Malignant Hyperthermia

Malignant Hyperthermia Study Notes

Pathophysiology

• Pharmacogenetic disorder of skeletal muscle

• Triggered by volatile anesthetics and succinylcholine

• Mutations in RYR1 gene (ryanodine receptor) - most common (~70%)

• Less commonly, mutations in CACNA1S gene (calcium channel)

• Triggered agents cause:

  • Uncontrolled calcium release from sarcoplasmic reticulum

  • Sustained muscle contraction

  • Hypermetabolism

  • Heat production

  • ATP depletion

  • Cell membrane breakdown

  • Severe metabolic derangements

Clinical Presentation

• Early signs:

  • Unexplained tachycardia

  • Unexplained increase in end-tidal CO₂ (earliest specific sign)

  • Muscle rigidity (especially masseter spasm after succinylcholine)

  • Tachypnea (if spontaneously breathing)

• Later signs:

  • Hyperthermia (rapid increase, can exceed 40°C)

  • Mottled skin, cyanosis

  • Metabolic acidosis

  • Mixed respiratory acidosis

  • Hyperkalemia

  • Cardiac arrhythmias

  • Myoglobinuria (cola-colored urine)

• Fulminant cases:

  • Severe hyperkalemia → cardiac arrest

  • DIC (disseminated intravascular coagulation)

  • Multiple organ failure

At-Risk Populations

• Autosomal dominant inheritance with variable penetrance

• Family history of MH or unexplained anesthetic complications

• Previous adverse reaction to anesthesia

• Certain myopathies:

  • Central core disease (strongest association)

  • King-Denborough syndrome

  • Some forms of muscular dystrophy

• Higher incidence in:

  • Young males

  • Athletic body types

• Prevalence estimates:

  • Clinical incidence: 1:10,000 to 1:250,000 anesthetics

  • Genetic susceptibility: ~1:2,000-3,000 individuals

Diagnosis

• Clinical diagnosis during crisis (based on signs and symptoms)

• Diagnostic criteria: Clinical Grading Scale (CGS)

  • Respiratory acidosis (increased ETCO₂)

  • Metabolic acidosis

  • Muscle rigidity

  • Muscle breakdown (increased CK, myoglobinuria)

  • Temperature increase

  • Cardiac involvement (arrhythmias, tachycardia)

  • Family history

• Laboratory findings:

  • Respiratory and metabolic acidosis

  • Hyperkalemia

  • Elevated CK (creatine kinase)

  • Elevated myoglobin (serum and urine)

  • Abnormal coagulation studies (late)

Management of Acute Crisis

• Immediate actions:

  • Stop triggering agents immediately

  • Call for help and MH cart/kit

  • Hyperventilation with 100% oxygen

  • Switch to non-triggering anesthetic technique

• Dantrolene administration (specific antidote):

  • Initial dose: 2.5 mg/kg IV, repeat until symptoms controlled

  • May need up to 10 mg/kg total

  • Prepare by dissolving in sterile water (not compatible with electrolyte solutions)

• Cooling measures:

  • Surface cooling

  • Cold IV fluids

  • Lavage of open body cavities if applicable

  • Avoid overcooling (target < 38°C)

• Treatment of metabolic abnormalities:

  • Hyperkalemia: Calcium, insulin/glucose, bicarbonate

  • Acidosis: Hyperventilation, sodium bicarbonate

  • Arrhythmias: Standard treatment (avoid calcium channel blockers)

• Monitor and treat:

  • Electrolytes, ABGs, coagulation, CK, myoglobin

  • Maintain urine output (>1 mL/kg/hr)

  • Monitor for compartment syndrome

Follow-Up Care

• Post-crisis monitoring in ICU (24-48 hours minimum)

• Continue dantrolene: 1 mg/kg IV q4-6h for at least 24-36 hours

• Monitor for:

  • Recrudescence (can occur within 24-36 hours)

  • Acute kidney injury

  • DIC

  • Compartment syndrome

  • Neurological injury

• Obtain specialty consultation:

  • MH expert/anesthesiologist

  • Critical care

  • Possibly nephrology, hematology

• Report to MH registry

• Genetic counseling

• Medical alert bracelet

• Family notification and screening

Definitive Testing

• Caffeine-halothane contracture test (CHCT)

  • Gold standard but invasive (muscle biopsy)

  • Performed at specialized centers

  • High sensitivity and specificity

• In vitro contracture test (IVCT)

  • European version of CHCT

• Genetic testing:

  • RYR1 and CACNA1S mutations

  • ~70% sensitivity (many variants of unknown significance)

  • Non-invasive but cannot exclude MH susceptibility if negative

• Family testing recommended for first-degree relatives

Prevention for MH-Susceptible Patients

• Avoid triggering agents:

  • All volatile anesthetics (sevoflurane, desflurane, isoflurane, etc.)

  • Succinylcholine

• Safe anesthetic agents:

  • All intravenous anesthetics (propofol, etomidate, ketamine, etc.)

  • All opioids

  • All local anesthetics

  • All neuromuscular blocking agents except succinylcholine

  • Nitrous oxide

• Prepare anesthesia machine:

  • Flush with high flow oxygen for >60 minutes

  • Replace or remove CO₂ absorbent

  • Change circuit and breathing bag

  • Consider dedicated "vapor-free" machine

• Have dantrolene immediately available

• Pretreatment with dantrolene not recommended routinely