CEREBRAL SALT WASTING

CEREBRAL SALT WASTING

Hyponatremia commonly seen with a number of intracranial diseases, especially head injuries, tumors, infections, and stroke

- up to 30% of patients with subarachnoid hemorrhage (SAH)

- may be a poor prognostic sign

Hypoosmolality can aggravate cerebral edema and lead to clinical deterioration

- may precipitate seizures and decreased level of consciousness

A number of disorders can result in this situation including syndrome of inappropriate ADH secretion (SIADH), use of certain medications, and cerebral salt wasting (CSW)

- each of these disorders is managed differently

Early accurate diagnosis and appropriate treatment of hyponatremia is, therefore, critical in management of patients with intracranial disorders

Definition:

CSW is defined as the renal loss of sodium during intracranial disease leading to hyponatremia and a decreased extracellular fluid volume (ie. hypovolemic hyponatremia)

ie. excessive natriuresis

- originally reported by Peters in 1950 in three patients with severe hyponatremia with encephalitis, hemorrhage and bulbar poliomyelitis who were unable to prevent sodium loss in urine

- hypothesized defect in neural regulation of renal tubular activity independent of pituitary-adrenal axis (which appeared normal)

- however term fell out of favor when SIADH discovered in 1957 (and two often equated)

- although laboratory criteria for SIADH may have been met, patients with CSW were more hypovolemic and had normal ADH secretion when tested

- in fact, volume depletion triggers appropriate ADH release which causes relative water retention, but overall negative salt balance more important than ADH

- when further patients were studied (eg. SAH, head injury), plasma volume was found to be reduced, ADH levels were appropriate for serum osmolality and patients did not respond to fluid restriction as expected for SIADH

NB: If hyponatremia is due to CSW, fluid restriction may actually aggravate the clinical condition (esp in vasospasm of SAH) and lead to cerebral infarction

- patients respond to salt and volume replacement (ie. opposite treatment!)

Pathogenesis:

Renal sodium handling affected by both humoral and neural mechanisms

1. Natriuretic factors:

- peptides that can cause natriuresis even if kidney is denervated

- atrial natriuretic peptide (ANP) released by heart in response to atrial stretch and induces natriuresis, diuresis, vasodilation and suppresses renin & aldosterone secretion

- ANP-secreting neurons are found in the hypothalamus but at very low levels relative to heart (so unlikely to directly account for CSW)

- neural factors may modulate cardiac release of ANP via cholinergic and adrenergic inputs from hypothalamus etc.

- disturbance of brain's control over ANP secretion may lead to excessive release and CSW (?)

- inconsistent relationship between ANP levels and CSW / hyponatremia

- brain natriuretic peptide (BNP) is largely of cardiac ventricular origin and has similar effects

- elevated levels found after SAH and with vasospasm (may be released with sympathetic stimulation after SAH); blocks aldosterone secretion and acts on kidneys directly

- also BNP in hypothalamus which may be injured directly after brain injury or SAH

- adrenomedullin is an endogenous peptide which vasodilates and causes natriuresis (structurally related to calcitonin) - found to be correlated with vasospasm (may counteract vasoconstriction but lead to natriuresis also)

2. Ouabain-like Compound: (OLC)

- can block natriuretic effect of ventricular infusion of hypertonic saline in rats with digoxin-specific antibodies suggesting OLC may be involved in CSW

- ouabain is an inhibitor of Na/K-ATP and may lead to natriuresis (unproven)

- OLC reactivity found in hypothalamus and medulla of rat brain

- reactivity found in SAH patients correlating with amount of bleeding and volume status

- likely not account for entire spectrum of CSW

3. Direct Neural Effects:

- sympathetic hyperactivity leads to decreased plasma volume

- decline in renal sympathetic input leads to natriuresis due to increased glomerular blood flow and decrease in renin release (reduced tubular reabsorption)

- brain injury could interrupt sympathetic output to kidneys

Anatomy:

- most often linked to lesions in region of hypothalamus or forebrain

Disorders associated with CSW:

1. Subarachnoid hemorrhage

- esp anterior communicating complex (close to hypothalamus)

- mild-moderate in over 30% of patients but rarely severe (< 125)

- peaks in first week at time of vasospasm onset and may correlate with higher risk of infarction

2. Traumatic brain injury

3. Cerebral Infections

- meningitis including TB meningitis (basal meningitis with hypothalamic involvement)

- encephalitis

4. Tumors

- glioma

- carcinomatous meningitis

Differential Diagnosis of CSW;

Hypovolemic:

- excessive diuretics (esp loop, thiazide)

- hypoadrenalism (Addison's disease)

- GI / skin losses

- CSW

Euvolemic or Hypervolemic:

- fluid overloading (with hypotonic solutions)

- congestive heart failure

- hepatic failure / cirrhosis

- SIADH

- hypothyroidism

Artefactual:

- hypertriglyceridemia

- hyperglycemia

Investigation:

1. History

- looking for precipitating causes incl. nature of intracranial event, time period, and medications

- may see anorexia, nausea / vomiting, weakness, orthostatic lightheadedness and syncope (in hypovolemic forms)

2. Examination: for volume status (see below)

3. Laboratory Tests:

- serum osmolality

- urine sodium and urine osmolality

- Urea (BUN)

- TSH

- consider cosyntropin stimulation test to r/o adrenal insufficiency

- stop unnecessary diuretics (esp if patient hypovolemic)

Differentiating CSW from SIADH:

- they both share the same laboratory characteristics with reduced serum osmolality, high urine osmolality (greater than serum)

- major difference is volume status

- poor skin turgor, shrunken eyes, dry mucous membranes, absence of perspiration, tachycardia

- orthostatic hypotension

- loss of weight on serial testing since admission (increased in SIADH)

- negative water balance on ins/outs charting

- low pulmonary capillary wedge presure (PCWP < 8 mm Hg) or low central venous pressure (CVP < 6 mm Hg) if invasive measurement of volume status available

- urine Na+ markedly elevated (variable in SIADH) & urine volume increased in CSW

- high BUN and Hematocrit supports CSW (prerenal azotemia and hemoconcentration)

- elevated serum K+ not usually seen in SIADH and implies CSW

- serum uric acid often increased in volume depletion (CSW) while low in SIADH

NB: ADH or ANP levels not useful in diagnosis of SIADH vs CSW

- some patients may have concurrent SIADH and CSW, often SIADH first then CSW becomes more significant a few days after event

Management of CSW:

1. Treat underlying neurological process

- esp if increased intracranial pressure or hydrocephalus as contributing factors

2. Volume replacement:

- maintain adequate hydration usually with intravenous isotonic saline solutions (0.9% NaCl)

- blood products useful if patient anemic

- colloids may also be used to expand volume and absorb interstitial / third-space fluid

- aim to match urine loss and keep positive fluid balance

3. Positive sodium balance:

- may add oral salt or hypertonic saline to ensure positive sodium balance

- amount of sodium required to correct deficit obtained by multiplying deficit in serum sodium by total body water (50-60% of ideal body weight) and correcting at no more than 1 mmol/L per hour

(risk of precipitating central pontine myelinolysis with rapid correction)

- may prevent further salt loss with volume expansion by using mineralocorticoid fludrocortisone which enhances sodium reabsorption by acting directly on tubule (but can cause hypokalemia, fluid overload and hypertension)

- very effective in preventing hyponatremia from SAH (ARR of 25%, NNT 4) and reduced need for dobutamine to augment cerebral perfusion

4. Close monitoring

- of serum sodium, volume status (incl. overload with pulmonary edema)

- follow ins and outs closely

- can monitor CVP or even PCWP

References:

Harrigan MR. Cerebral salt wasting syndrome. Critical Care Clinics 17(1); 2001

Rabinstein AA, Wijdicks EFM. Hyponatremia in critically ill neurological patients. The Neurologist 9(6); 2003: 290-300.

Last update: March 2004

Reviewed by: pending

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