Hyponatraemia Pharmacotherapy

Hyponatraemia pharmacotherapy corrects low serum sodium (under 135 mmol/L) at a safe speed. Moderate is 125 to 129 mmol/L and severe is under 125 mmol/L or any level with severe symptoms. Treatment depends on duration, symptoms and volume status. Overly rapid correction can cause osmotic demyelination syndrome.

Classification. Hypertonic saline; isotonic saline for hypovolaemia; fluid restriction; urea; vasopressin receptor antagonists (tolvaptan); loop diuretics; treatment of the cause (hormone replacement, stopping drugs).

Mechanism. Hypertonic saline raises extracellular sodium directly. Tolvaptan blocks the V2 receptor and produces free water loss. Urea acts as an osmotic diuretic. Fluid restriction limits free water intake.

Correction limits. Raise sodium by no more than 10 mmol/L in the first 24 hours and by 8 mmol/L in each following 24 hours (6 mmol/L in the first day if at high risk of osmotic demyelination: sodium under 105 mmol/L, alcohol use, malnutrition, liver disease or hypokalaemia).

Severe symptoms. Aim for a 5 mmol/L rise in the first hour, then stop hypertonic saline once symptoms ease.

Overcorrection. If the rise is too fast, stop saline, give desmopressin 2 micrograms intravenously, and replace free water with 5% glucose to bring sodium back down.

• First-line. Treat the cause; 3% saline for severe symptoms; 0.9% saline for hypovolaemia; fluid restriction for SIADH.
• Alternative. Urea; salt tablets with a loop diuretic.
• Specialist. Tolvaptan, hypertonic saline infusion regimens, hyponatraemia in cirrhosis or heart failure.
• Emergency. Seizures, coma, cerebral oedema (severe hyponatraemia with symptoms).

Selection. Do not use 0.9% saline in SIADH, since it can lower sodium. Avoid hypotonic fluids in at-risk patients. Check urine osmolality and sodium before choosing.

Contraindications. Hypertonic saline: heart failure with pulmonary oedema (caution), hypernatraemia. Tolvaptan: hypovolaemia, anuria, liver disease, urgent need to raise sodium. Fluid restriction: hypovolaemia.

Serious adverse effects.

• Osmotic demyelination syndrome: dysarthria, dysphagia, quadriparesis, locked-in state, usually 2 to 6 days after correction.
• Volume overload, pulmonary oedema, phlebitis with hypertonic saline.
• Liver injury, thirst and overcorrection with tolvaptan.
• Uraemic taste and nausea with urea.

Major interactions. Thiazides, SSRIs, carbamazepine, oxytocin, vincristine and cyclophosphamide cause hyponatraemia; tolvaptan with CYP3A4 inhibitors; desmopressin worsens hyponatraemia; loop diuretics add potassium loss.

Common prescribing errors.

• Correcting too quickly and not checking sodium at least every 2 to 4 hours.
• Using hypotonic fluids in at-risk patients.
• Using 0.9% saline for SIADH.
• Missing adrenal insufficiency or hypothyroidism.
• Using tolvaptan without a specialist plan.

Special groups.

• Pregnancy: treat symptoms with the usual adult measures; check for pre-eclampsia.
• Breastfeeding: compatible.
• Children: use isotonic maintenance fluids; hyponatraemia is a major risk with hypotonic fluids.
• Older adults: high risk from thiazides and SSRIs; slower correction.
• Kidney: treat the cause, restrict fluids and dose-adjust.
• Liver: very slow correction; high risk of demyelination.
• East Africa: tolvaptan is usually not available, so fluid restriction, urea and hypertonic saline are the realistic options; HIV, tuberculosis and meningitis are common causes of SIADH and adrenal insufficiency, and diarrhoeal disease with hypotonic fluid replacement is a frequent cause in children.

Monitoring. Sodium every 2 hours during active correction, then every 4 to 6 hours; urine sodium and osmolality; neurological state; fluid balance.

Referral and escalation. Seizures, coma, sodium under 120 mmol/L, a rise of more than 10 mmol/L in 24 hours, or suspected osmotic demyelination.

Comparison with alternative classes. Hypertonic saline corrects fast and saves lives in severe cases but needs close monitoring. Fluid restriction is safe but slow. Tolvaptan works but is costly and risks overcorrection and liver injury.