdomen may require staging.
§ Closure may increase intra-abdominal pressure.
§ Increased P-abdàdecreased venous returnàdecreased cardiac outputàdecreased systemic perfusion.
§ Measure SpO2 on the lower extremity to monitor for impaired venous return.
§ Nitrous oxide distends the bowel and may impair surgical closure.
§ Expect major fluid and electrolyte shifts.

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• Pyloric Stenosis
o Pyloric stenosis occurs when hypertrophy of the pyloric muscle creates a mechanical obstruction at the gastric outlet (between the stomach
and the duodenum). An olive shaped mass can be palpated just below the xiphoid process.
§ The infant presents with non-bilious projectile vomiting.
§ It occurs in the first 2-12 weeks of life.
§ It is more common in males.
o Pathophysiology
§ Vomiting depletes water, hydrogen, chloride, sodium, and potassium.
• Excessive vomiting leads to hyponatremic, hypokalemic,
hypochloremic, metabolic alkalosis + compensatory respiratory
acidosis.
• Metabolic alkalosis shifts the oxygen-hemoglobin dissociation
curve to the left (left=love), and this reduces oxygen release at the
tissue level.
§ The kidneys compensate for metabolic alkalosis by increasing bicarbonate excretion. The infant excretes alkalotic urine.
§ As dehydration continues, the kidneys retain Na+ and water under the influence of increased aldosterone. To maintain
electroneutrality, the kidneys lose hydrogen to the urine. This causes a paradoxical acidification of the urine.
§ If dehydration is not corrected, impaired tissue perfusion increases lactate production and produces metabolic acidosis. This is a late
complication!
o Anesthetic Management
§ Pyloric stenosis is a medical (not surgical) emergency.
§ Surgical correction (pyloromyotomy) should be postponed until the fluid, electrolyte, and acid-base status are optimized.
§ Severe dehydration should be corrected with 20 mL/kg of 0.9% NS.
§ Maintenance fluids consist of D5 0.45% NS at 1.5x the calculated maintenance rate.
§ Anticipate a full stomach, so empty the stomach before induction, intubate either awake or with RSI, and extubate awake.
§ Postoperative apnea is common. This is possibly due to the fact that CSF pH remains alkalotic even after serum acid-base status is
normalized.
• Necrotizing Enterocolitis
o NEC is necrosis of the bowel; usually the terminal ilium and proximal colon.
o Babies at risk:
§ Prematurity (<32 weeks)
§ Low birth weight (<1500g)
o Although the pathophysiology is incompletely understood, NEC is likely the result of early feeding. Impaired absorption by the gut leads to stasis,
bacterial overgrowth, and infection. This increases the risk of bowel perforation.
o Diagnosis includes: fixed dilated intestinal loops, pneumatosis intestinalis (gas cysts in the bowel), portal vein, air, ascites, and free air in the abdomen.
o Babies with NEC are managed medically, however bowel perforation necessitates bowel resection and usually colostomy. These patients often have a
metabolic acidosis and require substantial fluid replacement.
o Nitrous oxide is avoided, as it can cause accumulation of gas pockets inside the bowel.
o If retinopathy of prematurity is a concern, reduce FiO2.
o Bowel resection early in life can lead to short gut syndrome (nutrient malabsorption) as the patient ages.
• Retinopathy of Prematurity
o Retinopathy of prematurity causes abnormal vascular development in the retina. The immature retinal blood vessels are at risk of vasoconstriction and
hemorrhage. Dysfunctional healing creates scars. As the scars retract, they pull on the retina, causing retinal detachment and blindness.
o Pathophysiology
§ Vasculogenesis occurs 16 and 44 weeks post conception. This process begins at the macula then continues outwards towards the edges of
the developing retina over time.
§ Prematurity and hyperoxia are the two key risk factors that contribute to ROP.
• PaO2 in utero=20-30 mmHg
• PaO2 after delivery=55-85 mmHg
§ In the premature neonate, this higher PaO2 may lead to hyperoxia. Initially, the higher PaO2 slows the rate of vascular growth, and then it
can progress to an abnormal growth pattern where the vessels are at risk of vasoconstriction, bleeding, scar formation, fibrosis, and
ultimately retinal detachment.
§ The incidence of ROP is inversely proportional to post-conceptual age and birth weight. If you had to pick the most significant cause of ROP,
we would go with prematurity (not hyperoxia).
§ Other risk factors include:
• Mechanical ventilation
• Blood transfusion
• Intraventricular hemorrhage
• Sepsis
• Vitamin E deficiency
o Anesthetic Management
§ Until retinal maturation is complete, supplemental oxygen should be minimized to maintain SpO2 between 85% and 93% (up to 44
week post-conception).
• Preductal SpO2 is preferred, as it best predicts the oxygen saturation in the retinal vessels.
§ Although most cases of early stage ROP resolve on their own, surgical options for later stage disease include:
• Cryotherapy
• Laser therapy
• Scleral buckle
• Virectomy

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 • Miscellaneous Problems
o Apoptosis and Developmental Delay
§ Rapid brain growth occurs during the first 3 years of life.
§ Apoptosis is the process of programmed cell death. While this is a healthy response during normal development,
there are concerns that commonly used anesthetic agents can kill neurons, potentially causing a neurocognitive
delays later in life.
§ These concerns stem from rodent data; often the test subjects were exposed to supra-clinical doses for prolonged
periods of time.
§ Due to the unanswered nature of how, when, and to what significance this occurs in humans, Barash and Miller
recommend that we stay the course and do not deviate from current practice (i.e. do not withhold specific drugs
based on the currently available data.) to this point, it would not make sense to change practice without acceptable
evidence.
§ Drugs that Cause Apoptosis
• These agents tend to antagonize the NMDA receptor, stimulate the GABA receptor, or both.

o Kernicterus
§ Bilirubin is a byproduct of RBC breakdown. Any condition that increases serum bilirubin can cause kernicterus (fetal
encephalopathy).
• Glucuronyl transferase (phase II rxn) metabolizes bilirubin.
• This pathway is not mature at term, leaving the newborn vulnerable during the first few days of life.
• Risk factors: prematurity, low plasma protein concentration, and acidosis.
• Treatment of hyperbilirubinemia includes phototherapy and exchange transfusion (rarely needed).
CONGENITAL HEART DISEASE

• Fetal Circulation
o The fetal circulation differs from the adult circulation in 5 ways:
§ 1. The placenta is the organ of respiration (adult=lungs).
§ 2. The circulation is arranged in parallel (adult=series).
§ 3. Right-to-left shunting occurs across the foramen ovale and ductus arteriosus.
§ 4. The PVR is high. The lungs are collapses and filled with fluid, so there is very little pulmonary blood flow.
§ 5. The SVR is low. The placenta provides a large, low resistance vascular bed.
o The Pathway

o Transition to Extrauterine Life

§ The transition to extrauterine life brings forth several changes required for survival:
• 1. First breathàlung expansionàincreased PaO2 & decreased PaCO2àdecreased PVR
• 2. Placenta separates from uterine wall (or cord clamp)àincreased SVR
• 3. Decreased PVR + increased SVRàLA pressure>RA pressureàthe flap valve of the foramen ovale closes
• 4. Decreased PVRàreversal of blood flow through the ductus arteriosusàexposes the DA to increased PO2àDA closure
• 5. Decreased circulating PGE1 (released from the placenta)àDA closure
§ a ductus arteriosus that remains open produces a continuous systolic and diastolic murmur.

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 o Putting the Pieces Together

o Comparison: Fetus, Neonate & Adult

• Vascular Resistance: Pulmonary and Systemic

o Shunting occurs when there is an abnormal communication between the pulmonary and systemic circulations.
o Central to your understanding of shunt lesions is a solid foundation about the balance between pulmonary and systemic vascular resistances.
The vascular resistance is akin to a gatekeeper to ventricular ejection. In the patient with a cardiac shunt, blood follows the path of least
resistance, so a high vascular resistance increases the amount of blood that passes through the shunt.
o Which Way Does the Blood Flow?
§ The size and direction of the shunt is dependent on 3 factors:
• 1. Ratio of the PVR to SVR
o RàL shunt occurs when PVR is greater than SVR
o LàR shunt occurs when SVR is greater than PVR
• 2. Pressure gradients between the cardiac chambers or arteries involved
• 3. Compliances of the cardiac chambers
o Conditions that Affect PVR and SVR
§ Successful management of shunt lesions necessitates a solid understanding of the factors that affect PVR and SVR. Know this table!

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• Pathologic Shunts
o Cyanotic Shunt (RàL): Blue Baby
§ Blood bypasses the pulmonary circulation. Because shunted blood does not bind oxygen in the lungs, this fraction dilutes the final PO2 of the
blood ejected by the left ventricle.
§ Examples (remember the 5 T’s):
• Tetralogy of Fallot
• Transposition of the great arteries
• Tricuspid valve abnormality (ebstein’s anomaly)
• Truncus arteriosus
• Total anomalous pulmonary venous connection
§ Effect on Inhalation Induction
• The rate of rise of FA/FI is slowed, resulting in a slower inhalation induction.
• The fraction of blood that bypasses the lungs does not pick up anesthetic agent. This
dilutes the partial pressure of the anesthetic agent in the left heart, thereby reducing the
overall partial pressure of the agent in the arterial circulation.
• This difference is most profound with less soluble agents (N2O and Desflurane) and less
of an issue with more soluble agents (isoflurane).
§ Effects on IV induction
• A right-to-left shunt allows IV medication to bypass the lungs and directly enter the
systemic circulation. The drug reaches the vessel rich organs faster, thereby resulting in a faster onset.
o Acyanotic Shunt (LàR): Pink Baby
§ Instead of being pumped to the body, oxygenated pulmonary venous blood recirculates through the right heart and lungs.
§ Examples:
• Ventricular septal defect (most common)
• Atrial septal defect
• Patent ductus arteriosus
• Coarctation of the aorta
§ Effect on Inhalation Induction
• Negligible
§ Effect on IV induction
• Possibly prolonged
o Eisenmenger Syndrome
§ Eisenmenger’s syndrome can occur when patients with a left-to-right shunt develop pulmonary
hypertension. Increased right heart pressures cause a flow reversal, ultimately leading to a right-to-
left shunt, hypoxemia, and cyanosis.
• Tetralogy of Fallot
o Tetralogy of Fallot is the most common cyanotic congenital heart anomaly.
o Pathophysiology
§ Since “tetra” is the Greek prefix for the number 4, you’d be correct in thinking that there are 4 defects associated
with this condition.
• 1. Right ventricular outflow tract obstruction
• 2. Right ventricular hypertrophy due to high pressure load from the RV obstruction
• 3. Ventricular septal defect due to septal malalignment
• 4. Overriding aorta that receives blood from both ventricles
§ the problem begins with RVOT obstruction
• the degree of RVOT obstruction strongly correlates with the amount of shunt.
• With increasing RVOT obstruction, more deoxygenated blood is shunted through the VSD and out into the aorta.
• The body compensates with erythropoiesis, however this leads to polycythemia and increases the risk of
thromboembolism and stroke.
o Tet Spells
§ A “tet spell” presents as hypoxemia and cyanosis. Classically the child presents with a history of squatting during activity. this
maneuver kinks the arteries in the groin area and in turn increases SVR, reduces right-to-left shunt, and improves oxygenation. Stress
increases myocardial contractility and may cause spasm of the infravalvar region of the RVOT, so it should make sense that “tet
spells” occur during stressful circumstances such as exercise, crying, defecation, IV placement in the awake child, or during induction.
§ Perioperative Tet Spell Treatment:
• FiO2 100%
• Intravascular volume expansion
• Increase SVR with phenylephrine to augment the PVR to SVR ratio.
• Reduce SNS stimulation to improve dynamic RVOT obstruction—deepen
anesthesia, beta-blockade with short acting agent (esmolol)
• Inotropes worsen RVOT obstruction and are best avoided.
• Avoid excessive airway pressure
• An infant may be placed in a knee-chest position to mimic squatting
o Hemodynamic Goals
§ After reviewing the physiology of tetralogy of Fallot, the hemodynamic goals should make
perfect sense.
o Anesthetic Considerations
§ Ketamine (1-2 mg IV or 3-4 mg IM) is the best induction agent. It increases SVR and reduces shunting. Even though it increases contractility, this effect is minor
compared to the benefit of increasing SVR.
§ Histamine causes vasodilation and reduces SVR. Therefore, you should avoid morphine, meperidine, and atracurium.
§ The heart may take on a “boot shaped” appearance on CXR.
§ RV hypertrophy can cause right axis deviation.
§ Polycythemia is proportional to the degree of chronic hypoxemia.

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• Septal Defects
o In infants and children, a ventricular septal defect (VSD) is the most common congenital cardiac anomaly. A significant number
of these close by the time the child reaches 2 years of age.
o In adults, the most common congenital cardiac defect is a bicuspid aortic valve.
o Atrial Septal Defect
§ An atrial septal defect is an abnormal opening in the atrial septum, most commonly at the site of the fossa ovalis. This is also called
an ostium secundum ASD.
• Flow through the ASD is left to right.
• ASD is an acyanotic lesion.
• Because the LA and RA are relatively low pressure systems, the pressure gradient is usually low.
• Patients may remain symptom free for years.
• Early signs include poor exercise tolerance and later signs include atrial flutter, atrial fibrillation, and CHF.
• If pulmonary vascular disease develops, (Eisenmenger syndrome), the direction of the shunt may reverse (causing right-
to-left shunt).
• The hemodynamic effects of anesthetic agents are usually well tolerated.
• ASDs can cause paradoxical embolism during Valsalva-like maneuvers if RAP>LAP.
• Antibiotic prophylaxis is not indicated for an isolated ASD, but it is indicated within 6 months of surgical repair.
o Ventricular Septal Defect
§ A ventricular septal defect is an abnormal opening in the ventricular septum. The most common site is in the middle
of the ventricular septum, just below the septal leaflet of the tricuspid valve. This is also called a perimembranous
VSD.
• The physiologic consequence of the VSD is a function of the pressure gradients between the RV and LV, and in turn these
are dependent on PVR and SVR.
• If the VSD is small, pulmonary blood flow is only marginally increased. These patients tolerate anesthesia well.
• If the VSD is large, then RV and LV pressures equalize and PVR and SVR determine the direction of blood flow.
• Avoid situations that decrease PVR and increase SVR (either increases shunt flow).
• Positive pressure ventilation increases PVR and volatile agents decrease SVR. Both are well tolerated.
• VSD can cause paradoxical embolism during Valsalva-like maneuvers if RAP>LAP.
• If pulmonary vascular disease develops, (Eisenmenger syndrome), the direction of the shunt may reverse (causing right-
to-left shunt).
• Antibiotic prophylaxis is not indicated for an isolated VSD, but it is indicated within 6 months of surgical repair.
• Coarctation of the Aorta
o Coarctation of the aorta is the narrowing of the thoracic aorta, in the vicinity of the ductus arteriosus. It typically occurs just
before or after the ductus arteriosus, but in rare instances it occurs proximal to the left subclavian artery.
§ Preductal coarctation is less common and usually presents in the neonate.
§ Postductal coarctation is more common and usually presents in the adult.

§ Turner syndrome is strongly associated with coarctation of the aorta.

o Pathophysiology & Management
§ There is an increased LV afterload due to the obstruction of blood flow at the level of the coarctation.
• SBP is elevated in the upper extremities.
• SBP is reduced in the lower extremities.
§ Severe obstruction presents very early in life. In this situation, lower body perfusion depends on the PDA.
• DA closure can precipitate hemodynamic collapse.
• Prostaglandin E1 maintains DA patency.
• Inadequate blood flow to the lower body results in hepatic, renal, and intestinal ischemia.
• The SBP may be similar in all extremities while the PDA remains open.
§ Mild to moderate disease usually goes unnoticed for years.
• These patients form collateral pathways involving the internal thoracic, intercostal, subclavian, and/or
scapular arteries.
• Rib notching may be visible on CXR (this is due to increased vessel diameter).
• Diagnosis may be delayed until adulthood when the patient presents with secondary hypertension.
• Indications for surgical repair include exercise intolerance, chest pain, headaches, and lower extremity
claudication.
o Monitoring
§ The right arm is used for BP monitoring.

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• Miscellaneous Congenital Cardiac Defects
o Ebstein’s Anomaly
§ Ebstein’s anomaly is the most common congenital defect of the tricuspid valve. There is usually an ASD or PFO.
§ This condition is characterized by a downward displacement of the tricuspid valve and atrialization of the right
ventricle (d/t the ASD or PFO).
• Tricuspid regurgitation can be severe.
• Right-to-left shunting occurs at the level of the atria.
• Supraventricular tachycardia is common
• RV failure is common in the postoperative period.
o Transposition of the Great Arteries
§ The RV gives rise to the aorta and the LV gives rise to the pulmonary artery.
§ Right Ventricular Circuit:
• Systemic venous bloodàRVàaortaàrepeat
• This blood circulates through the systemic circulation but not the pulmonary circulation.
§ Left Ventricular Circuit:
• Pulmonary venous bloodàLVàlungsàrepeat
• This blood circulates through the pulmonary circulation but not the systemic circulation.
§ TGA is compatible with life in utero, because flow through the ductus arteriosus and foramen ovale allows
communication between both circulations. Survival outside of the womb depends on mixing of blood through an ASD
(best case scenario), VSD, or PFO. If no such communication exists, then death is imminent.
o Single-Ventricle Lesions
§ These patients may have a single right ventricle (hypoplastic left heart syndrome) or a single left ventricle (pulmonary
atresia).
§ The goal is to separate the pulmonary systemic circulations. This takes place in 3 stages:
• Neonatal: aortic reconstruction, systemic-pulmonary shunt, or PA band.
• Age 3-6 months: superior cavopulmonary connection
• Age 2-4 years: fontan operation
o Patient After Fontan Completion
§ The patient has a single ventricle that pumps blood into the systemic circulation.
§ There is no ventricle to pump blood into the pulmonary circulation.
• Blood flow into the lungs is completely dependent on negative intrathoracic pressure during spontaneous
breathing.
• Positive-pressure ventilation disrupts this arrangement and should be avoided/minimized.
• These patients are preload dependent-do not let them get dry!
o Truncus Arteriosus
§ Truncus arteriosus is characterized by a single artery that gives rise to the pulmonary, systemic, and coronary
circulations. With only one artery, there is no specific pathway for blood to enter the pulmonary circulation before
being pumped into the systemic circulation. There is usually a VSD as well.
§ Decreasing PVR or increasing pulmonary blood flow steals blood from the systemic and coronary circulations.

