氯胺酮诱发苏醒现象的药物遗传学：一项初步研究。
Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study.
作者信息
Aroke Edwin N, Crawford Sybil L, Dungan Jennifer R
机构信息
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.
出版信息
Nurs Res. 2017 Mar/Apr;66(2):105-114. 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.
背景
接受氯胺酮治疗的患者中，高达55%会出现类似精神分裂症的苏醒现象（EP），并增加受伤风险；然而，迄今为止，尚无研究调查健康患者中氯胺酮诱导的EP的基因关联。
目的
本研究旨在探讨探索CYP2B6*6和GRIN2B单核苷酸多态性与氯胺酮诱导的EP之间关系所需的可行性和样本量。
方法
这项横断面、药物遗传学候选基因试点研究招募了75例接受小型择期门诊手术的患者。使用临床医生评定的解离状态量表测量EP。使用逻辑回归和线性回归测试CYP2B6*6和GRIN2B（rs1019385和rs1806191）单核苷酸多态性与氯胺酮诱导的EP发生及严重程度的基因关联。
结果
47例患者（63%）接受了氯胺酮治疗并进行了基因分型，其中40%出现了EP。EP的发生及严重程度与CYP2B6*6或GRIN2B均无关联（p>.10）。对包含年龄、氯胺酮剂量、麻醉持续时间以及从给予氯胺酮到评估EP的时间的非基因型模型进行探索性分析，显著预测了EP的发生（p = .001）和严重程度（p = .007）。这项试点研究证明了在临床环境中开展药物遗传学研究的可行性，并且我们估计未来进行充分的基因关联研究需要380至570例病例。
讨论
在我们的试点样本中，年龄较小、剂量较高和麻醉持续时间较长显著预测了EP的发生及严重程度。尽管样本量较小限制了我们证明显著基因型差异的能力，但我们生成了效应大小、样本量估计值和非基因协变量信息，以支持未来评估这一不良事件的药物遗传学研究设计。
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