Sodium in Neurosurgery 12

Dharmarajan N Seeniappa

INTRODUCTION
Both intracranial pathophysiological processes and therapeutic maneuvers, such as mechanical ventilation, and
anesthetics, may lead to a number of abnormalities in fluid and electrolytes. Sodium is the most frequently found
electrolyte disturbance in neurological patients. This chapter reviews the regulatory mechanisms underlying water
and sodium metabolism, the two major determinants of body fluid homeostasis and the major disorders of water
metabolism, hyponatremia and hypernatremia with relevance to neurosurgery.

SODIUM AND WATER
In a normal individual residing in temperate climate, the
daily fluid intake comprises of 1–1.5 liters in 24 hours. Water
contributes in 60% of the body weight of which 65% water
is in the intracellular fluid (ICF) and remaining 35% is
present in extracellular fluid (ECF). The water in
intracellular space is also contributed by the cellular
metabolism. The total intake of water is balanced by the
inevitable, insensible losses from the body which is
approximately 500 ml. Daily urine output is approximately
1.5 liters.57 Sodium is primarily extracellular, whereas
potassium is primarily intracellular.50,77 In contrast, cells
contain mostly potassium, phosphate and proteins. This
distribution of solutes between cells and ECF is fundamental
for the maintenance of normal cell function.
Tonicity and volume of ECF and ICF are primarily
dependent on the amounts of sodium and water in the body.
Maintenance of normal body volume and osmolality (280–
295 mOsm/kg water) depends upon a balance between
oral intake and renal excretion. If the average daily sodium
intake far exceeds the normal daily requirement, the kidneys
are responsible for excreting the excess and are capable of
conserving sodium during periods of extreme sodium
restriction. The concentration of sodium is also determined
in part, by osmotically active ions present in the whole body
water, specifically the ratio of exchangeable sodium and
potassium.5
This delicate balance of fluid and that of sodium is
maintained by various physiological mechanisms. Two most
important examples are thirst and antidiuretic hormone
(ADH), synthesized in the supraoptic and paraventricular
nuclei of the hypothalamus. Normally, the increased insensible
losses from the body and decreased fluid intake cause
stimulation of thirst mechanism, increasingly craving for water
intake. There is also increase in plasma tonicity with
stimulation of osmoreceptors in the hypothalamus leading
to release of ADH from posterior pituitary gland which helps
in conservation of water with production of concentrated
urine. On the other hand if there is liberal fluid intake, the
thirst mechanism is suppressed and decreased ADH release
causes loss of excess water as dilute urine.
 Chapter 12 Sodium in Neurosurgery

