Hypernatraemic Encephalopathy

Hypernatraemic encephalopathy is brain dysfunction caused by hypertonicity with serum sodium over 150 mmol/L, usually over 160 mmol/L when symptomatic. Hypernatraemia reflects a deficit of water relative to sodium.

Epidemiology. It is common in older adults, hospitalised patients, intensive care patients and infants with gastroenteritis. Mortality is high in hospital acquired and severe cases, mostly from comorbidity.

Causes and associations.

• Water loss: fever, burns, diarrhoea, vomiting, osmotic diuresis (hyperglycaemia, mannitol), loop diuretics and diabetes insipidus (central or nephrogenic).
• Poor water intake: impaired thirst or access, dementia and sedation.
• Sodium gain: hypertonic saline, sodium bicarbonate, salt poisoning, high sodium feeds and dialysate errors.
• Drugs causing nephrogenic diabetes insipidus: lithium, amphotericin and demeclocycline.

Pathophysiology. Extracellular hypertonicity draws water from brain cells, which shrink and may tear cerebral veins, causing subdural, subarachnoid or intraparenchymal haemorrhage. Over 1 to 3 days brain cells generate osmolytes that restore volume, so rapid lowering of sodium in chronic hypernatraemia leads to cerebral oedema.

Presentation is thirst (if conscious), irritability, lethargy, weakness, hyperreflexia, tremor, seizures and coma. Signs of dehydration depend on the cause and the sodium level. Polyuria suggests diabetes insipidus or osmotic diuresis. In infants, look for a doughy skin feel, a high pitched cry and fever.

Red flags.

• Sodium over 160 mmol/L, reduced consciousness or seizures.
• Focal deficit, suggesting intracranial haemorrhage or venous thrombosis.
• Shock, polyuria with dilute urine, or an acute sodium load.

Measure serum sodium, osmolality, glucose, urea, creatinine, calcium, potassium, urine osmolality, urine sodium and urine volume. A urine osmolality under 300 mOsm/kg with serum hypernatraemia suggests diabetes insipidus, and a desmopressin test can separate central from nephrogenic forms. Do CT head if there are focal signs, seizure or coma.

Differential diagnosis.

• Central and nephrogenic diabetes insipidus.
• Osmotic diuresis (hyperglycaemia, mannitol).
• Sodium poisoning or iatrogenic load.
• Intracranial haemorrhage, sepsis and nonconvulsive seizures.

Restore circulation first. If hypotensive, give 0.9% sodium chloride 500 mL IV boluses until perfusion is restored, then switch to hypotonic fluid.

Water deficit. Free water deficit (litres) = total body water x (sodium/140 minus 1). Total body water is 0.6 x weight (kg) in men, 0.5 x weight in women and older men, and 0.45 x weight in older women. Add ongoing losses.

Rate of correction. For chronic or unknown duration, lower sodium by no more than 10 mmol/L in 24 hours (about 0.4 mmol/L/h). For clearly acute hypernatraemia (under 24 hours), correction of 1 mmol/L/h is acceptable.

Fluid choice. Oral or enteral water if possible. Otherwise 5% dextrose IV (watch glucose), or 0.45% sodium chloride when sodium and volume deficits coexist. Replace the deficit over 48 hours or longer in chronic cases.

Central diabetes insipidus. Desmopressin 1 to 2 microgram IV or SC every 12 hours, or intranasal 10 to 20 microgram every 12 hours. Monitor sodium to avoid hyponatraemia.

Nephrogenic diabetes insipidus. Stop lithium or the cause. Use a low sodium and low protein diet and hydrochlorothiazide 25 to 50 mg orally daily, with monitoring of potassium and lithium level.

Sodium overload. 5% dextrose with furosemide 20 to 40 mg IV, and haemodialysis in renal failure or severe poisoning.

Seizures. Lorazepam 0.1 mg/kg IV (maximum 4 mg).

Monitoring. Sodium every 2 to 4 hours, urine output and osmolality, glucose, GCS and neurological signs. If conscious level falls during correction, stop or slow correction and assess for cerebral oedema with CT.

Referral and escalation. Intensive care for sodium over 160 mmol/L with encephalopathy. Endocrinology for diabetes insipidus and nephrology for renal causes.

Special groups. In infants and children, correct at 0.5 mmol/L/h and no more than 10 to 12 mmol/L in 24 hours, using oral rehydration when possible. In older adults, correct slowly and review swallowing and access to fluids. In heart failure and renal failure, reduce volumes and consider dialysis.