Malignant hyperthermia (MH) is a rare, life-threatening reaction to certain anesthetic agents, pa

Malignant hyperthermia (MH) is a rare but potentially fatal pharmacogenetic disorder that occurs in susceptible individuals when exposed to certain anesthetic agents. It is characterized by a hypermetabolic crisis involving the skeletal muscles, triggered primarily by volatile inhalation anesthetics such as sevoflurane, desflurane, isoflurane, and the depolarizing muscle relaxant succinylcholine. Though infrequent, the condition demands immediate recognition and intervention to prevent severe complications or death. Malignant hyperthermia remains a critical concern in the practice of anesthesia due to its rapid onset and life-threatening consequences.

The underlying pathophysiology of MH involves an abnormal release of calcium from the sarcoplasmic reticulum within skeletal muscle cells. This is usually due to mutations in the RYR1 gene, which encodes the ryanodine receptor, a calcium channel involved in excitation-contraction coupling. Mutations lead to dysregulated calcium homeostasis, resulting in sustained muscle contraction, increased muscle metabolism, and excessive heat production. The condition may remain latent in affected individuals until they are exposed to triggering anesthetic agents, at which point the metabolic cascade is rapidly initiated.

Clinically, MH typically presents intraoperatively or shortly after anesthesia induction. Early signs include unexplained tachycardia, elevated end-tidal carbon dioxide (EtCO₂) despite adequate ventilation, and muscle rigidity, particularly masseter muscle rigidity following succinylcholine administration. As the condition progresses, hyperthermia becomes evident, often rising rapidly to above 40°C (104°F). Other manifestations may include metabolic acidosis, hyperkalemia, myoglobinuria, and arrhythmias. If not promptly treated, MH can lead to disseminated intravascular coagulation (DIC), renal failure, cardiac arrest, and death.

Diagnosis of MH is clinical and must be based on a high index of suspicion, especially in situations where sudden hemodynamic and metabolic deterioration occur without an obvious cause during anesthesia. Capnography, temperature monitoring, arterial blood gas analysis, and serum electrolytes play a key role in identifying the condition. The definitive diagnostic test for MH susceptibility is the caffeine-halothane contracture test (CHCT), which is performed on a muscle biopsy specimen. Genetic testing can also help identify mutations in the RYR1 or CACNA1S genes, though not all mutations are currently detectable.

Immediate management of malignant hyperthermia is a medical emergency. The first step is to discontinue all triggering agents and switch to safe anesthetic alternatives. Hyperventilation with 100% oxygen is initiated to correct hypercapnia and metabolic acidosis. The cornerstone of treatment is the administration of dantrolene sodium, a muscle relaxant that inhibits calcium release from the sarcoplasmic reticulum. The initial dose is 2.5 mg/kg intravenously, repeated as necessary until symptoms subside, up to a maximum of 10 mg/kg. Dantrolene should be readily available in all operating rooms and surgical centers where general anesthesia is administered.

https://directmbbsadmission.in/md-anesthesia/Supportive care is equally important and may involve active cooling methods such as ice packs, cooling blankets, and cold intravenous fluids to manage hyperthermia. Correction of metabolic acidosis with bicarbonate, management of hyperkalemia with glucose and insulin, and monitoring for complications such as rhabdomyolysis and acute renal failure are critical. Continuous monitoring in an intensive care setting is often required for at least 24 to 48 hours, as recrudescence of symptoms can occur.

Preventive strategies focus on identifying susceptible individuals preoperatively. A detailed family and personal history of anesthesia-related complications, unexplained deaths during surgery, or musculoskeletal disorders may warrant further investigation. In known susceptible patients, triggering agents should be strictly avoided, and non-triggering anesthetic techniques, such as total intravenous anesthesia (TIVA) with propofol, should be employed. Anesthetic machines must be prepared in advance by removing volatile agents and replacing the breathing circuit and CO₂ absorbent.

The incidence of MH varies geographically but is estimated to range from 1 in 10,000 to 1 in 250,000 anesthetics, depending on the population and prevalence of genetic mutations. Children and young adults appear to be at higher risk, with males more commonly affected than females. Despite its rarity, MH continues to be a significant cause of anesthesia-related morbidity and mortality when not promptly treated.

Advances in anesthesia monitoring, increased awareness among clinicians, and the availability of dantrolene have significantly reduced the mortality rate associated with malignant hyperthermia from over 80% in the past to less than 5% today. Organizations such as the Malignant Hyperthermia Association of the United States (MHAUS) play a vital role in education, research, and support for healthcare providers and families dealing with MH.