ANESTHESIA

SHORT NOTE

(1) Adrenaline is used along with local anaesthetic agents for nerve
block and spinal anaesthesia.
(Asked in 2021, 2016 – 12 MARKS FORMAT)

Introduction:
Adrenaline (epinephrine) is a sympathomimetic agent with α and β adrenergic activity. It is
commonly used as an adjuvant to local anesthetics (LAs) to enhance their efficacy and safety,
particularly in nerve blocks and spinal anesthesia.

Mechanism of Action:
Adrenaline exerts several effects when combined with local anesthetics:
➤ Vasoconstriction via α₁ receptor stimulation → Reduces local blood flow.
➤ Delays systemic absorption of the LA → Prolongs duration of action.
➤ Decreases peak plasma levels → Lowers systemic toxicity risk.
➤ Enhances depth and intensity of anesthesia in the localized area.

Therapeutic Advantages:
Prolongs Duration of Anesthesia
Reduces Dose Requirement of LA
Minimizes Systemic Toxicity
Improves Hemostasis during surgical procedures (e.g., dental surgeries)
Improved Anesthetic Efficacy in inflamed tissues by countering vasodilation

Adverse Effects / Precautions:

Tissue ischemia due to intense vasoconstriction → Avoid in end-artery areas (e.g., fingers, toes)
Delayed wound healing
Systemic absorption of adrenaline can lead to →
• Tachycardia
• Hypertension
• Arrhythmias
Not preferred in patients with cardiovascular disease, hyperthyroidism, or arrhythmias
 Pharmacokinetics (when added to LA):
➤ Delays absorption of LA from the site of injection
➤ Prolongs half-life of the local anesthetic in the tissue
➤ Metabolized by COMT and MAO enzymes

Rationale / Significance in Clinical Use:

➤ Enhances efficacy and reduces toxicity of LAs
➤ Particularly beneficial in nerve blocks and spinal anesthesia
➤ Decreases intraoperative bleeding by local vasoconstriction

Clinical Notes / Monitoring:

Use with caution in patients with cardiovascular disease
Avoid end-arterial injection sites
Monitor for systemic effects like hypertension or palpitations

Summary:
Adrenaline is a valuable adjuvant to local anesthetics due to its vasoconstrictive properties. It
prolongs the duration, reduces systemic toxicity, and improves local effectiveness. However, careful
consideration of patient comorbidities and injection site is essential to avoid complications.

Absolutely. Proceeding in the exact order you’ve given — next is:

SHORT NOTE

(2) Lignocaine (2019s – 12 MARK FORMAT)

Introduction / Definition:
Lignocaine (also called lidocaine) is a widely used amide-type local anesthetic with rapid onset and
intermediate duration of action. It is also classified as a class 1B antiarrhythmic agent.

Classification:
➤ Local Anesthetics
• Amide group: Lignocaine, Bupivacaine
• Ester group: Procaine, Tetracaine
➤ Antiarrhythmic drugs: Class 1B
 Mechanism of Action:
➤ Blocks voltage-gated Na⁺ channels in neuronal membranes → prevents generation & conduction
of action potentials
➤ Stabilizes neuronal membrane → prevents depolarization
➤ In heart: Decreases automaticity in damaged ventricular tissue

Therapeutic Uses:
Local anesthesia – surface, infiltration, nerve block, epidural, spinal
Antiarrhythmic – ventricular arrhythmias (post-MI)
Topical application – for sore throat, ulcers, mucosal anesthesia
IV regional anesthesia (Bier’s block)
Used in combination with adrenaline for prolonged effect

Adverse Effects:
CNS effects – drowsiness, dizziness, seizures at high doses
Cardiac effects – hypotension, bradycardia, arrhythmia (rare at therapeutic dose)
Allergic reactions (rare in amides)
Toxicity risk increases with rapid IV injection or accidental intravascular administration

Pharmacokinetics:
➤ Well absorbed through mucosa and injection sites
➤ Metabolized in liver by CYP450 enzymes
➤ t½ ~1.5–2 hrs
➤ Excreted via urine

