Malignant hyperthermia

Autosomal dominantly inherited disorder characterized by  skeletal muscle hypermetabolism following exposure to Halogenated inhalational anesthetics +/- Depolarising muscle relaxant like Succinylcholine 

Mutated Genes - RYR1 , CACNA1S , STAC3

Mechanism - Failure of RYR1 receptor to close leading to uncontrolled calcium release from skeletal muscle sarcoplasmic reticulum leading to sustained muscle contraction ,which leads to depletion of ATP and increased oxygen consumption and Co2 release and Heat production

Depletion of ATP leads to membrane integrity failure and leakage of Potassium , Creatine kinase and myoglobin into circulation


Etiology - 

Halogenated Inhalational anesthetics - Halothane , Isoflurane , Sevoflurane , Desflurane , Enflurane , Methoxyflurane

Inhalational anesthetic - Ether

General anesthetic - Cyclopropane 

Depolarising muscle relaxant - Succinylcholine , Decamethonium


Note - Nitrous oxide and Xenon are inhalational anesthetics but are not halogenated , so they dont cause malignant hyperthermia


Clinical features :-

Diagnosis :-

Gold standard diagnostic test - In vitro Caffeine Halothane Contracture Test

others - Screening for mutations of RYR1 gene and Dihydropyridine receptor gene , Muscle biopsy


Treatment Algorithm :- 

Stop all triggering /  offending drugs - 1st Step

Call For Help

Dantrolene[Ryanodine receptor antagonist]  2.5mg/kg IV every 5min until reaction subsides (max dose - 10mg/kg)

Hyperventilation with 100% oxygen to lower EtCO2

Cooling measures (ice packs , cold IV fluids , Cool water blankets , ice water immersion , Forced air cooling)

Treat arrhythmias (amiodarone ; avoid CCB's)

Lab studies (ABG, Electrolytes especially potassium , Serum and Urine Myoglobin , Coagulation profile)

Continue dantrolene 1mg/kg every 4 hours for 24-48hrs

Target urine output 2ml/kg/hr (Mannitol 3gms is added in each vial of Dantrolene)


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