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OB

• Respiratory Changes During Pregnancy

o Upper Airway
§ The parturient is at higher risk of difficult mask ventilation, difficult laryngoscopy, and difficult intubation.
§ Increased progesterone, estrogen, and relaxin cause vascular engorgement and hyperemia. Combined
with an increased extracellular fluid volume, this leads to upper airway swelling, affecting the nasal
passages, oropharynx, epiglottis, larynx, and trachea. Your anesthetic plan must take these changes into
account.
• Mallampati score increases during pregnancy.
• Difficult and failed intubation is 8 times higher in full term patients.
• The glottis opening is narrowed; a downsized (6.0-7.0) endotracheal tube should be used.
• A short handled laryngoscope (Datta handle) is useful for women with large breasts.
• Airway manipulation may cause tissue trauma and bleeding. The tissue in the nasopharynx in
particularly friable, so insertion of an artificial airway into the nasopharynx should be avoided.
• Airway edema is made worse by pre-eclampsia, tocolytics, and prolonged Trendelenburg
position.
o Lung Physiology
§ Early in pregnancy, relaxin relaxes the ligaments in the ribcage, allowing the ribs to assume a more
horizontal position. This increases the anterior-posterior diameter of the chest, which give the lungs more
space. As the gravid uterus grows, it shifts the diaphragm in a cephalad direction. These changes affect
lung physiology in the following ways:
• Functional residual capacity is reduced as a function of a decrease in expiratory reserve volume
and residual volume.
• An increased oxygen consumption paired with a decreased FRC hastens the onset of hypoxemia.
Failure to reverse hypoxemia results in brain death of the mother and the fetus.
• Total lung capacity, vital capacity, and closing capacity are unchanged.
o Arterial Blood Gas
§ Progesterone is a respiratory stimulant. It increases minute ventilation up to 50%. In consequence, mom’s PaCO2 falls
and she develops a respiratory alkalosis. Renal compensation eliminate bicarbonate to normalize blood pH. A small
reduction in physiologic shunt explains the mild increase in PaO2. This increases the driving pressure of oxygen across
the fetoplacental interface and improves fetal gas exchange.
D From Baseline Key Information
ABG
• Arterial pH No change -
• PaO2 ­ 104-108 mmHg (due to hyperventilation)
• PaCO2 ¯ 28-32 mmHg
• HCO3- ¯ 20 mmol/L
OxyHgb Dissociation Curve ­ P50 (right shift) Facilitates O2 transfer to fetus
Minute Ventilation ­50% Due to ­O2 consumption and ­CO2 production
• Tidal Volume ­40% Progesterone is a respiratory stimulant
• Respiratory Rate ­10%
Lung Volumes & Capacities
• Total lung capacity No change ­Ribcage diameter compensates for ­diaphragm position
• Vital capacity No change “
• Closing capacity No change
• Functional Cesidual Capacity ¯20% Diaphragm compresses the lungs
• Expiratory Reserve Capacity ¯20-25% “
• Residual Volume ¯15-20% “
Oxygen Consumption ­VO2/FRC ratioàhastens the onset of hypoxemia during
• Term ­20% apnea
• First stage of labor ­40% over prelabor
• Second stage of labor ­75% over prelabor
Mallampati Classification ­ Vascular engorgement & soft tissue edema

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• Cardiovascular Changes During Pregnancy
o Systemic alterations occurring in obstetric patients are the result of anatomic, hormonal, and metabolic changes. You must be
intimately familiar with these systemic variations to create an appropriate safe plan of anesthesia care.
Parameter D From Baseline Key Information
O2 Consumption ­20% To meet needs of growing mother and fetus
Cardiac Output ­40% Uterus receives 10% of the cadiac output
Uterine contraction causes autotransfusion ( preload)
• Heart Rate ­15%
• Stroke Volume ­30% Compared to pre-labor values, CO during labor:
st
• 1 stage: CO ­ 20%
nd
• 2 stage: CO ­ 50%
rd
• 3 stage: CO ­ 80%
CO returns to pre-labor values in 24-48 hours
CO returns to pre-pregnancy values in ~ 2 weeks
Twins cause CO to ­20% above a single fetus pregnancy
Blood Pressure
• MAP No change ­Blood Volume + ¯SVR = Net even effect on MAP
• SBP No change
• DBP ¯15%
Vascular Resistance Progesterone causes:
• SVR ¯15% • ­Nitric oxideàvasodilation
• PVR ¯30% • ¯Response to angiotensin and NE
Filling Pressures Pregnancy by itself does not alter filling pressure, however as noted above
• CVP No change autotransfusion during uterine contraction does increase filing pressure.
• PAOP No change
Cardiac axis Left deviation Gravid uterusàpushes diaphragm cephaladàheart pushed up and left

o Aortocaval Compression
§ You should also be aware of the consequences of aortocaval compression or “syndrome of supine hypotension.” In
the spine position, the gravid uterus compresses both the vena cava and the aorta. This decreases venous return to
the heart as well as arterial flow to the uterus and lower extremities. Decreased cardiac output compromises fetal
perfusion and can also cause the mother to lose consciousness. By displacing the uterus away from the vena cava and
aorta, we can reduce its compressive effect. We can accomplish this by elevating the mother’s right torso 15 degrees.
nd rd
This is called left displacement of the uterus. It should be used for anyone in their 2 or 3 trimester.
o Hematologic Changes

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• Neurologic, GI, Renal, and More Physiologic Changes During Pregnancy

• The Uterus
o Uterine blood flow progressively increases throughout the pregnancy to meet the demands of the growing fetus. At term, UBF reaches 500-700
mL/min or about 10% of the cardiac output.
o Uterine blood flow does NOT autoregulate—therefore it is dependent on MAP, cardiac output, and uterine vascular resistance. Since it is a low
resistance system, uterine blood flow is primarily dependent on MAP and cardiac output.

o Causes of Reduced Uterine Blood Flow:

§ Decreased Perfusion: maternal hypotension (Sympathectomy, hemorrhage, aortocaval compression)
§ Increased resistance: uterine contraction, hypertensive conditions that increase UVR
o Effects of Vasopressors on Uterine Perfusion: Phenylephrine vs Ephedrine
§ Classic teaching states that phenylephrine increases uterine vascular resistance and reduces placental perfusion. More recent
evidence suggests that phenylephrine is as efficacious as ephedrine in maintaining placental perfusion and fetal pH in healthy
mothers. In fact, mothers that received phenylephrine had higher fetal pH values (less fetal acidosis).
o Transfer of Anesthetic Drugs Across the Placenta
§ A drug will traverse a biologic membrane as described by the Fick people.

§ As you can see from this equation, the most important variables here are the diffusion coefficient (drug characteristics) and the
concentration gradient between the maternal and fetal circulation.
• Fetal acidosis can increase the concentration gradient, which leads to fetal ion trapping.
• Route of administration (how it affects peak plasma levels—IV will be higher than IM or SC)
§ Drug Characteristics that Favor Placental Transfer:
• Low molecular weight < 500 Daltons (most anesthetic drugs are smaller than 500 Daltons)
• High lipid solubility
• Unionized
• Nonpolar

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• Stages of Labor
o Labor is divided into 3 stages:
§ Stage 1—beginning of regular contractions to full cervical dilation (10 cm)
§ Stage 2—full cervical dilation to delivery of the fetus (pain in the perineum begins during stage 2)
§ Stage 3—Delivery of the placenta
o The Friedman curve illustrates the normal progress of labor.
§ Dysfunctional labor occurs when labor does not
follow the expected pattern. Oxytocin may be
required to help the labor progress.
§ Understanding this curve will help you answer
questions about anesthetic techniques used during
labor.
• NPO Guidelines
o Having a baby is serious work! The laboring mother
requires adequate nutrition and hydration to support her
and the baby during labor.
o It doesn’t matter when mom last ate or drank—she is
always considered a full stomach! According to the ASA
Practice Guidelines for Obstetric Analgesia, the laboring mother who is healthy may:
§ Drink a moderate amount of clear liquids throughout labor.
§ Eat solid food up to the point a Neuraxial block is placed.
o Having said this, the patients should remain NPO if there is a high probability of a surgical intervention requiring a
general anesthetic.
• Timing of Epidural Placement
o Although there continues to be misconceptions about Neuraxial anesthesia in OB, here’s what you need to know.
§ It does NOT prolong the first stage of labor.
§ It does NOT increase the risk of c-section.
o The American College of Obstetricians and Gynecologists (ACOG) Guidelines for Assessment of the Obstetric
Patient recommend that the timing of epidural placement should be individualized to each patient, and a patient
should NOT have to wait until she achieves a predetermined cervical dilation before she can receive analgesia.
• Labor Pain
o Pain Pathways
§ When evaluating labor pain, you must consider the patient’s stage of labor.
§ First Stage:
• Pain begins in the lower uterine segment and the cervix
• Pain signals travel to the T10-L1 posterior nerve roots.
§ Second Stage:
• Adds in pain impulses from the vagina, perineum, and pelvic floor.
• Pain impulses travel from the perineum to the S2-S4 posterior nerve
roots.
• Neuraxial techniques that provide analgesia to T10-L1 during the first
stage of labor must be extended to cover S2-S4 during the second
stage of labor.

§ Consequences of Uncontrolled Pain:

• Increased maternal catecholaminesàhypertension and reduced uterine blood flow
• Maternal hyperventilation à leftward shift of oxyHgb curveàreduced delivery of O2 to the fetus.
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 o Nitrous Oxide
§ Inhaled nitrous oxide is making a resurgence as a non-invasive alternative for labor analgesia.
• A common approach is 50% nitrous oxide + 500% oxygen self-administered by the patient via
facemask.
• When administered alone (not with opioids), a 50/50 N2O/O2 mixture is not associated with
hypoxia, loss of airway reflexes, or unconsciousness.
• N2O preserves uterine contractility and it does not cause neonatal depression.
o Combined Spinal Epidural Technique
§ The CSE technique provides the dual benefit of a rapid onset of spinal anesthesia and the ability to
prolong the duration of anesthesia with an indwelling epidural catheter. This technique is particularly
useful in labor and delivery.
§ The “needle through the needle” technique is the most common approach.
• The epidural space is identified with the epidural needle.
• A spinal needle is placed through the epidural needle, and then LA and/or opioid is injected into
the intrathecal space.
• The spinal needle is removed.
• An epidural catheter is threaded through the epidural needle.
§ The epidural volume extension technique involves injection of saline into the epidural space immediately
after the local anesthetic is administered into the subarachnoid space.
• Adding volume to the epidural space compresses the subarachnoid space, and this enhances the
rostral spread of the local anesthetic.
• Said another way, this technique pushes the LA towards the brain to achieve a higher level for a
given dose.
• Administering a smaller dose of local anesthetic in the subarachnoid space provides a more
stable hemodynamic profile as well as a faster recovery.
• Local Anesthetics
o Although we covered local anesthetic extensively in their own tutorial, here’s a summary of the key points as they
relate to obstetrics.

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• Total Spinal
o A total spinal may result from:
§ An epidural dose injected into the subarachnoid space.
§ An epidural dose injected into the subdural space.
§ A single shot spinal after a failed epidural block.
o An Epidural Dose is Injected into the Subarachnoid Space
§ This one is obvious. Moving on…
o An Epidural Dose is Injected into the Subdural Space
§ Although a rare and unpreventable event, it is possible to position the tip of the epidural catheter in the subdural space—between
the dura and the arachnoid. Neither catheter aspiration or a test dose will rule out subdural placement.
§ Within 10-25 minutes after the epidural is dosed, the patient will experience symptoms of an excessive cephalad spread of local
anesthetic. Because the subdural space is a potential space, it holds a very low volume. For this reason, the block height for a given
amount of local anesthetic will be much higher than if the same volume was administered in the epidural space.
o A Single Shot Spinal after a Failed Epidural Block
§ There are several theories that explain why a total spinal might occur with a single shot SAB after a failed epidural block.
• The volume given during the epidural had to go somewhere. It may compress the subarachnoid space, thereby reducing
its volume. This would cause a higher than expected spread with a given dose of local anesthetic.
• You’ll puncture the dura during the single shot spinal. It is possible the local anesthetic from the failed epidural leaks
through the hole to enter the subarachnoid space.
o Presentation
§ There is a rapid progression of sensory and motor block. Symptoms include dyspnea, difficulty phonating, and
hypotension. Loss of consciousness occurs as a result of cerebral hypoperfusion secondary to severe hypotension.
o Anesthetic Management
§ Initial treatment includes: vasopressors, IVF, left uterine displacement, and elevation of the legs.
§ If the patient loses consciousness or is unable to protect her airway, you should intubate the trachea.
§ Your differential diagnosis should include: anaphylactic shock, eclampsia, and amniotic fluid embolism.
• Fetal Heart Rate
o The heart rate is a surrogate measure of overall fetal wellbeing. It provides an indirect method to assess fetal hypoxia and acidosis. Use of this
modality guides clinical decision making, so that we can minimize the risk of fetal injury and demise.
o Fetal oxygenation is a function of uterine and placental blood flow. The fetus responds to stress with peripheral vasoconstriction, hypertension,
and a baroreceptor mediated reduction in heart rate.

o Baseline Heart Rate Variability

§ A healthy fetus should demonstrate heart rate variability (normally 6-25 bpm). This measurement excludes acceleration and
deceleration phenomena. Variability suggests an intact central nervous system and that the SNS and PNS are functioning in a healthy
manner. Also, it is an indicator of oxygenation and a normal acid-base status.
§ Variability can be categorized as:
• Minimal < 5 bpm
• Moderate 6-25 bpm
• Marked > 25 bpm
• Absent a worsening finding
§ The following will reduce variability:
• CNS depressant drugs (opioids, sedatives, anesthetic agents, barbiturates, magnesium sulfate)
• Hypoxemia
• Fetal sleep
• Acidosis
• Anencephaly
• Cardiac anomalies

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o Deceleration Phenomena
§ There are 3 types of fetal deceleration phenomena: early, late, and
variable.
§ Here’s a mnemonic to tie it together: VEAL CHOP
• Variable decels: Cord compression
• Early decels: Head compression
• Accelerations: Ok to give oxygen
Late decels: Placental insufficiency

o Three-Tier System for the Evaluation of FHR.

§ The American College of Obstetricians and Gynecologists recommends the three-tier system for the
evaluation of fetal heart rate.
• Category I strongly suggests normal acid-base status with no threat to fetal oxygenation
• Category III strongly suggests abnormal acid-base status with a significant threat to fetal
oxygenation
• Category II is not I or III and cannot predict a normal or abnormal acid-base status.
§ Category I
• Baseline heart rate between 110-160
• Moderate variability
• Accelerations absent or present
• Early decelerations absent or present
• No late or variable decelerations
§ Category II
• Bradycardia without absence of baseline FHR variability
• Tachycardia
• Variable variability
• Absent or minimal acceleration with fetal stimulation
• Recurrent variable decelerations
§ Category III
• Bradycardia
• Absent baseline variability
• Recurrent late deceleration
• Recurrent variable deceleration
• Sinusoidal pattern
§ Someone trained in fetal monitoring must monitor and document fetal status prior to and after any
anesthetic procedure.

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• Prematurity & Tocolysis
o Prematurity
§ Premature delivery is defined as delivery before 37 weeks gestation or less than 259 days from the last menstrual cycle. It is the
leading cause of perinatal morbidity and mortality, and this risk is even higher for newborns weighing less than 1500g. the incidence
of prematurity rises with multiple gestations and premature rupture of membranes.
§ Complications of premature delivery include:
• Respiratory distress syndrome
• Intraventricular hemorrhage
• NEC
• Hypoglycemia
• Hypocalcemia
• Hyperbilirubinemia
§ Corticosteroids (betamethasone) hasten fetal lung maturity. These drugs begin to take effect within 18 hours, with a peak benefit at
48 hours. Tocolytic agents stop labor ~24-48 hours. They provide a bridge that allows the corticosteroids time to work. Antibiotic
prophylaxis for chorioamnionitis is also given at this time. Tocolytic agents or corticosteroids are seldom given after 33 weeks
gestation.
§ Beta-2 Agonists
• Beta-2 stimulation increases intracellular cAMP. In turn, this turns on protein kinase, turns off myosin light-chain kinase,
andultimately relaxes the uterus. It also increases progesterone release, which contributes to additional myometrial
relaxation.
• Examples include: terbutaline and ritodrine
• Side Effects:
o Hyperglycemia results from glycogenolysis in the liver.
o The newborn of a hyperglycemic mother is at risk of post-delivery hypoglycemia. The mother’s glucose supply
is gone, but the insulin in the neonatal circulation remains.
o Hypokalemia results from an intracellular potassium shift.
o Beta-2 agonists cross the placenta and may increase FHR.
§ Magnesium Sulfate
• Magnesium is a calcium antagonist—it relaxes smooth muscle by turning off myosin light-chain kinase in the vasculature,
airway, and the uterus. Also, it hyperpolarizes membranes in excitable tissues.

• * Having 2 charts with 2 different ways to measure serum magnesium might seem a bit confusing. The problem is that you’ll find
this information presented differently from one book to the next, so we wanted to make sure that you have the most complete
picture. Having said this, md/dL appears to be the most common type of measurement.
• Side Effects:
o Pulmonary edema
o Hypotension
o Skeletal muscle weakness (synergism with nondepolarizers)
o CNS depression
o Reduced responsiveness to ephedrine and phenylephrine
• Treatment for Hypermagnesemia:
o Supportive measures
o Diuretics (to facilitate excretion of Mg+2)
o IV calcium (to antagonize Mg+2)
§ Calcium Channel Blockers
• CCBs block the influx of Ca+2 into the uterine muscle, which reduces Ca+2 release from the SR. in turn, this turns off
myosin light-chain kinases and relaxes uterine muscle.
• Nifedipine may be given orally.
• Co-administration with magnesium can contribute to skeletal muscle weakness.
§ Nitric Oxide Donors
• Nitric oxide is a vasodilator that is essential in maintaining smooth muscle tone. It increases cGMP, turns off myosin light-
chain kinases, and relaxes uterine muscle. They are rarely used due to hypotension.

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• Uterotonic Drugs
o Oxytocin
§ Synthesized in the supraoptic and paraventricular nuclei of the hypothalamus. It is release from the
posterior pituitary gland.
§ Endogenous oxytocin is released following stimulation of cervix, vagina, and/or breasts.
§ Pitocin is the synthetic equivalent.
§ May be given IV or injected directly into the uterus.
§ Indications: to induce or augment labor, stimulate uterine contraction, combat uterine hypotonia and
hemorrhage.
§ During C/S, it is administered after the delivery of the placenta.
§ Side effects: water retention, hyponatremia, hypotension, reflex tachycardia, coronary vasoconstriction.
§ Hepatic metabolism.
§ Half-life: 4-17 min
o Methergine
§ Eergot alkaloid
§ Second-line uterotonic
§ Dose: 0.2 mg IM
§ IV administration can cause significant vasoconstriction, hypertension and cerebral hemorrhage.
§ Hepatic metabolism
§ Half-life: 2 hours
o Prostaglandin F2 (Hemabate or Carboprost)
§ Third line uterotonic
§ Dose: 250 mcg IM or injected into the uterus.
§ Side effects: N/V, diarrhea, hypotension, or hypertension
• Cesarean Section: General Anesthesia
o Although regional anesthesia is the preferred technique for cesarean delivery, there are some situations where a
general anesthetic is more appropriate. These include:
§ Maternal hemorrhage
§ Fetal distress
§ Coagulopathy
§ Patient refusal of regional anesthesia
§ Contraindications to regional anesthesia

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o Blueprint for General Anesthesia
§ In this patient population, mortality is 17-times higher with a general anesthetic. Avoid it whenever
possible! Failure to successfully manage the airway is the most common cause of maternal death.
§ Here is a blueprint that details the most critical components of performing general anesthesia for
cesarean section:
• Plan for a difficult intubation.
• Triple prophylaxis against aspiration:
o Sodium citrate to neutralize gastric acid
o H2 receptor antagonist (ranitidine) to reduce gastric acid secretion
o Gastrokinetic agent (metoclopramide) to hasten gastric emptying and increases LES
tone
• Left uterine displacement to minimize aortocaval compression.
• Apply monitors and make sure that suction is functional.
• Allow the surgical team to prep and drape prior to induction.
• Preoxygenate for 3-5 minutes or give 4 vital capacity breaths.
• HELP position (head elevated laryngoscopy position). You should be able to envision a horizontal
line connecting the sternal notch and the external auditory meatus; the head and neck should be
above the chest.
• Induce anesthesia with one of the following:
o Propofol 2-2.5 mg/kg
o Etomidate 0.3 mg/kg
o Ketamine 1 mg/kg
o Neonatal depression is short lived because of redistribution
• A defasciculating dose is not needed for succinylcholine – pregnancy reduces the risk of myalgia.
• Use a short handled laryngoscope (Datta handle).
• Perform an RSI with a 6.0-7.0 endotracheal tube. The esophagus is compressed between the cricoid ring
and the sixth cervical vertebra.
• The BURP maneuver (backward, upward, rightward pressure on the thyroid cartilage) will improve your
laryngoscopic view.
• Confirm proper placement of ETT prior to surgical incision.
• Use a low concentration of volatile agent (0.8 MAC) + 50% nitrous oxide. Emergent cesarean section carry a
high risk of recall. Recognize that volatile agents reduce uterine contractility, but be sure to use enough
agent to cause amnesia.
• Maintain PaCo2 at 30-32 mmHg. Hyperventilation beyond this reduces uterine blood flow and causes a
leftward shift of the oxyhgb dissociation curve (decreased P50).
• The risk of neonatal acidosis increases when the time between uterine incision and delivery exceeds 3
minutes. Someone other than you who’s trained in neonatal resuscitation should be present.
• Give oxytocin after the placenta is delivered. Consider the use of an opioid and a benzodiazepine after the
baby is delivered.
• Blood loss varies, but transfusion is rarely required. Normal amniotic fluid volume is ~700 mL.
• Extubate when patient is fully awake. The patient is still considered a full stomach and is at risk for airway
obstruction.

