Chapter 16: Disorders of Serum Sodium Concentration

in the Elderly Patient

Michael F. Michelis
Division of Nephrology, Lenox Hill Hospital, New York, New York
HYPONATREMIA
Disorders of serum sodium concentration are the
most common electrolyte abnormalities seen in the
geriatric population.
1
Furthermore, the develop-
ment of serum sodium abnormalities is associated
with increased morbidity and mortality in affected
patients.
2
Often, however, the severity of the pri-
mary process contributing to the development of
the abnormal serum sodium is responsible for the
unsatisfactory outcome. The most common disor-
der of serum sodium concentration in the geriatric
population is hyponatremia. Factors contributing
to the development of hyponatremia in the elderly
include age-associated decreases in GFR and free
water clearance, as well as sodium losses from de-
creased activity of the renin-angiotensin-aldoste-
rone system and increased activity of natriuretic
hormones. The latter, however, may reflect the
early development of fluid retention as may occur
with excessive sodium intake from processed foods
or subclinical cardiac disease. In addition, studies
have suggested increased vasopressin activity in
some elderly patients.
Patients in outpatient settings exhibit hypona-
tremia in about 5%of those tested, with occurrence
rates increasing to as high as 20% in hospitalized
geriatric patients and 30%in patients seen in inten-
sive care units.
3
The most common cause of hypo-
natremia in this population involves abnormalities
of secretion of the pituitary hormone arginine va-
sopressin (AVP), also called antidiuretic hormone
(ADH).
Clinical Diagnosis
Successful evaluation of serum sodium abnormali-
ties in the elderly depends on obtaining a careful
history especially noting reports of weight loss that
can be associated with neoplastic disease, changes
in the level of daily activities that can be associated
with endocrine abnormalities, and medication his-
tory that can produce information implicating
drugs that facilitate sodium excretion or stimulate
AVP secretion. In addition, a thorough physical ex-
amination, including orthostatic BP changes, is es-
sential for the accurate determination of the pa-
tients body fluid status. This determination may be
especially difficult in elderly patients who may have
chronic changes in skin turgor that are more asso-
ciated with aging than they are with the state of
hydration.
Laboratory Diagnosis and Therapy
When the history and physical are completed, as-
sessment of laboratory data are essential (Figure 1).
First, a plasma osmolality must be obtained to
ensure that one is dealing with hypo-osmolar hypo-
natremia. Normo-osmolar hyponatremia as can
occur with certain compounds such as mannitol,
which can also cause hyperosmolality in normon-
atremic patients, and hyperosmolar hyponatremia
caused by hyperglycemia must be ruled out. Fur-
thermore, other serum studies are important to de-
cide whether levels of substances such as blood urea
nitrogenanduric acidare elevatedandthereby con-
sistent with volume depletion or whether these lev-
els seem to be diluted as would be seen with water
excess occurring in the syndrome of inappropriate
antidiuretic hormone secretion (SIADH). Finally,
urine sodium concentration and urine osmolality
must be measured to ascertain the endocrine and
renal responses to the hypo-osmolar state.
In dehydrated patients, levels of urine sodium
can be considered low (i.e., sodium conservation)
when the spot urine sodium concentration is 20
mEq/L; in older patients, where sodium conserva-
tionmay be limited,
4
levels upto30 mEq/Lmay also
Correspondence: Michael F. Michelis, Director, Division of Ne-
phrology, Lenox Hill Hospital, 100 East 77th Street, New York, NY
10075. E-mail: mfmich@[Link]
Copyright 2009 by the American Society of Nephrology
American Society of Nephrology Geriatric Nephrology Curriculum 1
be considered indicative of some degree of conservation of
sodium. These urine sodiumlevels will oftenbe associatedwith
urine osmolality values at least 1.5 times that of the plasma,
suggesting attempts at water conservation in response to fluid
deficits. Such patients generally respond to the replacement of
intravascular volume with normal saline. Patients who appear
dehydrated but who have elevated urine sodium levels (30
mEq/L) often have urine osmolalities closer to that of the
plasma levels and should be considered to have renal salt wast-
ing in the face of intravascular volume contraction. They
should also be treated with normal saline while attempts to
diagnose the underlying abnormality are made. Various for-
mulas such as the Adrogue-Madias formula (Figure 2) have
been used in an attempt to predict the increase in serum so-
dium that can occur when various concentrations of sodium
replacement therapy are employed.
5
If more or less than 1 L of
replacement fluid is used, the change in serum sodium will
vary directly in proportion to the amount of fluid adminis-
tered.
When patients appear to be fluid overloaded or edematous,
they may have one of several edema-forming states, including
congestive heart failure, nephrotic syndrome, and cirrhosis.
The poor renal perfusion associated with any of these states is
generally associated with urine sodium concentrations in the
lower ranges (20 to 30 mEq/L) and a tendency to urine os-
molalities closer to that seen in the plasma. These disorders are
generally treated by addressing the primary underlying abnor-
mality and using diuretic regimens.
In elderly hyponatremic patients who appear euvolemic
and have elevated urine sodium concentrations (20 or 30
mEq/L) and elevated urine osmolalities suggesting inappropri-
ate water retention, a diagnosis of SIADHis often made.
6
Here
it is important to rule out endocrine abnormalities such as
hypoadrenalism and hypothyroidism. In addition, a careful
search for drugs that stimulate AVP or facilitate the effects of
AVP in the kidney should be undertaken. If these consider-
ations are eliminated from diagnostic possibilities, the patient
should be evaluated for other causes of SIADH. Table 1 lists
some of the commonly associated central nervous system dis-
orders, tumors, and drugs associated with inappropriate AVP
secretion. Certain drug therapies such as SSRIs may pose a
special risk for the development of hyponatremia in the el-
derly, especially those who are older and smaller in body size.
7
HYPONATREMIA (DIFFERENTIAL DIAGNOSIS)

