Malignant hyperthermia !

An inherited muscle reaction to some anaesthetic gases and succinylcholine: muscles stiffen and overheat. It is fatal without fast treatment.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

A pharmacogenetic disorder of skeletal muscle in which exposure to volatile inhaled anaesthetics or succinylcholine causes uncontrolled calcium release inside muscle cells, leading to a life-threatening hypermetabolic crisis. Between exposures, susceptible people are usually well.

Who gets it

Crises are rare, reported in about 1 in tens of thousands of general anaesthetics, more often in children and young men, but the genetic susceptibility is more common. Every operating room where triggering agents are used, including in Colombia, needs a crisis protocol and access to the specific antidote.

Causes

Autosomal dominant mutations, most often in the ryanodine receptor gene (RYR1)
Less often in CACNA1S (dihydropyridine receptor) or STAC3
Triggers: volatile inhaled anaesthetics (such as sevoflurane, desflurane, isoflurane) and succinylcholine

Risk factors

Personal or family history of malignant hyperthermia or unexplained anaesthetic death
Central core disease and other RYR1-related myopathies
King-Denborough syndrome
Young age and male sex

Pathophysiology

The abnormal ryanodine receptor lets calcium leak uncontrolled from the sarcoplasmic reticulum when triggered. Sustained contraction and the energy spent pumping calcium back drive extreme oxygen use and CO2 and heat production. The result is hypercarbia, lactic acidosis, rigidity, muscle breakdown with hyperkalaemia and myoglobinuria, and, late, very high temperature.

Symptoms and signs

Unexplained rise in end-tidal CO2 despite increased ventilation (often the earliest sign)
Sinus tachycardia and arrhythmias
Masseter muscle rigidity after succinylcholine, or generalised rigidity
Tachypnoea in a spontaneously breathing patient
Rising temperature, often a late sign
Dark (cola-coloured) urine from myoglobin
Hot, sweaty or mottled skin

Diagnosis

Clinical: Recognised during or shortly after anaesthesia from the combination of rising end-tidal CO2, tachycardia, rigidity and later hyperthermia in a patient exposed to a triggering agent. Treatment starts on clinical suspicion, without waiting for tests.
Tests: Arterial blood gas (mixed respiratory and metabolic acidosis), potassium, creatine kinase, urine myoglobin, coagulation studies and kidney function. Susceptibility is confirmed later by the caffeine-halothane contracture test on a thigh muscle biopsy or by genetic testing.
Imaging: No imaging is needed for diagnosis.

Differential diagnosis

Inadequate anaesthesia or ventilation problems (hypercarbia)
Sepsis
Thyroid storm
Pheochromocytoma crisis
Neuroleptic malignant syndrome and serotonin syndrome
Iatrogenic overheating

Goal of treatment

Stop the trigger at once, reverse the muscle calcium release with the specific antidote, correct the metabolic and cardiac effects, and prevent kidney injury.

Treatment

Acute: Call for help, stop volatile agents and succinylcholine, hyperventilate with 100% oxygen at high gas flows, change to non-triggering intravenous anaesthesia and finish or abort surgery as soon as possible.
Medical: Dantrolene, a ryanodine receptor antagonist, is the specific treatment and is given intravenously as early as possible, repeated until signs resolve; hyperkalaemia, acidosis and arrhythmias are treated with standard measures (calcium channel blockers are avoided with dantrolene).
Conservative: Active cooling with cold intravenous fluids, ice packs and surface cooling until the temperature falls, and fluids to keep a good urine output.
Follow-up: Intensive care monitoring for at least 24 hours because of the risk of recurrence: temperature, end-tidal CO2, ECG, potassium, creatine kinase, urine output and colour, and coagulation.

Complications

Cardiac arrest from hyperkalaemia and arrhythmias
Rhabdomyolysis and acute kidney injury
Disseminated intravascular coagulation
Compartment syndrome
Recurrence within 24 hours
Brain injury and death

Prognosis

Mortality fell from very high levels to a few percent once dantrolene became available and monitoring of end-tidal CO2 became routine; delay in treatment greatly increases complications.

Prevention

Asking every surgical patient about personal and family history of anaesthetic problems
Trigger-free anaesthesia (regional or intravenous) in susceptible patients, with a flushed machine
Dantrolene immediately available wherever triggering agents are used
Genetic counselling and testing of relatives

Test yourself

Think of the answer, then tap the question to see it.

What is usually the earliest sign of malignant hyperthermia during anaesthesia?

An unexplained rise in end-tidal CO2, often with tachycardia.

Which gene is most often mutated in malignant hyperthermia?

RYR1, the gene for the skeletal muscle ryanodine receptor.

Which drugs trigger malignant hyperthermia?

Volatile inhaled anaesthetics and succinylcholine.

What is the specific treatment for a malignant hyperthermia crisis?

Dantrolene, after stopping the trigger, plus cooling and correction of hyperkalaemia and acidosis.

Which test confirms susceptibility after a suspected episode?

The caffeine-halothane contracture test on a muscle biopsy, or genetic testing.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Malignant hyperthermia: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2024); Malignant hyperthermia: a review (Orphanet Journal of Rare Diseases, 2015).

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