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• Nonobstetric Surgery during Pregnancy
o Overview
§ Approximately 2% of parturients undergo nonobstetric procedures involving anesthesia each year.
• Maternal risks arise from the anatomic and physiologic changes associated with pregnancy (difficult intubation and
increased risk of aspiration).
• Fetal risks include growth restriction, low birth weight, demise, and an increased incidence of preterm labor (highest
incidence = intraabdominal and pelvic surgery)
• In an ideal world, surgery is delayed 2-6 weeks after delivery. Otherwise, the second trimester is the best time for surgery
in the pregnant patient. This avoids the higher risk of teratogenicity during the first trimester and the increased risk of
preterm delivery that’s highest during the third trimester.
o Teratogenicity
§ Teratogenicity can occur at any time during pregnancy, however the risk is highest during organogenesis (day 13-60). Although there
is some evidence that links high-dose diazepam in the first trimester to cleft palate. Barash says that a preoperative benzodiazepine
is acceptable for treating preoperative anxiety.
§ Nitrous oxide is linked to birth defects in animals who receive it for 1-2 days
(inhibition of DNA synthesis). Human data is lacking, although many practitioners
avoid N2O during the first two trimesters.
o Anesthetic Management
§ Consider aspiration prophylaxis if mom is beyond 14 weeks gestation. Administer
an antacid (sodium citrate 15-30 mL) within 30 min of induction, ranitidine 1 hour
prior to induction and consider metoclopramide to facilitate gastric emptying.
§ If mom is beyond 14 weeks gestation, secure the airway with a rapid sequence
intubation and a 6.0-7.0 endotracheal tube.
nd rd
§ Use left uterine displacement in the 2 and 3 trimester.
§ Avoid hypoxemia, hyperventilation, hypotension, and acidosis.
§ Anesthesia and surgery do not increase the incidence of congenital anomalies.
§ Avoid NSAIDS after the first trimester, as they may close the ductus arteriosus.
§ Stick with drugs with a long track record of safety such as:
• Thiopental
• Opioids
• Inhalation agents
• All muscle relaxants
• Obstetric Hypertensive Disorders: Pathophysiology
o The specifics of obstetric hypertensive disorders can be
particularly troubling for students. Let’s define each
condition, then review the pathophysiology in greater
detail.
o The classic triad of preeclampsia consists of
hypertension that
develops after 20 weeks
gestation, proteinuria,
and generalized edema. It
should be noted that
Anesthesia and Co-Exiting
Disease states that
edema is no longer
required for diagnosis.
o Preeclampsia:
Pathophysiology
§ Preeclampsia is the most common critical pathology associated with the healthy parturient. It affects 5-7% of the
obstetric population. Although it’s etiology is unknown, it is more common in mothers < 20 years old as well as those
>35 years old. Patients with chronic renal disease and those that are homozygous for the angiotensinogen T235 have
the highest risk of developing preeclampsia.
§ The prevailing theory postulates that abnormal placental implantation creates an environment characterized by an
elevated vascular resistance and a reduction in placental blood flow. In turn, the placenta and fetus do not receive an
adequate supply of oxygen and metabolic substrate to develop in a normal way.
§ The healthy placenta produces thromboxane and prostacyclin in equal amounts; however, the patient with
preeclampsia produces up to 7 times more thromboxane than prostacyclin. Increased thromboxane favors
vasoconstriction, platelet aggregation, and a reduced placental blood flow. Furthermore, the diseased placenta
releases a variety of cytokinases that promote endothelial dysfunction throughout the body.

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o Severity of Disease
§ Preeclampsia can be categorized as mild or severe. Understand that not all patients progress in a step-wise fashion
from hypertension to preeclampsia to eclampsia. Indeed, 25-40% of patients will be normotensive when they have
their first seizure.

o Treatment
§ The definitive treatment for preeclampsia and eclampsia is delivery of the fetus and placenta. If the symptoms are
mild and the fetus is young, then the mother may be managed conservatively with observation and bed rest. When
the symptoms become severe or fetal distress ensues, immediate delivery is mandatory to ensure the safety of the
mother.
§ Unless the blood pressure exceeds 160/110, there is little need to administer antihypertensive medications. The
primary reasons why we medicated beyond 160/110 is to prevent cerebrovascular accident, myocardial ischemia, and
placenta abruption.
o Eclampsia
§ The presence of seizures differentiates between preeclampsia and eclampsia.
§ Seizure prophylaxis with magnesium sulfate:
• Load: 4g loading dose over 10 minutes
• Infusion: 1-2 g/hr
• Treatment for Mg toxicity: 10 mL of 10% calcium gluconate IV
• Fibrin deposition reduces organ perfusion and is common in patients with preeclampsia. Magnesium sulfate
decreases the rate of fibrin deposition in the vital organs.
o Anesthetic Management for Preeclampsia
§ Fluid management is balanced between a volume contracted patient and a “leaky” vasculature from endothelial dysfunction.
§ Neuraxial anesthesia assists with blood pressure control and provide betters uteroplacental perfusion.
§ Be sure to rule out thrombocytopenia (<100,000) before performing a Neuraxial block.
§ Due to airway swelling, these patients have a higher incidence of difficult intubation.
§ These patients have an exaggerated response to sympathomimetics and methergine.
§ If they are receiving magnesium therapy, they will exhibit an increased sensitivity to neuromuscular blockers.
§ Magnesium relaxes the uterus and increases the risk of postpartum hemorrhage.
o HELLP Syndrome
§ HELLP syndrome stands for: Hemolysis, Elevated Liver enzymes, and Low Platelet count.
• It develops in 5-10% of those with preeclampsia. These patients experience epigastric pain and upper
abdominal tenderness.
• Like preeclampsia, definitive treatment for HELLP syndrome is delivery of the fetus.
• Patients are at higher risk for DIC and intra-abdominal bleeding from the liver.

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 o Maternal Cocaine Abuse
§ Cocaine is an ester-type local anesthetic that inhibits NE reuptake in the presynaptic SNS neuron. Flooding the
synaptic cleft with NE increases SNS tone.
• CV risks include tachycardia, dysrhythmias, and myocardial ischemia.
• Acute intoxication increases MAC.
• Chronic use decreases MAC.
• OB risks include spontaneous abortion, premature labor, placental abruption, and low APGAR scores.
• Hypertension is probably best treated with vasodilators.
• Beta blockers can cause heart failure if the SVR is significantly elevated.
• Hypotension may not respond to ephedrine in chronic cocaine abuse (d/t catecholamine depletion).
Phenylephrine is the best option.
• Chronic cocaine abuse is associated with thrombocytopenia (check platelet count before Neuraxial
anesthesia).
• Disorders of the Placenta
o Placenta Accreta
§ The placenta normally implants into the decidua of the endometrium.
§ There are three types of abnormal placental implantation:
• Accrete—attaches to the surface of the myometrium
• Increta—invades the myometrium
• Percreta—extends beyond the uterus
§ Uterine contractility is impaired and there is a potential for tremendous blood
loss.
§ Though Neuraxial anesthesia is safe, GA is preferred.
§ Closely associated with placenta previa and previous cesarean sections.
§ Danny had a frightening case in the OR.
o Placenta Previa
§ Placenta attaches to the lower uterine segment.
§ It partially or completely covers the cervical os.
§ Associated with painless vaginal bleeding.
§ Potential for hemorrhage.
§ Often requires cesarean section.
§ Risk factors include:
• Previous cesarean sections
• History of multiple births
o Placental Abruption
§ Partial or complete separation of placenta from the uterine wall prior to delivery
§ Risk factors include:
• PIH
• Preeclampsia
• Chronic hypertension
• Cocaine use
• Smoking
• Excessive alcohol use
§ Results in hemorrhage and fetal hypoxia
§ Risk of amniotic fluid embolism leading to DIC
§ Vaginal delivery is possible if fetus is stable
§ Obtain large bore IV access and have blood products available
§ Prepare for cesarean section
Obstetric Bleeding
• Postpartum Hemorrhage
o The uterus receives 500-700 mL/min or 10% of the cardiac output. Blood loss can be rapid and profound!
o Uterine atony is the most common cause of postpartum hemorrhage. The risk of uterine atony is increased by
§ Multiparity
§ Multiple gestations
§ Polyhydramnios
§ Prolonged oxytocin infusion prior to surgery
o Other causes of obstetric bleeding include:
§ Retained placenta/placenta fragments—IV nitroglycerine provides uterine relaxation for placental extraction
§ Laceration to the cervix or vaginal wall
§ Uterine inversion
§ Coagulopathy
o An intrauterine balloon will tamponade the bleed when uterine massage, oxytocin, ergot alkaloids, and manual massage are ineffective. Follow
hemorrhage protocols at your institution.
o Ketamine, etomidate, midazolam, and opioids cause minimal cardiovascular depression and may be useful in this situation.
o In the hemodynamically unstable patient, it may be prudent to convert a regional anesthetic to a general anesthetic with RSI.

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 • Disseminated Intravascular Coagulopathy
o DIC is associated with:
§ Amniotic fluid embolism
§ Placenta abruption
§ Intrauterine fetal demise
o It is often accompanied by circulatory shock
Apgar Score & Neonatal Resuscitation
§ The Apgar score is used to assess the newborn and guide resuscitative efforts. Five parameters are evaluated at 1 and
5 minutes after delivery. The score at 1 minute correlates with fetal acid-base status, while the 5 minute score may be
predictive of neurologic outcome.
• Normal=8-10
• Moderate distress=4-7
• Impending demise=0-3
§ Know how to calculate the Apgar score

• Neonatal Resuscitation
o Healthy neonates do not require resuscitaiton. 10% of all newborns require some degree of resuscitation and 1% necessitate
full CPR.
o Radiant heat protects against hypothermia.
o The normal heart rate is 120-160 bpm. A heart rate < 100 bpm significantly reduces cardiac output and impairs tissue perfusion.
o The normal respiratory rate is 30-60 bpm.
o Breathing begins 30 seconds after delivery and a normal pattern is established at 90 seconds.
o Immediately after delivery, the normal SpO2 is 60%. It should rise to 90% after 10 minutes.
o Supplemental oxygen increases the risk of an inflammatory response. If assisted ventilation is required, use room air instead of
100% O2. If bradycardia or inadequate oxygenation persist, the use of supplement O2 must be balanced against this risk.
o While thick meconium should be removed from the airway, there is no clinical benefit gained from removing thin or watery
meconium.
o Compressions should be over the lower third of the sternum with
a depth of one third of the AP of the chest.
o Resolution of bradycardia is the best indicator of adequate
ventilation.
o If ventilation does not improve cardiovascular performance, then
emergency drugs can be given through 3 possible routes: umbilical
vein, endotracheal tube, or intraosseous

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Geriatric

• Geriatrics Overview & Metabolic Equivalents

o By 2050, individuals over 60 years of age will outnumber younger adults for the first time in history. As a result of this trend, your exposure to
geriatric patients is going to increase dramatically. We use the terms geriatric and elderly interchangeably and define this group as 65 years or
older.
o Life expectancy trends in the U.S. à
o Said to be the bearer of bad news, but most of you reading this are either at the APEX of
your physiologic function or have already begun the inevitable decline. In case you are
wondering, physiologic function begins to wane as early as age 30. Take heart in knowing
that, by taking care of yourself, it is possible to be the chronologically old, yet remain
physiologically young. Having said this, the most significant risk factor for developing
cancer is old age.
o Aging goes hand in hand with a progressive decline in the physiologic function as well as an
increased likelihood of coexisting disease. There are certain undeniable truths regarding gaining and anesthesia. The elderly have a reduced
functional reserve, and as a direct result of this, they are less able to adapt to the stress of surgery and anesthesia.
• Metabolic Equivalents
o We need a bedside tool that allows us to measure functional reserve nd identify those who are at greater perioperative risk. The concepts of
metabolic equivalents allows us to do this.
Metabolic Equivalent = Metabolic Rate of a Specific Physical Activity
Metabolic Rate at Rest
o By convention, one MET is equal to an oxygen consumption of 3.5 mL O2/kg/min. inability to achieve 4 METs is associated with increased
perioperative risk. For every MET a patient can achieve, mortality decreases by 11%.
o Answering “yes” to the following questions indicates the patient is ok for surgery without the need for additional cardiac testing—assuming
cardiac status is optimized:
§ 1. Can you walk up a flight of steps without stopping?
§ 2. Are you able to walk 4 blocks without stopping?

o Let’s look at how aging alters organ function. Much of this is rote memorization, however if you take time to understand the physiology behind
these changes, you’ll ease your workload. Furthermore, knowing how a small number of functions change will allow you to predict many of the
changes that accompany the aging process. We have constructed many tables for you with this concept in mind.
• Respiratory

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• Lung Volumes & Capacities
o The aged lung has a reduced elastic recoil, which causes it to become over filled with
gas. This process increases residual volume—the volume that remains in the lungs after
a full exhalation. The excess residual volume explains why the functional residual
capacity is increased.
o The reduction in elastic recoil is also the reason why the small airways have a greater
tendency to collapse—closing capacity increases. Closing capacity surpasses FRC at ~45
years old in the supine position and ~65 years old when standing. This means that the
small airways will collapse during tidal breathing, which sets the stage for V/Q
mismatch, increased anatomic dead space, and a reduction in PaO2.
o Vital capacity is reduced due to reduced lung elastic
recoil, increased chest wall stiffness, and weaker
respiratory muscles. Total lung capacity is
unchanged, because of the increase in RV and the
reduction in VC. Because the total lung capacity is
unchanged, a change in one volume or capacity
usually causes a change in another.

• Cardiovascular
o Cardiac disease is the most common coexisting
disease seen in the elderly. The 4 most
common conditions are hypertension, CAD,
CHF, and myocardial ischemia. The best
indicator of cardiac reserve is exercise
tolerance and the ability to perform physical
activities of daily living. In the postoperative
period, myocardial infarction is the most
common cause of death.

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• Autonomic Nervous System
o Autonomic dysfunction is associated with the normal aging process.

• Nervous System Postoperative Delirium vs Postoperative Cognitive Dysfunction

• Neuraxial Anesthesia

• The Kidney
o The kidney’s ability to regulate intravascular volume, electrolytes, acid/base balance, and plasma drug concentration is of profound importance. The
reduction in renal reserve is well tolerated in health. However, surgery or disease can overwhelm the kidney’s ability to maintain homeostasis.
Perioperative renal failure is associated with a very high mortality.
o Great care should be given to perioperative fluid management. Impairments of sodium handling, the ability to concentrate urine, and the capacity to
dilute urine predispose these patients to fluid overload as well as
dehydration. Additionally, venous compliance is reduced, which
adversely affects the ability of the venous circulation to function as a
reservoir. The kidneys also have a more difficult time correcting
electrolyte imbalances as well as titrating excess non-volatile acids.

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• The Liver

• Pharmacokinetics & Pharmacodynamics

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Across the Lifespan Notes

362
Chemistry & Physics

• Atomic Bonding
o Atoms
§ The atom is the basic building block that makes up all matter. It consists of 3
components:
• [Link] (+ charge)
• 2. Neutrons (no charge)
• 3. Electrons (- charge)
§ The protons and neutrons reside at the center of the atom, and together they form
the nucleus. The number of protons in the nucleus determines the atom’s atomic number.
§ The electrons orbit the nucleus in the electron cloud. Because electrons have a negative charge, they are attracted to
the positive charge of the nucleus. This keeps the electrons from flying away.
§ Electrons travel in predictable orbit patterns called shells.
• Each shell has a predefined number of electrons, and each shell must be complete before electrons can
begin to fill the next shell.
• The electrons in the outer most shell are called valence electron.
• An incomplete shell allows an atom to react with another atom.
• A full shell makes the atom non-reactive (inert).
§ Two or more atoms bonded together is called a molecule.
o Electrical Charge and Ions
§ An atom will have a:
• Neutral charge if: # electrons = # protons
• Positive charge if: # electrons < # protons
• Negative charge if: # electrons > # protons
§ An ion is an atom that carries a positive or negative charge.
• An atom with a positive charge (it has lost electrons) is called a
cation.
• An atom with a negative charge (it has gained electrons) is called an anion.
§ Metals tend to ionize, while non-metals do not.
o Chemical Bonding
§ 1. Ionic Bonds:
• an ionic bond involves the complete transfer of valence electron(s) from one atom to another. This leaves one atom with
a negative charge and the other with a positive charge. Metals tend to form ionic bonds.
o Common with acids and bases.
§ 2. Covalent Bonds:
• A covalent bond involves the equal sharing of electrons.
o A single bond is created when 1 pair of electrons is shared.
o A double bond is created when 2 pairs of electrons are shared.
o A triple bond is created when 3 pairs of electrons are shared.
§ 3. Polar Covalent Bonds:
• Polar covalent bonds are an “in-between” type of bond.
• Atoms share electrons, but the electrons tend to remain closer to one atom than
the other. This creates a polar molecule, where one area of the molecule is
relatively positive (d+) and the other is relatively negative (d-). A key example is
water, where the region near the oxygen atom is relatively negative (the electrons
spend more time near it) and the region near each hydrogen atom is relatively positive (the electrons spend less time
near it).
• How does this relate to the hydrogen bonding of water?
o Because water is a polar molecule, the oxygen of one water molecule is attracted to the hydrogen of another
water molecule. This forms the basis of the hydrogen bonding of water.
• How does this affect water’s function as a solvent?
o Another consequence of water being a polar molecule is that it’s also attracted to other polar molecules and
ions. This explains why a hydrophilic solute dissolves in water.
o By contrast, water does not dissolve non-polar substances like oil or fat (they are hydrophobic).
§ 4. Van der Waals forces:
• Van der Waals forces describe a very weak intermolecular force that holds molecules of the same type together.
• Electrons (and their negative charges) orbiting a molecule are in contrast motion. This creates temporary partial (+) and
(-) charges at different parts of the molecule at any given time. The net results in that electron rich areas of one molecule
will be attracted to electron poor areas of another molecule.
§ Molecular bonds in decreasing order of strength:
• Covalent > Ionic > Polar covalent > Van der Waals

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• Dalton’s Law of Partial Pressures
o Dalton’s law of partial pressures says that the total pressure is equal to the sum of the partial pressures exerted by each gas in
the mixture.
P total= P1 + P2 + P3…
o Ways to Apply Dalton’s Law
§ 1. Calculate the Partial Pressure of an Unmeasured Gas
• if you are given the P total and all the other pressures
except one, you can use simple algebra to figure out the
partial pressure of the unmeasured gas. We’ve included
some practice questions, and you can find the answers at
the bottom of the page.
• Practice questions: calculate P3.
o P total= 100mmHg
o P1= 20 mmHg
o P2= 20 mmHg
o P3= X mmHg
§ 2. Calculate the Total Pressure
• Add the partial pressures of each gas to determine the total partial pressure.
• Practice Question: Calculate the total partial pressure.
o P1= 30 mmHg
o P2= 40 mmHg
o P3=50 mmHg
o P total = X mmHg
§ 3. Convert Partial Pressure to Volumes Percent
• volume percent is a way to communicate a solution’s concentration. It is expressed as a volume fraction
over a denominator of 100. We’ve included two equations to help you wrap your mind around the concept.
• For a liquid: Volume percent = (Volume of solute / Volume of solution) x 100
• For a gas: Volume Percent = (Partial pressure/Total pressure) x 100
• Practice question: at sea level, the agent monitor measures the end-tidal isoflurane as 8 mmHg. Convert
this to volumes percent.
§ 4. Convert Volumes Percent to a Partial Pressure
• Partial pressure = Volumes percent x Total pressure
• Practice Questions: at sea level, the agent monitor measures the end-tidal sevoflurane as 2%. What is the
partial pressures of sevoflurane in the exhaled tidal volume?
§ Correct Answers
• 1. 20 + 20 + X = 100 (X=60 mmHg)
• 2. 30 + 40 + 50 = X (X=120 mmHg)
• 3. (8/760) x 100 = 1% isoflurane
• 760 x 0.04 = 15.2 mmHg
• Henry & Fick
o Henry’s Law
§ At a constant temperature, the amount of gas that dissolves in solution is directly proportional to the partial pressure
of that gas over the solution. Said another way, the higher the gas pressure, the more of it will dissolve into a liquid
(assuming a constant temperature).
§ Think of a bottle of soda. A high partial pressure of CO2 above the liquid forces some of the CO2 into the liquid. The
amount that dissolves is a function of the partial pressure of the gas.
§ Temperature Affects Solubility:
• ­temp=¯solubility
• ¯temp=­solubility
§ application: anesthetic emergence is prolonged in the
hypothermic patient. Why is this? The solubility of the gas is
increased, and less of it leaves the body per unit time.
§ Solubility Coefficients:
• Each gas has its own solubility coefficient. This
represents how easily the gas can be put into solution.
o Oxygen = 0.003 mL/dL/mmHg
o Carbon dioxide = 0.067 mL/dL/mmHg
• CO2 is ~20 times more soluble than O2. This is important for gas exchange across the alveolocapillary
membrane.