Confirm Hypoosmolality

Volume Assessment (Physical Examination)
and Urine Sodium Measurement






Hypovolemia Euvolemia Edema

Urine Na
>30 mEq/L
SIADH
Diuretic Use - Water Replacement
Endocrine Deficiency
Urine Na
>20-30 mEq/L
Addisons Disease
Polycystic Kidneys
Bicarbonaturia
Diuretic Use
Urine Na
<20 mEq/L
Congestive Heart Failure
Cirrhosis
Nephrotic Syndrome
Hypoalbuminemia
Urine Na
<20-30 mEq/L
Vomiting
Diarrhea
Pancreatitis
Figure 1. Hyponatremia (differential diagnosis).
ADROGU-MADIAS FORMULA


Infusate sodium concentration
Patient serum concentration
Change in serum sodium concentration with 1L of infusate =
Total body water + 1L
Figure 2. The Adrogue -Madias Formula for the prediction of the
change in serum sodium that can occur following intravenous
sodium replacement therapy.
Table 1. Common causes of SIADH
Central nervous system disease
Trauma
Stroke
Infection
Tumor
Intracranial bleeding
Neoplasms
Lung
Pancreas
Prostate
Throat
Lymphoma
Drugs
SSRIs
Carbamazepine
Opiates
Cyclophosphamide
Mirtazapine
2 Geriatric Nephrology Curriculum American Society of Nephrology
If primary causes of the syndrome SIADHcannot be imme-
diately eliminated, patients should be treated with therapies
that can reverse the hyponatremia.
8
In patients with a history
with confounding factors such as the possible prior use of di-
uretic agents, a trial of normal saline administration may be
used. In patients with severe hyponatremia, i.e., serumsodium
concentrations 110 mEq/L, it may be appropriate to use
multiple 100-ml intravenous aliquots of hypertonic (3%) sa-
line to improve the serum sodium levels to avoid more serious
complications of hyponatremia such as seizures or profound
coma. In patients with serum sodium concentrations in the
111- to 120-mEq/L range, therapies may include lesser
amounts of hypertonic saline, and greater reliance on fluid
restriction and agents that interfere with AVP effect, such as
demeclocycline and the new AVP receptor antagonists. With
lesser degrees of hyponatremia, i.e., serum sodium 121 to 129
mEq/L, fluid restriction, demeclocycline, and AVP receptor
antagonists can be used.
Other approaches to hyponatremia include saline infusions
and furosemide being used to replace existing hypotonic intra-
vascular fluid with fluid of a higher sodium concentration. In
hyponatremic patients with central nervous systemdisease, ce-
rebral salt wasting should be ruled out. This disorder is associ-
ated with natriuretic peptide responses as well as AVP effect,
sodium loss, and signs of volume deficit and should be treated
with volume replacement. These hyponatremic patients often
exhibit unusually high urine sodium concentrations.
New Therapies
Over the last several years, a newclass of drugs has beenstudied
that specifically block the effect of AVP on the collecting tu-
bule. One such drug that has been approved by the FDA for
clinical use, conivaptan, belongs to the group of drugs called
vasopressin receptor antagonists (vaptans), because they block
the binding of AVP to the AVP V2 receptor on the renal tu-
bule.
9
Conivaptan has been approved for use in hospitalized
patients in an intravenous preparation, and it has been ap-
proved for therapy of both euvolemic hyponatremia (e.g., SI-
ADH) and hypervolemic hyponatremia (e.g., heart failure).
Conivaptan is rapidly acting and can be given as an intrave-
nous bolus, which can be followed by 1 d to as many as 4 d of
intravenous infusion. Frequent monitoring of the results of intra-
venous therapy should be done during the phase of active correc-
tion, with serumsodiummeasurements every 4 to 6 h during the