HYPONATREMIA hypothyroidism, adrenal insufficiency, primary polydipsia

and cancers.5
The normal serum sodium level is 135–145 mEq/l. 2. Volume contracted hyponatremia is mainly caused by
Hyponatremia is common in the hospitalized elderly fluid loss from the intravascular space, which is induced
patients, especially with comorbid conditions like congestive by an intrinsic or a secondary renal loss of sodium, an
heart failure, nephrotic syndrome, cirrhosis of liver etc. and extrarenal loss of sodium or hypokalemia. The causes
associated with significant morbidity (Table 12.1).92 include cerebral salt wasting syndrome (CSWS),
Hyponatremia (less than 135 mEq/l) can occur with a hypokalemia, renal disorders producing sodium loss and
normal, an excess, or a deficit of sodium. It may be extrarenal sodium loss like in vomiting and diarrhea.2,5
subdivided into hyponatremia associated with high, normal, Hypervolemic hyponatremia is a common electrolyte
or low serum osmolality.25,78 disorder encountered in patients in neurology, either due
to SIADH or CSWS.20,22,24,25,39,71,72,73,79 The SIADH is a
Hypo-osmotic Hyponatremia
volume expanded condition, whereas CSWS is a volume
Most hyponatremic disorders are associated with contracted state that involves renal loss of sodium.
hyposmolality and are more commonly caused by water
retention.2,54 This subcategory, also known as dilutional Hyper-osmotic Hyponatremia
hyponatremia, may further be differentiated according to In hyperosmotic hyponatremia, solutes confined to the
the volume status: extracellular compartment induce shifts in transcellular
1. Volume expanded hyponatremia occurs when the intake water.2 This is also known as translocational hyponatremia.
of salt and water exceeds renal and extrarenal losses.5 Conditions causing hyperosmotic hyponatremia include
Disorders associated with interstitial fluid shift include hyperglycemia and the retention of hypertonic mannitol
congestive heart failure, nephrotic syndrome, cirrhosis, which results in hyponatremia because water shifts from
renal failure (acute and chronic), pregnancy and sepsis.2,5 the intracellular to the extracellular space, causing
Disorders associated with limited interstitial fluid shift dehydration of cells.2 Less common causes of hyperosmolar
are syndrome of inappropriate ADH secretion (SIADH), hyponatremia include, sorbitol, maltose and radiocontrast
administration.11,69 Each 100 mg/dl of glucose reduces
Table 12.1: Causes of hyponatremia
sodium by 1.6 mEq/l. Underlying cause needs must be
• Hypo-osmotic treated.
Volume-expanded hyponatremia
– SIADH Iso-osmotic Hyponatremia
– Hypothyroidism
– Adrenal insufficiency Iso-osmotic hyponatremia occurs in patients, who undergo
– Primary polydipsia transurethral resection of the prostate or hysterectomy.41
– Congestive heart failure During these procedures, patients may absorb large
– Nephrotic syndrome quantities of hyposmotic glycine or sorbitol irrigating
– Cirrhosis solutions leading to a dilutional reduction in the plasma
– Renal failure
sodium concentration. It may be seen in patients with
– Cancers and sepsis
extreme hyperlipidemia, and hyperproteinemia which is also
Volume-contracted hyponatremia
– CSWS known as pseudohyponatremia. 2,5,56 No treatment is
– Hypokalemia required.
– Renal disorders
• Hyper-osmotic Syndrome of Inappropriate Secretion
– Hyperglycemia of ADH (SIADH)
– Retention of hypertonic mannitol
– Sorbitol, and radiocontrast administration This refers to increased release of ADH that is inappropriate
• Iso-osmotic to the serum osmolality. Inappropriateness of ADH
– Sodium-free irrigants secretion is defined as ADH secretion that occurs despite
– Hyperlipidemia low effective osmolality and normal or expanded effective
– Hyperproteinemia vascular volume.67 In patients with SIADH, excess water is 153
 Section 2 Cerebral Homeostasis and Perioperative Care