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 o Applications of Henry’s Law
§ Oxygen Delivery:
• Knowing the oxygen solubility coefficient also helps us calculate oxygen delivery. Multiplying the PaO2 by
oxygen’s solubility coefficient (0.003 mL/dL/mmHg) allows us to calculate how much oxygen is dissolved in
the blood.
DO2 = CO x [(1.34 x Hgb x SpO2) + (PaO2 x 0.003)] x 10
• Therefore, we are applying Henry’s law when we increase the FiO2 or place the patient in a hyperbaric
oxygen chamber. Keep in mind, however, that dissolved oxygen represents only a small fraction of the total
oxygen content (CaO2) in the blood. The vast majority of oxygen is bound to hemoglobin.
o Fick’s Law of Diffusion
§ Ficks law of diffusion describes the transfer rate of gas through a tissue medium.
Rate of Transfer is Directly Proportional to: Rate of Transfer is Inversely Proportional to:
Partial pressure difference (driving force) Membrane thickness
Diffusion coefficient (solubility) Molecular weight
Membrane surface area
§ Applications of Fick’s Law:
• Diffusion hypoxia
• A patient with COPD has a reduced alveolar surface area, and therefore has a slower rate of inhalation induction
• Calculation of cardiac output
• Drug transfer across the placenta
• The Gas Laws
o Understanding the gas laws allows us to predict a gas behavior. It also helps you score easy points on boards.
o To predict how a gas will behave in a given context, you must know the equation for each law and be able to manipulate it
algebraically. In each equation, variable 1 represents the original value and variable 2 represents the new value.

o Boyle’s law has an inverse relationship:

§ As one variable gets larger, the other gets smaller.
§ As one variable gets smaller, the other gets larger.
o Charle’s law and Gay-Lussac’s law have direct relationships:
§ As one variable gets larger, the other gets larger.
§ As one variable gets smaller, the other gets smaller.
o Know Which Variable is Constant in Each Equation
§ You’re also expected to understand which variables remain constant in each gas law, and the mnemonic “Paid TV Can Be Great” can help you.
• The top row represents the variables in each equation (pressure, temperature, and volume).
• The bottom row represents the gas laws (Charles, Boyle, and Gay-Lussac).
• The red variable directly above each gas law is NOT included in that law (it is a constant).
• The green variables are included in the particular law.
o Know Some Examples of the Gas Laws in Practice
§ Boyle’s law (P x V):
• Diaphragm contraction increases tidal volume
• Pneumatic bellows
• Squeezing a bag valve mask
• Using the bourdon pressure gauge to calculate how much O2 is left in a cylinder (assumes a given flow rate)
§ Charles’s law (V/T):
• LMA cuff ruptures when placed in an autoclave
§ Gay-Lussac’s law (P/T):
• Oxygen tank episodes in a heated environment
o The Ideal Gas Law (Universal Gas Law)
§ The ideal gas law unifies all 3 gas laws into a single equation, where: PV=nrT
• P=pressure
• V=volume
• N=number of moles
• R=constant 0.0821 liter-atm/K/mole
• T=temperature
§ If you were asked to think about this conceptually, then you could reduce it to: P=T/V

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• Ohm’s Law & Poiseuille’s Law
o Flow is defined as the movement of electricity, fluid, or air per unit time.
o Ohm’s Law
§ Ohm’s law says that the current passing through a conductor is directly proportional to the voltage and inversely
proportional to the resistance. We can adapt Ohm’s law to understand fluid flow.

o Poiseuille’s Law
§ Poiseuille’s law is a modification of Ohm’s law that incorporates vessel diameter, viscosity, and tube length.

o A Few Points About Flow

§ Altering the radius of the tube exhibits
the greatest impact on flow.
• R=1^4: 1 x 1 x 1 x 1=1
• R=2^4: 2 x 2 x 2 x 2=16
• R=3^4 3 x 3 x 3 x 3=81
• R=4^4: 4 x 4 x 4 x 4=256
§ Viscosity is the result of friction from intermolecular forces as a fluid passes through a tube.
§ A fluid’s viscosity is inversely proportionate to its temperature.
• Decreased temperature increases viscosity and resistance.
• Increased temperature decreases viscosity and resistance.
o Application of Poiseuille’s Law: Administration of PRBCs
§ We can deliver packed the red blood cells faster if we:
• Increase the radius with a large bore IV.
• Increase the pressure gradient with a pressure bag and/or increase the height of the IV pole.
• Decrease the viscosity by diluting the blood with 0.9% NaCl and/or running it’s through a fluid warmer.
• Decrease the length by not using longer tubing than you really need.
• Reynold’s Number
o There are 3 types of flow: laminar, turbulent, and transitional.
o Reynold’s number allows us to predict the type of flow that will occur in a given
situation. There are no units associated with this number.
§ Laminar flow is dependent on gas viscosity (Poiseuille’s law)
§ Turbulent flow is dependent on gas desnity (graham’s law)
o Laminar Flow (Re<2,000):
§ All the molecules travel in a parallel pattern.
§ Due to cohesive forces, the molecules in the center of the tube travel at the fastest rate, while the molecules near the walls of the
tube travel at the slowest rate.
§ Examples of laminar flow:
• Airflow in the terminal bronchioles
• Blood flow in the systemic circulation
o Turbulent Flow (Re > 4,000):
§ All the molecules travel in a chaotic pattern (produces eddies).
§ Turbulent flow tends to be produced by a/an:
• Orifice (change to a narrow diameter)
• High gas flow
• Acute angle in tube (>25 degrees)
• Branching in the tube
§ Examples of turbulent flow:
• Flow through an orifice: glottis or annular space when FGF rate is high.
• Flow at angles: airflow thorugh medium-sized bronchi
§ The patient with status asthmasticus suffers from an increased airway resistance, and this increases flow turbulence and the work of
breathing.
• Because turbulent flow is primarily dependenton gas density, we can improve flow by having the patient inhale a lower
density gas.
• An oxygen/helium mixture (Heliox) decreases Reynold’s number and can improve airflow when airway resistance is high.
• A helium/oxygen mixture is also useful for the patient with epiglottitis.
• Helium does NOT improve flow if it is already laminar.
o Transitional Flow (Re = 2,000 to 4,000):
§ This type of flow displays a turbulent pattern in the center of the tube and a laminar pattern near the walls of the tube.
§ Some texts do not make the distinction between transitional and turbulent flow. In this situation, they define turbulent flow as
>2,000.

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• Bernoulli, Venturi & Coanda
o It’s easy to confuse the Bernoulli principle, venture effect, and Coanda effect, so let’s examine all three.

o Bernoulli’s Principle (Velocity & Pressure)

§ Bernoulli’s principle describes the relationship between the pressure and velocity of a moving fluid (or gas).
• If the fluid’s velocity is high, then the pressure exerted on the walls of the tube will be low.
• If the fluid’s velocity is low, then the pressure exerted on the walls of the tube will be high.
§ Why is this? As fluid moves from a wider tube to a narrower tube (a constriction), the volume of that fluid that moves a given
distance in a given time does not change. Therefore, if the width of the tube suddenly becomes smaller, then the fluid in the
constricted region must move faster to achieve that result. And because the fluid’s velocity has increased at the area of the
constriction, there is a pressure drop at the area of the constriction.
• Example: think of a river. When the river is wide, the water moves slowly, but when it becomes narrow, the water moves
much faster. This is because the same volume of water is moving through the wide and narrow parts of the river at any
given time. When the water is moving slowly, the pressure exerted on the riverbank is higher, and when the river
narrows, the velocity of the water increases, so it exerts less pressure on the riverbank.
o Venturi Effect (Air entrainment)
§ The Venturi effect is an application of the Bernoulli principle. As air flow in a tube moves past the point of constriction, the pressure
at the constriction decreases (Bernoulli principle), and if the pressure inside the tube falls below atmospheric pressure, then air is
entrained into the tube (Venturi effect).
§ Adjusting the diameter of the constriction allows for control of the pressure drop and the amount of air that is sucked into the tube.
The key here is air entrainment!
• Examples: jet ventilator, Venturi, and nebulizer.
o Coanda Effect (Jet flow/Curves)
§ The Coanda effect describes how a jet flow attaches itself to a nearby surface and continues to flow along that surface even when
the surface curves away from the initial jet direction.
• Examples: wall hugging jet or mitral regurgitation and water that follows the curve of a glass.
• Law of Laplace
o In spheres and cylinders, the law of Laplace illustrates the relationship between the wall tension, internal pressure, and radius. Before we go
further, you need to understand the difference between pressure and tension.
§ Pressure is a pushing force. It pushes the walls of the object apart.
§ Tension is a pulling force. It holds the walls of the object together.
o Surface Tension of a Sphere
§ Tension = (Pressure x Radius)/ 2
§ Examples: alveolus, cardiac ventricle, saccular aneurysm
o Surface Tension of a Cylinder
§ Tension = (Pressure x Radius)
§ Examples: blood vessels, aortic aneurysm
o Law of Laplace and the Alveolus
§ Type II pneumocytes begin producing surfactant between 22-26 weeks gestation with peak
production occurring at 35-36 weeks.
§ Surfactant reduces alveolar surface tension and prevents alveolar collapse.
• Each alveolus contains the same amount of surfactant.
• Larger alveoli have a relatively lower concentration of surfactant.
• Smaller alveoli have a relatively higher concentration of surfactant.
• The concentration of surfactant is illustrated by the thickness of the green around each alveolus.
§ As the radius changes, so does the concentration of the surfactant, but the surface tension remains constant. This prevents smaller
alveoli from collapsing and emptying into larger alveoli.
o Law of Laplace and the Left Ventricle
§ The ventricle develops wall tension to overcome afterload, and we can apply the law of Laplace to
give us deeper isnight into this process.
• Wall Tension= (LV Pressure x Radius) / (LV Wall Thickness x 2)
§ From this equation you can see that wall tension (wall stress) is reduced by:
• ¯ intraventricular pressure
• ¯ radius
• ­ wall thickness
§ The law of Laplace also helps us understand why the patient with systemic hypertension
compensates with left ventricular hypertrophy.

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• Radiation Safety
o An anesthesia providers become more involved in non-invasive procedures, particularly those outside of the OR, we are at
increased risk of exposure to ionizing radiation. Some of these locations include:
§ Computed tomography
§ Cardiac cath lab
§ Electrophysiology lab
§ Interventional radiology
§ Nuclear medicine
§ Radiation therapy
§ Anywhere fluoroscopy is used (inside and outside of the OR)
o Ionizing Radiation Explained Simply
§ Simply put, ionizing radiation can remove electrons from atoms, and this creates free radicals. As you might imagine,
this can wreak havoc on the cellular level. Risks include tissue injury, chromosomal damage, and malignancy.
• Most exposure is the result of scattered x-rays (not direct exposure).
• The roentgen (R) is how we quantify exposure.
• The roentgen equivalent in man (rem) is a unit of dose equivalent. This relates the human tissue absorption
to the effective biological damage of the radiation.
• The yearly maximum radiation exposure is 5 rem.
• The yearly maximum exposure for the fetus of a pregnant worker is 0.5 rem or 0.05 rem/month.
• In the non-pregnant person, the eye and thyroid are most susceptible to injury.
• In the pregnant person, the fetus is most susceptible to injury.
o How to Protect Yourself
§ The 3 ways to limit radiation exposures are:
• 1. Distance
• 2. Duration
• 3. Shielding
§ distance is an easy way to protect yourself from ionizing radiation. The minimum safe distance from the radiation
source is 6 feet. For example, 6 feet of air confers the same protection as 9 inches of concrete or 2.5 mm of lead. A
lead apron by comparison usually contains 0.25-0.5 mm of lead.
§ Radiation exposure obeys the inverse square law. It states that the amount of exposure is inversely proportional to
the square of the distance of the source.
• Intensity = 1/Distance ^2
§ We can quantify the amount of exposure at two different locations with the
following equation:
Intesnity1 = Distance 2^2
Intensity2=Distance1^2
§ Practice Question:
• During a surgical procedure with fluoroscopy, the patient receives
40 mR at a distance of 1 foot from the radiation source. How much
radiation will the anesthesia provider receive if she stands 5 feet
from the radiation source?
o Intensity1 = 40 mR
o Intesnity2 = X
o Distance1 = 1 ft
o Distance2 = 5 ft
40 = 5^2
X 1^2

40 = 25
X 1

25X= 40

X = 1.6 mR
• Other methods to minimize radiation exposure: do not stand in the x-ray beam’s path
o Minimize exposure time
o Lead apron
o Lead glasses
o Lead shields
o Use a dosimeter (on the shirt collar near the thyroid gland). A pregnant provider should wear a
second dosimeter under her apron.

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Miscellaneous (But Still Important) Concepts
o Boiling point is the temperature at which a liquid’s vapor pressure equals atmospheric pressure.
§ ­ P atm ® ­ boiling point (example: hyperbaric oxygen chamber)
§ ¯ P atm ® ¯ boiling point (example: high altitude)
o Specific heat the amount of heat required to increase the temperature of 1 gram of a substance by 1 degree C
o Vapor pressure – in a closed container, molecules from a volatile liquid escape the liquid phase and enter the gas phase. The molecules in the gas phase
exert a pressure on the walls of the container. This is vapor pressure.
o Vaporization is the process by which a liquid is converted to a gas. This requires energy (heat).
o Heat of vaporization is the number of calories required to vaporize 1 mL of liquid.
o Latent heat of vaporization is the number of calories required to convert 1 gram of liquid to vapor without a temperature change in the liquid. Let’s
apply this to what happens inside the vaporizer:
§ Anesthetic liquid in the vaporizer exerts a vapor pressure inside the vaporization chamber. This means some of the agent exists as a liquid
and some exists as a gas.
§ Fresh gas flows over the anesthetic liquid, carrying away some of the agent that exists in the gas phase.
§ This cools the remaining liquid, which reduces the vapor pressure of that liquid. Therefore, there are fewer anesthetic molecules that enter
the gas phase.
§ The net result is a decrease in the vaporizer output.
§ Modern vaporizers compensate for this temperature change in several ways:
• 1. They use metals with a high thermal conductivity. They transfer heat easily like copper and bronze.
• 2. They use a temperature compensation valve to modulate the amount of FGF that is directed into the vaporizing chamber (sevo,
iso)
• 3. They apply direct heat to the anesthetic liquid (des).
o The Joule-Thompson effect says that a gas stored at high pressure that is suddenly released escapes from its container into a vacuum. It quickly loses
speed as well as a significant amount of kinetic energy, resulting in a fall in temperature. This explains why an oxygen cylinder that is opened quickly feels
cool to the touch. Conversely, rapid compression of a gas intensifies its kinetic energy, causing the temperature to rise.
o Adiabatic process describes a process that occurs without gain or loss of energy (heat). For example, a very rapid expansion or compression of a gas
where there is no transfer of energy is an example of an adiabetic process.
o Critical temperature is the highest temperature where a gas can exist as a liquid. Said another way, it is the temperature above which a gas cannot be
liquefied regardless of the pressure applied to it.
o The critical temperature for nitrous oxide is 36.5 C, which explains why it primarily exists as a liquid inside the cylinder (room temperature is about 20 C).
Conversely, the critical temperature of oxygen is -119 C, so it exists as a gas inside the cylinder.
o Critical temperatures of common gases (highest to lowest):
§ Nitrous oxide = 36.5 C (liquid in the cylinder at room temp)
§ Carbon dioxide = 31 C (liquid in the cylinder at room temp)
§ Oxygen = -119 C
§ Air = -140 C
§ Nitrogen = -147 C
o Critical pressure is the minimum pressure required to convert a gas to a liquid at its critical temperature.
o Temperature
§ There are 3 scales that we use to measure temperature: Kelvin, Celsius, and Fahrenheit.
§ Converting between Celsius and Kelvin is easy, because both scales have the same size degrees. There are 100 degrees between the boiling
and freezing points of water on both scales.
• Celsius = K + 273.15
• Kelvin = C + 273.15
§ Converting between Celsius and Fahrenheit is different, because there are 180 degrees between the boiling and freezing points of water on
the Fahrenheit scale and only 100 degrees on the Celsius scale.
• Boiling point for water = 212 F or 100 C
• Freezing point for water = 32 F or 0 C
§ To account for this, we need to use a conversion factor in each equation:
• Celsius = (F – 32) x 5/9
• Fahrenheit = (C x 1.8) + 32
§ What is the significance of the 5/9 and 1.8? the ratio 1.8 is based on the number of degrees between the boiling and freezing points of water
on each scale: 180 : 100 or 1.8 : 1 or 9/5.
§ When converting Fahrenheit to Celsius, the ratio is backwards , which explains why 5/9 is used in that equation.
o Pressure
§ Pressure = Force / Area
• ­ area® ¯ pressure
• ¯ area® ­ pressure
§ you should be able to convert between the common units of pressure. All the following are equal:
• 1 atm= 760 mmHg = 760 torr = 1 bar = 100 kPa = 1033 cm H2O = 14.7 lb/inch^2
• 1 mmHg = 1.36 cm H2O
• 1 cm H2O = 0.74 mmHg
o Avogadro’s number says that 1 mole of any gas, is made up of 6.023 x 10^23 atoms.
o A mole of gas is equal to the molecular weight of that gas in grams.
§ Helium molecular weight = 4
§ One mole of helium = 4 g and contains 6.023 x 10^23 atoms.
o Diatomic gases (O2) need to account for both molecules, so you have to double the atomic weight.
§ Oxygen atomic weight = 16
§ Oxygen is diatomic, so the molecular weight of O2 = 16g x 2 = 32g
§ One mole of oxygen (O2)= 32g and contains 2x (6.023 x 10^23) atoms.

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Miscellaneous

• Thermoregulation: Mechanisms of Heat Transfer

o Hypothermia is defined as a core body temperature less than 36 degrees C. Patients at extremes of age are at the greatest risk of developing
perioperative hypothermia.
o Maintenance of Body Temperature
§ The body regulates core temperature between 36.7-37.1 degrees Celsius.
• You should think of this process as a reflex, with an afferent limb, control center, and efferent response.

o The 4 Mechanisms of Heat Transfer

§ The law of conservation of energy states that energy cannot be created nor destroyed. Therefore, heat “loss’ is a misnomer and this
phenomenon is more accurately termed heat “transfer.” We will continue to use both terms interchangeably, as one could argue that heat is
lost from the patient to the environment.
§ Radiation ~ Infrared (60%)
• Radiation is the #1 source of heat loss.
• Heat follows a temperature gradient. Fi the patient is warmer than the environment, then heat is lost to the environment in the
form of infrared radiation.
• Most heat is lost through the skin.
• Covering the patient reduces radiant heat loss.
§ Convection ~ Air (15-30%)
• Convection is the #2 source of heat loss.
• It is the transfer of heat by the movement of matter.
• Think of convection as “wind chill.” Air movement over the body whisks away the heat that has radiated from the body. The body
radiates more heat to replace what was taken away by the air flow and the cycle continues.
• Laminar flow increases the amount of heat lost to convection.
§ Evaporation ~ Water Loss (20%)
• It takes a significant amount of energy to vaporize water, this is called the latent heat of vaporization.
• The rate of this process is a function of the exposed surface area and the relative humidity of the environment.
• Water can be lost by evaporation from respiration, wounds, and exposure of internal organs during surgery.
§ Conduction ~ Contact (<5%)
• Heat is lost when the patient comes into direct contact with a cooler object.
• The amount of conductive heat loss is a function of the temperature gradient and the thermal conductivity of the object.
• Examples include a cold OR table, IV fluids, and irrigation fluids.
§ *Nagelhout states that conduction is the #3 source of heat loss and evaporation is #4. Barash, Flood and Miller agree with what’s written
above.
o The 3 Stages of Intraoperative Heat Transfer
§ When no attempts are made to maintain normothermia, heat transfer
follows a triphasic curve.
§ Phase I
• With general, spinal, or epidural anesthesia, there is a
redistribution of heat from the central compartment (thorax,
abdomen) to the peripheral compartment (extremities and
skin).
• Anesthetic agents impair the thermoregulatory response in
the hypothalamus, prevent shivering, and cause vasodilation.
• Only a nominal amount of heat is lost to the environment during phase I. again, heat redistribution is way more important during
this phase!
• Simple interventions, such as placing even 1 warm blanket on the patient before entering the OR, minimizes the central to
peripheral temperature gradient and goes a long way towards preserving core temperature.
§ Phase II
• Heat loss to the environment exceeds heat production.
§ Phase III
• An equilibrium develops between heat lost to the environment and heat production.
o Perioperative Events that Contribute to Heat Loss
§ Re-calibration of the hypothalamic set point
§ Drug induced vasodilation
§ Impaired shivering
§ Core to peripheral temperature redistribution
§ Cool ambient temperature
§ Cold operating room table
§ Administration of room temperature fluids and cold blood products

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• Consequences of Perioperative Hypothermia
o Perioperative hypothermia increases the risk of morbidity and mortality.

o Shivering
§ Shivering increases oxygen consumption up to 400-500%. This increases the risk of myocardial ischemia and
infarction.
§ Pharmacologic modalities used to treat postoperative shivering include:
• Meperidine
• Clonidine
• Dexmedetomidine
o Benefits of Perioperative Hypothermia
§ Although there are many reasons why perioperative
hypothermia contributes to poor outcomes, there are
several circumstances where it can improve outcomes.
How does hypothermia help? Oxygen consumption is
reduced by 5-7 % for every 1 degree C reduction in body
temperature. Induced hypothermia is useful during:
• Cerebral ischemia (stroke)
• Cerebral aneurysm clipping
• Traumatic brain injury
• Cardiopulmonary bypass
• Cardiac arrest
• Aortic cross clamping
• Carotid endarterectomy
o Temperature Measurement
• Airway Fires & Laser Safety
o There are 3 ingredients required to produce a fire. These include a/an:
§ Ignition source: electrosurgical cautery, laser
§ Oxidizer: oxygen, nitrous oxide
§ Fuel: endotracheal tube, drapes, surgical supplies
o Fire Protocol
§ You should understand the ASA Operating Room Fire Guidelines.

