Which are the causes of Malignant hyperthermia?

Malignant hyperthermia (MH) is a rare but potentially life-threatening condition that can occur during or after the administration of certain medications used for general anesthesia. It is characterized by a rapid rise in body temperature, muscle rigidity, and a fast heart rate. MH is primarily caused by a genetic mutation that affects the regulation of calcium in muscle cells. When triggered, this mutation leads to a cascade of events that result in the release of excessive calcium from the muscle cells, leading to muscle hyperactivity and the production of heat.

Genetic Predisposition: The most significant cause of MH is an inherited genetic mutation. The majority of MH cases are caused by mutations in the RYR1 gene, which encodes a protein called the ryanodine receptor. This receptor plays a crucial role in regulating calcium release from the sarcoplasmic reticulum, a structure within muscle cells. Mutations in the RYR1 gene disrupt the normal function of the ryanodine receptor, leading to uncontrolled calcium release and subsequent muscle hyperactivity.

Triggering Agents: While the genetic mutation is necessary for the development of MH, it is not sufficient on its own. MH is typically triggered by the administration of certain medications used during general anesthesia, particularly volatile anesthetics (such as halothane, isoflurane, and sevoflurane) and the depolarizing muscle relaxant succinylcholine. These triggering agents cause an abnormal release of calcium from the sarcoplasmic reticulum in individuals with the genetic predisposition, leading to the characteristic signs and symptoms of MH.

Other Factors: Although the genetic mutation and triggering agents are the primary causes of MH, there are several other factors that can contribute to its development:

• Familial History: Individuals with a family history of MH are at a higher risk of developing the condition. If a close relative has experienced MH or has been diagnosed with the genetic mutation, it is important to inform the healthcare team before undergoing anesthesia.


• Prolonged Surgery: MH is more likely to occur during lengthy surgical procedures, especially those involving the use of triggering agents. The longer the exposure to these medications, the higher the risk of developing MH.


• Heat and Exercise: Engaging in intense physical activity or being exposed to high temperatures before or during anesthesia can increase the risk of MH. Heat and exercise can further elevate body temperature, exacerbating the hyperthermic response associated with MH.


• Metabolic Disorders: Certain metabolic disorders, such as central core disease and multiminicore disease, are associated with an increased risk of MH. These conditions involve abnormalities in muscle structure and function, making individuals more susceptible to the effects of triggering agents.


• Previous MH Episode: Individuals who have previously experienced an episode of MH are at a significantly higher risk of recurrence. It is crucial for these individuals to inform their healthcare providers about their history to ensure appropriate precautions are taken.

Conclusion: Malignant hyperthermia is primarily caused by an inherited genetic mutation that affects the regulation of calcium in muscle cells. This mutation, combined with the administration of triggering agents during anesthesia, leads to the characteristic signs and symptoms of MH. Other factors such as familial history, prolonged surgery, heat and exercise, metabolic disorders, and previous MH episodes can further increase the risk of developing this potentially life-threatening condition. It is essential for healthcare providers to be aware of these causes and take appropriate precautions to prevent and manage MH in susceptible individuals.