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

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