What is the management of hypokalemic periodic paralysis?

Management of Hypokalemic Periodic Paralysis

For acute attacks of hypokalemic periodic paralysis, administer oral potassium chloride 20-60 mEq as first-line treatment, reserving IV potassium (in mannitol, never glucose) for severe cases, and initiate long-term prophylaxis with acetazolamide or dichlorphenamide while avoiding glucose-containing solutions and high-carbohydrate meals that trigger attacks. 1, 2, 3

Acute Attack Management

Oral Potassium Replacement (First-Line)

• Administer oral potassium chloride 20-60 mEq for acute attacks when the patient can tolerate oral intake. 1, 4
• Oral potassium preparations are preferred over IV administration whenever possible, as they are safer and effective for most attacks. 1, 2
• Controlled-release potassium chloride preparations should be reserved for patients who cannot tolerate or refuse liquid/effervescent preparations due to risk of intestinal and gastric ulceration. 1

Intravenous Potassium (Severe Cases Only)

• For severe attacks with serum potassium <2.0 mEq/L or with muscle paralysis/ECG changes, administer IV potassium chloride in mannitol solution (NOT glucose) at rates up to 40 mEq/hour with continuous cardiac monitoring. 5, 2
• IV potassium in 5% glucose solutions is contraindicated as glucose worsens weakness and prevents potassium rise—use 5% mannitol as the diluent instead. 2
• Standard IV potassium rates should not exceed 10 mEq/hour or 200 mEq per 24 hours when serum potassium is >2.5 mEq/L. 5
• Central venous administration is strongly preferred over peripheral IV to avoid pain and ensure adequate dilution. 5

Critical Pitfall: Never use glucose-containing IV solutions for potassium replacement in hypokalemic periodic paralysis, as glucose triggers further potassium shifts into cells and worsens paralysis. 2

Long-Term Prophylactic Treatment

First-Line Prophylaxis

• Acetazolamide is the standard prophylactic treatment for preventing attacks in most patients with hypokalemic periodic paralysis. 4, 3
• Dichlorphenamide represents an alternative carbonic anhydrase inhibitor with similar efficacy for long-term prophylaxis. 4
• Only 50% of patients respond adequately to acetazolamide, necessitating alternative approaches in non-responders. 3

Alternative Prophylactic Agents

• For patients who worsen on acetazolamide (due to its kaliopenic effect), triamterene 50-100 mg daily is highly effective and may virtually abolish attacks. 6
• Topiramate, an antiepileptic with carbonic anhydrase inhibitory properties, may decrease attack severity and warrants consideration as an alternative. 7
• Potassium-sparing diuretics emerge as important alternatives when classical acetazolamide treatment fails. 3

Important Caveat: Some patients paradoxically worsen on acetazolamide due to its potassium-lowering effects—if attacks increase in frequency or severity after starting acetazolamide, switch to triamterene or another potassium-sparing agent. 6

Monitoring and Follow-Up

Target Potassium Levels

• Maintain serum potassium in the 4.0-5.0 mEq/L range to prevent both attacks and cardiac complications. 8
• Check serum potassium periodically during prophylactic treatment, with more frequent monitoring during dose adjustments. 8, 1

Long-Term Complications

• Patients require regular nephrology follow-up to monitor for progressive proximal myopathy, a long-term complication of hypokalemic periodic paralysis. 4
• Nephrologists play a crucial role not only in diagnosis but in ongoing management and surveillance for myopathy development. 4

Trigger Avoidance and Lifestyle Modifications

Common Attack Triggers

• Advise patients to avoid high-carbohydrate meals, which trigger potassium shifts into cells and precipitate attacks. 4
• Prolonged rest following exercise is a classic trigger that patients should recognize and manage. 4
• Glucose administration (oral or IV) can provoke attacks and should be avoided. 2

Genetic Considerations

• Most cases result from autosomal dominant calcium channel (CACNA1S) or sodium channel (SCN4A) mutations, with family history typically present. 4, 3
• Patients with CACNA1S mutations present with lower serum potassium levels during attacks, specific triggers, and higher rates of dyspnea during crises compared to SCN4A mutations. 3

Special Considerations

Concurrent Medications

• Avoid potassium-wasting diuretics (thiazides, loop diuretics) which can precipitate attacks. 8
• If patients are on RAAS inhibitors for other conditions, routine potassium supplementation may be unnecessary and potentially harmful. 8
• Correct any concurrent hypomagnesemia, as this makes hypokalemia resistant to correction. 8

Cardiac Monitoring

• Continuous ECG monitoring is essential during IV potassium administration for severe attacks to detect arrhythmias. 5
• Both hypokalemia and hyperkalemia increase mortality risk, particularly in patients with underlying cardiac disease. 8