Keywords basilar top aneurysm - electrolyte imbalance - salt wasting
Introduction
Hyponatremia is a commonly seen in patients with neurosurgical diseases. When hyponatremia
is associated with central nervous system disease, first possibility one would normally
consider is syndrome of inappropriate antidiuretic hormone secretion (SIADH). Another
uncommonly diagnosed but a frequent cause of severe hyponatremia in postneurosurgical
procedures is cerebral salt-wasting syndrome (CSWS).[1 ] Treatments are entirely different for these two conditions, as vigorous sodium and
fluid replacement is the treatment of choice for CSWS, whereas fluid restriction is
the treatment of choice in SIADH. Therefore, there is a need to differentiate these
two conditions on an emergency basis, and management must be done appropriate to the
condition. CSWS, specifically in neurosurgical cases, has been reported sporadically
in neurosurgery and neurology journals. The identification of CSWS is important for
the treating interventional radiologist/neuroradiologist, as they are increasingly
involved in the management of various neurovascular diseases. The clinical recognition
and management of CSWS are highlighted in the following prototypic case.
Case Description
Brief Clinical History
A 64-year-old diabetic and hypertensive woman presented with sudden-onset severe intensity
holocranial headache and multiple episodes of vomiting. She was evaluated in a nearby
hospital with plain computed tomography (CT), followed by CT angiography, which showed
a basilar top aneurysm and subarachnoid hemorrhage (SAH, fisher grade 3). She was
referred to neurointerventional department of the hospital for further management.
On admission patient was stable, her Glasgow coma scale (GCS) was 15/15, with no neurologic
deficits. Cerebral angiogram ([Fig. 1A ]) was done on the fifth post ictus day, and it showed a wide necked basilar top aneurysm,
measuring 12 × 11 × 10 mm, incorporating both posterior cerebral arteries (PCA). Endovascular
coiling of the aneurysm ([Fig. 1B ]) with balloon assistance was done under general anesthesia on the eighth post ictus
day. The patient was extubated on the same day after procedure, and she was stable
with no neurologic deficits. She received oral nimodipine, phenytoin, and dexamethasone
from outside institution, which was continued during hospitalization.
Fig. 1 DSA lateral projection (A ) showing a wide-necked basilar top aneurysm, DSA post near-complete coiling (B ) lateral projection image.
Clinical Course during Hospitalization
In the immediate postoperative day (eighth day of ictus), her serum potassium level
was found low (2.6 mEq/dL), which was initially corrected with injection of potassium
chloride (KCl) of 40 mEq and later with oral KCl supplements. She became intermittently
drowsy on the ninth day of ictus, and magnetic resonance imaging (MRI) including diffusion
sequence showed no acute infarcts or other additional observations. Her serum sodium
levels dropped to 124 mEq/dL from baseline value of 135 mEq/dL. Oral salt correction
was initially attempted, and her sodium level remains static with no further drop
for the next 4 days. Her hemoglobin was low in postinterventional period (8.5 g%),
which was corrected with 1 unit of packed red blood cell. Her hemoglobin, however,
rose to 12.4 g%, which was more than the expected correction with a single unit of
transfusion, and this observation suggested the existence of negative water balance.
On fifth post coiling day, her drowsiness worsened and clinical examination revealed
moderate hydration and postural hypotension.
Serum and urine biochemistry was done for further evaluation. Her serum sodium dropped
further to 112 mEq/L, but her serum potassium was within normal limits (4 mEq/L).
Urine-specific gravity was 1.016. Serum osmolality decreased to 268 mOsm/L and urine
osmolality was 216 mOsm/L. Her urinary output was 3,800 mL with a negative water imbalance
of 340 mL. Intravenous correction of serum sodium level was initiated with 200 mL
of intravenous 3% sodium over 8 hours, followed by maintenance intravenous normal
saline. Next day, her drowsiness improved and her serum sodium increased above 120
mEq/L. Aggressive oral and intravenous sodium correction was continued for the next
3 days, and her serum sodium levels stabilized above 120 mEq/L. At discharge, her
serum sodium was 123 mEq/L and the patient remained fully conscious, ambulant with
no significant complaints. Her serum sodium level at 3-month clinical follow-up was
135 mEq/L.
Analysis of Clinical History and Biochemical Investigations
Hyponatremia is defined as a serum sodium level of less than 135 mEq/L. Thorough history
and physical examination, followed by laboratory investigations, can guide the physician
to establish the possible cause of hyponatremia in SAH patients.