• In reality, the OR team is going to perform many of these tasks simultaneously, but for the purposes of the
NCE you should understand the stepwise process presented above.
• Do NOT squeeze the reservoir bag as you extubate the patient. This can create a blow torch effect tat the
distal end of the endotracheal tube and/or push debris into the lower airway.
o Laser Light
§ Laser is an acronym for Light Amplification by Stimulated Emission of Radiation. Laser light differs from ordinary light,
because it is:
• 1. Monochromatic (the light is a single wavelength)
• 2. Coherent (the light oscillates in the same phase)
• 3. Collimated (the light exists as a narrow parallel beam)

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 o Types of Lasers
§ You may encounter several different types of lasers, each with specific uses and unique safety considerations.
• Long wavelength lasers absorb more water and do not penetrate deep into tissue.
• Short wavelength lasers absorb less water and penetrate deeper into tissue.
o Laser Safety
§ Nagelhout has an entire chapter dedicated to laser surgery! Here is
a list of key facts and strategies to employ when a laser is in use:
• Use < 30% FiO2. Be able to do this calculation when
using an air and oxygen mixture. Can’t remember?
Check out Q9 in the Anesthesia Machine Tutorial.
• Nitrous oxide supports combustion. Do not use it!
• A source of water or saline must be immediately
available.
• Most endotracheal tubes are flammable. These include ETTs made from polyvinyl chloride, red rubber, and silicone.
• Laser reflective tape is no longer advised it’s smarter to use a laser resistant ETT.
• Laser resistant ETTs are NOT laser proof!
• The cuff is the most vulnerable component of the ETT.
• Laser resistant tubes do NOT have laser resistant cuffs!
• Fill the cuff with saline (dye is optional). This helps absorb the thermal energy produced by the laser, which makes the balloon
less likely to ignite.
• Many laser resistant ETTs have 2 cuffs. The proximal cuff is filled with saline or dye. If it becomes perforated by the laser, then the
distal cuff will hopefully remain intact and permit continued PPV.
• The choice of ETT should be based on the type of laser and its wavelength.
• If a CO2 laser is used, then the LaserFlex tube is a good choice.
• If the Nd:YAG laser is used, the the lasertubus is a good choice.
• Since the ETT is a source of fuel, a technique that does not require an ETT removes one component of the fire triangle.
Techniques include spontaneous ventilation, intermittent PPV via facemask and apnea, or jet ventilation.
• Gas may be used to cool the tip of the laser probe, so gas embolus is another risk of laser surgery (especially during laparoscopic
uterine surgery).
• Laser resistant ETTs do not reduce the risk of fire when electrosurgical cautery is used.
• Protect the patient’s eyes by taping the eyelids closed, avoiding petroleum based lubricants, covering the eyelids with saline
soaked gauze, and using protective glasses that are specific to the laser being used (see chart above).
o Atmospheric Contamination
§ Tissue vaporization creates a plume of fine particulates.
§ When we breathe contaminated air, these particulates collect in our alveoli.
§ There is no compelling evidence of viral transmission by inhaling the smoke, although those exposed to the plume have complained of
tearing, nausea, and headaches.
§ Eukaryotic cells (tumor cells) have also not been shown to transmit through laser particulate, however bacterial spores may remain visible.
§ Using a smoke evacuator and high efficiency masks are the best ways to protect yourself.
• Burns: Overview
o A burn is an injury to the skin and underlying tissue caused by heat, electricity, chemicals, radiation, or friction. Patients with extensive burn injuries
require aggressive fluid resuscitation as well as surgery for debridement and skin grafting to prevent bacterial sepsis.
o Complications include hypovolemic shock, inhalation injury, sepsis, contractures, and scarring.
o Classification of Burn Injury
§ Superficial (1st degree)
• Epidermis only
• Stinging, tender, and sore
§ Partial-Thickness (2nd degree)
• Superficial dermal: epidermisàupper dermis
• Deep dermal: epidermisàlower dermis
• Very painful
§ Full Thickness (3rd degree)
• Complete destruction of the epidermis and dermis
• No sensation (nerve endings are obliterated)
§ Full-Thickness (4th degree)
• Extends to muscle and bone
• No sensation (nerve endings are obliterated)
o Rule of 9’s
§ Burn severity is a function of the depth of the burn as well as the fraction of the total body
surface area (TBSA) consumed by the burn.
• The TBSA is divided into areas representing 9% (or multiples of 9%).
• Due to rounding, the numbers do not add to 100.
• This concept is important for calculating fluid requirements.
§ Children
• The child’s palm (excluding the fingers) represents 1% of his TBSA.
• Notice the child’s head is 19% of the TBSA (9.5% back).
• As a general rule: for every year of age > 1 year up to 10 years, you can decrease
head surface area by 1% and increase each leg by 0.5%.

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• Burns: Fluids Resuscitation & Key Points
o Immediately after a burn, microvascular permeability increases and this creates a capillary leak.
o The magnitude of the leak becomes greater in the presence of a/an major burn, inhalation injury, or a delay in resuscitative efforts.
o Consequences of the Capillary Leak
§ 1. Increased vascular permeability àedema formation
§ 2. Loss of protein-rich fluid to the interstitial space àdecreased plasma oncotic pressureàedema formation
§ 3. Loss of intravascular volume->hypovolemia & shock
§ 4. Hypovolemiaàhemoconcentration
o Fluid shifts and edema formation are greatest in the first 12 hours and begin to stabilize by 24 hours. This explains why fluid requirements are
higher in the first 24 hours following a burn.
§ Albumin should be avoided during the first 24 hours, because it is the lost to the interstitial space.
§ Hemolysis is common during the initial stage, however profound hypovolemia promotes hemoconcentration.
§ A rising hemoglobin in the first few days suggests inadequate volume resuscitation.
§ Consider transfusion if Hct<20 (healthy pt) or Hct<30 (pre-existing cardiovascular disease).
o Fluid Resuscitation Guidelines
§ There are 2 commonly used fluid resuscitation formulas used for the acutely burned patient: Parkland and Modified Brooke.

• *These formulas underestimate the fluid requirements of infants and small children.
o Clinical End Points of Burn Resuscitation

o Other Key Points:

§ Electrical Burns
• Often leaves little visible damage on the skin, but can cause great damage to the viscera.
• Myoglobinemia is the result of extensive muscle damage. Remember that myoglobin is nephrotoxic and needs to be
flushed out of the body.
• Dysrhythmias are common.
§ Abdominal Compartment Syndrome
• May result from aggressive fluid resuscitation.
• Abdominal compartment syndrome is defined as intraabdominal pressure>20 mmHg (transduction of bladder pressure)
AND evidence of organ dysfunction (hemodynamic instability, oliguria, increased PIP).
• Treatment include neuromuscular blockade, sedation, diuresis, and abdominal decompression via laparotomy.
§ Airway Complications
• Administration of high FiO2 is the first priority in all burn patients.
• Fiberoptic bronchoscopy is the gold standard of diagnosing the extent of airway injury.
• Tracheal intubation should occur early. An awake fiberoptic approach is probably the safest method, however other
modalities may be used.
• A surgical airway increases the risk of pulmonary sepsis and late pulmonary complications. It should be used only as a last
resort.

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 § Carbon Monoxide Poisoning
• CO binds to hemoglobin with an affinity 200 times that of oxygen.
• CO shifts the oxyhemoglobin dissociation curve to the left (left = love), which impairs offloading of oxygen to the tissues.
• Oxidative phosphorylation is also impaired.
• Inadequate oxygen delivery and utilization causes metabolic acidosis.
• Blood takes on a cherry red appearance.
• The pulse oximeter is NOT accurate in the patient with CO poisoning, because it is unable to distinguish between HgbO2 and
HgbCO.
• The SpO2 may give a falsely elevated result.
• Treatment includes 100% FiO2 or hyperbaric oxygen.
§ Other
• Up-regulation of extrajunctional receptors begins after 24 hours.
• Succinylcholine is safe within the first 24 hours following the burn, but its use can cause lethal hyperkalemia after 24 hours.
• The dose of non-depolarizing NMBs should be increased 2-3 fold (there are more receptors).
• Patients may require multiple surgical procedures. Ketamine is a good choice for analgesia, while etomidate is a poor choice due
to the risk of adrenocortical suppression.
• Patients have impaired temperature regulation and increased risk of perioperative hypothermia (evaporation is the primary
mechanism of heat loss).
• Patients become hypermetabolic after a burn. This increases catabolism, oxygen consumption, heart rate, and respiratory rate.
• Electroconvulsive Therapy
o Electroconvulsive therapy is an important modality in the treatment of medication-resistant depression as well as mania, catatonia, suicidal
ideation, and some types of schizophrenia.
o Physiologic Response
§ The seizure caused by ECT results in profound physiologic changes.
• Initial response: increased PNS activity during the tonic phase (lasts ~15 seconds)
• Secondary response: increased SNS activity during the clonic phase (lasts several minutes)

o Contraindications
§ Contraindications are typically related to an increased SNS response or increased ICP.
• The most common causes of death are myocardial infarction and cardiac dysrhythmias. Having said this, patients with co-
existing cardiovascular disease can safely undergo ECT if hemodynamics are well managed.

o Drug Selections & Seizure Duration

§ The efficacy of ECT is primarily dependent on the seizure duration. The best response is obtained when the seizure lasts > 25
seconds.

§ Methohexital is the “gold standard,” as it produces a rapid recovery and has no effect on seizure duration. The other
drugs are compared relative to methohexital.
§ Propofol reduces seizure duration, but blunts the hemodynamic response.
§ Etomidate causes myoclonus and increases the risk of PONV. It’s also associated with more hypertension after ECT.
§ Ketamine increases the SNS response and prolongs recovery.
§ Glycopyrrolate is used as an antisialagogue and reduces the risk of asystole.
§ Esmolol is used to blunt the SNS response.
o Drug Interactions
§ lithium prolongs the duration of action of succinylcholine AND nondepolarizing neuromuscular blockers.
§ Patients on MAOIs who receive indirect acting sympathomimetics can experience hypertensive crisis.

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• Drug Induced Hyperthermic Syndromes
o Not all drug-induced hyperthermia is malignant hyperthermia. Other causes of drug-induced hyperpyrexia include:
§ 1. Neuroleptic malignant syndrome
§ 2. Serotonin syndrome
§ 3. Anticholinergic poisoning
o 1. Neuroleptic Malignant Syndrome
§ NMS is caused by dopamine depletion in the basal ganglia a/””””””””:

????/d hypothalamus.
• Causes: dopamine antagonists or withdrawal from dopamine agonists.
• Be able to contrast NMS with malignant hyperthermia.

o 2. Serotonin Syndrome
§ serotonin syndrome occurs when there’s excess 5-HT activity in the CNS and PNS.
§ Key drug interactions that increase the risk of serotonin syndrome:
• SSRI + meperidine or fentanyl
• MAOI + meperidine or ephedrine

o 3. Anticholinergic Poisoning
§ Anticholinergic poisoning is the result of excessive Ach blockade in the CNS and PNS.

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• Eye Physiology & Opthalmology
o Ocular Perfusion
§ The ophthalmic artery is the main blood supply to the eye. It branches off the internal carotid artery near the circle of
Willis.
• The ophthalmic artery divides into the central retinal artery and posterior ciliary arteries.
• The superior and inferior ophthalmic veins transport venous blood to the cavernous sinus.
o Intraocular Pressure
§ Intraocular perfusion pressure = MAP – IOP
§ The globe is a relatively noncompliant compartment. Therefore, IOP
is determined by the choroidal blood volume, aqueous fluid volume,
and extraocular muscle tone.
• Normal IOP = 10 to 20 mmHg
• Aqueous humor is produced by the ciliary process
(posterior chamber)
• Aqueous humor is reabsorbed by the canal of Schlemm
(anterior chamber)
§ IV anticholinergics do not increase IOP.
§ LMA placement and/or removal has a minimal effect on IOP.
§ Ketamine may or may not increase IOP, but it does cause rotary
nystagmus and blepharospasm. For this reason, it should be avoided
during eye surgery.
o Open Globe Injury
§ An increased IOP in the patient with an open globe injury can cause
permanent blindness!
• Succinylcholine increases IOP by 5-15 mmhg for up to 10
minutes. This is not reliably blocked by a defasciculating
NMB.
• Although its use in an open globe injury is controversial, there are no reports of blindness associated with
its use. Therefore, succinylcholine is okay to sue in the patient with an open eye injury and a full stomach.
Rocuronium 1.2 mg/kg is also a suitable option.
o Glaucoma
§ Glaucoma is caused by a chronically elevated IOP that leads to retinal artery compression.
• Open angle glaucoma is caused by sclerosis of the trabecular meshwork. This impairs aqueous humor
drainage.
• Closed angle glaucoma is caused by a closure of the anterior chamber. This creates a mechanical outflow
obstruction.
§ IOP is reduced by drugs that reduce aqueous humor production or facilitate aqueous humor drainage (causes miosis).
§ Drugs that Decrease Aqueous Humor Production
• Acetazolamide inhibits carbonic anhydrase and decreases aqueous humor production.
• Timolol is a non-selective beta antagonist that decrease aqueous humor production.
§ Drugs that Facilitate Aqueous Humor Drainage
• Echothiophate is an irreversible cholinesterase inhibitor that promotes aqueous humor drainage via the
canal of Schlemm.
• It can prolong the duration of succinylcholine and ester-type local anesthetics.
o Strabismus Surgery
§ Strabismus surgery corrects the misalignment of the extraocular muscles and re-establishes the visual axis. There are
3 key considerations in this population:
• 1. Increased risk of malignant hyperthermia
• 2. Increased risk of PONV
• 3. Increase risk of activating the oculocardiac reflex (afferent CN V + efferent CN X)
o Ocular Gas Bubble Placement
§ Sulfur hexafluoride is a gas that is placed over the retinal reattachment, vitrectomy, and macular hole repair.
§ Nitrous oxide can expand the SF6, compromise retinal perfusion, and cause permanent blindness.
• Discontinue it 15 minutes before the SF6 bubble is placed.
• Avoid it for 7-10 days after the SF6 bubble is placed.
§ Alternative to SF6 and time to avoid N2O:
• Silicone oil = 0 days
• Air bubble = 5 days
• Perfluoropropane (C3F8) = 30 days
§ *Eye injury is covered in Q16 of CNS I: Brain Tutorial.
§ * The oculocardiac reflex is covered in Q19 of ANS: Anatomy & Physiology Tutorial.

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• Transverse Abdominal Plane Block
o The transverse abdominal plane block (TAP) is a unilateral, peripheral nerve block that targets the nerves of the anterior and lateral abdominal
wall.
§ It’s best suited for abdominal procedures (general, GYN, and urologic) that involve the T9 to L1 distribution.
§ Bilateral TAP blocks are required for a midline incision or laparoscopic surgery.
o Anatomy
§ Abdominal wall structures organized from superficial to deep:
Subcutaneous tissue à external oblique muscle àinternal oblique muscle àtransverse abdominis muscleàperitoneum
§ Innervation of the anterolateral abdominal wall arises from the anterior rami of T7-L1. These nerves are blocked by placing local
anesthetic just below the fascial plane between the internal oblique muscle and the transverse abdominis muscle.
o Landmarks
§ The landmarks of the TAP block form triangle of Petit. These include:
• External oblique muscle
• Latissimus dorsi muscle
• Iliac crest
o Technique
§ An ultrasound probe is positioned a few cm superior and parallel to the iliac crest.
§ The needle is advanced until the tip is positioned in the facial plane between the internal
oblique and transverse abdominis muscles.
§ If using a blind technique, then you must feel for 2 pops: 1) after the needle transverses the
external oblique muscle and 2) after the needle transverses the internal oblique muscle.
§ Following a negative aspiration, 15-20 mL of local anesthetic is injected.
o Complications
§ Complications can occur with ultrasound guidance. They include:
• Peritoneal puncture
• Liver hematoma
• Miscellaneous Pain Topics
o Pain Terminology

o Antidepressants for Chronic Pain

§ Pain modulation occurs in the spinal cord. In the setting of central sensitization, the efficacy of the descending inhibitory pain pathway is
impaired. Recall that this pathway uses norepinephrine and serotonin as inhibitory transmitters, so it makes sense that antidepressants that
increase the concentrations of these neurotransmitters can treat chronic pain. The pain pathways are covered in the Opioid Agonists &
Antagonists Tutorial.
• TCAs have the most significant side effects: QT prolongation and
orthostatic hypotension.
• The combination of an SNRI and SSRI can precipitate serotonin
syndrome.
o Complex Regional Pain Syndrome
§ There are 2 types of CRPS:
• Type I (reflex sympathetic dystrophy)
• Type II (causalgia)
§ Complex regional pain syndrome is characterized by neuropathic pain with
autonomic involvement. Risk factors include female gender, previous trauma, or
previous surgery. The key distinction is that type II CRPS is always preceded by nerve injury (type I is not).
§ Treatment:
• Ketamine infusion
• Memantine (an NMDA antagonist)
• Gabapentin
• Regional sympathetic blockade
• Physical therapy

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 o Thoracic Paravertebral Block
§ Local anesthetic injected into the paravertebral space (a potential space) targets the ventral ramus of the spinal nerve as it exits the
vertebral foramen.
§ This creates a unilateral sensory and sympathetic block along that specific dermatome.
§ You can think of the paravertebral block as a single shot, unilateral epidural block.
§ You’ll have to perform one block at each dermatome to be anesthetized.
§ The thoracic paravertebral block provides analgesia for breast surgery, thoracotomy, and rib fracture.
o Celiac Plexus Block
§ This block is useful for the management of cancer pain of the upper abdominal organs:
§ Examples: distal esophagus, stomach, liver, pancreas, small intestine, and colon (except the descending colon).
§ Complications: orthostatic hypotension, retroperitoneal hematoma, hematuria, diarrhea, AAA dissection, back pain, and retrograde
migration of the injectate (a problem is a neurolytic is used).
o Superior Hypogastric Plexus Block
§ This block is useful for the management of cancer pain of the pelvic organs:
§ Examples: uterus, ovaries, prostate, descending colon.
§ Complications: retrograde migration of the injectate (a problem if a neurolytic is used).
o Sphenopalatine Block
§ The sphenopalatine block can be used to relieve postdural puncture headache.
§ We didn’t find this in the texts (if you find a reference, please let us know).
o Retrobulbar Block
§ The optic nerve is unique, because it is the only cranial nerve that is part of the central nerve system (it is enveloped by the meningeal sheath
and bathed in CSF),. Because of this, local anesthetic injected into the optic sheath is permitted direct entry to the brain. It’s like giving a
subarachnoid block in the optic sheath!
• Local anesthetic injected into the optic sheath can migrate towards the optic chiasm, where it anesthetizes CN Ii and III on the
side opposite the block. This results in contralateral amaurosis (blindness).
• Local anesthetic that reaches the brainstem can cause apnea (post-retrobulbar block apnea syndrome). This complication
typically becomes evident 2-5 minutes after injection. Spontaneous ventilation usually resumes in 15-20 minutes, but a full
recovery may require up to an hour.
• It’s important to assess the contralateral pupil before performing a retrobulbar block. If the pupil starts small, but dilates shortly
after the block, you should anticipate the development of post-retrobulbar block apnea syndrome and be ready to provide
cardiopulmonary support until the local anesthetic is cleared from the CSF.
• Antibiotics

o History of PCN Allergy

§ Previous literature suggested a high rate of cross-reactivity between PCN and cephalosporins (up to 10%). These numbers are grossly
overstated (due to contamination during the manufacturing process). The likelihood of cross-reactivity is based on the R1 side chain,
and the true rate < 1%. Third and fourth generation cephalosporins are associated with the lowest rate of cross-reactivity (very rare).
§ If a patient reports an allergy to PCN, then s/he may receive a cephalosporin if the reaction:
• Was NOT IgE mediated (anaphylaxis, bronchospasm, urticarial).
• Did NOT produce exfoliative dermatitis (Stevens-Johnson Syndrome).
§ If the patient experienced any of these complications, then vancomycin or clindamycin are acceptable alternatives.
o Key Facts
§ The most common side effect of prophylactic antibiotics (including cephalosporins) is pseudomembranous colitis.
§ Cephalosporins act by disrupting bacterial cell wall synthesis (peptidoglycan).
§ Cefazolin should be redoes q4h during surgery.
§ Vancomycin acts by disrupting bacterial cell wall synthesis.
§ Vancomycin is the drug of choice for patients with active MRSA.
§ To reduce histamine release and hypotension, vancomycin should be administered at a rate of 10-15 mg/kg over 1 hr.
§ The histamine response to vancomycin can be minimized by diphenhydramine 1 mg/kg + cimetidine 4 mg/kg 1 hour before
anesthesia.
§ Most antibiotics cross the placenta, and some of these can impact fetal development. The following drugs are contraindicated:
chloramphenicol, erythromycin, fluoroquinolones, and tetracyclines.