Clinical Significance:
Lignocaine is the gold standard for local anesthesia
Preferred in outpatient and minor surgical procedures
Rapid onset and good safety profile make it widely used
Safer alternative to ester-type agents (less allergenic)

Clinical Notes:
➤ Max safe dose: 4.5 mg/kg without adrenaline, 7 mg/kg with adrenaline
➤ Monitor CNS symptoms at higher doses
➤ Use preservative-free lignocaine for spinal or epidural use

Summary:
Lignocaine is a fast-acting, intermediate-duration amide local anesthetic with a wide range of clinical
applications, both as an anesthetic and antiarrhythmic. It has a favorable safety profile and is
considered essential in modern medicine.

COMPARE AND CONTRAST

(1) Pancuronium vs Atracurium (2017s – 12 MARK FORMAT)
Feature Pancuronium Atracurium

Non-depolarizing muscle relaxant Non-depolarizing muscle relaxant

Type
(steroid group) (benzylisoquinoline)

Onset & Intermediate onset, intermediate

Slow onset, long duration
Duration duration

Hepatic metabolism & renal Hofmann elimination (non-enzymatic

Metabolism
excretion degradation)

Organ Independent of kidney/liver – safer in

Requires kidney & liver function
Dependence failure

Histamine release → hypotension,

Adverse Effects Tachycardia (vagolytic effect), ↑ BP
bronchospasm

Long surgeries, patients without Preferred in patients with hepatic/renal

Use
organ compromise dysfunction

Cumulative
Yes, due to slower elimination No, safe for infusion
Effect

Reversal Agent Neostigmine + atropine Same

COMPARE AND CONTRAST

(2) Succinylcholine vs d-Tubocurarine (2016s – 12 MARK FORMAT)
Feature Succinylcholine d-Tubocurarine

Non-depolarizing neuromuscular
Type Depolarizing neuromuscular blocker
blocker

Mechanism of Persistent depolarization → Competitive antagonist at nicotinic

Action desensitization receptor
Feature Succinylcholine d-Tubocurarine

Rapid onset (<1 min), ultra-short

⏱ Onset & Duration Slow onset, long duration
duration (~5 min)

Metabolism Plasma pseudocholinesterase Liver metabolism, renal excretion

Clinical Use Rapid sequence intubation, ECT Long procedures (rarely used now)

Hyperkalemia, malignant Histamine release, hypotension,

Side Effects
hyperthermia, apnea bronchospasm

Reversible with anticholinesterase

Reversal Not reversed by neostigmine
(e.g., neostigmine)

Dependence on
Yes (plasma cholinesterase levels) Yes (kidney/liver)
Organ Function

PHARMACOLOGICAL BASIS (1): Malignant Hyperthermia with

Succinylcholine (2020 S) – 12 Marks

Introduction

Malignant hyperthermia (MH) is a rare, potentially fatal, pharmacogenetic disorder of skeletal

muscle metabolism. It is triggered by certain anesthetics, especially succinylcholine and volatile
halogenated agents, in genetically predisposed individuals.

Pathophysiology

The primary abnormality lies in the ryanodine receptor (RYR1 gene mutation) on the
sarcoplasmic reticulum in skeletal muscles.
Exposure to triggering agents like succinylcholine leads to:

• Uncontrolled calcium release from sarcoplasmic reticulum

• Sustained muscle contractions → hypermetabolism

• Heat production, lactic acidosis, hypercapnia, and rhabdomyolysis

Role of Succinylcholine

➤ Succinylcholine is a depolarizing neuromuscular blocker.

➤ It prolongs depolarization at the neuromuscular junction, stimulating RYR1 channels abnormally
in MH-susceptible individuals.
➤ This causes a massive calcium efflux and triggers MH.

Clinical Features of MH

• Rapid rise in body temperature (>40°C)

• Tachycardia, tachypnea, and hypercarbia

• Muscle rigidity (especially masseter muscle)

• Metabolic and respiratory acidosis

• Hyperkalemia → arrhythmias

• Myoglobinuria → risk of renal failure

Management

Immediate cessation of triggering agents

Dantrolene sodium – the drug of choice

• Inhibits calcium release from sarcoplasmic reticulum

Cooling measures (cold IV fluids, cooling blankets)
Correction of acidosis and electrolyte imbalance
Monitoring and supportive ICU care

Clinical Importance

• Preoperative screening is critical in patients with family history of MH.

