Hypokalemic Periodic Paralysis

Introduction

• hypoPP is a rare channelopathy affecting sodium or calcium channels, typically with autosomal dominant inheritance, although sporadic mutations also occur.^1-2 The disease has a prevalence of 1 in 100,000 and appears in the first or second decade of life. Attacks can occur once or several times throughout life.²
• The manifestation of the disease is a sudden onset of paralysis, either generalized or focal, that is associated with low serum potassium levels. The duration of paralysis can be short-lived or last several hours. Paralysis begins early in the morning or upon awakening in the middle of the night.^3,4
• Attacks can be triggered under several circumstances, including prolonged rest after strenuous exercise, a carbohydrate-rich meal the day prior, viral illness, and inadequate sleep. Offending medications known to trigger an attack include beta agonists, corticosteroids, and insulin.¹

Etiology and Pathophysiology

• Mutations in type I hypoPP are due to mutations in CACNA1S, a dihydropyridine-sensitive skeletal muscle calcium channel gene.³ This gene encodes for a protein involved in the interaction between dihydropyridine receptors (DHPR) and ryanodine receptors.⁴
• Mutations in type 2 hypoPP are related to mutations in SCN4A, a voltage-sensitive skeletal muscle sodium channel gene. The gene encodes a protein, NaV1.4, which is structurally similar to DHPR.⁴
• Regardless of the genotypical origin of the disease, paralysis occurs with hypokalemia. The defective sodium or calcium gene allows for an accessory flow of ions across skeletal muscle cell membranes.
• Potassium levels that fall below 3.0 mEq/L will paradoxically cause skeletal muscle fibers to undergo sustained depolarization, failure of excitation-contraction coupling and ultimately weakness due to inexcitable muscle.^5–7
• Affected muscles include the proximal muscles. The diaphragm and muscles innervated by cranial nerves are usually spared.⁵ With severe attacks, respiration, ocular movements, and swallowing function can be affected.
• An association with MH has been reported; however, several cases of succinylcholine or halogenated agents being used without issue have been documented. It is recommended to avoid triggering agents until further evidence is available that suggests there is no possible association between hypoPP and MH.⁵
• The use of neuromuscular blocker agents should be done with caution. Depolarizing agents can potentially lead to weakness. Judicious use of nondepolarizing agents is advised.⁸

Anesthetic Considerations

Perioperative Considerations

Other Considerations

• Performance of a regional anesthetic is preferred. If general anesthesia is performed, avoidance of MH triggering agents is encouraged. Regional anesthesia allows for continued reporting of any changes in symptoms prior to the occurrence of an attack. Although there are reports of hypokalemia associated with spinal anesthesia, it has been safely performed.⁹
• Epinephrine and other beta-adrenergic agonists can result in hypokalemia, especially if added to local anesthetic mixtures during regional anesthetics.
• Insulin also lowers serum potassium levels, and it should be used with caution in patients with hypoPP.
• Minimizing severe acute pain is also critical, as stress hormones such as cortisol can lead to hypokalemia and trigger a paralytic attack.³

Treatment of an Acute Attack

• Administration of oral or intravenous potassium until normalization of serum potassium1
• Supportive care in the case of respiratory muscle weakness⁴

Prevention of an Attack

• The ongoing prevention of attacks has been achieved through the use of carbonic anhydrase inhibitors. These diuretics induce potassium loss, but somewhat counterintuitively, they help reduce the frequency of paralytic attacks by poorly understood mechanisms.³
• Some patients also benefit from the use of a potassium-sparing diuretic such as spironolactone, either as monotherapy or in combination with a carbonic anhydrase inhibitor.³