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• Infection Control
o Key Facts
§ Handwashing is the most important method of infection prevention.
§ Wearing gloves is not a substitute for hand hygiene!
§ The central venous catheter is the most common source of bloodstream infection in hospitalized patients.
§ The CDC says that chlorohexidine is the preferred method of skin prep prior to central line placement.
§ Alcohol based products are flammable and must be allowed to dry for two minutes. Consider this when draping the patient for surgery.
o SCIP Protocol
§ The Surgical Care Improvement Project provides 7 measures designed to reduce the incidence of perioperative surgical site infection.
• A prophylactic antibiotic is administered within 60 min of surgical incision (vancomycin is 120 min).
• The choice of antibiotic is determined by the site of surgery.
• Prophylactic antibiotics are discontinued with 24 hrs of surgery (48 hrs for cardiac patients).
• Cardiac surgery patients must achieve glycemic control (< 200 mg/dL)
• Postop wound infection is diagnosed during the initial hospitalization.
• Surgical patients receive appropriate hair removal.
• Colorectal patients are normothermic upon
arrival to PACU (> 36 C).
o Infection Precautionsà
o Human Immunodeficiency Virus
§ The most common cause of occupational exposure to HIV
is a needle-stick injury with a hollow-bore needle.
§ Seroconversion rates after exposure to HIV-infected
blood:
• Percutaneous injury (needle-stick) = 0.3%
• Mucus membrane exposure = 0.09%
o Creutzfeldt-Jakob Disease
§ Prion disease can lead to encephalopathy and dementia. Creutzfeldt-Jakob disease is the classic example. Etiologies include:
• Consumption of contaminated animal protein
• Contaminated implants (corneal or dural tissue)
• Cadaveric pituitary hormone supplementation
§ There is no data to support transmission through blood, air, or droplets. Standard precautions are recommended.
• Tuberculosis
o Mycobacterium tuberculosis is a bacillus that thrives in an aerobic environment. It targets the anterior apical segments of the lung, but it can also infect
the brain, kidney, joints, spine, and GI tract. Patients experience a productive cough, hemoptysis, weight loss, fever, night sweats, anorexia, and general
malaise.
o Diagnosis
§ The tuberculin skin test (Mantoux test) is the most common test for TB.
• Result is read within 48-72 horus.
• Positive result = site of induration is > 10 mm (>5 mm if patient is immunocompromised, such as HIV)
• A positive skin test necessitates a CXR. Positive findings include apical infiltrates and/or nodules.
• A negative CXR rules out TB.
§ Other tests include the acid-fast bacillus test (examines sputum) and interferon release assays (QuantiFERON TB Gold In-Tube test and the T-
SPOT TB test).
o Treatment
§ Isoniazid is a first-line agent, but side effects include peripheral neuropathy and hepatotoxicity. Pyridoxine can be added to reduce the
incidence of liver damage.
§ Rifampin causes thrombocytopenia, leukopenia, anemia, and kidney failure.
§ Rifampin causes the urine, sweat and tears to take on an orange/red color.
§ Other first-line agents include pyrazinamide, streptomycin, and ethambutol.
o Special Considerations
§ Infection results from inhalation of aerosolized droplets. For this reason, any procedure that requires contact with the airway is considered
high risk. Bronchoscopy is associated with the highest risk of skin test conversion in health care personnel. Endotracheal intubation is the
second highest risk procedure.
• The patient and staff should wear N95 masks.
• A high efficiency particulate air filter (HEPA) is placed between the y-piece and the patient’s airway.
• A bacterial filter is place in the expiratory limb of the circle circuit.
• A dedicated anesthesia machine and/or ventilator is ideal.
• Pre- and postoperative care should take place in a negative pressure isolation room.
§ Elective procedures should be delayed until the patient is on antituberculous chemotherapy, has 3 negative acid-fast bacillus tests, and
demonstrates symptom improvement.

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• White Blood Cells
o White blood cells can be divided into granulocytes (neutrophils, basophils, and eosinophils) and agranulocytes (monocytes and
lymphocytes):
• Granulocytes
o Neutrophils Agranulocytes
§ Fight bacterial and fungal infection. • Monocytes
§ Make up 60)% of all WBCs (most abundant WBC type). o Phagocytosis.
o Basophils o Release cytokines
§ Essential component of hypersensitivity reactions. o Present pieces of pathogens to T-
§ Release histamine, leukotrienes, prostaglandins (mast cells do lymphocytes.
the same thing).
• Lymphocytes
§ Epinephrine prevents degranulation (release of intracellular
o B-lymphocytes: humoral immunity
contents) by binding to beta-2 receptors on the cell membrane.
(produce antibodies)
o Eosinophils
o T-lymphocytes: cell mediated immunity
§ Defend against parasites. (does not produce antibodies).
• Allergic Reaction
o Types of Hypersensitivity Reactions
§ Type I: immediate hypersensitivity
• Antigen + antibody interaction in a patient who has been
previously sensitized to the antigen.
• IgE mediated reaction.
• Tryptase is release from mast cells during an allergic reaction. It is
the best lab test to determine if an allergic response has occurred.
• Examples: anaphylaxis, extrinsic asthma
§ Type II: Antibody-Mediated:
• IgG and IgM antibodies bind to cell surfaces or extracellular
regions.
• The reaction activates the complement cascade.
• Examples: ABO-incompatibility, heparin-induced
thrombocytopenia
§ Type III: Immune Complex Mediated:
• An immune complex is formed and deposited into the patient’s
tissue (normally these complexes are cleared from the body).
• The reaction activates the complement cascade.
• Examples: snake venom reaction, protamine induced
vasoconstriction
§ Type IV: Delayed:
• Allergic reaction is delayed at least 12 hours following exposure.
• Examples: contact dermatitis, graft-vs-host reaction, tissue
rejection
o Treatment of Intraoperative Anaphylaxis
§ Discontinue the offending agent.
§ Airway support: increase FiO2 and provide airway support.
§ Epinephrine: start with 5-10 mcg IV for hypotension and 0.1-1 mg IV for CV collapse.
§ Liberal IV hydration: crystalloid 10-25 mL/kg or colloid 10 mL/kg (repeat if necessary).
§ H1-receptor antagonist: Diphenhydramine 0.5-1.0 mg/kg IV
§ H2-receptor antagonist: ranitidine 50 mg IV or famotidine 20 mg IV.
§ Hydrocortisone 250 mg IV (prevents delayed release of inflammatory compounds – does
not produce an immediate effect)
§ Albuterol for bronchospasm
§ Vasopressin for refractory hypotension. Start at 0.01 unit/min
§ *epinephrine treats anaphylaxis in 3 ways. It prevents degranulation, provides CV
support, and dilates the airways.
o Common Culprits for Perioperative Allergic Reaction
§ #1 Neuromuscular blockers (succinylcholine is most common—see the NMB tutorial for
our in-depth analysis)
§ #2 Latex (high risk groups= spina bifida/myelomeningocele, atopy, health care workers,
and allergy to banana, kiwi, mango, papaya, pineapple, tomato)
§ #3 Antibiotics (beta-lactams are most common)
§ Others: protamine, contrast media, colloids, opioids, hypnotics, and local anesthetics

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• Chemotherapeutics
o While an in-depth analysis of chemotherapeutics is a low yield strategy, we think you should have a basic understanding of the drug classes and
unique side effects of the agents listed on this page. Our “chemo man” should help you recall what you need to know.

o Most chemotherapeutic agents cause bone marrow suppression and thrombocytopenia. Bleomycin is a key exception.
o A history of severe N/V can impact volume status and electrolyte balance.
o Mucositis (ulceration of mucus membranes) may be a reason to avoid an oral airway, nasal airway, LMA, or esophageal temperature probe.
o The PK/PD profile of your anesthetic agents may be impacted by drugs that impact the heart, kidneys, and liver.
o Tamoxifen is a selective estrogen receptor modulator. Tumors that do not express estrogen receptors are not responsive to tamoxifen. This
drug causes hot flashes and increases the risk of endometrial cancer.
• GI Hormones and Barrier Pressure
o GI Hormones
§ We want you to know the 5 key hormones that regulate digestive activity.
• Gastrin: when food enters the stomach, gastrin increases stomach acid and stiulates chief cells to secrete
pepsinogen. In the presence of stomach acid, pepsinogen is converted to pepsin (aids in protein digestion).
• Secretin: tells the pancreas to secrete bicarbonate and the liver to secrete bile.
• Cholecystokinin: tells the pancreas to release digestive enzymes and the gallbladder to contract.
• Gastric inhibitory peptide: slows gastric emptying and stimulates pancreatic insulin release.
• Somatostatin: the universal “off” switch for digestion

§ Key Points:
• Gastrin is increased in the patient with Zollinger-Ellison syndrome (gastrin secreting tumor à increased
stomach acidàgastric ulceration).
• Gallbladder pain after a fatty meal is caused by increased CCK
release.
• Somatostatin is the treatment for carcinoid tumor.
o Gastric Barrier Pressure
§ The likelihood of gastroesophageal reflux is determined by barrier pressure. The
higher the barrier pressure, the lower the likelihood of reflex.
§ Barrier pressure is reduced by:
• Decreased LES tone
• Increased intragastric pressure
§ Things that decrease barrier pressure:
• Anticholinergics (decreased LES tone)
• Cricoid pressure (decrased LES tone)
• Pregnancy (decreased LES tone and increased intragastric pressure)
§ Things that increase barrier pressure:
• Succinylcholine (increased LES tone + Increased gastric pressure = 0 net
change)

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• Postoperative Nausea and Vomiting
o The Vomiting Center
§ The vomiting center resides in the nucleus tractus solitaries (medulla). Sensory input to the vomiting center arises
from the chemoreceptor trigger zone, GI tract, and vestibular system. Understand the location fo reach type of
receptor.

o Key Points
§ Compared to general anesthesia with a volatile anesthetic, TIVA and/or regional anesthesia reduce the risk of PONV>
§ The blood-brain barrier is poorly developed at the CTZ. This explains why it’s stimulated by noxious chemicals (ethanol,
chemotherapeutics).
§ Headache and/or diarrhea are the most common side effects of ondansetron.
§ Ondansetron should be administered 30 min prior to emergence.
§ Dexamethasone should be administered during induction.
§ 5-HT3 antagonists and butyrophenones (droperidol) can prolong the QT interval.
§ Droperidol has a black box warning for QT prolongation (d/t case reports with alrge doses-clinically effective edoses are much
lower).
§ Dopamine antagonists can cause extrapyramidal symptoms. These drugs are contraindicated in the patient with Parkinson’s disease.
§ Metoclopramide is contraindicated in the patient with bowel obstruction (due to prokinetic effect).
§ Motion induced nausea is the result of M1 and H1 stimulation in the vestibular system of the inner ear.
§ Patients undergoing middle ear surgery should receive antiemetic agents that targe the vestibular
system.
§ Transdermal scopolamine is best applied > 4 hours prior to the induction of anesthesia. It lasts for
72 hours.
§ Prochlorperazine produces significant sedation.
§ Propofol 10-20 mg produces an antiemetic effect.
§ Midazolam may reduce PONV by decreasing DA activity in the CTZ.
§ Ephedrine 25 mg IM may reduce PONV by maintaining blood pressure and cerebral perfusion.
§ The P6 acupressure point is nonpharmacologic method of reducing PONV.

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Orthopedic Surgery
Bone Cement Implantation Syndrome
• Methyl methacrylate (bone cement) is used to bind orthopedic implants to the patient’s bone during orthopedic surgery.
o Methyl methacrylate increases intramedullary pressure in the bone (up to 50 mmhg), and this can produce microemboli (fat, bone, marrow, cement) that travel to the lungs.
This results in V/Q mismatch (increased dead space), and in extreme cases, it can potentiate right heart failure.
o Residual methyl methacrylate can enter the systemic circulation where it causes bradycardia, dysrhythmias, hypotension (decreased SVR), pulmonary hypertension (increased
PVR), hypoxia, and cardiac arrest. Collectively, this constellation of complications is called bone cement implantation syndrome (BCIS).
• Hip arthroplasty is associated with the greatest risk of BCIS, but other procedures include knee arthroplasty, vertebroplasty and kyphoplasty.
o In the awake patient under regional anesthesia, the first signs of BCIS are usually dyspnea and altered mental state.
o Under general anesthesia, the first sign of BCIS is usually a decreased EtCO2.
• First line treatment includes 100% FiO2, IV hydration, and phenylephrine for hypotension. Fat Embolism Syndrome
Pneumatic Tourniquet
• Fat embolism syndrome is a recognized complication of long
• Inflation bone trauma. The risk is greatest inside the first 72 hours of
injury, and this explains why prompt stabilization of the injury is
oThe pneumatic tourniquet is used to reduce blood loss during surgery on an
important.
extremity. Cells distal to the tourniquet shift to anaerobici metabolism, and • Risk factors: pelvic fracture, femoral fracture, and
metabolic byproducts accumulate as long as the tourniquet is inflated. To reduce instrumentation of the femoral medullary canal
the risk of ischemic damage, the maximum inflation time is 2 hours. • The triad of FES includes:
§ Inflation pressure for upper extremity surgery: 70-90 mmHg above SBP o Respiratory insufficiency (hypoxemia, bilateral
§ Inflation pressure for lower extremity surgery: 2x over SBP infiltrates on CXR, ARDS)
o When used for a bier block, the tourniquet must remain inflated for at least 20 o Neurologic involvement (confusion to coma)
minutes after the local anesthetic is injected. Premature release increases the risk o Petechial rash (skin of neck and axilla, oral mucosa,
conjectiva)
of seizure and/or cardiac arrest.
• Treatment is supportive. Some data says corticosteroids improve
§ Bier block upper extremity: 300 mmHg outcome, while others do not.
§ Bier block lower extremity: 300 mmHg or 2x over SBP (whichever
Tourniquet Pain
is higher)
• Deflation Tourniquet pain typically begins 45-60 minutes after inflation.
o Tourniquet release stresses the body in 2 ways:
§ Restoring blood flow to the extremity produces a relative • Tissue ischemia is most likely the cause of tourniquet pain.
decrease in the circulating blood volume. • Tourniquet pain is transmitted by c fibers (slow pain).
§ The products of cellular hypoxia enter the systemic circulation. • Pain begins as a dull, aching, and burning. It can progress to
o Releasing the tourniquet produces transient changes that include: agonizing pain despite otherwise susccessful regional
§ Increased EtCO2 anesthesia.
§ Decreased core body temperature • Pain is unresponsive to analgesics.
§ Decreased blood pressure • Some patients will require general anesthesia in this situation.
§ Decreased SvO2 (SaO2 is usually normal) • Under general anesthesia, tourniquet pain manifests as
§ Metabolic acidosis hypertension and tachycardia. Consider esmolol for the
Nonsteroidal Antiinflammatory Drugs (NSAIDs) patient with CAD.

NSAIDs inhibit the cyclooxygenase enzyme and reduce the production of prostaglandins.

• COX-1 is always present. It maintains normal physiologic function.

• Inhibition of the COX-1 enzyme impairs platelet function, causes gastric irritation, and reduces renal blood flow.
• COX-2 is not always present. It is expressed during inflammation.
• Inhibition of the COX-2 enzyme produces analgesic, anti-inflammatory, and antipyretic effects. Unlike opioids, there is a ceiling effect to analgesia.

• Key Facts
o COX-2 inhibitors were supposed to be associated with fewer side effects (normal COX-1 processes are not affected).
o Almost all the COX-2 inhibitors have been removed from the market due to concerns about cardiovascular risk. Celecoxib is available.
o Ketorolac 30 mg IV ~morphine 10 mg IV.
o Ketorolac can only be taken for 5 days.
o Aspirin irreversibly inhibits COX-1 and COX-2. Platelet inhibition lasts for the life of the platelet.
o Aspirin toxicity can cause a gap metabolic acidosis.
o Aspirin exacerbated respiratory disease (Samter’s triad) refers to the combination of asthma, allergic rhinitis, and nasal polyps. These patients can
develop life threatening bronchospasm following aspirin administration.
o Acetaminophen is NOT an NSAID. It’s an analgesic and antipyretic, but it’s not an anti-inflammatory.
o The exact mechanism of action is unclear, however it’s been suggested that acetaminophen inhibits prostaglandin synthesis (COX-3 inhibition?).
Additionally, analgesia may be produced by activating the descending inhibitory pain pathway in the spinal cord.
o Acetaminophen is the most common cause of liver failure in the US. The max dose is 4 g per day.

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• Herbal Supplements

o Key Points
§ The FDA does not regulate herbal medications, because they are considered dietary supplements.
§ In an ideal world. These agents are discontinued at least 2 weeks before surgery, but this is difficult to achieve. Some drugs have more
specific recommendations (discussed above), but understand that there are no current guidelines that say surgery must be postponed in the
patient taking an herbal supplement.
§ In the absence of medications or disease that affect hemostasis, there are no strict recommendations that herbal supplements must be
discontinued before a patient receives a regional anesthetic.
§ Remember the 4 G’s that increase the risk of bleeding: garlic, ginger, ginkgo, and ginseng.
• Patient Safety
o We’ve finally arrived at the last page of the last tutorial. It’s been a heck of a journey, and we’re so thrilled that you made it through!!! And so, we
conclude with patient safety, because this is what it’s all about…
o Anesthesia Morbidity and Mortality
§ Human error is the #1 cause of anesthetic mortality (51-77% of all anesthetic related deaths). Even so, anesthesia is safer today than at any
other point in history.
§ The American Society of Anesthesiologists estimated anesthetic mortality as it relates to ASA physical status classification.
• ASA 1= 0.04 deaths per 10,000 anesthetics
• ASA 2= 0.5 deaths per 10,000 anesthetics
• ASA 3= 2.7 deaths per 10,000 anesthetics
• ASA 4= 5.5 deaths per 10,000 anesthetics
§ As the surgical landscape shifts towards more outpatient procedures, there is a corresponding change in the distribution of anesthetic
morbidity and mortality.
• In the 1980s, complications related to surgical anesthesia accounted for 80% of closed claims cases.
• Since the year 2000, this has decreased to only 65%, however claims related to regional anesthesia, acute pain management, and
chronic pain management have increased.
§ According to closed claims analysis, the most common cause of injury that result in claims filed are:
• Regional anesthesia= 20%
• Respiratory events = 17%
• Cardiovascular events=13%
• Equipment failure=10%
o Anesthesia Machine Morbidity and Mortality
§ Human error is the most common cause of equipment related morbidity and mortality. Safety checklists are one way to mitigate the risk of
patient injury.
§ The 2008 ASA Pre-Anesthesia Checkout Procedure Recommendations provides a fresh update to the previous guidelines set forth by the FDA
in 1993. They divided the pre-procedure anesthesia machine checkout procedures into those that must be completed once a day vs. those
that must be performed before every patient.
§ You must complete the following tasks before every patient:
• Verify adequate suction to clear the patient’s airway.
• Verify the presence and function of required monitors and alarms.
• Check that the vaporizers are filled and the ports are tightly closed.
• Determine that the carbon dioxide absorbent is not exhausted.
• Perform a high-pressure leak test.
• Assess the unidirectional valves by ensuring that gas flows in the correct direction during inspiration and expiration.
• Document that you completed the procedures listed above.
• Set the ventilator appropriately, and conduct the anesthesia time out.
• ***The oxygen monitor must be calibrated once a day (not before every case).

