Seizures, Sodium 108, and Two New Drugs

Step 1 - confirm true hypotonic hyponatraemia. Measured osmolality 224 mOsm/kg is low, and calculated osmolality (2 × 108 + 6.2 + 2.6 ≈ 233) is within 10 mOsm/kg of the measured value. There is therefore no osmolal gap, and pseudohyponatraemia (severe hypertriglyceridaemia, paraproteinaemia) and hyperosmolar states (hyperglycaemia, mannitol) are excluded.

Step 2 - assess volume status. She is clinically euvolaemic: no oedema, no raised JVP, no postural drop, moist mucosae, low urea (2.6) with normal creatinine. Urine osmolality 486 (>100) shows ADH is acting when it should be fully suppressed, and urine sodium 64 (>30) shows sodium is being lost renally rather than being appropriately conserved.

Step 3 - the pattern. Euvolaemia, urine osmolality >100, urine sodium >30, normal thyroid and adrenal function and no diuretic-related volume depletion equals SIADH (Bartter and Schwartz criteria). The 09:00 cortisol of 512 nmol/L is adequate in acute illness, though a short Synacthen test is reasonable if there is any doubt.

Step 4 - the cause. Two drugs are implicated. Indapamide, a thiazide-like diuretic, impairs the diluting segment and produces a hyponatraemia that is amplified by ADH, characteristically in elderly women within the first weeks of therapy. Escitalopram increases ADH release and is a recognised cause of SIADH. Together they are a classic combination. Clear chest radiograph and normal CT brain argue against pulmonary or CNS causes; there is no malignancy history.

Action. Stop indapamide and escitalopram today. Recheck sodium after withdrawal. Only if hyponatraemia persists should an occult malignancy (small-cell lung cancer) or other SIADH cause be hunted. Fluid restriction alone is far too slow for a patient who is fitting.

Deficit calculation. Sodium deficit = total body water × (target Na − current Na). In an elderly woman, TBW ≈ 0.45–0.5 × 58 kg = 26–29 L. To raise sodium from 108 to 114 (a 6 mmol/L rise) needs 26 × 6 = 156 mmol to 29 × 6 = 174 mmol. Three per cent saline contains 513 mmol/L, so 174 ÷ 513 = 0.34 L, i.e. about 300–340 mL of 3% saline over the correction period. The formula is only an estimate; the measured sodium drives the prescription.

Prescription.

• Seizures mean severely symptomatic hyponatraemia: give 100–150 mL of 3% NaCl over 10–20 min, and repeat up to twice more at 10–20 min intervals until seizures stop or sodium has risen 4–6 mmol/L. A 100 mL bolus raises sodium by roughly 1.5–2 mmol/L in this patient.
• Once seizures are controlled, stop the hypertonic saline. Target a total rise of ≤8–10 mmol/L in 24 h (sodium 116–118) and ≤18 mmol/L in 48 h.
• Do not use isotonic saline as maintenance: in SIADH with high ADH, it can worsen hyponatraemia through the desalination phenomenon.
• Correct hypokalaemia promptly - it is an independent risk factor for osmotic demyelination.
• Monitor sodium and glucose hourly at first, then 2–4 hourly; strict input/output chart, hourly urine output and daily weights. A sudden diuresis is the warning sign of overcorrection.
• ODS risk factors here: sodium <105, chronicity, female sex, and the possibility of poor nutrition - so aim at the lower end of the range (≤8 mmol/L/24 h).
• Give 3% saline through a large peripheral vein for short courses; use central access if repeated boluses are anticipated.
• Treat the underlying cause simultaneously: stop the implicated drugs, and look for and treat the precipitant.

What has happened. Sodium has risen 12 mmol/L in 6 h - about 2 mmol/L/h, far outside the ≤8–10 mmol/L/24 h limit and into the range where osmotic demyelination occurs. Two mechanisms usually combine: the prescribed hypertonic saline, and an abrupt water diuresis once indapamide and escitalopram are withdrawn and ADH falls, so urine output may surge to several hundred mL per hour.

Priorities.

1. Stop all sodium-containing fluids immediately.
2. Re-lower the sodium deliberately with a desmopressin clamp. Give desmopressin 1–2 µg IV/SC 6–8-hourly to abolish the water diuresis, and replace free water with 5% dextrose (or nasogastric water) to bring the sodium back towards 114–116 mmol/L within the first 24 h. The volume can be estimated with the same deficit equation run in reverse; in practice run 5% dextrose at 1–2 mL/kg/h and recheck hourly.
3. Monitor sodium hourly while the clamp is running, then 4-hourly once stable. Document every intervention with timestamps.
4. Look actively for osmotic demyelination: dysarthria, dysphagia, ataxia, behavioural change, parkinsonism, quadriparesis, seizures. These typically appear 2–6 days after correction. If suspected, arrange MRI (T2/FLAIR hyperintensity in the central pons and extrapontine structures) and involve neurology and ICU. There is no proven rescue therapy; case reports describe re-lowering, steroids and IVIG.
5. Involve nephrology and critical care early, and re-address the airway if her drowsiness is not explained by the sodium alone.

The teaching point. The commonest cause of overcorrection is failing to anticipate the post-drug, post-obstruction water diuresis. Once the sodium is above about 120 mmol/L and the patient is asymptomatic, the safest fluid is often free water plus desmopressin, not more saline.