Malignant hyperthermia
Overview
Malignant hyperthermia (MH) - a rare but potentially fatal pharmacogenetic disorder of skeletal muscle calcium regulation triggered by volatile anaesthetics or suxamethonium. One of the few true anaesthetic emergencies.
Pathophysiology
•Mutation in RYR1 gene (chromosome 19q13.2) - autosomal dominant, ~70% of cases; less commonly CACNA1S
•Mutant ryanodine receptor (RYR1) → uncontrolled Ca²⁺ release from sarcoplasmic reticulum → sustained muscle contraction → massive ATP consumption → CO₂, lactate, hyperthermia, rhabdomyolysis
•Dantrolene works by blocking the mutant RYR1, closing the calcium leak at its source
Risk factors
•Family history of MH - first-degree relatives carry ~50% risk (autosomal dominant)
•Associated myopathies - central core disease, multiminicore disease, King-Denborough syndrome
•Male sex - higher clinical incidence
Presentation
•Masseter spasm - often the earliest sign, especially after suxamethonium; sustained jaw rigidity after induction
•Tachycardia - early feature; catecholamine-driven
•Rising end-tidal CO₂ - early and sensitive; often the first monitored parameter to become abnormal
•Generalised rigidity - limbs, trunk, chest wall; may impede ventilation
•Hyperthermia - core temperature >40°C; can rise >1°C every 5 minutes; a LATE sign
•Arrhythmias - ventricular ectopics/VT driven by hyperkalaemia and acidosis
•Dark urine - myoglobinuria; late sign indicating significant rhabdomyolysis
Investigations
•ABG - combined metabolic (raised lactate, low HCO₃⁻) and respiratory acidosis (raised pCO₂); most immediately actionable
•CK - markedly elevated (often >10,000 IU/L); serial measurement guides recovery
•Electrolytes - hyperkalaemia (life-threatening, drives arrhythmias); monitor for AKI
•Urinalysis - dark urine = myoglobinuria; guides need for forced diuresis
•Clotting screen - DIC is a recognised complication
•ECG - sinus tachycardia, ventricular ectopics, or VT
•Gold standard (post-acute): in vitro contracture test (IVCT) / caffeine-halothane contracture test (CHCT) on fresh muscle biopsy (vastus lateralis) at a specialist MH unit - used for susceptibility testing after the episode, not during
Management
Step 1 · Eliminate trigger
- 1Stop all volatile anaesthetics immediately
- 2Discontinue suxamethonium
- 3Switch to total intravenous anaesthesia (TIVA) with propofol
- 4Halt surgery if possible; call for help
Step 2 · Antidote
- 1Dantrolene 2.5 mg/kg IV bolus - repeat every 5 minutes until EtCO₂ and HR improve
- 2Dantrolene must be immediately available wherever general anaesthesia is administered
- 3Continue dantrolene infusion for 24-48 hours post-episode (recrudescence occurs in ~25%)
Step 3 · Active cooling
- 1Ice packs to groins and axillae
- 2Cold IV saline
- 3Target core temperature reduction
Step 4 · Supportive care
- 1Treat hyperkalaemia and arrhythmias
- 2Forced diuresis if myoglobinuria present (protect renal tubules)
- 3Correct metabolic acidosis
- 4ICU transfer for ongoing monitoring
Follow-up
•Refer to specialist MH centre for genetic testing (RYR1/CACNA1S sequencing) ± IVCT if inconclusive
•Screen all first-degree relatives - ~50% risk given autosomal dominant inheritance
•Issue MH alert bracelet and anaesthetic alert card; record prominently in notes
•Future GA is safe with TIVA (propofol + non-depolarising NMBs e.g. rocuronium); anaesthetic machine must be flushed of volatile agents
•Regional anaesthesia is entirely safe and preferred where possible
Prognosis
•Fatal if untreated; with prompt dantrolene and cooling, mortality approaches zero
•Recrudescence in ~25% - reason for continuing dantrolene for 24-48 hours
•Poor prognostic indicators: core temperature >42°C, severe metabolic acidosis, DIC, hyperkalaemia with arrhythmia
Triggers
•Volatile anaesthetics - halothane, sevoflurane, desflurane, isoflurane
•Depolarising neuromuscular blocker - suxamethonium