What causes risks of hyperkalemia and hyperthermia with succinylcholine (a depolarizing neuromuscular blocking agent)?

From the Guidelines

Succinylcholine poses significant risks of hyperkalemia and hyperthermia, particularly in patients with certain underlying conditions, and its use should be avoided in these high-risk patients, opting instead for non-depolarizing neuromuscular blocking agents like rocuronium, as supported by the most recent guidelines and studies, including those published in 2023 1. The mechanism behind these risks involves the initial depolarization of muscle membranes by succinylcholine, leading to a shift of potassium from the intracellular to the extracellular space. While this shift is minimal in healthy individuals, it can be dangerously exaggerated in patients with conditions such as burns, crush injuries, neuromuscular diseases, or denervation injuries, due to the upregulation of acetylcholine receptors throughout the muscle membrane 1. Key factors that increase the risk of hyperkalemia and hyperthermia with succinylcholine include:

• Previous history of malignant hyperthermia
• Severe burns or crush injuries
• Spinal cord injury
• Neuromuscular disease
• Myopathy
• Prolonged immobility
• Denervation injuries
• Genetic susceptibility to malignant hyperthermia, often associated with mutations in the ryanodine receptor. Given the potential for severe and life-threatening complications, it is crucial for clinicians to carefully assess patient risk factors before administering succinylcholine. The most recent and highest quality study, published in 2023 1, highlights the importance of considering alternative neuromuscular blocking agents, such as rocuronium, especially in patients with traumatic brain injury, where the use of succinylcholine may be associated with an increased risk of mortality. In clinical practice, the decision to use succinylcholine should be made with caution, taking into account the patient's medical history, current condition, and the potential risks and benefits of its use. Whenever possible, non-depolarizing neuromuscular blocking agents should be considered as a safer alternative to minimize the risks of hyperkalemia and hyperthermia.

From the FDA Drug Label

Succinylcholine should be administered with GREAT CAUTION to patients suffering from electrolyte abnormalities and those who may have massive digitalis toxicity, because in these circumstances succinylcholine may induce serious cardiac arrhythmias or cardiac arrest due to hyperkalemia GREAT CAUTION should be observed if succinylcholine is administered to patients during the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury The risk of hyperkalemia in these patients increases over time and usually peaks at 7 to 10 days after the injury Succinylcholine administration has been associated with acute onset of malignant hyperthermia, a potentially fatal hypermetabolic state of skeletal muscle. The risk of developing malignant hyperthermia following succinylcholine administration increases with the concomitant administration of volatile anesthetics

The risks of hyperkalemia and hyperthermia with succinylcholine are caused by:

• Administration of succinylcholine to patients with electrolyte abnormalities or massive digitalis toxicity
• Administration of succinylcholine to patients during the acute phase of injury following major burns, multiple trauma, extensive denervation of skeletal muscle, or upper motor neuron injury
• Concomitant administration of volatile anesthetics with succinylcholine, which increases the risk of developing malignant hyperthermia 2, 2, 2

From the Research

Risks of Hyperkalemia with Succinylcholine

• The use of succinylcholine, a depolarizing neuromuscular blocking agent, can lead to hyperkalemia, a condition characterized by elevated potassium levels in the blood 3, 4, 5.
• This risk is particularly high in patients with certain conditions, such as spinal cord injuries, neuromuscular diseases, infections, and trauma 3, 5.
• The mechanism by which succinylcholine leads to hyperkalemia is thought to involve the release of potassium from denervated muscle cells 3.
• Hyperkalemia can be life-threatening, leading to cardiac arrest and other complications 3, 5.

Risks of Hyperthermia with Succinylcholine

• Succinylcholine can also lead to malignant hyperthermia, a rare but potentially fatal condition characterized by a rapid rise in body temperature 6.
• This risk is thought to be associated with the use of succinylcholine in combination with volatile anesthetics, such as sevoflurane 6.
• Malignant hyperthermia can occur rapidly after the administration of succinylcholine, and early recognition and treatment are critical to preventing serious complications 6.

Prevention and Treatment of Hyperkalemia and Hyperthermia

• To minimize the risks of hyperkalemia and hyperthermia, it is essential to carefully select patients for succinylcholine use and to monitor them closely during and after administration 3, 4, 5.
• Alternative neuromuscular blocking agents, such as rocuronium, may be considered in patients at high risk of hyperkalemia or hyperthermia 4.
• Research is ongoing to develop new treatments for the side effects of succinylcholine, including the use of supramolecular therapeutics to reverse hyperkalemia and other complications 7.