Toxicology & Substance Use · Topic 14 of 17

Malignant Hyperthermia

Toxicology · anesthesia emergency

Malignant Hyperthermia

An inherited hypermetabolic crisis under anesthesia: stop the volatile agent, hyperventilate with 100% oxygen, and give dantrolene 2.5 mg/kg IV.

Key numbers

Dantrolene 2.5 mg/kg IV, repeat2.5 mg/kg IV

Cool when core temperature exceeds 39 °Ccool > 39 °C, stop < 38

ICU 24 hours; 25% relapse25% relapse

01 · CauseTriggered by volatile anesthetics, succinylcholine

MH is an inherited (autosomal dominant, usually RYR1 ryanodine-receptor) skeletal-muscle reaction to potent volatile anesthetics (sevoflurane, desflurane, isoflurane, halothane) and succinylcholine; it may follow the first exposure but averages 3.

02 · Look forRising ETCO₂ and jaw rigidity early

Suspect MH when rising end-tidal CO₂ despite increased minute ventilation, jaw (masseter) rigidity and tachycardia appear 10 minutes to several hours into inhalational anesthesia; hyperthermia (often ≥ 40 °C) and acidosis follow.

03 · GiveDantrolene 2.5 mg/kg IV, repeat

Give dantrolene 2.5 mg/kg IV rapidly, repeated as often as needed until end-tidal CO₂, rigidity and heart rate fall; if > 10 mg/kg brings no response, reconsider the diagnosis.

Diagnosis & monitoring

Work-up

ICU 24 hours; 25% relapseMonitor in the ICU for at least 24 hours — 25% of MH episodes relapse; continue dantrolene 1 mg/kg IV every 4–6 hours for at least 24 hours.

Do right now

In this order

First moves

Stop triggers; hyperventilate with 100% oxygen

→

Dantrolene 2.5 mg/kg IV, repeat2.5 mg/kg IV

→

Cool when core temperature exceeds 39 °Ccool > 39 °C, stop < 38

→

Hyperkalemia: calcium, bicarbonate, insulin with glucose

Why each step

Stop triggers; hyperventilate with 100% oxygenStop volatile agents and succinylcholine, call for help and the dantrolene/MH cart, and hyperventilate with 100% oxygen at 10 L/min; if surgery must continue, use non-triggering IV anesthesia.

Dantrolene 2.5 mg/kg IV, repeatGive dantrolene 2.5 mg/kg IV rapidly, repeated as often as needed until end-tidal CO₂, rigidity and heart rate fall; if > 10 mg/kg brings no response, reconsider the diagnosis.

Cool when core temperature exceeds 39 °CCool actively when core temperature exceeds 39 °C (or sooner if rising fast) and stop cooling once it falls below 38 °C.

Hyperkalemia: calcium, bicarbonate, insulin with glucoseTreat hyperkalemia (K⁺ > 5.9 mEq/L or ECG changes) with calcium chloride 10 mg/kg (max 2 g) or calcium gluconate, bicarbonate 1–2 mEq/kg, and insulin 10 units IV with 50 mL of 50% dextrose.

Management

Orders

Check blood gas; bicarbonate for acidosisObtain an arterial or venous blood gas; combined respiratory and metabolic acidosis is typical — consider sodium bicarbonate 1–2 mEq/kg when base excess is worse than −8.

Refer for contracture or genetic testingAfter an episode, or with a family history or an unexplained severe anesthetic reaction, refer for susceptibility testing: the caffeine–halothane contracture test (gold standard) or genetic testing.

Red flags & don'ts

Avoid harm

Avoid calcium channel blockers for arrhythmias avoidTreat arrhythmias with standard drugs such as amiodarone or short-acting beta-blockers, but avoid calcium channel blockers (verapamil, diltiazem).

Myoglobinuria: diurese and alkalinize the urine complicationRhabdomyolysis (CK > 10,000 IU/L presumes myoglobinuria) threatens the kidneys: keep urine output > 1–2 mL/kg/h and alkalinize with a bicarbonate infusion. DIC, usually above 41 °C, is the usual cause of death.

The rules

Know these

Susceptible patients: non-triggering anesthesia onlyIn susceptible patients or those with a strong family history, prefer local or regional anesthesia and avoid potent inhalational agents and depolarizing relaxants; IV agents, opioids and nondepolarizing blockers are non-triggering. Keep dantrolene available.

Malignant hyperthermia or NMS?

Commonly confused

Trigger	Volatile anesthetic or succinylcholine
Onset	Minutes to hours after anesthesia starts
First clue	Rising end-tidal CO₂, jaw rigidity
Cause	Inherited (usually RYR1), autosomal dominant

Commonly confused

Tell apart

Light anesthesia raises heart rate, not temperatureInadequate anesthesia raises muscle tone and heart rate but not temperature; perioperative sepsis rarely causes fever so soon after induction; thyroid storm and pheochromocytoma rarely present immediately after induction.

More detail

Reference

Show 5 reference facts

Dantrolene formulations: Dantrium or Revonto 20 mg vials, each reconstituted with 60 mL sterile water; Ryanodex 250 mg vials, each reconstituted with 5 mL sterile water.

Triggering agents cause uncontrolled calcium release from the sarcoplasmic reticulum, producing sustained contraction, hypermetabolism, CO₂ production, and respiratory and metabolic acidosis.

MH occurs in about 1 in 35,000–68,000 surgical discharges; a similar reaction can occur in some muscular dystrophies and myotonias, and rare cases follow exercise or heat without anesthesia.

Follow heart rate, core temperature, end-tidal CO₂, blood gases, K⁺, CK, urine myoglobin and coagulation studies; dantrolene can be stopped after 24 hours of metabolic stability, temperature < 38 °C, falling CK and no rigidity.

The MHAUS hotline (1-800-644-9737) gives 24-hour expert guidance; if MH occurs outside the operating room, call anesthesiology immediately.

Pearl

A rising end-tidal CO₂ despite more ventilation is the early alarm — give dantrolene early, not after the fever.

Sources · Merck Manual Professional — Malignant Hyperthermia (May 2025) · MHAUS — Managing a Crisis: Emergency Treatment for an Acute MH Event · MHAUS — Post Acute Phase: Management in PACU or ICU · Merck Manual Professional — Neuroleptic Malignant Syndrome (Nov 2025) · Rosenberg H, Pollock N, Schiemann A, et al. Malignant hyperthermia: a review. Orphanet J Rare Dis 2015;10:93 · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).