Malignant Hyperthermia and Hyperthermia Syndromes
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Direct answer
Malignant hyperthermia is a pharmacogenetic crisis of skeletal muscle, most often caused by RYR1 mutations and triggered by volatile anaesthetics or succinylcholine. It produces hypermetabolism, with a rising end-tidal carbon dioxide, tachycardia, masseter spasm and hyperthermia. Stopping the trigger, giving 100 percent oxygen with hyperventilation and administering intravenous dantrolene form the core of treatment.
What you must remember
- Genetics: autosomal dominant inheritance, most often from RYR1 mutations, with CACNA1S mutations in a minority of families.
- Triggers: volatile anaesthetics such as halothane, sevoflurane, desflurane and isoflurane, and succinylcholine; nitrous oxide and intravenous agents are not triggers.
- Earliest sign: a rising end-tidal carbon dioxide from hypermetabolism, often before the temperature climbs.
- Clinical signs: masseter spasm after succinylcholine, tachycardia, mixed acidosis, hyperkalaemia, rhabdomyolysis and, late, disseminated intravascular coagulation.
- Dantrolene: blocks calcium release from the ryanodine receptor; the standard initial intravenous dose is 2.5 mg/kg, repeated until the signs settle.
- Avoid: calcium channel blockers such as verapamil, which can cause hyperkalaemia and cardiovascular collapse in this setting.
- Diagnosis: the caffeine-halothane contracture test and genetic testing for RYR1 variants, with family screening.
- Associations: central core disease and King-Denborough syndrome are linked to RYR1 mutations.
A stepwise approach to an intraoperative crisis
The crisis can progress within minutes, so stopping the trigger and calling for help come before any diagnosis is confirmed.
- Stop the triggers: stop the volatile agent and succinylcholine, and switch to a non-triggering technique such as total intravenous anaesthesia.
- Call for help: alert the theatre team and bring dantrolene to the table at once, since delay costs lives.
- Hyperventilate with oxygen: give 100 percent oxygen at high fresh gas flow to wash out carbon dioxide and restore ventilation.
- Give dantrolene: administer 2.5 mg/kg intravenously and repeat the dose until the hypermetabolism settles.
- Cool and correct: cool the patient with ice packs and cold fluids, and treat hyperkalaemia and acidosis guided by blood gases.
- Monitor and escalate: check urine output, creatine kinase and coagulation, and move the patient to intensive care.
Recrudescence can occur hours after the crisis has apparently resolved, so the patient needs continued monitoring with dantrolene kept available. Ice-cold saline and cooling are supportive measures, not substitutes for the antidote.
Where the exam tries to catch you
Most lost marks come from confusing the crisis with a simple fever or from using the wrong drug.
- Trap: treating the rising temperature with antipyretics as in ordinary fever Correct: dantrolene is the specific antidote, and paracetamol does not reverse the hypermetabolism.
- Trap: using a calcium channel blocker to treat the tachycardia Correct: verapamil can cause hyperkalaemia and collapse in malignant hyperthermia, so it is avoided.
- Trap: waiting for a high temperature before suspecting the crisis Correct: the earliest signs are rising end-tidal carbon dioxide, tachycardia and masseter spasm, so act on those.
- Trap: labelling every intraoperative fever as malignant hyperthermia Correct: sepsis, transfusion reactions and heat stroke also cause fever, and the rising carbon dioxide and trigger history decide the diagnosis.
Frequently asked questions
Which anaesthetic agents trigger malignant hyperthermia?
Volatile anaesthetics such as halothane, sevoflurane, desflurane and isoflurane trigger malignant hyperthermia, and so does succinylcholine. Nitrous oxide and intravenous agents are not triggers, so total intravenous anaesthesia is used in susceptible patients.
What is the earliest clinical sign of malignant hyperthermia?
The earliest clinical sign of malignant hyperthermia is a rising end-tidal carbon dioxide, which reflects hypermetabolism and often appears before the temperature rises. Tachycardia, masseter spasm and a mixed acidosis usually follow.
How does dantrolene work in malignant hyperthermia?
Dantrolene works in malignant hyperthermia by blocking calcium release from the ryanodine receptor in skeletal muscle, which halts the hypermetabolic cycle. It is given intravenously in repeated doses until the signs settle, and it should be kept available wherever triggering anaesthetics are used.
Why should verapamil be avoided in malignant hyperthermia?
Verapamil should be avoided in malignant hyperthermia because it can cause hyperkalaemia and cardiovascular collapse in a patient whose potassium is already rising. Dantrolene is the drug of choice, and calcium channel blockers are not part of the standard treatment.
Which conditions must be separated from hyperthermia syndromes like malignant hyperthermia?
Heat stroke, neuroleptic malignant syndrome, serotonin syndrome, thyroid storm and sepsis all cause hyperthermia and must be considered in the differential. The clinical context, medication history and end-tidal carbon dioxide help separate them from malignant hyperthermia.