Hyperkalemic Periodic Paralysis

Introduction

• Normal physiology of skeletal muscle contraction involves an efferent motor neuron releasing acetylcholine at the neuromuscular junction to open a ligand-gated sodium channel to begin the initial depolarization of the muscle unit.¹
• HYPP impairs normal muscle cell depolarization by altering the function of the skeletal muscle sodium channel on the sarcolemma.²
• HYPP is a rare genetic disorder characterized by variable muscle dysfunction ranging from weakness to paralysis, and is associated with elevated serum potassium levels during episodes of muscle dysfunction.^2-3
• This genetic condition exhibits an autosomal-dominant inheritance pattern, affects all genders equally, and has a prevalence of 1:200,000.³

Etiology and Pathophysiology

• HYPP is caused by a mutation of the SCN4A gene, which is located on chromosome 17. This gene encodes NaV1.4, a protein that regulates sodium ion influx into skeletal muscle cells.^2-4
  • In HYPP, skeletal muscle sodium channels remain open for an extended period, resulting in greater sodium influx into the muscle cell and prolonged depolarization of the motor unit.³
• Prolonged depolarization of muscle tissue causes episodes of muscle stiffness and, eventually, desensitization of the sodium channel to acetylcholine.³
  • This progressive desensitization of the channel to acetylcholine results in episodes of paralysis characteristic of periodic paralysis.
• During episodes of weakness or paralysis, muscle cells release potassium ions into the extracellular space, causing hyperkalemia.

Clinical Presentation

• The onset of symptoms typically occurs within the first decade of life and presents with episodes of muscle weakness.³
• Attacks are more common in childhood and early adulthood; however, as the patient ages, these attacks typically give way to baseline generalized weakness.³
• Acute attacks typically manifest as generalized weakness; however, some patients present with focal weakness limited to a single limb. Respiratory function is usually preserved during episodic attacks.³
• HYPP can be precipitated by anesthesia, cold exposure, exercise, fasting, or ingestion of potassium-rich foods.³
• During acute HYPP attacks, patients may present with elevated serum potassium levels on laboratory studies and can exhibit electrocardiogram (ECG) changes associated with hyperkalemia³ (Figure 1).

Management and Prevention

Acute Attacks

• Direct intervention/treatment is typically not indicated, as HYPP attacks are generally mild and short in duration.³
• For patients with elevated potassium levels and moderate-severe weakness/paralysis, one source recommends inhaled beta agonists such as albuterol for acute management.³

Prevention

• Nonpharmacologic: A low-potassium, high-carbohydrate diet is recommended, with avoidance of high-intensity exercise.3
• Pharmacologic: Carbonic anhydrase inhibitors or thiazide diuretics have shown some efficacy in the prevention of acute HYPP attacks.³

Anesthetic Considerations

• It is important to note that patients with HYPP can experience prolonged paralysis following neuromuscular blockade for surgery.³
• Succinylcholine is contraindicated in HYPP patients to prevent extended post-operative myotonia and exacerbation of hyperkalemia.⁴
  • Use of short-acting nondepolarizing paralytics and avoidance of acetylcholinesterase inhibitors is preferred in HYPP patients undergoing general anesthesia for surgery.⁴
• There have been no reported adverse reactions in patients with HYPP to anesthetic gases, thiopental, propofol, or midazolam.⁴
• Monitor and maintain patient temperatures and serum potassium levels during and following the anesthetic case.⁴
• Continuous ECG monitoring during the anesthetic case for hyperkalemia-induced rhythm disturbances.⁴
• The estimated risk of malignant hyperthermia in HYPP patients during anesthetic cases is low.⁵