Malignant Hyperthermia: Recognition + Dantrolene
Crisis Management · 9 min read
MH is the disease anesthesia made famous. Triggers in your hands, mortality dropped from ~70% pre-1979 to <5% with dantrolene + rapid recognition. The first 10 minutes determine outcome.
Pathophysiology — RyR1 hypersensitivity
Mutations in the RYR1 gene (occasionally CACNA1S) produce a hypersensitive skeletal muscle ryanodine receptor on the sarcoplasmic reticulum. Triggering agents — volatile anesthetics (sevoflurane, desflurane, isoflurane, halothane) and succinylcholine — cause uncontrolled Ca²⁺ release from SR. Sustained myocyte contraction → ATP depletion → hypermetabolism → CO₂ production, hyperthermia, lactic + respiratory acidosis, K+ release, rhabdomyolysis. Without treatment: cardiac arrest from hyperkalemia or DIC.
Dantrolene drug entry →Recognition — the cardinal signs
EARLY (the only ones that matter): unexplained rising EtCO₂ despite increased minute ventilation; tachycardia + tachypnea (in spontaneous patients); muscle rigidity (especially masseter rigidity after succinylcholine — distinct from incomplete jaw relaxation). LATER: hyperthermia (often a LATE sign — don't wait), mottled skin, dark urine (myoglobinuria), severe acidosis, hyperkalemia. The triad of hypercarbia + tachycardia + rigidity is virtually diagnostic in the OR setting.
Step 1 — STOP triggers + call for help
Discontinue ALL volatile anesthetic + succinylcholine immediately. Switch to TIVA (propofol + remifentanil OR midazolam infusion). Switch to high-flow 100% O₂ at 10 L/min via a NEW circuit (replace soda lime canister + breathing circuit ASAP — the contaminated circuit holds residual volatile). HYPERVENTILATE to lower EtCO₂ + clear acidosis. Call MH HOTLINE 1-800-MH-HYPER (1-800-644-9737). Activate institutional MH cart. Get help — this requires a TEAM.
Step 2 — DANTROLENE
DANTROLENE 2.5 mg/kg IV bolus, repeat every 5-10 minutes until symptoms resolve (typical total 4-10 mg/kg, occasionally more). Use RYANODEX (250 mg vial in 5 mL) when available — fast reconstitution. Older dantrolene (Revonto/Dantrium) requires 60 mL sterile water per 20 mg vial — slow. Onset 5-10 min. Mechanism: RyR1 channel blocker, terminates Ca²⁺ release. Dantrolene saves lives — give it as soon as MH is suspected; do not wait for laboratory confirmation.
MH algorithm →Step 3 — Concurrent supportive care
ACTIVE COOLING: cold IV saline (NOT lactated Ringer — lactate worsens acidosis); ice packs to groin/axillae/neck; cold gastric lavage; cold peritoneal lavage if severe; STOP cooling at core 38°C to avoid overshoot. HYPERKALEMIA: calcium chloride 1 g IV, insulin 10 U + D50 50 mL, sodium bicarbonate 1-2 mEq/kg if pH <7.2, hyperventilation. Arrhythmias: standard ACLS but AVOID calcium channel blockers (verapamil + dantrolene → severe hyperkalemia + cardiovascular collapse). Place A-LINE, FOLEY, central line, NG. Send labs: ABG, K+, CK, urine myoglobin, coagulation studies (DIC late sign).
Step 4 — Post-crisis + follow-up
Continue dantrolene 1 mg/kg IV q6h × 24-48 h (or 0.25 mg/kg/h infusion) — recurrence in 25% within 24 h. ICU admission for monitoring. Repeat labs q6h until trending down. Counseling: patient + family carry MH risk. Refer to MHAUS for genetic testing (RYR1 panel) + MH-susceptible (MHS) registration. Future anesthesia: TIVA, regional, or 'clean' machine (no volatiles past 20 hours, removed vaporizer, autoclave-cleaned circuit, fresh CO₂ absorber). MH-triggering ban — IDENTITY band + chart flag for life.
Drugs that are SAFE in MH-susceptible patients
Safe: all IV anesthetics (propofol, etomidate, ketamine, dexmedetomidine, midazolam, opioids), all non-depolarizing NMB (rocuronium, vecuronium, cisatracurium), local anesthetics (no class effect — both amides and esters safe), nitrous oxide (controversial — no clear evidence of triggering, but some texts list as 'avoid'). UNSAFE: all volatile anesthetics, succinylcholine. Anti-RyR mutation testing identifies most cases when family history positive.
References
- · MHAUS Guidelines 2024 (mhaus.org)
- · Miller's Anesthesia 9e Ch 47 (Malignant Hyperthermia)
- · Glahn et al. Br J Anaesth 2010 — Recognition + treatment review
- · Larach et al. Anesth Analg 2010 — MH-AUS Registry mortality data