Table 12.2: Causes of SIADH multiple sclerosis, and many other stress reactions precipitate
SIADH.35,47,48,49 SIADH has been reported after spinal
• Brain and Spinal surgery
surgery by many authors14,21,29 especially in patients following
• Cerebral disorders (e.g. trauma, CVA, tumor, meningitis)
• Chest disorders (e.g. pneumonia, empyema)
spinal fusion. Postoperative SIADH in cases of neurological
• Positive pressure ventilation or spinal surgery, has been attributed to invasion of the dura
• Bone marrow transplant or stem cell therapy mater and traction on the neural pathways.53
• Ectopic antidiuretic hormone secretion
• Long-term medications: Cerebral Salt Wasting Syndrome
– Diuretics
– Carbamazepine The term cerebral salt wasting syndrome (CSWS) was
– Chlorpromazine introduced before the syndrome of inappropriate
– Vasopressin analogs antidiuretic hormone secretion, described in 1957. But
– Indapamide reports of CSW appeared a quarter century later in the
– Selective serotonin reuptake inhibitors neurosurgical literature. A valid diagnosis of CSWS requires
– Theophylline evidence of inappropriate urinary salt losses and reduced
– Amiodarone
effective arterial blood volume.85In this syndrome, there is
true sodium depletion due to primary loss of sodium in the
retained in the extracellular and intracellular compartments,
urine, resulting in serum hypotonicity which in turn inhibits
decreasing the concentration of sodium and other solutes.
thirst and secretion of ADH.
Syndrome of inappropriate antidiuretic hormone
In the absence of adrenal insufficiency, renal disease or
(SIADH) is characterized by hyponatremia, serum hypo-
diuretic use which may display a similar picture, the postulated
osmolality and urine osmolality which is greater than serum
mechanisms include, disruption of neural input into the
osmolality, continued loss of sodium in spite of
kidney or the central elaboration of a circulating natriuretic
hyponatremia in the absence of renal function disorders
factor or both.38,39,55,71,93,95 The natriuretic factors that play
and endocrine dysfunction. There is suppression of
a role in CSWS include the brain natriuretic peptide (BNP)
aldosterone secretion resulting in disproportionate loss of
and atrial natriuretic peptide (ANP).15,41,65,94 ANP is released
sodium in urine further depleting sodium store in ECF.
from the heart in response to atrial stretch and induces
The causes of SIADH are listed in the Table 12.2.
vasodilation as well as natriuresis and diuresis. Normal levels
The excess of ADH may be drug induced pituitary release
of ANP are found in patients with CSW associated with
of ADH or the ectopic production of ADH.78 In pulmonary
intracerebral hemorrhage, subarachnoid hemorrhage and
diseases, certain pulmonary cells (source is not entirely clear)
pituitary surgery.28,44,95 BNP is secreted by the cardiac
can be induced to secrete ADH in the setting of inflammation
ventricles and displays biological effects similar to those of
or infection. Malignant tumors originating in many sites can
ANP and has also been localized to the hypothalamus.86
release ectopic ADH, particularly small cell lung carcinomas.
A decrease in sympathetic tone leads to a decreased
Several drugs have been implicated. Any patient with
glomerular filtration rate, a decreased renin release, and a
suspected SIADH should have their medications, carefully
decreased renal tubular sodium resorption resulting in
checked. Oxytocin has ADH properties and can cause
natriuresis and diuresis seen within CSWS. Intracranial
hyponatremia. Drugs like hypoglycemic agents, antineoplastic
disease may stimulate the sympathetic release of cardiac
agents, tricylcic antidepressants and diuretics can precipitate
BNP, which may suppress aldosterone secretion and alter
SIADH.
renal function. BNP may be directly released by the brain
The mechanism, by which CNS disorders cause SIADH,
when this organ is damaged, thereby limiting extreme rises
is not well understood. It has been hypothesized that injury
in ICP.15 BNP may stimulate the sympathetic release of
to the CNS disrupts or alters the osmoregulation of ADH
cardiac BNP, which may suppress aldosterone secretion and
release by the neurohypophysis, stimulating inappropriate
alter renal function.15,88
release of ADH.3,66 Cerebral abscess, hypopituitarism,
encephalitis, Gullian-Barre Syndrome, head injuries,
Reset Osmostat Syndrome
meningitis, subarachnoid hemorrhage, concussion,
hydrocephalus, acute strokes or intracerebral hemorrhage, The reset osmostat syndrome occurs when the threshold
154 cavernous sinus thrombosis, electroconvulsive therapy, for antidiuretic hormone secretion is reset downward.
 Chapter 12
Patients with this condition have normal water load
