Malignant Hyperthermia

Definition: hypermetabolic crisis in susceptible patients exposed to trigger agents (halogenated volatiles or succinylcholine).

Mechanism: abnormal Ca²⁺ release from sarcoplasmic reticulum via mutant RYR1 receptor → sustained skeletal muscle contraction → ↑ ATP usage → ↑ O₂ consumption, ↑ CO₂, severe lactic acidosis, hyperthermia, rhabdomyolysis, hyperkalemia, arrhythmia.

Genetics: autosomal dominant with variable penetrance. 80% of cases involve RYR1 mutations; > 80 genetic defects identified.

Incidence: 1:15,000 pediatric, 1:40,000 adult. Highest in upper Midwest US (gene prevalence).

Up to 50% of MH episodes occur in patients with prior uneventful anesthetic exposure.

Risk factors: personal/family hx, pediatric age, myopathies (Central Core, King-Denborough), unexplained fevers/cramps, exercise-induced rhabdo, trismus on induction (precedes 15–30% of MH).

Triggers: - All halogenated volatiles (sevoflurane, isoflurane, desflurane, halothane, enflurane) — NOT N₂O - Succinylcholine

Sequence: 1. ↑ Cytoplasmic free Ca²⁺ - Masseter rigidity (trismus) — esp. after sux - Generalized rigidity (absolute MH association if present) 2. Hypermetabolism - ↑ EtCO₂ (most sensitive and specific early sign) - Sympathetic surge: ↑ HR, ↑ BP - ↑ O₂ consumption (↓ ScvO₂); compensatory tachypnea - ↑ heat production (LATE sign; temp can rise 1–2 °C every 5 min) - ↑ ATP utilization → metabolic acidosis 3. Cell damage & rhabdomyolysis - Leakage of K⁺, myoglobin, CK; dark urine 4. Systemic complications - Acute renal failure, hyperkalemia, arrhythmia, DIC, compartment syndrome, cerebral edema, death

1. STOP the trigger - Stop all volatile agents and succinylcholine - Disconnect the vaporizer; switch to high-flow O₂ 10 L/min via clean circuit (or charcoal filter — change CO₂ absorbent) - Switch to TIVA with propofol

2. Hyperventilate with 100% O₂; ↑ minute ventilation 2–3× to blow off CO₂

3. Get help — call MHAUS (1-800-MH-HYPER / 1-800-644-9737)

4. Dantrolene - 2.5 mg/kg IV bolus every 5 min until reaction abates (often up to 10 mg/kg) - Cumulative doses up to 30 mg/kg may be required - Ryanodex (new formulation): 250 mg vial reconstituted in 5 mL sterile water — fast prep, fewer vials - Old dantrolene: 20 mg vial + mannitol in 60 mL sterile water — slow to prepare, need many staff - Continue 1 mg/kg IV q6 h × 24–48 h after acute event

5. Cool the patient - Cold saline IV (avoid LR) - Ice packs to axillae, groin - Lavage open cavities, NG, bladder - Stop cooling at 38 °C to avoid hypothermia

6. Treat hyperkalemia - Calcium, insulin/glucose, bicarbonate - NOT calcium channel blockers with dantrolene — risk of cardiovascular collapse

7. Treat dysrhythmias with standard antiarrhythmics (avoid CCBs)

8. Acid-base with bicarbonate

9. Maintain urine output > 1 mL/kg/h to prevent myoglobinuria-induced renal injury (consider mannitol, furosemide)

10. ICU transfer for 24–48 h monitoring (recrudescence can occur)

• 24–48 h ICU monitoring (recrudescence in 25%)
• Repeat lytes, CK, myoglobin, BUN/Cr, coags
• Refer for MH testing (caffeine-halothane contracture test or genetic testing)
• Issue MedicAlert bracelet
• Counsel family — first-degree relatives have 50% risk → genetic testing
• Add to MHAUS registry

• Trigger-free anesthetic: TIVA (propofol, opioid, non-depolarizing NMBA, dexmedetomidine)
• Run anesthesia machine on high-flow O₂ × 10–90 min depending on machine (changes have made this faster); follow MHAUS recommendations for specific machine
• Remove vaporizers, change CO₂ absorbent and circuit, fresh tubing/bag
• Dantrolene available in OR
• No pretreatment with dantrolene needed (modern recommendation)
• Standard monitoring + EtCO₂, temperature
• Acceptable for outpatient surgery if uneventful 4–6 h observation post-op