Title

Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study

UMMS Affiliation

Graduate School of Nursing; Department of Medicine, Division of Preventive and Behavioral Medicine

Date

3-1-2017

Document Type

Article

Disciplines

Anesthesia and Analgesia | Chemical and Pharmacologic Phenomena | Medical Genetics | Medical Pharmacology | Nursing | Pharmaceutical Preparations | Pharmacology | Psychiatry and Psychology

Abstract

BACKGROUND: Up to 55% of patients who are administered ketamine experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury; however, to date, no studies have investigated genetic association of ketamine-induced EP in healthy patients.

OBJECTIVES: The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP.

METHODS: This cross-sectional, pharmacogenetic candidate, gene pilot study recruited 75 patients having minor elective outpatient surgeries. EP was measured with the Clinician Administered Dissociative State Scale. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 and rs1806191) single-nucleotide polymorphisms and ketamine-induced EP occurrence and severity were tested using logistic and linear regression.

RESULTS: Forty-seven patients (63%) received ketamine and were genotyped, and 40% of them experienced EP. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > .10). Exploratory analysis of nongenotype models containing age, ketamine dose, duration of anesthesia, and time from ketamine administration to assessment for EP significantly predicted EP occurrence (p = .001) and severity (p = .007). This pilot study demonstrates feasibility for implementing a pharmacogenetic study in a clinical setting, and we estimate that between 380 and 570 cases will be needed to adequately power future genetic association studies.

DISCUSSION: Younger age, higher dose, and longer duration of anesthesia significantly predicted EP occurrence and severity among our pilot sample. Although the small sample size limited our ability to demonstrate significant genotype differences, we generated effect sizes, sample size estimates, and nongenetic covariates information in order to support future pharmacogenetic study design for evaluating this adverse event.

Rights and Permissions

Citation: Nurs Res. 2017 Mar/Apr;66(2):105-114. doi: 10.1097/NNR.0000000000000197.

Comments

Edwin N. Aroke undertook this study as a doctoral student (view his dissertation) in the Graduate School of Nursing at UMass Medical School.

Related Resources

Link to article in PubMed

PubMed ID

28252572