Inhalation anesthetics and succinylcholine (Adverse Reactions)

The presence of variants in the RYR1 or CACNA1S genes that increase susceptibility to malignant hyperthermia is associated with severe adverse reactions to potent volatile anesthetic agents or succinylcholine.

Volatile halogenated anesthetics such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane and depolarizing muscle relaxants such as succinylcholine are contraindicated in individuals carrying variants in the RYR1 or CACNA1S genes that increase susceptibility to malignant hyperthermia (MH).

Since almost all patients susceptible to MH have no phenotypic changes without anesthesia, MH is not detected without specific diagnostic tests or exposure to anesthetics that induce MH.

MH can occur during anesthesia and in the early postoperative period, but no later than one hour after discontinuation of volatile agents. Early signs are tachycardia, increased end-expiratory carbon dioxide concentration, muscle rigidity, and increased body temperature.


  • Desflurane (e.g. Suprane®)
  • Enflurane
  • Halothane
  • Isoflurane (e.g. Forane®, Terrell®)
  • Methoxyflurane
  • Sevoflurane (Ex: Sevorane®, Sojourn®, Ultane®)
  • Succinylcholine (Ex: Anectine®, Quelicin®)

Genes analyzed



Alshabeeb MA, Alyabsi M, Aziz MA, Abohelaika S. Pharmacogenes that demonstrate high association evidence according to CPIC, DPWG, and PharmGKB. Front Med (Lausanne). 2022 Oct 25;9:1001876.

Gonsalves SG, Dirksen RT, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes. Clin Pharmacol Ther. 2019 Jun;105(6):1338-1344.

Rosenberg H, Pollock N, Schiemann A, et al. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015 Aug 4;10:93.

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