• Succinylcholine should be avoided in genetically predisposed individuals.

• MH is a medical emergency with high mortality if not treated immediately.

Summary

Malignant hyperthermia is a life-threatening complication of succinylcholine due to genetically

defective calcium regulation. Dantrolene is life-saving. Proper perioperative vigilance is crucial for
prevention and early management.

PHARMACOLOGICAL BASIS (2): Succinylcholine Produces

Apnoea in Some Individuals (2017s) – 12 Marks
 Introduction

Succinylcholine is a depolarizing neuromuscular blocker used for rapid muscle relaxation in

anesthesia. Apnea is a rare but significant adverse reaction due to prolonged neuromuscular
blockade in certain individuals.

Mechanism of Apnoea

Normally, succinylcholine is rapidly hydrolyzed by plasma pseudocholinesterase

(butyrylcholinesterase).
In some individuals, there is a genetic deficiency or atypical variant of pseudocholinesterase
enzyme.

Genetic Basis

➤ Autosomal recessive trait leads to atypical enzyme that poorly metabolizes succinylcholine.
➤ The dibucaine number test is used to assess enzyme activity.

• Normal: >80

• Heterozygous: 40–60 (mild prolongation)

• Homozygous atypical: <30 (marked prolongation → apnea)

⏱ Effect on Neuromuscular Block

• Normally, effect lasts 3–5 minutes.

• In enzyme-deficient individuals → block lasts 30 minutes to several hours

• Leads to prolonged apnea, requiring mechanical ventilation.

Clinical Significance

• Unanticipated apnea during anesthesia recovery

• Need for artificial respiration until muscle function recovers

• Potential medico-legal implications

Management

Monitor muscle tone and respiratory status post-op

Provide ventilatory support until succinylcholine is cleared
Avoid re-use of succinylcholine in susceptible individuals
Consider testing relatives of known patients
 Precautions

• Pre-anesthetic history of prolonged apnea is critical

• Genetic counseling may be advised in familial cases

Summary

Succinylcholine-induced apnea is due to pseudocholinesterase deficiency, especially in patients with

genetic variants. Prevention by careful screening and preparedness with ventilatory support is
essential.

PHARMACOLOGICAL BASIS (3): Adrenaline is Added to

Lignocaine but Not to Bupivacaine for Local Anaesthesia (2017) – 12
Marks

Introduction

Adrenaline is commonly added to local anesthetics to prolong their action and reduce systemic
toxicity. However, its combination depends on the pharmacokinetics and safety profile of the
anesthetic used.

Lignocaine + Adrenaline

Lignocaine is a short-acting amide local anesthetic.

Adding Adrenaline (epinephrine) has several benefits:

• Vasoconstriction → ↓ systemic absorption

• Prolonged local action

• ↓ Risk of toxicity

• ↓ Bleeding (hemostasis during surgery)

Bupivacaine and Adrenaline

Bupivacaine is a long-acting local anesthetic with high cardiotoxic potential.

Vasoconstriction by adrenaline may:

• Impair local blood flow

• Enhance risk of neurotoxicity and cardiotoxicity

 • Increase chance of ischemia, especially in nerve blocks

Pharmacokinetic Basis

• Lignocaine: Rapid onset, short duration → safe with adrenaline

• Bupivacaine: Slow onset, long duration → adding adrenaline doesn't increase duration
significantly, but raises risk

Clinical Implication

Adrenaline is safely combined with lignocaine for:

• Dental blocks

• Minor surgical procedures

Avoid adrenaline with bupivacaine, especially:

• In end-arterial sites (digits, nose, penis, ears)

• In high-risk cardiac patients

Summary

Adrenaline potentiates lignocaine action by vasoconstriction but is avoided with bupivacaine due to
the risk of ischemia and cardiotoxicity. The choice of vasoconstrictor addition is based on the safety
and duration of the anesthetic agent.