Hypokalaemic Paralysis

Hypokalaemic paralysis is acute flaccid weakness caused by low serum potassium, usually under 3.0 mmol/L, from an intracellular potassium shift or total body potassium depletion. The main primary causes are thyrotoxic periodic paralysis and familial hypokalaemic periodic paralysis.

Epidemiology. Thyrotoxic periodic paralysis affects about 2% of East Asian and Hispanic patients with hyperthyroidism and is far more common in men aged 20 to 40 years. Familial hypokalaemic periodic paralysis is autosomal dominant (CACNA1S, SCN4A), with onset in adolescence.

Causes and associations.

• Shift without depletion: thyrotoxicosis, familial periodic paralysis, insulin, beta agonists and high carbohydrate meals.
• Renal loss: loop and thiazide diuretics, primary hyperaldosteronism, Gitelman and Bartter syndromes, renal tubular acidosis, liquorice excess, amphotericin and hypomagnesaemia.
• Gastrointestinal loss: diarrhoea, vomiting and laxative misuse.
• Toxins: barium poisoning and toluene inhalation.

Pathophysiology. Excess thyroid hormone upregulates sodium potassium ATPase and raises beta adrenergic sensitivity, so insulin or exercise related catecholamines drive potassium into cells. In familial disease, channel gating defects cause paradoxical depolarisation of muscle at low potassium.

Presentation is sudden symmetric proximal weakness, legs more than arms, commonly on waking or after rest following exercise or a heavy carbohydrate meal. Reflexes are reduced, and sensation and consciousness are normal. Attacks last hours to days. Look for tremor, tachycardia, goitre and weight loss.

Red flags.

• Respiratory muscle weakness or bulbar involvement.
• ECG changes (U waves, QT prolongation, ST depression, arrhythmia) or potassium under 2.5 mmol/L.
• Paralysis with hypertension (aldosterone excess) or with diarrhoea.
• Barium or toluene exposure.

Measure potassium, magnesium, phosphate, glucose, creatinine, bicarbonate, blood gas, thyroid function, creatine kinase and ECG. A spot urine potassium to creatinine ratio under 1.5 mmol/mmol suggests a shift or gut loss, and a higher value suggests renal loss. In hypertensive patients check aldosterone and renin. Phosphate and magnesium are often low in thyrotoxic attacks.

Differential diagnosis.

• Hyperkalaemic and normokalaemic periodic paralysis.
• Guillain-Barre syndrome, myasthenia gravis and myelopathy.
• Rhabdomyolysis, polymyositis and hypophosphataemia.
• Conversion disorder.

Potassium replacement (cautious). The total deficit is often small in shift disorders, and overcorrection causes rebound hyperkalaemia.

• Potassium chloride orally 20 mmol every 1 to 2 hours, rechecking potassium hourly, up to a total of about 60 to 90 mmol in the first 24 hours.
• If oral intake is impossible or arrhythmia is present, potassium chloride 10 mmol/h IV in 0.9% sodium chloride (not dextrose) with continuous ECG. Use a central line for rates over 10 mmol/h, to a maximum of 20 mmol/h.
• Stop replacement when potassium reaches 3.5 mmol/L and strength improves.
• Avoid dextrose, insulin and beta agonists.

Thyrotoxic periodic paralysis. Propranolol 3 mg/kg orally (usually 40 to 80 mg) can reverse attacks and prevent rebound hyperkalaemia by blocking the beta adrenergic drive. Then treat thyrotoxicosis with carbimazole 15 to 40 mg daily (reduced as control improves) and propranolol 20 to 40 mg orally every 6 hours, or definitive therapy. Attacks stop when euthyroid.

Familial periodic paralysis. Avoid triggers and high carbohydrate meals. Prevention is acetazolamide 125 to 250 mg orally twice daily, increasing to a maximum of 1000 mg daily, or dichlorphenamide 50 mg orally twice daily. Potassium sparing diuretics (spironolactone 50 to 100 mg daily, triamterene) are alternatives. Acetazolamide can worsen some SCN4A forms, so review the response.

Barium poisoning. Potassium chloride IV at higher rates with continuous ECG, and haemodialysis for severe cases.

Correct magnesium and phosphate. Magnesium sulphate 2 g (8 mmol) IV over 20 minutes when magnesium is under 0.7 mmol/L. Correct phosphate if low.

Monitoring. Potassium hourly during repletion, ECG, respiratory rate and vital capacity, glucose and thyroid function.

Referral and escalation. Intensive care for respiratory weakness or arrhythmia. Endocrinology for thyrotoxicosis or aldosterone excess, and neurology with genetic testing for familial forms.

Special groups. In children, potassium chloride is 0.5 mmol/kg orally, with IV rates up to 0.5 mmol/kg/h. In pregnancy, control thyrotoxicosis with propylthiouracil in the first trimester and avoid carbimazole. In renal impairment, use lower replacement rates and check potassium often.