first day, perhaps two to three times a day during the second day,
andless frequently during the subsequent 2 d. Withlesser degrees
of hyponatremia, it is still unclear what the specific indications for
therapy are, and what the benefits of changes in the level of hypo-
natremia may be, but it has been suggested that central nervous
system function and gait stability may be adversely affected by
even mild to moderate degrees of chronic hyponatremia.
Rate of Correction
Acute hyponatremia should be treated more aggressively,
whereas chronic hyponatremia should be addressed in a more
conservative manner. Current recommendations are that se-
rum sodium should not increase 12 mEq/L over a 24-h pe-
riod and no more than 18 mEq/L over a 48-h period.
Complex Clinical Syndromes
Finally, complicated situations have been described in which
patients are hyponatremic and seem to have excess AVP activ-
ity as well as sodium depletion syndromes.
10
On attempts at
correction with saline, including hypertonic saline, patients
may exhibit a response in which volume correction shuts off
AVP secretion and causes a profound water diuresis with rapid
increases in the serum sodium concentration and a tendency
toward too rapid correction. When this occurs, reversal ther-
apy may be required with the administration of free water
and/or AVP (usually as the AVP agonist desmopressin). In
addition, patients on drugs that stimulate AVP secretion may
have the effects of these drugs wear off during the period that
therapies are undertaken, also resulting in unexpectedly rapid
correction.
Conclusion
Disorders of serumsodium, especially hyponatremia, are com-
mon in the geriatric population and often are related to excess
vasopressin secretion. A trial of saline administration may be
considered before standard approaches to therapy that now
include vasopressin blocking drugs. Complex clinical syn-
dromes often occur and may be related in part to drugs asso-
ciated with inappropriate vasopressin secretion.
HYPERNATREMIA
Hypernatremia is a common occurrence in elderly patients.
2
The issues relating to the development of an increased serum
sodium can involve deficient free water intake, abnormal reg-
ulation of AVP secretion, decreased renal responsiveness to
AVP secretion, and finally free water losses that are associated
with inadequate replacement.
Clinical Diagnosis
The evaluation of elderly patients with hypernatremia starts
with a careful history. Details in the history that are important
involve decreases in weight, decreases in intake either because
of lack of interest or availability, and history from caretakers
about types of fluids and types of nutritional additives used
and/or laxative use. Physical examination would involve the
assessment of volume status, with particular attention to the
degree of BP decrease in cases where severe hypernatremia is
associated with significant hypotension.
Laboratory Diagnosis and Therapy
Hypernatremia can be defined as a serum sodium concentra-
tion greater than the normal level, which is usually considered
up to 145 mEq/L. In general, patients with hypernatremic
states can be segregated by their measured urine osmolality.
American Society of Nephrology Geriatric Nephrology Curriculum 3
The ratio of urine osmolality to plasma osmolality is useful in
defining AVP responses. Also, as in the hyponatremic patient,
assessment of spot urine sodium concentration will be helpful
to discern the type of hypernatremic state that has developed
(Figure 3).
Variable but low urine osmolalities and variable urine so-
dium concentrations can be seen with central diabetes insipi-