excretion and intact urine diluting ability after an oral water
loading test. It may be distinguished from SIADH by
observing response to water load (10–15 ml/kg orally or
IV). Normal subjects and those with reset osmostat, secrete
the entire water load over 4 hours without any worsening
of the hyponatremia.
The condition is chronic, but stable hyponatremia.62It
can be caused by pregnancy, quadriplegia, malignancy,
malnutrition, or any chronic debilitating disease. There is
no need of correction for this type of hyponatremia.
Clinical Features
Hyponatremia in neurological disorders may be acute or
become chronic.50 Both the severity and the course of
development of hyponatremia are important determinants of
the signs and symptoms that evolve.2,7 Serum hypo-osmolality
would increase cerebral edema and intracranial pressure.7,90
When hyponatremia occurs rapidly, the brain does not
compensate and the patient can become symptomatic. If the
hyponatremia occurs gradually over several days, the brain can
decrease its solute content, thereby lowering intracellular
osmolality and decreasing water influx into cells. Clinical
features include nausea, vomiting, irritability, personality
changes anorexia, convulsions and coma.2,63
Management
Following are the mandatory in the management of
hyponatremia:84
• Serum osmolality and urine osmolality.
• Routine blood investigations which include blood sugars,
serum creatinine, blood urea, uric acid. 62 Sodium
decreases approximately 1.5 mmol/l for every 100
mg/dL rise in serum glucose concentration.69 Anemia
may be the cause of hyponatremia.79
• Laboratory studies should also include Aldosterone level,
Cortisol level, Thyroid function, Corticotropic hormone
level, ADH level. Hypothyroidism and adrenal
insufficiency must be ruled out (especially in severe head
injur y and postoperative patients undergoing
hypothalamic or pituitary surgery).62
• Urine spot sodium. In general, a spot test showing urine
sodium concentration of less than 30 mmol/l
differentiates patients with hypovolemic hyponatremia
from patients with euvolemic hyponatremia (who have
urine sodium concentration greater than 30 mmol/l on
spot testing).23
Sodium in Neurosurgery
• Random urine sodium concentrations tend to be less
than 100 mEq/l in CSWS. SIADH rarely, if ever,
leads to a random urine sodium of greater than
100 mEq/l.16
• Blood Volume status can be assessed by measurement of
the Central Venous Pressure (CVP), Pulmonary Capillary
Wedge Pressure (PCWP) or by, if possible, radioisotope
scanning.62 Central venous pressure measurements have
become the gold standard in the neurosurgical literature;
a central venous pressure less than 5 cm H2O is said to be
inconsistent with SIADH and diagnostic of CSW.27
It is worthwhile to keep in mind that serum sodium
estimation by flame photometry (instead of specific
electrode estimation of serum sodium) causes decreased
estimation of serum sodium (laboratory artifact).
The diagnostic criteria for SIADH78 include:
• Hyponatremia
• Low serum osmolality (less than 280 mOsm/l)
• High urine osmolality (more than 100 mOsm/kg H2O)
• High ratio of urine: serum osmolality, often 2:1 or more
• High urinary sodium (more than 18 mEq/l)
• Normal renal, adrenal and thyroid function
• Normal serum potassium and acid base balance.
In CSWS, there is low or postural hypotension, with
tachycardia and other signs of dehydration in addition to
the cerebral symptoms of hyponatremia. The electrolyte
imbalances observed in CSWS are similar to that of SIADH.
SIADH requires fluid restriction and CSWS requires fluid
(Flow chart 12.1). Hence, it is most important to find out the
cause of hyponatremia. More often, clinical examination and
basic investigations may not help. SIADH usually occurs after
a week, whereas CSWS occurs early. The most reliable test to
differentiate between SIADH and CSWS is to measure the
serum ADH and blood volume measurement71 practically,
which are not always possible. Differentiating hypovolemia
and euvolemia may be clinically difficult especially, if the classic
features of volume depletion such as postural hypotension and
tachycardia are absent,60 which happens often. Features of
SIADH and CSWS are listed in Table 12.3.
There is no consensus about the optimal treatment of
symptomatic hyponatremia. Patients who remain
asymptomatic with sodium levels above125 mEq/l, may
be observed with unrestricted salt intake.6,56,46,51 Mild to
moderate hyponatremia (120–125 mEq/l) due to SIADH
responds to fluid restriction in the region of 600–800 ml/
day. This may not be feasible in the critically ill patient,
who may require minimum fluid load greater than 600-
800 ml/day; simply to administer medication and to 155
 Section 2 Cerebral Homeostasis and Perioperative Care

