Hyponatraemic Encephalopathy

Hyponatraemic encephalopathy is brain dysfunction from cerebral oedema caused by hypotonic hyponatraemia, usually with serum sodium under 130 mmol/L and especially when the fall is rapid. It is a medical emergency, since seizures, respiratory arrest and brainstem herniation can occur.

Epidemiology. Hyponatraemia is the commonest electrolyte disorder in hospital. Symptomatic encephalopathy is uncommon, and premenopausal women, children and postoperative patients are at higher risk of severe brain swelling.

Causes and associations.

• Drugs: thiazide diuretics, selective serotonin reuptake inhibitors, carbamazepine, oxytocin, desmopressin, cyclophosphamide, vincristine and MDMA.
• Syndrome of inappropriate antidiuresis (lung disease, central nervous system disease, malignancy, nausea, pain).
• Excess water intake: primary polydipsia, beer potomania, marathon running and hypotonic intravenous fluids.
• Postoperative state, bowel preparation, adrenal insufficiency, hypothyroidism, heart failure, cirrhosis and nephrotic syndrome.

Acute and chronic. Acute is under 48 hours, and chronic is 48 hours or more or unknown. Chronic hyponatraemia carries a high risk of osmotic demyelination if corrected too fast.

Pathophysiology. Water moves into brain cells as extracellular osmolality falls. The brain adapts by losing solute over 24 to 48 hours. A rapid fall leaves little time to adapt, and brain swelling follows. Hypoxia and female sex worsen the risk.

Presentation is headache, nausea, vomiting, confusion and lethargy, then seizures, coma and respiratory arrest. Moderate symptoms are nausea without vomiting, confusion and headache. Severe symptoms are vomiting, seizures, somnolence and GCS 8 or under. Non-cardiogenic pulmonary oedema may occur.

Red flags.

• Seizure, GCS 8 or under, or respiratory arrest.
• Sodium under 120 mmol/L, or a fall of over 10 mmol/L in 24 hours.
• Marathon or exercise associated hyponatraemia with headache and vomiting.
• Postoperative state, MDMA use or recent oxytocin.

Confirm true hypotonic hyponatraemia with serum osmolality (under 275 mOsm/kg). Measure urine osmolality and sodium, glucose, potassium, urea, creatinine, uric acid, cortisol, thyroid function and triglycerides, and assess volume status. Treatment is not delayed for investigations in severe symptoms. Do CT head if there are focal signs or seizure with trauma.

Differential diagnosis.

• Pseudohyponatraemia and translocational hyponatraemia from hyperglycaemia.
• Intracranial haemorrhage, meningitis, stroke and hypoglycaemia.
• Cerebral salt wasting.

Severe symptoms (seizure, coma, vomiting, respiratory distress).

• 3% sodium chloride 150 mL IV over 20 minutes (or 2 mL/kg). Check sodium after each bolus. Repeat up to twice, for a total of 3 doses, if symptoms persist, aiming for a rise of 5 mmol/L in the first hours.
• Stop when symptoms improve or sodium has risen 5 mmol/L. Then continue treatment directed by the cause.
• Give a benzodiazepine for seizures (lorazepam 0.1 mg/kg IV, maximum 4 mg) and secure the airway when needed.

Moderate symptoms. 3% sodium chloride 150 mL IV over 20 minutes as a single bolus, or a slower infusion of 0.5 to 2 mL/kg/h, with sodium checks every 4 hours.

Correction limits. Raise sodium by no more than 10 mmol/L in the first 24 hours and 8 mmol/L in each following 24 hours. Use 8 mmol/L in 24 hours in high risk patients (sodium 105 mmol/L or under, alcohol use disorder, malnutrition, advanced liver disease, hypokalaemia). Potassium replacement also raises sodium.

Overcorrection. If the limit is exceeded or sodium rises too fast, stop hypertonic saline, give desmopressin 2 microgram IV every 8 hours and 5% dextrose 3 mL/kg/h IV, and check sodium every 1 to 2 hours, to lower it again.

Cause directed treatment.

• Stop offending drugs and hypotonic fluids.
• Hydrocortisone 100 mg IV for adrenal insufficiency.
• Water restriction to 500 to 1000 mL daily and treatment of the cause in SIADH.

Children. 3% sodium chloride 2 to 3 mL/kg IV over 10 to 20 minutes, repeated up to twice, with the same correction limits.

Monitoring. Sodium every 20 minutes during boluses, every 1 to 2 hours for the first 6 hours, then every 4 hours for the first 24 hours. Watch urine output (a sudden large water diuresis predicts overcorrection), GCS and neurological signs. Osmotic demyelination appears 2 to 6 days after overcorrection, with dysarthria, dysphagia, quadriparesis and a locked in state.

Referral and escalation. Intensive care for seizures, GCS 8 or under, or need for repeated hypertonic saline. Nephrology and endocrinology for the cause.

Special groups. Premenopausal women and children need early treatment. In heart failure and cirrhosis, use small volumes of 3% sodium chloride.