Key Facts

Malignant hyperthermia is a rare but life-threatening anaesthetic emergency. It results from uncontrolled intracellular calcium release in skeletal muscle, leading to hypermetabolism, rhabdomyolysis, and multi-organ failure if not treated promptly.

Epidemiology

Incidence is approximately 1 in 10,000-15,000 paediatric anaesthetics and 1 in 50,000-100,000 adult anaesthetics. MH susceptibility follows an autosomal dominant pattern with variable penetrance. Approximately 1 in 3,000-5,000 individuals carry a susceptibility gene.

Aetiology

Genetic basis:

• RYR1 gene mutations (chromosome 19q13.1) — most common (~70%)
• CACNA1S gene mutations (L-type calcium channel) — less common
• Autosomal dominant with incomplete penetrance — a patient may have had previous uneventful anaesthetics before triggering an episode

Triggering agents:

• All volatile anaesthetic agents (halothane, sevoflurane, desflurane, isoflurane)
• Suxamethonium
• NOT triggered by: Propofol, ketamine, midazolam, non-depolarising NMBAs, local anaesthetics, N2O, opioids

Pathophysiology

Mutant ryanodine receptors on the sarcoplasmic reticulum have increased sensitivity to triggers. Exposure causes massive, sustained calcium release into the myoplasm, resulting in sustained muscle contraction → hypermetabolism → increased O2 consumption, CO2 production, heat generation → metabolic acidosis, hyperkalaemia, rhabdomyolysis → if untreated: DIC, renal failure, cardiac arrest.

Early Signs

• Rising ETCO2 (earliest sign — often before other manifestations)
• Tachycardia (unexplained)
• Masseter spasm after suxamethonium (may be isolated or herald full MH)

Established MH

• Hyperthermia (temperature rise 1-2°C every 5 min — may exceed 43°C)
• Generalised muscle rigidity
• Tachycardia, arrhythmias (VT, VF)
• Metabolic acidosis (mixed respiratory and metabolic)
• Hyperkalaemia
• Myoglobinuria (dark/cola-coloured urine)
• DIC (late)

Late Complications

• Rhabdomyolysis → acute renal failure
• DIC → haemorrhage
• Multi-organ failure
• Cerebral oedema

Red Flags

• Unexplained rising ETCO2 during anaesthesia — always consider MH
• Masseter spasm after suxamethonium — may proceed to full MH in ~15-30% (abandon volatile, continue TIVA, observe)
• Core temperature rising rapidly (>2°C/hr) — strongly suspicious
• Family history of anaesthetic death — must investigate for MH susceptibility

Bedside

• ETCO2 monitoring: Rising trend is the earliest sign
• Core temperature: Oesophageal, bladder, or rectal probe — rising rapidly
• ECG: Tachycardia, arrhythmias, hyperkalaemic changes

Bloods

• ABG: Mixed metabolic and respiratory acidosis, hyperkalaemia, raised lactate
• CK (creatine kinase): Massively elevated — may exceed >10,000 U/L; peaks at 12-24 hours
• Potassium: Dangerously elevated — treat urgently
• Myoglobin (serum and urine): Elevated — myoglobinuria causes renal damage
• Coagulation: DIC screen (PT, APTT, fibrinogen, D-dimer)
• Renal function: Rising creatinine from rhabdomyolysis

Imaging

• Not acutely required

Special Tests

• In vitro contracture test (IVCT): Gold standard — performed on fresh muscle biopsy (vastus lateralis) at specialist centres; tests muscle response to halothane and caffeine
• Genetic testing: RYR1 and CACNA1S mutations — can confirm susceptibility but cannot exclude it (some mutations unknown)
• Family screening: All first-degree relatives of confirmed MH patients should be tested

Non-pharmacological

• Stop all trigger agents immediately: Turn off vaporiser, disconnect from anaesthesia machine
• Call for help: Declare MH emergency, assign roles
• Hyperventilate with 100% O2: High fresh gas flow (>10 L/min) to wash out volatile
• Active cooling: IV cold saline (40mL/kg), ice packs to groins/axillae, cold gastric/bladder lavage; target temp <38.5°C then stop cooling (avoid overshoot)
• Change to TIVA: Propofol, opioids, non-depolarising NMBAs are all safe

Pharmacological

• Dantrolene sodium 2.5mg/kg IV: Given as rapidly as possible; repeat every 5-10 minutes until ETCO2 falling, temperature decreasing, and rigidity resolving (max 10mg/kg initially; may need more)
• Hyperkalaemia treatment: Calcium gluconate 10% 0.2mL/kg IV, insulin/dextrose, salbutamol nebuliser
• Treat arrhythmias: Amiodarone 5mg/kg IV (NOT calcium channel blockers — dangerous interaction with dantrolene)
• Sodium bicarbonate 8.4%: 1-2 mmol/kg if severe acidosis (pH <7.1)
• IV fluids: Aggressive crystalloid (target UO >2 mL/kg/hr to protect kidneys from myoglobin)
• Continue dantrolene: 1mg/kg IV 6-hourly for 24-48 hours post-event

Surgical/Interventional

• Not applicable acutely; muscle biopsy for IVCT is a later elective procedure

Referral Criteria

• All suspected MH episodes — report to MH Investigation Unit (Leeds)
• All first-degree relatives — screening referral
• Issuing of MH alert card/bracelet
• Register with UK MH hotline for advice

• Mortality: Reduced from >70% (historical) to <5% with early recognition and dantrolene
• Key prognostic factor: Time to dantrolene administration — survival correlates inversely with delay
• Recrudescence: MH can recur in 25% within 24-36 hours — continued monitoring and dantrolene maintenance essential
• Long-term: MH susceptibility is lifelong; all future anaesthetics must use trigger-free techniques (TIVA)
• Undiagnosed MH susceptibility: Estimated prevalence ~1 in 3,000-5,000 individuals

MH Emergency Treatment Algorithm

Triggering vs Non-Triggering Agents