Malignant Hyperthermia (MH) is a severe, inherited disorder of the skeletal muscle. It manifests as a life-threatening, hypermetabolic reaction triggered by certain anesthetic medications. This pharmacogenetic syndrome involves a genetic predisposition interacting with specific drugs, causing the body’s metabolic processes to spiral out of control. Timely recognition and intervention are necessary to prevent severe complications or death.
What Triggers Malignant Hyperthermia
Susceptibility to MH is an inherited trait, often linked to a mutation in the RYR1 gene, which codes for the ryanodine receptor in skeletal muscle cells. This receptor acts as a calcium release channel within the muscle’s sarcoplasmic reticulum. A defect causes this receptor to become hypersensitive, leading to the crisis when exposed to triggering agents. These agents include volatile anesthetic gases (sevoflurane, isoflurane, or desflurane) or the muscle relaxant succinylcholine. Exposure causes the defective ryanodine receptor to open uncontrollably, flooding the muscle cell with calcium ions. This sustained influx leads to prolonged, excessive muscle contraction and a rapid increase in cellular metabolism. This hypermetabolism consumes oxygen and energy stores rapidly, generating heat and metabolic waste products.
The Initial Indicators of an MH Crisis
The first signs of an MH crisis usually emerge immediately after exposure to the trigger agent, often while the patient is under general anesthesia. The earliest and most consistent sign is an unexplained and rapid rise in end-tidal carbon dioxide (EtCO2), registered by monitoring equipment. This excessive carbon dioxide production, or hypercarbia, results directly from the muscle cells’ uncontrolled hypermetabolism. Hypercarbia is often accompanied by a rapid heart rate, known as tachycardia, as the body attempts to compensate for the sudden metabolic demands. Another initial indicator is muscle rigidity, which can be localized or generalized. If succinylcholine was administered, a spasm of the jaw muscles, called masseter muscle rigidity, may be observed first. Recognition of this triad—hypercarbia, tachycardia, and muscle rigidity—is the basis for early diagnosis and treatment.
Identifying the Late and Severe Signs
Signs appearing later indicate that the hypermetabolic state has overwhelmed systemic regulatory mechanisms, leading to organ damage. The most dramatic late sign is extreme, rapid hyperthermia, a dangerously high body temperature. Paradoxically, a significant temperature elevation is often one of the final signs to appear, typically following the initial metabolic and muscular changes. Core body temperature can rise extremely rapidly, sometimes exceeding 105°F (40.5°C).
Rhabdomyolysis and Acidosis
Uncontrolled muscle activity causes widespread destruction of muscle tissue, known as rhabdomyolysis. This muscle breakdown releases large quantities of cellular contents, including myoglobin, into the bloodstream. Myoglobin in the urine gives it a dark, cola-colored appearance, which is a late indicator of severe muscle damage and impending kidney injury. Simultaneously, the extreme metabolic activity produces overwhelming amounts of lactic acid, leading to severe metabolic acidosis and a sharp drop in blood pH.
Systemic Failure
If the crisis remains unchecked, damage to blood vessel linings and the release of clotting factors can lead to Disseminated Intravascular Coagulation (DIC). DIC is a systemic disorder characterized by simultaneous, widespread clotting and bleeding. These late-stage manifestations—hyperthermia, rhabdomyolysis, severe acidosis, and DIC—represent the systemic collapse of organ function.
Emergency Management and Long-Term Outlook
The immediate and most important step in managing a suspected MH crisis involves stopping the administration of all triggering anesthetic agents and calling for specialized assistance. The definitive treatment for Malignant Hyperthermia is the immediate intravenous administration of Dantrolene sodium. Dantrolene is a direct-acting skeletal muscle relaxant that interferes with the calcium release channel of the ryanodine receptor. By blocking the uncontrolled calcium efflux, Dantrolene reverses the underlying physiological process of hypermetabolism and halts excessive muscle activity.
Supportive Care
Supportive care measures must be initiated simultaneously to manage the effects of the metabolic storm. This includes active cooling of the patient to bring the high core temperature down, and hyperventilating with 100% oxygen to help eliminate excess carbon dioxide. Sodium bicarbonate may be administered to treat severe metabolic acidosis. Aggressive fluid management is necessary to maintain adequate urine output and protect the kidneys from myoglobin-induced damage. Following a crisis, patients require intensive care monitoring for at least 24 hours to watch for recurrence, and genetic testing is advised to confirm MH susceptibility for future anesthetic planning.