Flow chart 12.1: Management of hyponatremia

Table 12.3: Features of SIADH and CSWS

Parameter SIADH CSWS

• Blood pressure Normal Low or normal
• Heart rate Slow or normal Tachycardia or normal
• Hydration Well hydrated Decreased
• Body weight Normal or Increased Decreased
• Hematocrit Normal or low Elevated
• Serum uric acid Normal or low Normal or low
• Serum potassium Normal or low Normal or high
• Serum albumin Normal or low Normal or high
• Serum osmolality Low Low
• Urine osmolality High High
• Urea and creatinine Normal or low Normal or high
• Urine volume Normal or low Normal or high
• Urine concentration High High
• Random urine sodium <100 meq/l >100 mEq/l
• Extracellular volume Increased or normal Decreased
• Central venous pressure > 5 cm H2O < 5 cm H2O
• Average day of appearance 8th day 4–5th day

maintain cerebral perfusion pressure. Alternate treatments
may be indicated occasionally. Demeclocycline (600–1200
mg/day) inhibits the action of ADH on kidney; sodium
phenytoin, reduces the secretion of ADH from pituitary
and lithium carbonate may help. Demeclocycline induces a
156 negative free water balance by causing nephrogenic diabetes
insipidus and should be used with caution in patients with
hepatic or renal insufficiency.26,32,42 Use of a newer class of
pharmacologic agents, the vasopressin receptor antagonists,
known as vaptans has been reported.84 They induce an
excretion of increased amounts of water without altering
sodium or potassium excretion.
 Chapter 12
Hyponatremia, in acute intracranial diseases is mostly
caused by CSWS.24,39,79 Therefore, while awaiting the
laborator y results, treatment with fluid and salt
supplementation seems justified in patients with intracranial
disorders of acute symptomatic hyponatremia and
natriuresis. 24,79,66 Most neurosurgical patients with
hyponatremia and natriuresis have hypovolemia, with or
without anemia. Fluid and salt replacement and a blood
transfusion rather than fluid restriction often results in the
correction of the hyponatremia.79
Marked hyponatremia may require hypertonic saline (3%)
infusion (250 ml) over 6–8 hours in addition to decreasing
free water with frusemide in doses up to 1mg/kg. The initial
correction rate with hypertonic saline should not exceed
1–2 mEq/l per hour, and normal or hypernatremia should
be avoided in the first 48 hours.13,36,37,82,83 Fludrocortisone
acetate in the doses of 0.2 mg via intravenous or oral route
has been used for the treatment of CSWS.40 It acts on the
renal tubules and increases sodium absorption. However,
it can cause complications like pulmonar y edema,
hypertension and hypokalemia. Correction with hypertonic
solution should be discontinued once the sodium level
reaches 125 mEq/l.
In hyponatremia, the sodium deficit (mEq/l) is
equivalent to 0.6 × body weight (kg) × (desired [Na] –
actual [Na]). Rate of correction is important, but a
consensus on the rate of correction is not available in the
literature.3 It has been suggested that risk of demyelinating
lesions is much higher, if the serum level of sodium is
corrected faster than 12 mEq/l in 24 hours or 18 mEq/
l in 48 hours.82 Some authors have suggested correcting
the serum level of sodium at a rate of 1–2 mEq/l per
hour, while keeping the total magnitude of correction to
less than 25 mEq/l over the first 48 hours.81,91
We recommend a correction rate of 0.5 mEq/l per hour
and less than 10 mEq/l in the first 24 hours. Perioperative
hyponatremia, often an acute process (48 hours), is
associated with a higher risk of developing complications
from hyponatremia and is rarely associated with
demyelinating complication with rapid correction. Rapid
correction is justified in such patients.3
Investigation and treatment of the underlying disease
should be carried out along with the management of
hyponatremia including discontinuation of the attributing
drugs. Monitoring of other electrolytes like potassium and
their simultaneous management is equally important during
the management of hyponatremia. Frequent reassessments,
with serial weight measurements, clinical evaluations of
Sodium in Neurosurgery
extracellular fluid volume status, and determinations of
serum sodium concentration, are essential to determine if
the desired therapeutic goals are being reached.
Outcome
Hyponatremia is the most common electrolyte abnormality
found in hospitalized patients.54 It is not only a marker of
serious underlying disease, but when severe, can itself be
the cause of major neurologic damage and death.4,8
Mortality rates as high as 17.9% have been reported in acute
hyponatremia.52 Morbidity also can result from rapid
correction of hyponatremia.82,83 Poor prognostic factors for
severe hyponatremia in hospitalized patients include the
presence of symptoms, sepsis, and respiratory failure.65
Children and menstruating women carry more risk.
Osmotic Demyelination Syndrome
This syndrome is a preventable complication of overly rapid
correction of chronic hyponatremia.83 If hyponatremia is
corrected too rapidly, irreversible brain damage may occur
consisting of demyelination of areas where white and gray
matter are closely admixed in the pons.46,87,89 This damage
was previously known as central pontine myelinolysis (CPM)
and is now called osmotic demyelination syndrome (ODS)
