Study Notes: Malignant Hyperthermia (MH)

Definition

Malignant Hyperthermia (MH) is a rare, life-threatening hypermetabolic reaction of skeletal muscle triggered by certain anesthetic agents in genetically susceptible individuals.
It is characterized by uncontrolled calcium release from the sarcoplasmic reticulum → sustained muscle contraction, heat generation, and metabolic crisis.

Pathophysiology

• Caused by mutations (often in the RYR1 gene) affecting calcium channels in skeletal muscle.

• When exposed to triggering agents, calcium floods the muscle cytoplasm → continuous contraction → increased ATP consumption, CO₂ production, heat, and potassium release.

• Results in:

  • Hypercarbia (↑ EtCO₂)

  • Hyperthermia (↑ body temperature)

  • Muscle rigidity

  • Rhabdomyolysis → Myoglobinuria → Renal failure

  • Hyperkalemia → Arrhythmias or cardiac arrest

Triggering Agents

Category	Examples
Depolarizing neuromuscular blocker	Succinylcholine
Volatile anesthetic gases	Isoflurane, Sevoflurane, Desflurane, Halothane

Halothane is rarely used in the U.S. but still used in some countries.

Epidemiology

• Prevalence (genetic susceptibility):

  • ~1 in 15,000 in children

  • ~1 in 40,000 in adults

• Incidence of MH events: Extremely rare.

• Mortality: Historically up to 80%; currently 5–30% with prompt recognition and treatment.

• U.S. data: ~8 deaths over 5 years (~1.6 deaths/year) — less likely than being struck by lightning.

Clinical Signs

Early Indicators:

• Unexplained rise in end-tidal CO₂ (EtCO₂) despite hyperventilation

• Tachycardia (first vital sign change)

• Muscle rigidity (especially masseter spasm after succinylcholine)

• Rapidly increasing temperature

Later Findings:

• Hyperkalemia

• Acidosis (metabolic + respiratory)

• Myoglobinuria (dark urine)

• DIC (disseminated intravascular coagulation)

• Multi-organ failure

MH typically occurs during anesthesia, rarely postoperatively in PACU.

Diagnosis

Clinical suspicion is critical — there is no rapid bedside test.
Two diagnostic tests exist:

1. Caffeine–Halothane Contracture Test (CHCT):

   • Gold standard; measures muscle contraction response to caffeine and halothane.

   • Invasive, costly, limited to few centers.

   • Not done <6 months after an MH episode.

2. Genetic Testing:

   • Detects known RYR1 or CACNA1S mutations.

   • Low sensitivity (negative test doesn’t rule out MH).

   • Positive test helpful for family screening.

Prevention (for Known or Suspected MH-Susceptible Patients)

• Schedule as first case of the day.

• Remove all triggering agents from anesthesia machine.

• Replace:

  • Breathing circuit

  • CO₂ absorbent

  • Vaporizers (remove or cover with red tape)

• Flush anesthesia machine:

  • High fresh gas flows for 10–90 min depending on model.

  • Use charcoal filters if available to absorb residual agents.

• Use Total Intravenous Anesthesia (TIVA) — Propofol-based.

• Avoid succinylcholine.

Treatment — EMERGENCY PROTOCOL

1. Discontinue all triggering agents immediately.

2. Call for help and activate MH emergency protocol.

3. Administer Dantrolene (life-saving antidote):

   • Dose: 2.5 mg/kg IV every 5 minutes until symptoms resolve.

   • Continue infusion as relapse can occur.

   • Do NOT use calcium channel blockers (risk of hyperkalemic arrest).

4. Switch to 100% FiO₂, high flow rates, hyperventilate to blow off CO₂.

5. Actively cool the patient:

   • Administer cold IV fluids (Isolyte, NS)

   • Use ice packs, cooling blankets if available.

6. Treat complications:

   • Hyperkalemia: Insulin + Dextrose, Calcium (if not using Dantrolene), and Sodium Bicarbonate.

   • Acidosis: Sodium Bicarbonate.

   • Renal protection: Furosemide (diuresis), monitor urine output via Foley catheter.

   • DIC or rhabdomyolysis: ICU-level supportive care.

7. Monitor in ICU for ≥24 hours for recurrence.

Malignant Hyperthermia Cart Contents

• Dantrolene (Ryanodex or Dantrium)

• Refrigerated IV fluids (Isolyte)

• Sodium Bicarbonate

• Furosemide (Lasix)

• Insulin and Dextrose

• Cooling equipment

• Instructions & MH hotline contact information

💰 Cost:

• Ryanodex: $2,581 per 250 mg vial (5 mL reconstitution).

• Dantrium: $62 per 20 mg vial (requires 60 mL sterile water each).

• Ryanodex preferred in emergencies due to speed of reconstitution.

Takeaways

• MH = An anesthesiologist’s nightmare but survivable if recognized early.

• Always monitor EtCO₂, temperature, and muscle tone.

• Dantrolene saves lives — timing is everything.

• Do not use calcium channel blockers with Dantrolene.

• Preparedness (MH cart, protocols, simulation training) prevents catastrophe.

• Anesthesiologists are experts in rapid resuscitation.