Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for the Use of Potent Volatile Anesthetic Agents and Succinylcholine in the Context of RYR1 or CACNA1S Genotypes

Stephen G Gonsalves; Robert T Dirksen; Katrin Sangkuhl; Rebecca Pulk; Maria Alvarellos; Teresa Vo; Keiko Hikino; Dan Roden; Teri E Klein; S Mark Poler; Sephalie Patel; Kelly E Caudle; Ronald Gordon; Barbara Brandom; Leslie G Biesecker

doi:10.1002/cpt.1319

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. doi: 10.1002/cpt.1319. Epub 2019 Jan 24.

Authors

Stephen G Gonsalves¹, Robert T Dirksen², Katrin Sangkuhl³, Rebecca Pulk⁴, Maria Alvarellos³, Teresa Vo⁵, Keiko Hikino⁶, Dan Roden⁷, Teri E Klein³, S Mark Poler⁸, Sephalie Patel⁹, Kelly E Caudle¹⁰, Ronald Gordon¹¹, Barbara Brandom¹², Leslie G Biesecker^{1

13}

Affiliations

¹ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
² Department of Pharmacology & Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
³ Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
⁴ Center for Pharmacy Innovation and Outcomes, Geisinger Medical Center, Danville, Pennsylvania, USA.
⁵ Department of Pharmacy Practice, College of Medicine Internal Medicine, College of Pharmacy, University of South Florida, Tampa, Florida, USA.
⁶ Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA.
⁷ Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁸ Departments of Anesthesiology, Geisinger Medical Center, Danville, Pennsylvania, USA.
⁹ Department of Anesthesiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
¹⁰ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹¹ Department of Anesthesiology, University of California San Diego, San Diego, California, USA.
¹² Department of Anesthesiology, Mercy Hospital UPMC, North American MH Registry of MHAUS, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
¹³ Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Abstract

The identification in a patient of 1 of the 50 variants in the RYR1 or CACNA1S genes reviewed here should lead to a presumption of malignant hyperthermia susceptibility (MHS). MHS can lead to life-threatening reactions to potent volatile anesthetic agents or succinylcholine. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of these agents in patients with these RYR1 or CACNA1S variants (updates at https://cpicpgx.org/guidelines and www.pharmgkb.org).

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Practice Guideline

MeSH terms

Anesthetics, Inhalation / administration & dosage
Anesthetics, Inhalation / adverse effects*
Calcium Channels, L-Type / genetics*
Genotype
Humans
Malignant Hyperthermia / etiology
Malignant Hyperthermia / genetics
Neuromuscular Depolarizing Agents / administration & dosage
Pharmacogenetics / methods
Pharmacogenetics / standards*
Practice Guidelines as Topic / standards*
Ryanodine Receptor Calcium Release Channel / genetics*
Succinylcholine / administration & dosage
Succinylcholine / adverse effects*
Volatilization

Substances

Anesthetics, Inhalation
CACNA1S protein, human
Calcium Channels, L-Type
Neuromuscular Depolarizing Agents
RYR1 protein, human
Ryanodine Receptor Calcium Release Channel
Succinylcholine

Abstract

Publication types

MeSH terms

Substances

Grants and funding