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o Agencies That Mandate Patient Safety
§ The American Society for Testing and Materials sets the standards for the required components of the anesthesia machine. The
standards documents is called the ASTM F1850.
§ The United States Department of Transportation sets the standards for compressed gas cylinders.
§ The Food and Drug Administration sets the standards for food and drugs. Herbal supplements are outside of the domain of the FDA.
The FDA also created the 1993 FDA Anesthesia Machine Pre-Use Checkout Procedures.
§ The Occupational Safety and Health Administration sets the standards for acceptable occupational exposure to volatile anesthetics.
§ The Joint Commission on Accreditation of Health Care Organizations certifies hospital that meet specific safety standards. I took a
picture of this while walking through my old neighborhood (no joke!).
o Safety in the MRI Suite
§ The MRI scanner emits a strong electromagnetic field, which can turn ferrous objects into projectile weapons jeopardizing the safety
of patients and staff. To minimize this risk, the American College of Radiology divides the MRI suite into 4 zones based on the
proximity of the magnet.

§ Key Points:
• Ferromagnetic objects are NOT allowed in zone 4.
• Safe metals include: stainless steel, titanium, aluminum, and copper.
• Make sure patient does not have a pacemaker, ICD, aneurysm clip, metal implant, implantable pump, or shrapnel. If the
patient has any of these thing, someone must verify that all the components are made from non-ferrous metals.
• MRI safe gas cylinders are silver with a color code at the top.
• EKG may experience T wave and ST segment artifacts.
• Nausea is a common side effect of IV contrast media. The rate of allergic reaction is <1%.

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OBESITY
• Causes
o One third of American adults are obese, and over 20% of children and adolescents are overweight or obese.
§ According to the National Institute of Health, adult obesity ranks only second to smoking as the leading cause of
preventable death.
§ Children obesity is more common than diabetes, cystic fibrosis, and all cancers.
o While the origin of this endemic stems from a combination of genetic, environmental, endocrinologic, and socioeconomic
factors, the bottom line is that there is a caloric supply and demand mismatch. For a person’s weight to remain stable, energy
intake must equal energy utilization. Excess intake results in weight gain, while starvation leads to weight loss.
o Most fat is stored in adipocytes concentrated in the intraperitoneal cavity
and subcutaneous tissue, however some fat also accumulates in the liver.
Each gram of fat provides 9 calories of physiologically available energy. For 1 gram of fat=9 calories
a point of comparison, each gram of carbohydrate and protein provides 4
calories of physiologically available energy. 1 gram of carb & protein=4
o While excess food consumption and inadequate physical activity are the most common factors leading to obesity, there are a
variety of medically related etiologies as well.

o This tutorial will cover the anesthetic implications of obesity, common coexisting conditions, and current treatment options
designed to reverse this devastating disease.
• Adipose as an Endocrine organ
o The body requires adipose for its ability to function as a readily available energy supply. Additionally, fat serves as an insulator.
o Adipose becomes pathologic when it releases significant quantities of free fatty acids and cytokines. A terminal consequence of
excess adipose tissue is insulin resistance and inflammation throughout the body. Of all the fat storage sites, visceral fat
releases the highest quantities of these compounds and appears to pose the most significant health risk.
o In the obese patient, the distribution of adipose tissue plays a key role in the development of coexisting disease.
o Android Obesity
§ Android obesity (apple shape) is more common in men. It is characterized by central or abdominal visceral fat
accumulation. A waist size >40 inches for men and >35 inches for women is associated with an increased risk of
ischemic heart disease, hypertension, dyslipidemia, insulin resistance, and death.
o Gynecoid Obesity
§ Gynecoid obesity (pear shape) is more common in women. It is characterized by gluteal and femoral fat
accumulation. Unlike abdominal fat that is metabolically active, gynecoid fat is metabolically inactive and is primarily
used for energy storage. Patients with gynecoid fat accumulation are more likely to develop joint disease and varicose
veins. Interestingly, this type of fat is associated with a reduced incidence of non-insulin dependent diabetes.
o Metabolic Syndrome
§ Metabolic syndrome (syndrome X) incorporates several disease states that coincide with obesity. Cardiovascular risk
is 50-60% greater than the general population. Diagnosis of metabolic syndrome requires at least 3 of the following
signs:
• Large waist circumference (men>40 inches & women > 35 inches)
• Triglycerides > 150 mg/dL
• High density lipoprotein (HDL) < 40 mg/dL for men and <50 mg/dL for women
• Blood pressure>130/85
• Fasting glucose > 100 mg/dL

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• Definition of Obesity and BMI
o The body mass index (BMI) relates a person’s weight to his height. While it is not a perfect measure of fat mass, it is the most
commonly used clinical tool used to define obesity. It does not take fat distribution (android or gynecoid) into account. Also,
BMI can be skewed in those with a large percentage of muscle mass, such as athletes or body builders.
o The risk of obesity related morbidity increases in direct proportion to BMI.
o Body Mass Index Calculation

§
§ In this question, you were asked to calculate the BMI of a patient
who is 176 lbs and 74 inches tall. On the NCE, you may need to
convert weight (lb to kg) and/or height (in to cm to m). in our
example, we required you to do it all.
1. Convert weight from pounds to kilograms (Conversion = lbs/2.2)
176 lbs/2.2 = 80 kg
2. Convert height from inches to centimeters (Conversion = in x 2.54)
74 inches x 2.54=187.96cm
3. Convert centimeters to meters (Conversion = cm/100)
187.96/100=1.8796 m
2
4. BMI = kg / m
2
80 kg / 1.876m =80/3.53289616=22.64
a. *To avoid rounding errors, we recommend that you wait to round until you arrive at the final answer.
• Total Body Weight & Ideal Body Weight
o Total Body Weight (TBW)
§ This is what you see when you step on the scale. This one is easy.
o Ideal Body Weight (IBW)
§ Ideal body weight describes the BMI associated with the lowest risk of body weight related comorbidities. We can
estimate the ideal body weight with the following formulas.
Men (kg) = Height (cm) – 100
Women (kg) = Height (cm) – 105
§ You were asked to calculate the ideal body weight of a women who is 5’3’’.
§ 1. Convert height to centimeters.
• 63 inches x 2.54 cm = 160.02 or 160 cm
§ 2. Enter the height into the formula for a woman.
• IBW (kg) = Height (cm) – 105
• 160 – 105 = 55 kg
§ the ideal body weight for this patient is 55 kg.
• Respiratory Effects of Obesity
o Obesity creates a restrictive ventilatory defect. In effect,
this compresses the lungs and reduces lung volume and
compliance. An increase in pulmonary blood flow further
reduces compliance.
o Lung Volumes and Capacities
§ Lung inflation is inhibited due to the following:
• Chest fat compresses the rib cage and
hinders its outward expansion.
• Abdominal fat shifts the diaphragm cephalad and compresses the lungs.
• Kyphosis and lordosis develop over time and alter the geometry of the ribcage.
§ FRC is inversely proportional to BMI. The reduction in FRC (due to a decrease in ERV) below closing capacity creates a situation
where distal airway collapse occurs during tidal breathing. This leads to V/Q mismatch, shunt, and hypoxemia. Premature airway
closure also increases dead space.
§ General anesthesia causes FRC to fall by 50%. In the non-obese patient, FRC is reduced by only 20%. A higher oxygen consumption
coupled with a smaller FRC predisposes this population to rapid desaturation during apnea.
§ While the obese patient may experience hypoxemia, PaCO2 is usually normal. This is explained by the high diffusing capacity of CO2
and the favorable characteristics of the CO2 dissociation curve. An elevated PaCO2 signals impending respiratory failure.
§ Vital capacity and total lung capacity are reduced.
§ Other changes include:
• Fat is metabolically active organ, so these patients have an increased oxygen consumption and carbon dioxide
production. Minute ventilation must be increased to maintain normal blood gas tensions.
• The extra weight on the chest increases the work of breathing. A rapid and shallow breathing pattern provides the most
energy efficient way to achieve this goal.

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• Ventilatory Management of the Obese Patient
o The combination of a smaller FRC and an increased oxygen consumption predisposes the obese patient to oxygen desaturation during apnea.
Obese patients may experience arterial desaturation in half the time of the normal adult.
o Prevention of Hypoxemia during Induction
§ When the obese patient lays supine, the posterior cervical fat forces the patient into neck flexion. Optimal positioning for airway
management is accomplished with the head-elevated laryngoscopy position (HELP). The idea is to elevate the head, shoulders, and upper
body above the chest. You should be able to envision a horizontal line drawn from the sternal notch to the external auditory meatus. This
creates the most favorable alignment of the oral, pharyngeal, and laryngeal axes and improves your chances for successful mask ventilation,
intubation, and LMA placement.
§ The patient should be preoxygenated with 100% FiO2 until end-tidal O2>90% with CPAP 10 cm H2O. this will increase the time before
desaturation occurs by 50%.
§ Placing the patient in reverse Trendelenburg position relieves pressure on the thorax and improves FRC> the patient should be extubated in
this position as well.
o Atelectasis – Prevention and Reversal
§ Keep FIO2 < 80% during anesthetic maintenance to prevent absorption atelectasis.
§ To recruit collapsed alveoli, you must do 2 things:
• Re-open collapsed alveoli with a recruitment maneuver (Valsalva). Give a breath to ~40 cm H2O and hold for 10 seconds. This
may temporarily reduce venous return, blood pressure, and heart rate.
• Hold open the re-expanded alveoli with PEEP or CPAP 5-10 cm H2O. This improves FRC, V/Q matching, and arterial oxygenation. It
may reduce venous return and cause hypotension.
o Lung Protective Strategy for Mechanical Ventilation
§ Use a tidal volume 6-8 mL of ideal body weight. Higher tidal volumes only minimally increase PaO2 and may cause shear stress to the
lungs.
§ Control PaCO2 by adjusting the respiratory rate, not by increasing tidal volume.
o Prevention of Pulmonary Aspiration
§ Obesity alone does not mandate a rapid sequence intubation. There is conflicting evidence regarding the effects of obesity on gastric
pH, residual gastric volume, and gastric emptying time. Despite these conflicts, there is no data that illustrate an increased incidence
of pulmonary aspiration on the basis of BMI alone, and that the decision for a RSI should be made on a case by case basis. Patients
with other risk factors, such as GERD or diabetes, should be considered candidates for aspiration prophylaxis and RSI.
o Postoperative Oxygenation
§ Postoperative hypoxemia may occur immediately after extubation or up to 2-5 days following surgery. Patients with OSA are at the
highest risk. Strategies to maximize postoperative oxygenation include:
• CPAP or BiPAP after extubation – especially if patient uses it at home
• Elevate the HOB 30 degrees
• Early ambulation
• Control surgical pain—non-opioid analgesics and regional anesthesia will minimize respiratory depression
• Incentive spirometry
• Cardiovascular Effects of Obesity
o Blood Volume & Cardiac Output
§ The expansion of intravascular blood volume and a high cardiac output state are the key changes that lead to the cardiovascular
complications of obesity.
§ The proliferation of adipocytes requires that the vasculature grow in order to support their growth. In effect, this increases the size
of the circulation and necessitates an increased blood volume and cardiac output.
§ Since heart rate is usually unchanged in the obese patient, and increased stroke volume is responsible for the increased cardiac
output. Indeed, cardiac output increases 100 mL/min for every extra kilogram of fat.
§ A larger vascular network, blood volume, and oxygen consumption place a higher workload on the myocardium. Venous return must
match cardiac output, so the heart dilates to accept the larger incoming volume. Additionally, it becomes thicker to compensate for
the increased walls tress. This reduces ventricular compliance and causes diastolic dysfunction. Eventually the heart dilates beyond
its ability to increase wall thickness. At this point, the patient will experience
systolic dysfunction and ultimately biventricular heart failure.
§ Hypertension is the result of hyperinsulinemia, SNS and RAAS activation, as well as
an elevated cytokine concentration in the plasma.
§ Common EKG Changes
• Low voltage EKG – increased distance between heart and leads.
• Left axis deviation – the stomach pushes the heart up and to
the left. Also, there is LVH secondary to volume overload and
HTN
• Right axis deviation – right ventricular hypertrophy from OSA
and volume overload.
• QT prolongation – increases the risk of sudden death
• Ischemia – oxygen supply and demand mismatch
• Dysrhythmias – caused by fatty infiltration of the conduction
system, myocardial hypertrophy, hypoxemia, hypercarbia,
obesity hypoventilation syndrome, and ischemic heart disease
§ The presence of tricuspid regurgitation on TEE may be the most useful confirmation of pulmonary hypertension.

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Implications for Dosing Anesthetic Drugs
o No doubt that you’ve learned that some drugs are based on ideal body weight, while others on total body weight. As a general rule:
Water soluble drugs are calculated with ideal body weight (IBW)
Lipid soluble drugs are calculated with total body weight (TBW)
o Unfortunately, these maxims DO NOT always apply for morbidly obese patients.
o Furthermore, these calculations may be different depending on whether you are giving an initial or
maintenance dose. This is because the loading dose is primarily dependent on the volume of distribution, while
the maintenance dose is determined by clearance.
o Intravenous Agents in the Obese Population
§ The volume of distribution of a drug in the obese patient is altered by:
• Increased blood volume – requires a higher dose to achieve a given plasma concentration.
• Increased cardiac output – faster drug delivery to the vessel rich group
• Altered plasma protein binding – altered free fractions available
• Lipid solubility of the drug – large fat mass greatly increased Vd for lipophilic drugs
§ An increased body weight comes with an increased volume of distribution for both hydrophilic and lipophilic drugs. Remember that fat mass AND
muscle mass increase. This means that the Vd for water soluble drugs will increase some because the plasma volume is larger, but the Vd for fat
soluble drugs will increase a whole lot more because of the large fat mass.
Vd lipophilic drugs >>> Vd hydrophilic drugs * both increase!
§ This presents a problem with the dosing regimen used in the non-obese population:
• Using IBW may under dose a drug because the Vd is larger in the obese patient.
• Using TBW may overdose a drug because fat is less vascular than other tissue, and a greater percentage of the loading dose will go to
the vessel rich group.
• Dosing based on lean body weight solves this issue.
o Lean Body Weight
§ The best way to think about lean body mass is to view it as the ideal body weight
plus the extra muscle mass that occurs with weight gain. There is a somewhat
complicated way to calculate this, but it’s low yield for the NCE and not worth
committing to memory. You can estimate lean body weight by:
LBW= IBW x 1.3
o Inhalation Agents in the Obese Population
§ Volatile agents are lipophilic, so agents with the lowest blood:gas coefficients should be
used. Sevoflurane or desflurane provide a faster emergence than isoflurane or
propofol.
§ MAC is unchanged by obesity.
§ There is increased defluorination with isoflurane and desflurane, however this is not
linked to postoperative hepatic or renal dysfunction. Defluorination with sevoflurane is
unchanged.
§ Nitrous oxide is generally avoided, because it restricts the maximum FiO2 that can be
delivered.
o We want to begin by acknowledging that the textbooks contain a good deal of conflicting
information on this topic. For this reason, we have painstakingly sifted through a large number of
texts to find the most commonly cited guidelines. If the majority of reference agreed on a particular recommendation, we included that recommendation. In some
instances, we found an even split, so in these situations we included both guidelines. This is one of the reasons why we use multiple references throughout our entire
review. It is just one more way we make sure to give you the best coverage possible!
o This may be a difficult subject to wrap your head around. While it’s prime content for the NCE, we’d be shocked if you got more than one question on this topic. Most of
us want to understand everything that we read, and that is the hallmark of a good student. Even so, time is finite, so you must use it wisely. If you’re just not getting it,
move on to the next topic. There is too much ground to cover to waste valuable time on any single topic—this one or another that gives you great difficulty.
o Propofol
§ The loading dose of propofol is based on lean body weight. This is because the offset is caused by redistribution and not clearance (which
would depend on Vd). Pharmacokinetic modeling has determined that the maintenance dose is best based on total body weight.
o Succinylcholine
§ Even though succinylcholine is a water soluble drug, the dose for intubation is calculated with total body weight. This is a clear exception
to the rule for water soluble drugs. Shortly stated, the combination of an increased blood volume (increased Vd) and increased
Pseudocholinesterase activity (increased clearance) necessitates a TBW dose be given to ensure adequate paralysis.
o Nondepolarizing Neuromuscular Blockers
§ Rocuronium and vecuronium are distributed throughout body water and are dosed on LBW.
§ Loading doses of cisatracurium and atracurium should probably be dosed on TBW. When it comes to maintenance dosing, however, there
isn’t consensus on the best way to dose these drugs.
o Fentanyl, Sufentanil, & Remifentanil
§ Because of their fat solubility and large Vd, the initial doses of fentanyl and sufentanil are based according to TBW. Maintenance dosing is
based on LBW. An increased Vd correlates with a prolonged elimination half-life.
§ Remifentanil is the exception. Since it is rapidly cleared by plasma esterases, it does not behave like a high Vd drug, so remifentanil is
always based on LBW.
o Midazolam
§ Midazolam is administered by TBW because of an increased central volume of distribution. Just about all the books seem to agree on this.
Dosing in this way will prolong the elimination half-life and its duration of effect. In practice, it may cause over sedation in the obese
patient who is sensitive to respiratory depressant drugs.
o Epidural Local Anesthetic
§ Engorgement of the epidural veins and an increased epidural fat content will cause a greater spread of local anesthetic in the epidural
space. For this reason, the dose should be reduced to 75% of the normal dose.
o Oral Drugs: There is no difference in absorption of orally administered medications in the obese population.