because the pathology also involves extrapontine areas
(EPM), such as internal capsule, basal ganglia, cerebellum,
and Cerebrum. CPM and EPM usually occur together;
symptoms of extrapontine myelinolysis are often masked
in the critically ill patient.19 EPM can also occur without
CPM. CPM and EPM are the same disease, sharing the
same pathology, associations, and duration with different
clinical manifestations.34
The pathogenesis of ODS is unknown. ODS, unless
severe, is predominantly a lesion of the basis pontis, sparing
the tegmentum. The predilection for myelinolysis in the
pons is thought to be a result of the grid arrangement of
the oligodendrocytes in the base of pons, which limits their
mechanical flexibility and therefore, their capacity to swell.
This limitation makes them prone to damage when sodium
is replaced. This is a region of maximal admixture of gray
and white matter elements. EPM similarly seem to involve
similar regions of gray-white apposition. Microscopically
the lesion shows degeneration and loss of oligodendrocytes
with preservation of axons unless the lesion is very
advanced.58
Although, initially described as occurring in alcoholics and
the undernourished,1 ODS has also been reported in adults 157
 Section 2 Cerebral Homeostasis and Perioperative Care
with a variety of serious illnesses and after certain surgical
procedures and even in toddlers with psychogenic polydipsia.
Patients initially present with seizures from hyponatremia,
then recovering rapidly as sodium is restored, only to
deteriorate several days later.19 Clinical manifestations vary
according to the site of involvement and include, akinesis,
ataxia, catatonia, choreoathetosis, cogwheel rigidity,
disorientation, dysarthria, dystonia, emotional labiality, extra
pyramidal symptoms, gait disturbance, movement disorders,
mutism, myoclonus, myokymia, parkinsonism, rigidity and
tremor.58 The clinical picture can evolve over days, and some
of the manifestations may be symptomatically treatable.58
Osmotic demyelination syndrome(ODS) must be
considered in a patient who has failed to recover as expected
after a severe illness needs intravenous fluids. Patients may
manifest symptoms after hypnatremia has been corrected.
MRI is the primary method for diagnosis. Findings on T1-
weighted scans show a symmetric region of low signal
involving the basilar pons with sparing of the descending
corticospinal tracts as well as the peripheral pontine tissues.
Flair (Fig. 12.1) and T2-weighted images show an area of
high signal corresponding to the abnormal region identified
on T1-weighted scans.74 Lesions on MRI may appear days
to weeks after the onset of symptoms; in some cases, these
may resolve, over months. MRI may be negative. MRI
changes may be delayed10 MRI severity has no prognostic
value.
158
Fig. 12.1: Axial MRI (FLAIR) hyperdense pontine lesion in ODS
There is no specific therapy. Steroids, thyrotrophin
releasing hormone, plasmapheresis and four immuno-
globulins have all shown good outcomes.31 There have been
no of clinical trials. Outcome is not uniformly bad. A large
series of 34 cases showed that only two died, 10 survived
but were left dependent, 11 had some deficits but were
independent, and 11 recovered completely.61
HYPERNATREMIA
Hypernatremia refers to a serum sodium concentration
exceeding 145 mEq/l. Unlike hyponatremia, hypernatremia
always represents a hyperosmolar state. Hypernatremia
results from water loss or sodium retention. Hypervolemic
hypernatremia results from pure Na+ overload. It is rare
and frequently iatrogenic (e.g. administration of hypertonic
sodium bicarbonate during cardiopulmonary resuscitation).
Non iatrogenic causes include primary hyperaldosteronism
and Cushing’s syndrome.
The underlying cause of hypernatremia in the vast majority
of patients is water loss in excess of solute.77 The two defense
mechanisms against hypernatremia are stimulation of ADH
release (resulting in maximal urinary concentration) and
thirst.70 Release of ADH occurs at a slightly lower serum
osmolality than does stimulation of thirst, but thirst is the
main defence mechanism against hypernatremia.
In adults, hypernatremia is more common after the age
of 60, primarily because increased age is associated with
decreased osmotic stimulation of thirst and decreased
maximal urinary concentration. Those at the highest risk
are patients with altered mental status, intubated patients,
infants, and elderly patients.33,54
Diabetes insipidus (DI) is the most common cause of
hypernatremia in neurosurgical practice. It may be defined
as an hourly urine output of more than 300 ml with urinary
specific gravity of less than 1.003 persisting more than two
consecutive hours. There is either an absence of ADH
secretion (central or neurogenic Dl) or failure of the kidney
to respond to ADH (nephrogenic Dl).76 Central DI results
from destruction of thirst centers in the hypothalamus,
caused by multiple disorders such as hypothalamic tumors,
granulomatous diseases, stroke, subarachnoid hemorrhage
and head injuries.75 Common causes of central DI is listed
in Table 12.4.
Causes of nephrogenic DI include obstructive or
tubulointerstitial diseases as well as advanced renal failure,
and many drugs (lithium is a common cause).
In adults, acute hypernatremia has been associated with