On clinical assessment, patients with CSWS will have features of hypovolemia, such
as orthostatic changes in blood pressure and pulse, dry mucous membranes, flat neck
veins, weight loss, and negative fluid balance. In SIADH, the patient will be either
normovolemic or euvolemic, with positive water balance. The patient under discussion
had negative water balance, orthostatic hypotension, giddiness, and dry mouth, all
of which favors CSWS.
First step in biochemical investigations is to evaluate the serum sodium level to
assess the degree of hyponatremia and categorize into mild (130–135 mEq/L), moderate
(125–130 mEq/L), or profound (< 125mEq/L). The patient had initially moderate hyponatremia
followed by profound hyponatremia.
The next step is to evaluate whether the serum osmolality is low, normal (275–295
mOsm/L), or increased. When it is normal or increased, the differentials include hyperlipidemia,
hyperproteinemia, hyperglycemia, or mannitol infusions. The serum osmolality in CSWS
or SIADH will be less. The serum osmolality in this patient measured approximately
268 mOsm/L, which excluded the cause of hyponatremia due to endogenous macromolecules
Then urine osmolality must be then evaluated. The normal random urine osmolality should
average between 300 and 900 mOsm/L. Some cases of hypotonic hyponatremia may be due
to primary polydipsia, and in such patients, urine osmolality will be less than 100
mOsm/L due to preserved kidney dilution capacity. The urine osmolality of CSWS and
SIADH is usually high. In this patient, urine osmolality was 216 mOsm/L.
The next step is to assess the random urinary sodium concentration of the patient.
Urinary sodium will be low (< 20 mEq/L) in hypovolemia cases, whereas it will be elevated
(> 40 mEq/L) in SIADH as well as in CSWS. In this case, the patient had high urine
sodium level of 51 mOsm/L.
Assessment of water balance helps in the differentiation of CSWS from SIADH. The output
is unusually high in CSWS with negative fluid balance. This patient had high urinary
output with negative water balance suggesting a clinical diagnosis of CSWS. Other
investigations such as serum creatinine, blood urea nitrogen, hematocrit (as in this
case), fractional excretion of uric acid, phosphate, and urate after correction may
help identify hemoconcentration that would favor the diagnosis of CSWS. [Table 1 ] highlights the important clinical and biochemical parameters to differentiate CSWS
and SIADH.
Table 1
Overlapping findings and clinical, biochemical differences between CSWS and SIADH
Parameters
CSWS
SIADH
Abbreviations: CSWS, cerebral salt-wasting syndrome; FENa, fractional excretion of
Na; FEP, fractional excretion of phosphate; FEUA, fractional excretion of uric acid;
SIADH, syndrome of inappropriate antidiuretic hormone secretion.
a FEUA = (Urinary uric acid [mg/mL] × serum creatinine [mg/mL] ÷ (serum uric acid [mg/mL]
× urinary creatinine [mg/mL]) × 100%. Normal = < 10%.
Serum sodium
Low
Low
Urine sodium
Increased (> 40 mEq/L)
Increased (> 40 mEq/L)
Serum osmolality
Decreased
Decreased
Urine osmolality
High
High
Urine volume
Increased
Low or normal
Water balance
Negative
Normal/positive
Sodium balance
Negative
Variable
Extracellular volume
Low
Normal/increased
Hematocrit
Increased
Normal
Serum creatinine
Increased
Decreased
Blood urea nitrogen
Increased
Decreased
Serum potassium
Normal/increased
Normal
Serum uric acid
Normal/decreased
Decreased(< 4 mg/dL)
FEUAa
Increased
Increased
After correction of hyponatremia
Serum uric acid and increased FENa persist
Serum uric acid and increased FENa resolve
FEP
Elevated
Normal
Patient condition
Postural hypotension, dry mucous membranes.
No signs of dehydration
Central venous pressure
Low
Increased or normal
Pulmonary capillary wedge pressure
Low
Increased or normal
Brain natriuretic peptide
Increased
Normal
Management
Fluid and sodium replacement, Fludrocortisone
Water restriction, Demeclocycline
Management of Cerebral Salt-Wasting Syndrome
In symptomatic patients with acute hyponatremia (duration of < 48 hours), urgent correction
by 4 to 6 mmol/L has to be initiated to prevent brain herniation and neurologic damage
from cerebral ischemia.[2 ] For severe symptoms, intravenous infusion of 100 to 150 mL (2 mL/kg) of 3% NaCl
over 15 to 20 minutes could be administered, repeated if necessary, to attain an increase
in serum sodium values up to 2 mmol/L in the first hour and up to 4 to 5 mmol/L in
4 hours. This rapid correction is always with the objective to control the severe
symptoms, mainly seizures. In patients with mild to moderate symptoms, 3% NaCl is
infused at 0.5 to 1 mL/kg/h.