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• Obstructive Sleep Apnea:
o During normal inspiration, diaphragmatic contraction and chest wall expansion create a negative pressure to draw air into the lungs. What you
should appreciate is that the upper airway is also subjected to this negative pressure. In consequence, there is a tendency for the soft tissue in
the upper airway to collapse.
o You can think of the pharynx as a collapsible tube. Airway patency is maintained by the balance between pharyngeal muscles that dilate the
airway and the negative pressure of inspiration that collapses it.

o The upper airway is composed of soft tissue and bony support. Bone
remains in a relatively fixed location, however the position of the soft
tissue is dynamic throughout the respiratory cycle. In the obese, fat
tends to accumulate in the lateral walls of the pharynx. This causes the
internal diameter to narrow, decrease air flow, and increase the
tendency for the airway to collapse. Furthermore, obesity reduces lung
volumes, which causes a reduction in longitudinal pharyngeal traction.
Impairment of the neural pathways that control the pharyngeal dilator
muscles also contributes to the potential for airway obstruction.
o Obstructive Sleep Apnea
§ Obstructive sleep apnea is defined as the cessation of airflow
for at least 10 seconds (apnea) with 5 or more unsuccessful
efforts to breathe (obstruction) and a greater than 4% reduction in SaO2.
§ Hypopnea is also a common phenomenon in OSA. It is defined as a 50% reduction in airflow for 10 seconds, 15 or more times per
hour, and is linked to snoring and decreased oxygen saturation.
§ The incidence of OSA is directly proportional to BMI. OSA increases with a BMI > 30 kg/m2, abdominal fat distribution, and large
neck girth (>17 in for men and >16 inches for women). OSA is an independent risk factor for the development of hypertension,
cardiovascular morbidity, and death.
o Diagnosis
§ Up to 60-70% of patients with OSA remain undiagnosed. Since it is a major contributor to perioperative morbidity. It
is imperative that all patients should be screened for OSA>
§ Classic Triad of Dysfunctional Sleep
• Apnea or snoring with hypopnea during sleep
• Arousal from sleep
• Daytime somnolence
§ Polysomnography
• Polysomnography is the definitive test for OSA> the results of this test allow for the calculation of the
apnea-hypopnea index (AHI), which is used to quantify the severity of OSA.
AHI= Number of Episodes of Apnea and Hypopnea
Hours of sleep
§ The American Academy of Sleep Medicine defines OSA as:
• Mild=5-15 episodes/hr
• Moderate = 15-30 episodes/hr
• Severe = > 30 episodes /hr
§ Patients with severe sleep apnea are at higher risk for difficult mask ventilation and difficult intubation.
§ STOP-BANG
• Most patients with OSA haven’t had
a sleep study, and even more don’t
even realize they have OSA! The
STOP-BANG scoring system is a
bedside tool that allows you to
predict the likelihood that a patient
has undiagnosed OSA.
High risk for OSA = > 3 questions answered yes

Low risk for OSA = < 3 questions answered yes

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 • Obesity Hypoventilation Syndrome
o Obesity hypoventilation syndrome is a long term consequence of untreated OSA. Over time, the respiratory center in the medulla fails to
respond to hypercarbia appropriately. The classic presentation of OHS includes episodes of apnea during sleep WITHOUT any respiratory effort.
Pickwickian syndrome is the old school name for OHS.
o Diagnostic Criteria
§ BMI>30 kg/m2
§ Awake PaCO2>45 mmHg
§ Dysfunctional breathing during sleep
o Signs
§ Obesity § Compensatory metabolic alkalosis
§ Hypersomnolence during the day § Polycythemia
§ Hypoxemia § Pulmonary hypertension
§ Hypercarbia § Right heart failure
§ Respiratory acidosis
o The administration of any respiratory depressant drug puts these patients at high risk of airway obstruction of respiratory arrest. When
planning your management, try to think of multi-modal approaches to pain that do not impact respiratory drive, such as regional anesthesia,
NSAIDs, acetaminophen, ketamine, dexmedetomidine, etc.
• Bariatric Procedures
o Bariatric surgery is the most effective treatment for the reversal of obesity. Additionally, it usually leads to the resolution of comorbidities such
as hypertension and type 2 diabetes.
o There are 3 approaches to surgical weight loss:

o Gastric Bypass & Anastomic Leak

§ Gastric bypass is associated with a a2% incidence of anastomotic leak. These patients should not receive ketorolac.
§ The most common signs and symptoms include:
• Tachycardia (72%)
• Fever (63%)
• Abdominal pain (54%)
§ Unexplained tachycardia is the most sensitive sign of an anastomotic leak. An unexplained heart rate > 120 bpm is alarming, even if
the patient shows no other symptoms.
§ Other signs and symptoms of anastomotic leak:
• Shoulder pain (usually left) • Oliguria
• Pelvic pain • Increased thirst
• Substernal pressure • Restlessness
• Dyspnea • Hiccup
• Hypotension
Implications of Appetite Suppressants
o Ma Huang
§ Certain non-prescription appetite suppressants may be a source of drug interactions in the perioperative period. Many of these drugs contain
Ma huang. This is a natural source of ephedrine, an indirect acting adrenergic agonist and thermogenic agent. Any drug interactions that
would occur with ephedrine will apply here as well. Complicaitons of adrenergic overstimulation, including hypertension, CVAs, seizures, and
death, have occurred with the use of Ma huang containing drugs.
o Phentermine
§ A norepinephrine reuptake inhibtiro that acts as an appetitie suppresnat and increases BMR. adrenergic overstimulation may occur.
o Sibutramine
§ A norepinephrine and serotonin reuptake inhibitor that acts as an appetite suppressant and increases BMR. Risks include adrenergic
overstimulation and serotonin syndrome.
o Orlistat
§ A lipase inhibitor that reversibly binds to lipase and hinders the absorption and digestion of consumed fats. Since fat and the vitamins it
contains (D, A, K, E) are not absorbed by the gut, they must be supplemented orally. Insufficient quantities of vitamin K will impair synthesis
of clotting factors 2, 7, 9, and 10 and may cause a coagulopathy.

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Positioning and Nerve Injury
• Cardiovascular Changes of Complications
o The Effect of Gravity in the Non-Anesthetized Patient
§ The awake patient has a variety of compensatory mechanisms designed to minimize the hemodynamic impact of
position changes. For example, moving from the sitting to standing position activates the SNS (baroreceptor reflex).
This combats the effect of gravity (venous pooling), ensuring perfusion of the brain and the other vital organs.
o The Effect of Gravity in the Anesthetized Patient
§ The body’s protective mechanisms are attenuated by:
• General anesthesia (impaired baroreceptor responsiveness & decreased SNS
tone)
• Neuraxial anesthesia (Sympathectomy)
• Positive pressure ventilation (increased intrathoracic pressureàdecreased
venous return)
• PEEP (increased intrathoracic pressureàdecreased venous return)
• Muscle relaxants (decreased skeletal muscle toneàdecreased venous
return)
§ The net result is that the blood volume tends to follow gravity.
§ Can you predict how this affects preload during surgical positioning?
o Trendelenburg & Lithotomy:
§ Blood shifts towards the central circulationàincreased venous returnàincreased position on the Frank-Starling curve
§ MAP stays the same or increases:
• Although venous return initially increases, this is followed with vasodilation and a slower heart rate.
• While some sources say that Trendelenburg can be used to treat hypovolemic shock, there is no evidence to
support this, and it may actually impair cerebral perfusion.
§ Venous pressure increases:
• Hydrostatic pressureàedema of the face, eye, and airway.
• Intracranial hypertension
§ The Trendelenburg and lithotomy positions contribute to
unrecognized hypovolemia. Only after the patient returns to the
supine position is the volume deficit unmasked (decreased SV, CO &
BP)
§ Patients with poor myocardial function may not be able to tolerate
the volume shift (increased preload overshoots the peak of the Frank-
Starling curve putting the patient into heart failure).
o Sitting, Flexed Lateral & Prone
§ Blood shifts away from the central circulationàvenous pooling à decreased venous returnàdecreased position of
the Frank-Starling Curve.
• Since anesthesia impairs baroreceptor responsiveness, the SNS is unable to provide full compensation for
the preload reduction.
• This explains why these positions are associated with a higher incidence of hemodynamic instability
(decreased SV, CO & BP)
§ The risk of cerebral hypoperfusion is increased when the brain is higher than the heart.
• Can you remember how the BP changes when the head and heart aren’t in the same plane?
• If using an arterial line, zero the transducer at the external auditory meatus.
o Interventions That Promote CV Stability
§ Move the patient slowly
§ Use a lighter plane of anesthesia
§ IV hydration

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Respiratory Changes & Complications
• Compared to the awake spontaneously breathing patient, the patient who is anesthetized and spontaneously breathing has a/an:
o Decreased tidal volume
o Decreased FRC
o Increased closing volume
• Gravity & Pulmonary Function
o Just as gravity affects the distribution of blood volume in the anesthetized patient, it
also affects the position of the abdominal viscera.
• Although we covered how position changes affect the V/Q relationship in Pulmonary II:
Physiology, we want to make sure that you understand:
o 1. Which lung is dependent and non-dependent in each position.
o 2. How each position affects the V/Q relationship and respiratory gas tensions.
• Positioning and the Endotracheal Tube
o securing the endotracheal tube after intubation fixes its location. For the rest of the
procedure, the position of the tip of the ett is at the mercy of the patient’s neck
position as well as the position of the carina in the chest.
o Neck Position
§ Remember, “the tube goes where the nose goes.”
• Neck flexion pushes the ett towards the
carina. This increases the risk of
endobronchial intubation.
• Neck extension pulls the ett tip towards
the vocal cords. This increases the risk of
inadvertent extubation.
o Carina Position
§ In the Trendelenburg position, the abdominal
contents shift cephalad. This pushes the diaphragm
towards the ett, increasing the risk of endobronchial
intubation.
• Airway Edema
o Edema of the face, tongue, pharynx can affect airway patency.
§ Prone and Trendelenburg; increased hydrostatic
pressureàedema formation
§ Sitting: neck flexion impairs venous drainage from the headàedema formation
§ Equipment (oral airway, esophageal temp probe): impairs lymphatic drainageàedema formation
o If you have a concern about the patency of the airway prior to extubation, you can:
§ 1. Perform a leak test to assess for air movement around the endotracheal tube while the patient is spontaneously ventilating.
§ 2. Visually inspect the larynx with direct laryngoscopy.
Injury: Brachial Plexus
• In every surgical position, the brachial plexus is susceptible to stretch and compression injuries.
• Stretch Injury
o Stretch injury occurs because the brachial plexus is anatomically fixed at two locations: the cervical vertebrae and the axillary fascia.
o As a general rule, the risk of stretch injury is highest when the arms are Abducted>90 degrees and/or the head is rotated to one side.
• Compression Injury
o Compression injury usually occurs when the brachial plexus is compressed as it passes between the clavicle and first rib or by an external force
(shoulder brace or bean bag).
• Position Related Considerations
o Supine
§ Arm Abduction > 90 degrees stretches the brachial plexus around the head of the humerus
§ Neck rotation stretches the brachial plexus on the contralateral side
§ Excessive sternal retraction during cardiac surgery can compress the brachial plexus under the first rib.
o Trendelenburg:
§ Although shoulder braces were developed to prevent the patient from sliding on the OR table, they cause more harm than good!
§ The best answer is to never use shoulder braces. A non-sliding mattress is a safer option.
§ If shoulder braces are used, they should be placed at the distal end of each clavicle (over the acromion).
§ Shoulder braces applied near the base of the neck or midway along the clavicle increases the risk of a compression injury.
§ A bean bag that envelopes the shoulders can also cause a compression injury.
o Prone
§ The shoulders should not be allowed to sag forward.
§ The arms should not be extended over the head (keep the shoulders and elbows at 90 degrees or less).
§ Assess for thoracic outlet syndrome. During the preoperative interview, ask the patient to clasp her hands behind her head. If she
complains of pain, it may be prudent to tuck the arms in the prone position.
o Lateral Decubitus:
§ An axillary roll is placed distal to the axilla.
§ A roll placed inside the axilla can cause neurovascular compression. A poor SpO2 signal in the dependent arm is a good monitor for
this.

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Injury: Ulnar Nerve

• The ulnar nerve is the most commonly injured peripheral nerve. Although its anatomy renders it susceptible to compression, it’s critical
to understand that this isn’t the only cause of ulnar neuropathy that develops during hospitalization.
• Anatomy of the Cubital Tunnel
o Boundaries of the cubital tunnel:
§ 1. Medial epicondyle of the humerus
§ 2. Olecranon process of the ulna
§ 3. Cubital tunnel retinaculum (creates the roof of the cubital tunnel)
o the ulnar n. emerges from the cubital tunnel between the humeral and ulnar heads of
the flexor carpi ulnaris.
o Mechanism of Injury
§ External compression
§ Elbow flexion àincrease distance between the medial epicondyle and
olecranon àdecreased cubital tunnel sizeàincreased pressure on the ulnar
n.
• Risk Factors for Ulnar Injury
o Ulnar neuropathy isn’t always caused by intraoperative positioning. Indeed, the ASA Closed Claims analysis can’t determine
substandard care in the majority of patients who develop this complication. Furthermore, there are a host of additional risk
factors that predispose patients to ulnar nerve injury. These include:
§ Male gender (especially if > 50 years old)
§ Preexisting ulnar neuropathy
§ Extremes of body habitus (very thin or obese)
§ Prolonged hospital stay/bedrest
o Many cases of ulnar neuropathy don’t present until > 24 hours after surgery
• What is the Best Way to Position the Forearm in the Supine Patient?

• Presentation=Claw Hand
th th
o Impaired sensation of the 4 and 5 digits
o Inability to Abduct or oppose the pinky finger
o Chronic injury presents with claw hand (muscular atrophy)
• What Should You Do if a Patient Presents with Post-Operative Nerve Injury?
o Sensory Deficits:
§ Sensory deficits are more common, less serious, and tend to resolve on their own (usually 5 days or less).
§ Barash sayst to get a neurology consult if the injury persists for more than 5 days or if it becomes worse. Miller says to provide
reassurance and offer appropriate follow up. On the same page, however, Miller goes on to say that if a patient experiences a post-
operative nerve injury, it’s prudent to consult with a neurologist within the first week of injury.
o Motor Deficits:
§ Motor deficits are less common, more serious, and those that involve demyelination may take up to 4 to 6 weeks to recover.
§ The most severe injuries (axonal injury or complete disruption) may cause intense pain and disability. If these injuries are reversible
(some are and some are not), they may require 3 to 12 months for recovery. Physical therapy will be required to prevent muscular
atrophy and contracture.
§ A patient with a motor deficit requires a neurologic consult with EMG and/or nerve conduction studies.
Injury: Median Nerve
o Median nerve injury is a pretty uncommon event.
o Etiology
§ IV placed in the antecubital space
§ Carpel tunnel syndrome—the median nerve is the only nerve that passes through the carpel tunnel
§ Elbow hyperextension
§ Forced elbow extension during positioning after a neuromuscular blocker has been administered
o Presentation
§ Reduced sensation over palmar surface of the thumb, index finger, middle finger, and lateral aspect of the ring finger.
Unable to oppose the thumb (chronic injury can lead to the ape hand deformity).
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Injury: Radial, Long Thoracic & Suprascapular

• Radial Injury
o The radial nerve passes along the spiral groove at the lateral aspect of the humerus (about 3 fingerbreadths above the lateral
epicondyle).
o Etiology
§ External compression by an IV pole
§ Excessive cycling of the NIBP cuff
§ Upper extremity tourniquet
§ Sheets that are too tight (if the arms are tucked)
o Presentation = Wrist drop
§ Inability to extend the hand at the wrist
• Long Thoracic Injury
o The long thoracic nerve arises from C5-C7. It innervates the serratus anterior muscle.
o Etiology:
§ Trauma
§ Preexisting neuropathy (possibly due to a virus)
o Presentation = Scapular Winging
§ Dorsal protrusion of the scapula
• Suprascapular Injury
o The suprascapular nerve is anchored between the cervical spine and the suprascapular notch.
o Etiology
§ Ventral circumduction of the dependent shoulder in the lateral position can stretch the suprascapular nerve.
o Presentation: Dull Shoulder Pain
Injury: Lower Extremity

• Obturator Injury
o Etiology:
§ Excessive flexion of the thigh towards the groin
§ Excessive traction during lower abdominal surgery
§ Forceps delivery
o Presentation
§ Inability to ADDuct the leg
§ Reduced sensation over the medial aspect of the thigh
o Prevention
§ Minimize hip flexion
• Femoral Injury
o Etiology
§ Excessive traction during lower abdominal surgery
o Presentation
§ Impaired knee extension and hip flexion
§ Reduced sensation over the anterior thigh and anteromedial aspect of the leg
• Saphenous Injury
o Etiology
§ MEDIAL aspect of the leg leans against the supporting cradle in the lithotomy position (the saphenous n. resides near
the tibia)
o Prevention
§ Place padding between leg and stirrup
o Presentation
§ Reduced sensation over anteromedial aspect of the leg
• Common Peroneal Injury
o Etiology
§ The common peroneal nerve is highly susceptible to injury when the patient is placed in stirrups. This nerve wraps
around the fibular head, and it can be compressed when the lateral aspect of the leg leans against the stirrup bar.
o Presentation
§ Foot drop
§ Inability to evert the foot
§ Inability to extend the toes dorsally
o Prevention
§ Place padding between the leg and stirrup
§ Pad under the fibular head
§ Knees should be flexed with minimal rotation

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 • Sciatic Injury
o Etiology
§ Lithotomy—extreme hip flexion and/or external rotation of the legs
§ Sitting—straight legs
o Prevention
§ Ample padding under buttocks
§ Avoid excessive external rotation of the hips
§ Flex table at the knees
o Presentation
§ Foot drop
• Pudendal Injury
o Etiology
§ Injury occurs when the nerve is compressed against a perineal post on an orthopedic fracture table
o Prevention
§ Adequate padding between the perineal post and the patient
o Presentation
§ Loss of penile sensation
§ Crush injury to genitalia
• What Happens if We Leave the Patient’s Legs Crossed During Surgery?
o Many patients have the tendency to cross their legs prior to anesthetic induction, as this relieves pressure on the lower back. If
the leg remain in this position during the case, then 2 nerves can be injured.
o Top legàsural injury:
§ Pressure from the superior aspect of the dependent leg will damage the sural nerve on the underside of the superior
leg.
o Bottom legàsuperficial peroneal injury:
§ Pressure from the underside of the superior leg will damage the superficial peroneal nerve of the dependent leg.
Complications: Other

• Lower Extremity Compartment Syndrome

o Compartment syndrome is most common in the lithotomy position.
o The lithotomy position is associated with increased leg compartment pressure, and raising the legs above the heart reduces
lower extremity perfusion pressure. Taken together, these changes set the stage for leg ischemia àedema àmore
ischemiaàmore edema…
o This can progress to Rhabdomyolysis and/or reperfusion injury.
o Risk factors for lower extremity compartment syndrome include:
§ Surgical time >2-3 hours
§ Increased BMI
§ Decreased tissue oxygenation (hypotension)
o Compartment syndrome is treated with fasciotomy.
• Air Embolism
o Although the sitting position is most commonly associated with venous air entrainment, this complication can occur in any
position that produces a pressure gradient between the atmosphere and the veins at the surgical site.
§ Venous air embolismàright heartàpulmonary vasculatureàincreased dead space & increased RV workload
§ Paradoxical air embolism à right heartàpatent foramen ovaleàleft heartàsystemic circulationàstroke
o VAE is covered in Respiratory III: Pathophysiology
• Midcervical Tetraplegia
o Midcervical tetraplegia is associated with hyperflexion of the neck (chin to chest). Ischemia occurs as a result of stretching
and/or compression of the midcervical spinal cord (usually C5).
§ This complication is most common in the sitting position.
§ You should be able to place at least 2 fingers in-between the chin and the chest.
• The Prone Position and Intraabdominal Pressure
o When you place the patient in the prone position, your primary objective is to minimize pressure on the abdomen and the vena
cava. This confers several benefits:
§ Improves pulmonary mechanics
§ Improves venous return
§ Decreases venous pressure

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 o In the prone position, a positioning device (chest rolls, Wilson frame, or Jackson table) and padding distribute the patient’s
weight to the thoracic cage and the boney pelvis. This allows the abdomen to hang freely, which promotes normal
diaphragmatic excursion throughout the respiratory cycle.
§ If the abdomen is compressed, intraabdominal pressure increases, which reduces pulmonary compliance and
increases intrathoracic pressure.
§ Venous pressure is also increased, and this can cause back bleeding via the epidural veins during spinal surgery.
o When compared to the Wilson frame and chest rolls, the Jackson table is the best option to preserve normal pulmonary
mechanics (compliance is better and PIP is lower).
• The Prone Position and ARDS
o The prone position provides optimal V/Q matching, which explains why we use the prone position for patients with ARDS.
• The Supine Position and Anterior Mediastinal Mass
o Remember the 4 Ts to recall the tumors likely to occur in the anterior mediastinum:
§ 1. Thymoma
§ 2. Teratoma
§ 3. Thyroid
§ 4. “Terrible” lymphoma
o a tumor of the anterior mediastinum can compress 3 vital structures:
§ tracheobronchial tree
§ pulmonary artery
§ superior vena cava (may present with superior vena cava syndrome: edema of the face, neck, and upper torso)
o Be very cautious of the patient who becomes dyspneic or coughs when he assumes the supine position!
o Anesthetic management aims to minimize the compressive effect of the tumor. Spontaneous ventilation preserves the normal
airway distending pressure gradient, but this gradient is often abolished during positive pressure ventilation. The sitting
position and maintenance of spontaneous ventilation will minimize, but no always prevent, compression of the vital chest
structures.
o Three key factors worsen tracheobronchial compression:
§ 1. The supine position
§ 2. Induction of general anesthesia
§ 3. Positive pressure ventilation
o a reinforced endotracheal tube should be selected for intubation either awake or following a technique that preserves
spontaneous respirations.
o If the mass compresses the tracheobronchial tree before the airway is secured, it may be impossible to advance the
endotracheal tube beyond the tumor. It is also possible for the tumor to compress the tracheobronchial tree past the distal tip
of the endotracheal tube, causing complete obstructive of the airway.
o Should airway collapse occur, repositioning the patient laterally or prone may restore patency to the airway. A ridge
bronchoscope should be available. Emergent femoral-femoral cardiopulmonary bypass may be required if ventilation via the
lungs becomes impossible.

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Notes

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