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

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.