This patient was finally diagnosed as CSWS and hyponatremia correction along with
fluid resuscitation was started. Over 8 hours, 200 mL of 3% sodium infusion was administered
to raise her sodium level by 4 mmol/L (rapid correction) along with infusion of normal
saline for correction of hypovolemia. After this, normal saline infusion was continued
for slow correction for the first 24 hours and oral salt was given to correct the
serum sodium, once serum sodium was elevated above 120 mEq/L. These measures were
repeated over several days to maintain her sodium in the range of 123 to 127 mEq/L.
Because CSWS may persist for 3 to 4 weeks after the insulting event, the patient was
on close monitoring of serum electrolytes after discharge.
Discussion
Hyponatremia is commonly seen following SAH and is frequently attributed to either
CSWS or SIADH. Cerebral salt wasting is a disorder of sodium and water transport in
the kidneys that occurs in patients with cerebral diseases in the setting of normal
adrenal and thyroid function, leading to hyponatremia and extracellular volume depletion.
Two mechanisms have been discussed in literature regarding mechanism of CSWS. One
is increased activity of the sympathetic nervous system and dopamine release due to
brain injury, leading to elevated renal pressure–natriuresis response and urinary
sodium loss. Another mechanism is probably due to the release of brain natriuretic
peptides by the injured brain.
In a retrospective study by Kao et al,[3 ] hyponatremia was detected in 59.2% patients, of whom 35.4% were categorized as SIADH
and 22.9% as CSWS. They also found that hyponatremia was associated with significantly
longer hospital stay (17 days in hyponatremic group vs. 9 days in eunatremic patients
group) compared with eunatremic patients. Therefore, there is a need to assess the
hyponatremia, its cause, and manage it appropriately. In a retrospective study of
259 patients of SAH, it was shown that advanced age and smoking were associated with
increased likelihood and duration of hyponatremia respectively.[4 ] Therefore, older patients and patients with a smoking history should therefore be
monitored more closely for hyponatremia and may benefit from more aggressive therapy.
Both CSWS and SIADH present with low serum osmolality, high urine osmolality, and
a high urine sodium level. Basic difference between these two conditions is the amount
of the extracellular fluid (ECF) volume. In CSWS, ECF loss will be seen along with
urinary sodium loss, and hence patients will be in hypovolemic dehydrated state. Patients
with SIADH may be either in euvolemic or hypervolemic condition. Management of CSWS
patients[5 ] is directed at correcting the sodium loss and ECF loss. Intravenous fluids, either
isotonic or hypertonic saline, are used to correct intravascular volume and serum
sodium depletion.
In intractable situations, aggressive management with hypertonic saline may be required
several times a day to stabilize and improve sodium levels. Once euvolemia is achieved,
the patient should be maintained in a positive salt balance and to prevent volume
depletion by matching the urinary output with volume repletion. Close monitoring of
serum sodium levels is important to assess the extent of correction and prevent overcorrection
leading to osmotic demyelination syndrome. Fludrocortisone, a potent mineralocorticoid
(in doses of 0.1–1 mg/d), which causes reabsorption of sodium and water in the distal
renal tubule, leading to expansion of the ECF, may be given in CSWS patients. Long-term
therapy is not required, as CSWS is a transient condition that will usually resolve
within 3 to 4 weeks, once the underlying cerebral pathology is corrected. A close
coordination with the critical care team could be invaluable in the appropriate management
of these patients.
Conclusion
As such, there is a reasonably good chance that most neurointerventionalists will
encounter the diagnostic dilemma of persistent hyponatremia due to cerebrovascular
diseases at some point in their career. Both SIADH and CSWS are potential etiologies,
and their biochemical profiles have considerable overlapping findings. Biochemical
and clinical assessment of the patient's extracellular volume status may help differentiate
this condition. Accurate diagnosis is important, as the two conditions are treated
differently.
Contributions of Authors
AR—data collection, data analysis, data interpretation, manuscript preparation, and
critical revision
SKK—concept and design, data collection, data analysis, data interpretation, manuscript
preparation, and critical revision
SV—data analysis, data interpretation, and critical revision
JER—data analysis, data interpretation, and critical revision