dus depending on the extent of the lesion, sodium intake, and
intravascular volume status. Central diabetes insipidus may be
associated with varying degrees of AVP deficiency, which can
be the result of a variety of intracerebral lesions (Table 2).
Water deprivation tests with clinical follow-up and AVP
administration can be used to help diagnose central versus
nephrogenic diabetes insipidus. Measurement of plasma AVP
levels can also be useful to differentiate central from nephro-
genic diabetes insipidus.
1
Patients with more isotonic urine
and urine sodiumconcentrations that tend to be elevated, 20
to 30 mEq/L, can have disorders associated with osmotic di-
uresis, diuretic therapy, and other instances of renal dysfunc-
tion where endocrine and renal responses cannot offset fluid
and sodium losses, which are mandated by osmolar excretion
or renal disease. Urine osmolalities that are clearly higher than
measured plasma osmolality and urine sodium levels 20 to
30 mEq/L generally are associated with endocrine and renal
responses to extreme fluid losses. This can be seen with de-
creased thirst or water availability or gastrointestinal losses
such as vomiting and diarrhea and lack of water replacement
particularly in warmenvironments as may be seen in a nursing
home situation. Hypernatremia in the elderly is commonly
associated with fluid loss, limitation in urinary concentrating
ability, intravascular volume depletion, and inadequate re-
placement caused by decreased thirst, limited mentation, lim-
ited fluid availability, and/or inadequate fluid prescription.
Central nervous system disorders associated with lack of
AVP secretion are treated with intravenous or oral dilute fluid
and, as needed, AVP replacement therapy. Patients with neph-
rogenic disorders should be initially approached therapeutically
by avoiding, if present, the agent or agents associated with resis-
tance to the effects of AVP. Additional therapy for nephrogenic
diabetes insipidus can include decreases in the intravascular vol-
ume with a mildly restricted sodiumdiet and thiazide diuretics.
Rate of Correction
In general, water deficits are calculated using a standard for-
mula (Figure 4), andphysicians are generally advisedto correct
half of the deficit over the first 24 h.
Patients in shock must be treated aggressively with rapid
volume replacement with normal saline. Once the patient
shows a normal BP, hypotonic replacement can be performed
at a more moderate rate. This replacement may consist of hy-
potonic saline, dextrose, and water with careful monitoring of
serum glucose or oral water administration. Rare cerebral le-
sions that damage or eliminate osmoreception can result in
unusual clinical syndromes in which volume expansion results
in significant water diuresis and hypernatremia.
11
As with hy-
ponatremic states, water deficits are more rapidly replaced in
more acute conditions and more slowly replaced when the pa-
tients are relatively asymptomatic and the condition has ex-
isted for some time. Too rapid dilute replacement therapy can
be associated with the development of cerebral edema.
12
Cen-
tral nervous system function should be monitored carefully.
Conclusion
Physiologic changes associated with aging and lack of mobility
may facilitate the development of hypernatremia in elderly pa-
tients. Careful history and laboratory evaluation are essential
to determine the correct diagnosis and can include measure-
ment of plasma vasopressin levels. Calculation of water deficits
will assist in developing a sound therapeutic plan and avoid
improper rates of correction.
HYPERNATREMIA (DIFFERENTIAL DIAGNOSIS)

