Malignant hyperthermia
Background
- Life-threatening hypermetabolic reaction to volatile anesthetic agents or succinylcholine
- Caused by uncontrolled skeletal muscle calcium release via ryanodine receptor (RyR1) mutations
- Autosomal dominant inheritance with variable penetrance[1]
- Incidence: ~1:5,000 to 1:50,000 anesthetics
- Mortality: <5% with early recognition and dantrolene; historically >70% without treatment
- Can also be triggered by extreme heat and exertion in susceptible individuals (exertional heat stroke variant)
Triggering Agents
- Volatile inhalational anesthetics: sevoflurane, desflurane, isoflurane, halothane
- Succinylcholine
- Safe agents: propofol, etomidate, ketamine, nitrous oxide, all non-depolarizing paralytics, opioids, benzodiazepines, local anesthetics
Clinical Features
- Often occurs intraoperatively but can present in the PACU or ED
- Earliest sign: unexplained rise in end-tidal CO2 and tachycardia
- Masseter muscle rigidity (particularly after succinylcholine) — early warning sign
- Generalized skeletal muscle rigidity
- Rapidly rising temperature (may exceed 40°C; >1°C rise every 5 min)
- Tachycardia, dysrhythmias, unstable blood pressure
- Dark urine (myoglobinuria)
- Metabolic and respiratory acidosis
- Hyperkalemia, elevated CK, myoglobinuria
- Late: DIC, renal failure, cardiac arrest
Differential Diagnosis
- Neuroleptic malignant syndrome (NMS) — antipsychotics, slower onset (days)
- Serotonin syndrome — serotonergic drugs, clonus prominent
- Heat stroke — environmental exposure
- Thyroid storm
- Pheochromocytoma crisis
- Sepsis
- Drug-induced hyperthermia (cocaine, amphetamines, MDMA)
Evaluation
- Elevated and rapidly rising end-tidal CO2
- ABG: combined respiratory and metabolic acidosis
- BMP: hyperkalemia, hypercalcemia
- CK: markedly elevated (often >10,000 U/L)
- Coagulation studies: may show DIC
- Urinalysis: myoglobinuria
- Core temperature monitoring
- Definitive diagnosis: caffeine-halothane contracture test (done later, not acutely)
Management
Immediate
- STOP all triggering agents immediately
- Call for Malignant Hyperthermia Hotline: 1-800-644-9737 (MHAUS)
- Hyperventilate with 100% O2 at high fresh gas flows
- Change anesthesia circuit and CO2 absorber if possible
Dantrolene
- Dantrolene 2.5 mg/kg IV bolus, repeat every 5-10 minutes until symptoms resolve[2]
- Maximum total dose: up to 10 mg/kg (no absolute ceiling if still symptomatic)
- Reconstitute with sterile water (each 20 mg vial in 60 mL) — time-consuming; assign dedicated team
- Newer formulation (Ryanodex): 2.5 mg/kg in single vial, faster to prepare
- Continue dantrolene 1 mg/kg IV q4-6h for 24-48 hours to prevent recrudescence
Cooling
- Aggressive active cooling: ice packs to axillae/groin, cooling blankets, cold IV saline
- Target temperature <38.5°C
- Avoid overcooling
Supportive
- Treat Hyperkalemia: calcium gluconate, insulin + glucose, sodium bicarbonate
- IV fluids to maintain urine output >2 mL/kg/hr (prevent myoglobin-induced AKI)
- Treat dysrhythmias (avoid calcium channel blockers with dantrolene — risk of hyperkalemia)
- Monitor for DIC, rhabdomyolysis, Compartment syndrome
Disposition
- ICU admission for all MH episodes
- Monitor for recrudescence (recurrence in 25% within 24 hours)
- Genetic counseling and testing for patient and family