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Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study

Aroke, Edwin N.; Crawford, Sybil L.; Dungan, Jennifer R.

doi: 10.1097/NNR.0000000000000197

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.

Edwin N. Aroke, PhD, CRNA, is Staff CRNA, the University of Massachusetts Medical Center, Worcester. At the time this research was completed, Dr. Aroke was PhD student, University of Massachusetts, Worcester Graduate School of Nursing.

Sybil L. Crawford, PhD, is Professor, Biostatistics Research Group, University of Massachusetts, Worcester.

Jennifer R. Dungan, PhD, RN, is Assistant Professor, School of Nursing, Duke University, Durham, North Carolina.

Accepted for publication July 21, 2016.

The authors thank Nancy Morris, APRN, PhD, Associate Professor of the Graduate School of Nursing, University of Massachusetts, Worcester, for her guidance during the study and constructive critique that has helped to improve the quality of the manuscript. The authors also thank William Kobertz, PhD, Professor of Molecular Pharmacology, University of Massachusetts, Worcester, for assisting with laboratory space and sample storage. Sample processing was partially funded by University of Massachusetts Medical School CTSA Grant UL1TR001453.

Editor’s note: Dr. Kathleen Hickey was Action Editor for this paper (OMICs: Special Issue).

The authors give special thanks to the perioperative care unit nurses at Hahnemann campus for facilitating recruitment of participants.

The authors have no conflicts of interest to report.

Corresponding author: Edwin N. Aroke, PhD, CRNA, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655 (e-mail:

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