Urine Osmolality




Hypotonic
Urine

UNa Variable

Complete or Partial
Central Diabetes Insipidus
Nephrogenic Diabetes Insipidus
Isotonic or Mildly
Hypotonic Urine

UNa >20-30 mEq/L

Osmotic Diuresis
Renal Disease
Diuretics
Hypertonic
Urine

UNa <20-30 mEq/L

GI Losses
Skin Losses
Burns
Decreased Thirst
Figure 3. Hypernatremia (differential diagnosis).
Table 2. Cerebral lesions that can affect hypothalamic
function
Trauma
Infection
Tumors
Hystiocytosis
Vascular abnormalities
CALCULATION FOR H2O DEFICIT

(70 kg Patient x 50% Total Body Water Factor for Older Patient) = 35L

NL TBW 35L X NL SNa 140 mEq/L = Present Body Water
Present SNa (e.g. 160 mEq/L)
Present Body Water = 30.6L
Deficit = 4.4L




NL = Normal
TBW = Total Body Water
SNa = Serum Sodium
Figure 4. The calculation for H
2
O deficit in an elderly hypernatre-
mic patient is outlined.
4 Geriatric Nephrology Curriculum American Society of Nephrology
TAKE HOME POINTS
Differential diagnosis of hyponatremia should be performed with con-
firmation of hypoosmolality by means of measurement of plasma os-
molality
After volume assessment is attempted, spot urine sodium levels should
then be evaluated to separate salt conserving and salt losing states
Urine osmolality will further aid in assessing whether appropriate re-
sponses to the plasma dilution are occurring
Therapy should proceed in a manner formulated to avoid too rapid or
overcorrection
Hypernatremia may be preventable in controlled situations such as a
nursing home by avoiding warm environments and excess protein in
the diet, and provision of adequate hydration
Normal saline may be required as initial therapy for hypotensive, hy-
povolemic, hypernatremia
Standard measurements including plasma osmolality, urine osmolality,
and spot urine sodium concentration will help in the differential diag-
nosis
Too rapid correction or overcorrection should be avoided
DISCLOSURES
None.
REFERENCES
*Key References
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3. Miller M: Hyponatremia and arginine vasopressin dysregulation:
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1589, 2000*
6. Ellison DH, Berl T: The syndrome of inappropriate antidiuresis. N Engl
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8. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH:
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of the aquaretic agent conivaptan for treatment of hyponatremia. Int
Urol Nephrol 40: 725730, 2008
10. Mohmand HK, Issa D, Ahmad Z, Cappuccio JD, Kouides RW, Sterns
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American Society of Nephrology Geriatric Nephrology Curriculum 5
REVIEW QUESTIONS: DISORDERS OF SERUM
SODIUM CONCENTRATION IN THE ELDERLY
PATIENT
1. Hyponatremia is common in elderly patients. Which of the
factors listed is not a common cause for its development?
a. Central nervous system disease
b. Neoplasm
c. Living in warm climates
d. Antidepressant drug therapy
e. Endocrine disorders
2. Diagnostic evaluation of hyponatremic patients include mea-
surement of:
a. Serum osmolality
b. Urine sodium level
c. Urine osmolality
d. Serum BUN and uric acid level
e. All of the above
3. SIADH can result from the use of SSRIs. What would be ap-
propriate therapy in such a patient?
a. Discontinue the drug
b. Water restriction
c. Use a diuretic which works on the Loop of Henle
d. Use a vasopressin blocking drug
e. All of the above
4. A patient has a serum sodium level of 116 mEq/L. Hypertonic
saline infusion is started. In 6 h, the serum sodium level is 126
mEq/L. Which treatment would be least appropriate?
a. Change to normal saline infusion
b. Stop the hypertonic saline infusion
c. Administer a quantity of free water and consider vasopres-
sin therapy
d. Increase the frequency of serum sodium measurements
e. Closely observe the patient for CNS changes
5. Which factor would not contribute to the development of hy-
pernatremia in elderly patients?
a. Sodium intake
b. Immobility
c. Careful control of environmental temperature
d. Drug therapy
e. Decreased alertness
6. What fluid or fluids would be first choice for a patient with
hypernatremia and hypotension?
a. 1/2 normal saline
b. Dextrose and water alternating with normal saline
c. Normal saline
d. Dextrose and water alternating with 1/2 normal saline
e. Dextrose and water
7. A patient with hypernatremia has an elevated plasma vaso-
pressin level, hypertonic urine, and urine sodium level 20
mEq/L. The most likely diagnosis would be:
a. Fluid losses via the skin or GI tract
b. Complete central diabetes insipidus
c. Osmotic diuresis with increased dietary protein
d. Excess diuretic use
e. Abrupt discontinuation of SSRI use
6 Geriatric Nephrology Curriculum American Society of Nephrology