a mortality rate as high as 75% and chronic hypernatremia
 Chapter 12 Sodium in Neurosurgery
Table 12.4: Common causes of central diabetes insipidus
• Brain surgery
• Brain trauma
• Primary or metastatic brain tumors
• Infiltrative diseases
• Hypoxic or ischemic encephalopathy
• Radiation to the brain
• Infection such as meningitis or encephalitis
• Cerebral edema
• Intracranial hemorrhage
is associated with a mortality rate of around 60%.43,69 Even
in survivors, severe morbidity in the form of permanent
neurological squeal is quite common.
Clinical Features
The onset of polyuria is usually abrupt in central DI. This
is in contrast to nephrogenic DI and primary polydipsia, in
which onset of polyuria is almost always gradual. Patients
with diabetes insipidus usually do not present with
neurologic symptoms because of the powerful thirst
mechanism, which protects them from hypernatremia.
Instead, these patients complain of polydipsia, polyuria and
nocturia.30 If the oral replacement is not adequate/possible
neurological symptoms develop. Neurologic manifestations
(e.g. lethargy, weakness, irritability, hyperreflexia, seizures,
coma, and even death) are the result. The earliest symptoms
are restlessness, irritability, and muscular irritability and it
progresses to lethargy, coma, seizures and death. The
mortality rate ranges from 16% to 60%, depending on the
patient population examined.68
The symptoms are due to changes in tonicity. The
hypertonicity of the ECF draws water out of brain cells, leading
to shearing of the vessels of the brain. The rate of onset of
hypernatremia determines the symptoms as in hyponatremia;
with prolonged hypernatremia (several days) the brain water
returns to normal. This occurs because brain cells generate
new solutes, termed “idiogenic osmoles”, which increase the
osmolality of brain cells to equal that of the ECF. This occurs
in response to any increase in ECF tonicity, whether it is due
to hypernatremia, hyperglycemia, or other causes.80,96
Idiogenic osmoles have been postulated to be the molecules
which fill up the gap between the measured change of
osmolality and total changes contributed by electrolytes.9, 59
Management
Treatment of hypernatremia follows the same general
principles as that of hyponatremia.12,18
Symptomatic patients need to be rapidly treated: however
patients with long standing hypernatremia should be gradually
corrected. If the correction is too rapid, idiogenic osmoles in
brain cells will not have time to disappear and will pull excess
water into the brain cells, causing cerebral edema. The current
recommendation is to lower the serum sodium concentration
by about 0.5 mEq/l per hour and to replace no more than
half the water deficit in the first 24 hours.17
As mentioned above, hypernatremia and hyperosmolality
commonly result from fluid restriction, osmotic challenge
(mannitol and tube feeding) and diabetes insipidus. The
diagnosis of iatrogenic cause should be apparent by review
of the intake and output and drug charts. These resolve
with appropriate fluid replacement.
Awaken patients may regulate their own intake whereas
in the obtunded patients, losses from urine output can be
replaced intravenously. Patients with hypovolemic
hypernatremia should be treated with isotonic saline
particularly, if there is evidence of circulatory collapse.54
Otherwise, if the volume depletion is mild without evidence
of circulatory failure, hypotonic fluids such as one-quarter
saline (0.2% saline), half isotonic saline (0.45%), pure water,
or 5% dextrose should be used.2 Even in cases of circulatory
failure, once hemodynamic stability is achieved, hypotonic
fluids should be used.54 When administering dextrose
containing solutions, blood glucose should be closely
monitored, because hyperglycemia will worsen the hypertonic
state and may lead to osmotic diuresis.45 Again, frequent
monitoring of electrolytes is key to successful management.
Prolonged chasing of urinar y volume with IV
replacement can result in nephrogenic diabetes insipidus
that is unresponsive to subsequent ADH. With frank DI,
5–10 units of aqueous vasopressin subcutaneously every
3–4 hours.17 Vasopressin is preferred over desmopressin
because vasopressin has a shorter duration of action.54 When
permanent DI develops, therapy is started with pitressin
tannate in oil which has prolonged action (12–36 hr). Long
term therapy is conveniently continued with desmopressin
acetate by nasal insufflations.
159
 Section 2 Cerebral Homeostasis and Perioperative Care

KEY POINTS
• The most common electrolyte imbalance in neurosurgery.
• In cases of neurological deterioration with no obvious surgical cause, electrolyte disturbances should be suspected
in addition to hypoxia and hypercapnia.
• Hyponatremia may be due to SIADH and CSWS; CSWS is more common in acute intracerebral pathology.
• SIADH requires fluid restriction and CSWS requires fluid replacement; hypernatremia may, in addition to fluid
replacement, require judicious use of aqueous pitressin.
• The correction should be slow, not exceeding 10 mEq/l in the first 24 hours; the exception is perioperative
hyponatremia, often an acute process (48 hours), associated with a higher risk of developing complications.

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