Urgent considerations

See Differentials for more details

A rapid decline in serum sodium levels can lead to cerebral oedema and central nervous system symptoms including headache, muscle cramps, reversible ataxia, psychosis, lethargy, apathy, anorexia, and agitation. If no acute intervention is initiated to increase the sodium level, patients can develop coma, brainstem herniation, respiratory arrest, and death. To prevent this, urgent restoration of sodium levels is required and is accomplished by infusion of hypertonic saline (3%).[2][15][17]​​​​ The rate of infusion varies according to severity of symptoms, and guidance varies considerably.[2][15][17]​​​ Consult local protocols. Close monitoring of serum sodium and electrolytes is crucial until symptoms resolve. See BMJ Best Practice topic Hyponatraemia for more details.

The goal in treating chronic asymptomatic hyponatraemia is normalising sodium level gradually by using a conservative approach, such as fluid restriction in euvolaemic states or infusing isotonic saline in hypovolaemic states, aiming to increase sodium level not more than 12 mmol/L (12 mEq/L) in 24 hours, although guidance varies, with some stating that this therapeutic limit is still set too high.[15]​ If there is a high risk of osmotic demyelination syndrome, the rate should be lower.[9][10] Consult local protocols for guidance. A vasopressin receptor antagonist is indicated to treat chronic hyponatraemia in syndrome of inappropriate antidiuretic hormone secretion (SIADH) or secondary to congestive heart failure.[18] However, these agents should be used with caution because of the potential risk of hepatotoxicity and rapidly increased serum sodium levels.[19] Furthermore, there is no clear evidence that vasopressin receptor antagonists decrease mortality in this setting. [ Cochrane Clinical Answers logo ]

Adrenal disease

Patients with adrenal insufficiency may present with chronic hyponatraemia. However, adrenal crisis is life-threatening and requires immediate intervention and diagnosis.[20] Patients usually present with weakness, postural hypotension, and fatigue, and in severe cases may have hypovolaemic shock. If the clinical suspicion of adrenal insufficiency is high, treatment with intravenous fluids and glucocorticoid replacement should be started immediately; diagnostic tests should not delay treatment.

Hyponatraemia and hyperkalaemia are commonly encountered in these patients, however, the absence of hyperkalaemia should not exclude consideration of adrenal insufficiency, especially in children with volume depletion.[15]​ A morning serum cortisol and cosyntropin (adrenocorticotropic hormone [ACTH]) stimulation test establishes the diagnosis. A morning cortisol level less than 83 nanomol/L (3 micrograms/dL) confirms the diagnosis of adrenal insufficiency. If the morning cortisol level is indeterminate (i.e., 83-496 nanomol/L [3-17] micrograms/dL), then cosyntropin stimulation testing is recommended. A rise in the cortisol level to 497 nanomol/L (18 micrograms/dL) or above in 1 hour is a normal response and excludes the diagnosis of adrenal insufficiency. 

In undiagnosed patients with adrenal crisis, dexamethasone can be given intravenously/intramuscularly without interfering with the ACTH stimulation test. Once the diagnosis is confirmed, large glucocorticoid doses are given initially followed by smaller, physiological doses. See BMJ Best Practice topic Adrenal suppression.

Thyroid disease

Thyroid function tests should be ordered to exclude hypothyroidism. Albeit rare, severe hypothyroidism has been associated with hyponatraemia.[21][22]

SIADH and cerebral salt-wasting syndrome

Patients who develop hyponatraemia as a result of head injury, intracranial surgery, subarachnoid haemorrhage, stroke, or brain tumours may have cerebral salt-wasting syndrome or SIADH. These conditions are difficult to distinguish, and controversy exists as to whether the distinction is clinically important.

Cerebral salt-wasting syndrome tends to produce hypovolaemic hyponatraemia with hyposmolar or normosmolar urine and a high urine output, whereas SIADH produces euvolaemic hyponatraemia with hyperosmolar urine and a low urine output. Urinary sodium levels are similar with both conditions.

Asymptomatic SIADH is usually treated with water restriction, and sodium replacement is reserved for symptomatic patients.​[15][23] However, there is a lack of evidence supporting fluid restriction as first-line therapy for people with SIADH. One consecutive, prospective evaluation of 183 patients with SIADH found that up to 60% had criteria that would predict lack of response to fluid restriction.[24]

All patients with cerebral salt-wasting syndrome require fluid and sodium replacement using hypertonic saline, and some may require oral sodium supplementation after intravenous fluids are discontinued.

Osmotic demyelination syndrome

Osmotic demyelination syndrome (which includes central pontine myelinolysis and extrapontine myelinolysis) is a rare condition that can occur when hyponatraemia is corrected too rapidly.[10]​ Brain cells that have adapted to hyponatraemia shrink if the extracellular osmolality is restored too rapidly, causing demyelination and irreversible axonal damage. The pons is most frequently affected, but some patients develop axonal damage in other regions. The risk is greater if the presenting hyponatraemia being treated was severe, or if a period of hypernatraemia occurred during correction.

Patients present with lethargy, altered mood, confusion, seizures, intracerebral haemorrhage, horizontal gaze paralysis, and a spastic quadriplegia. The prognosis is poor.

The condition can be avoided by using the correct approach to treat hyponatraemia. Sodium replacement is required for symptomatic patients, and should be undertaken slowly. The rate of sodium correction should not exceed 12 mmol/L (12 mEq/L) in 24 hours.​[9][15]​ More rapid sodium correction is indicated to prevent coning (herniation of the brain through the foramen magnum) in patients with severe central nervous system symptoms of cerebral oedema.

In cases of overly rapid correction of sodium, consideration should be given to administering electrolyte-free water and desmopressin.[2]​​[9][15]​​ Consult local protocols for guidance.

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