Cyproheptadine Has No Role in Malignant Hyperthermia Treatment
Cyproheptadine is not indicated for malignant hyperthermia and should never be used in its treatment—dantrolene is the only specific and effective pharmacologic therapy for this life-threatening condition. 1, 2
Why Cyproheptadine is Not Used
Cyproheptadine is mentioned only in the context of serotonin syndrome, not malignant hyperthermia, where it may be considered in severe cases after discontinuation of serotonergic agents and supportive care with benzodiazepines. 3 These are completely different hyperthermic syndromes with distinct pathophysiology:
Malignant hyperthermia results from abnormal calcium release from the sarcoplasmic reticulum triggered by volatile anesthetics and succinylcholine, representing an inherited genetic disorder affecting the ryanodine receptor. 3
Serotonin syndrome arises from excessive serotonin activity due to proserotonergic drugs, presenting with hyperreflexia, clonus, and myoclonus—features absent in malignant hyperthermia. 3
The Only Correct Treatment: Dantrolene
Dantrolene is the sole clinically acceptable and effective treatment for malignant hyperthermia, reducing mortality to virtually 0% when administered promptly. 4, 5 The drug works by:
Directly targeting the ryanodine receptor (the calcium release channel of the sarcoplasmic reticulum) to prevent abnormal calcium release. 6, 7
Indirectly preventing calcium release from the sarcoplasmic reticulum and accelerating calcium uptake back into the SR. 8
Treatment Algorithm for Malignant Hyperthermia
Immediate Actions (First 60 Seconds)
- Stop all volatile anesthetics and succinylcholine immediately. 1, 2
- Remove the vaporizer and insert activated charcoal filters on inspiratory and expiratory limbs. 2
- Hyperventilate with 100% oxygen at 2-3 times normal minute ventilation. 1, 2
- Declare an emergency and call for help—multiple personnel are needed. 1, 2
Dantrolene Administration (Primary Treatment)
- Administer dantrolene 2-3 mg/kg IV immediately as the initial bolus. 1, 2
- Reconstitute each 20 mg vial with 60 mL sterile water (requires vigorous shaking up to 5 minutes). 2
- Give additional 1 mg/kg boluses until ETCO2 falls below 6 kPa, core temperature drops below 38.5°C, and normal minute ventilation is achieved. 2
- Maximum doses may exceed 10 mg/kg if necessary—do not delay or limit dantrolene based on arbitrary dose caps. 1
Active Cooling Measures
- Administer 2000-3000 mL of chilled (4°C) 0.9% saline IV. 1, 2
- Apply wet cold sheets, fans, and ice packs to axillae and groin. 2
- Use any available cooling devices (cooling blankets, intravascular catheters). 2
Management of Metabolic Complications
- Hyperkalemia: Calcium chloride 0.1 mmol/kg IV, plus 50 mL of 50% dextrose with 50 IU insulin (adult dose). 1, 2
- Acidosis: Hyperventilate to normocapnia; give sodium bicarbonate IV only if pH < 7.2. 1, 2
- Arrhythmias: Amiodarone 300 mg (3 mg/kg) IV; consider beta-blockers if tachycardia persists. 1, 2
- Maintain urine output > 2 mL/kg/h using furosemide 0.5-1 mg/kg, mannitol 1 g/kg, and crystalloid fluids. 1
Critical Pitfalls to Avoid
- Never waste time changing the anesthetic circuit or machine—simply disconnect the vaporizer immediately and use high-flow oxygen. 1
- Never delay dantrolene administration while waiting for diagnostic confirmation—early treatment is critical for survival. 1
- Dantrolene is only effective when given before total calcium depletion from the sarcoplasmic reticulum, making vigilant monitoring and immediate treatment essential. 8
Post-Crisis Management
- Monitor in ICU for at least 24 hours after the crisis, as recrudescence can occur. 2, 3
- Establish invasive monitoring (arterial line, central venous catheter) and continuously measure core temperature, serum potassium, creatine kinase, myoglobin, and renal function. 2
- Counsel patient and family about the genetic nature of the condition and refer to specialized MH investigation units for diagnostic testing (in-vitro contracture testing is the gold standard). 1
- Warn all blood relatives about their risk of malignant hyperthermia. 2