Contents

Search

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.
  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