Define Malignant Hyperthermia. Describe its clinical features, management and pathophysiology.

Definition & Trigger

Malignant hyperthermia (MH) is a rare, inherited (autosomal dominant) life-threatening hypermetabolic crisis of skeletal muscle, triggered by exposure to potent volatile anaesthetic agents and/or suxamethonium. A defect (commonly in the ryanodine receptor) leads to uncontrolled release of calcium in muscle, causing sustained contraction and a massive rise in metabolism.

Clinical Features

The earliest and most sensitive sign is an unexplained rise in end-tidal CO₂ (from increased production), with tachycardia, and often masseter/generalised muscle rigidity. Later: a rapidly rising temperature (a late sign), metabolic and respiratory acidosis, hyperkalaemia, arrhythmias, and rhabdomyolysis (myoglobinuria, high creatine kinase) leading to renal failure. It is fatal if untreated.

Management

Management is urgent: stop the trigger (discontinue volatile/suxamethonium), call for help and hyperventilate with 100% oxygen; give dantrolene (the specific treatment — it reduces calcium release) in repeated doses; and provide active cooling and supportive treatment of hyperkalaemia, acidosis, arrhythmias and myoglobinuria (fluids to protect the kidneys). Continue monitoring in intensive care.

Susceptible Patients

Patients with a personal or family history of MH (or of an unexplained anaesthetic death) must have a trigger-free anaesthetic — total intravenous anaesthesia with a vapour-free machine, avoiding all volatiles and suxamethonium — with dantrolene available. Susceptibility is confirmed by specialist muscle (in-vitro contracture) testing.

Pathophysiology in Detail

The crisis of malignant hyperthermia arises from an inherited abnormality — most often of the ryanodine receptor that controls calcium release from the sarcoplasmic reticulum of skeletal muscle. When a susceptible patient is exposed to a triggering agent, this channel releases calcium in an uncontrolled way, so the muscle cannot relax and enters a state of sustained contraction; the enormous, futile consumption of oxygen and ATP that follows generates heat and carbon dioxide, depletes energy stores and, as membranes fail, releases potassium and myoglobin into the circulation. This single underlying defect therefore explains the whole clinical picture — the rising carbon dioxide and temperature, the rigidity, the acidosis and hyperkalaemia, and the rhabdomyolysis that threatens the kidneys — and it explains why dantrolene, which reduces this calcium release, is the specific antidote.

Distinguishing MH from Mimics

Not every rise in temperature or carbon dioxide under anaesthesia is malignant hyperthermia, and part of the skill is distinguishing it from conditions that mimic it: inadequate ventilation or exhausted soda lime raise carbon dioxide without hypermetabolism, sepsis and a warm environment raise temperature, thyroid storm and certain drug reactions produce hypermetabolic pictures, and light anaesthesia produces tachycardia and hypertension. What points to malignant hyperthermia is the combination — an unexplained, progressive rise in end-tidal carbon dioxide that outstrips ventilation, with tachycardia, rigidity and a later temperature rise, in the context of a triggering agent — and because the condition is rapidly fatal if missed, it is treated on suspicion while these alternatives are considered.

Rising EtCO₂ with masseter spasm is the earliest sign.

• MH: inherited (ryanodine receptor) hypermetabolic muscle crisis; triggers = volatile agents & suxamethonium.
• Earliest sign: unexplained rising ETCO₂ + tachycardia; rigidity; late → hyperthermia, acidosis, hyperkalaemia, rhabdomyolysis.
• Treat: stop trigger, 100% O₂/hyperventilate, dantrolene, active cooling, correct K⁺/acidosis, protect kidneys.
• Susceptible patients: trigger-free TIVA, vapour-free machine, dantrolene available.
• Nitrous oxide & IV agents do not trigger MH.