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malignant hyperthermia/hyperthermia of anesthesia

Etiology: - inhalation anesthetics or muscle relaxants such as succinylcholine Pathology: - inherited abnormality of skeletal muscle sarcoplasmic reticulum - rapid increase in intracellular Ca+2 levels in response to inhalation anesthetics or muscle relaxants Genetics: - heterogeneous disorder - type 1 associated with mutation in RYR1 gene ryanodine receptor 1 (at least 25%) (autosomal dominant) - type 2 associated with mutation in gene for voltage-dependent sodium channel of skeletal muscle on chromosome 17q11.2-q24 - type 3 associated with unidentified gene on chromosome 7q21-q22 - type 4 associated with unidentified gene on chromosome 3q13.1 - type 5 (autosomal dominant) associated with defect in CACNA1S (1%) Clinical manifestations: - hyperthermia - muscle rigidity - masseter rigidity - rigor mortis-like - hyporeflexia - accelerated muscle metabolism - rhabdomyolysis - tachycardia - tachypnea, increased minute ventilation - hypertension - cardiovascular instability - hyperkalemia-induced rhythms - premature ventricular contractions - ventricular tachycardia, ventricular fibrillation - agitation [4] - skin mottling - pupils normal [4] - hypoactive bowel sounds [4] - brown urine (myoglobinuria) - metabolic acidosis - rapid development of signs/symptoms (1/2 hour - 24 hours) Laboratory: 1) arterial blood gas: - metabolic acidosis (lactic acidosis) - increased arterial pCO2 2) elevated serum creatine kinase 3) serum K+: hyperkalemia 4) urinalysis - myoglobinuria 5) abnormal coagulation tests 6) molecular diagnostic testing - CACNA1S gene mutation Differential diagnosis: - parkinsonian hyperpyrexia syndrome - neuroleptic malignant syndrome Management: 1) cessation of anesthesia 2) 100% O2 3) dantrolene 4) supportive measures - treat hyperkalemia - treat hypercarbia 5) patients who require surgery a) regional anesthesia - spinal, epidural or peripheral nerve block b) local anesthetics in combination with (a) c) general anesthesia with non-triggering agents [2] - barbiturates, benzodiazepines, opioids, propofol, etomidate, ketamins, nitrous oxide - non-depolarizing neuromuscular blockers

Related

adenylate kinase-1 (AK1, ATP/AMP phosphotransferase, myokinase) hyperthermia (pyrexia) ryanodine receptor (RyR)

General

muscular disease; myopathy pharmacogenetic disease

Database Correlations

OMIM correlations

References

  1. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 88
  2. Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. 2005 Jun 15;293(23):2918-24. PMID: 15956637
  3. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025
  4. Sinert RH Fast Five Quis: Serotonin Syndrome Medscape. 2121. June 4. https://reference.medscape.com/viewarticle/951841 - Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20 PMID: 15784664 Review https://www.nejm.org/doi/10.1056/NEJMra041867
  5. Litman RS, Smith VI, Larach MG, et al. Consensus statement of the Malignant Hyperthermia Association of the United States on unresolved clinical questions concerning the management of patients with malignant hyperthermia. Anesth Analg. 2019;128:652-9. PMID: 30768455