【罂粟摘要】丙泊酚麻醉术后恶心呕吐相关的临床和遗传因素

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丙泊酚麻醉术后恶心呕吐相关的临床和遗传因素

贵州医科大学  麻醉与心脏电生理课题组

翻译：马艳燕

编辑：宋雨婷

审校：曹莹

背景

尽管采取了各种治疗措施来减少术后恶心呕吐(PONV)，但PONV的发生率仍然保持在30%左右。指导预防性治疗的临床危险因素已经确定，但与PONV相关的遗传因素仍然知之甚少。本研究的目的是通过进行全基因组关联研究（GWAS）和相关的临床因素作为协变量来探索影响PONV的临床和遗传因素，并系统地尝试复制先前报道的PONV关联。采用Logistic回归模型对相关临床因素进行分析。

方法

本试验为一项观察性病例对照研究，于2006年8月1日至2010年12月31日在赫尔辛基大学医院进行。1000名同意接受乳腺癌手术且PONV风险增加的女性，使用标准化的丙泊酚麻醉和止吐药物。在因临床原因和基因分型失败而排除后，包括187名PONV患者和628名对照患者在内的815名患者被纳入。记录术后7天内出现的PONV。以术后2-24小时的PONV为主要预后指标。GWAS研究了PONV和653034个遗传变异之间的关联。重复实验包括16个基因的31个变种。

结果

术后7天内PONV的总发病率为35%，其中3%在术后0-2小时出现，23%在术后2-24小时出现。年龄、美国麻醉医师协会健康状态分级、恢复室使用的羟考酮量、吸烟状况、PONV病史和晕动症病史是Logistic回归模型中具有统计学意义的预测因素。计算了该模型在0.75(95%可信区间0.71-0.79)曲线下的受试者工作特征面积。Gwas发现了6个与PONV相关的变异(P <1×10−5)。在先前报道的变异体中，与DRD2变异体rs18004972(TaqIA)的关联被复制(P =0.028)。

结论

GWAS方法没有发现任何高影响的PONV易感性变异。研究结果为多巴胺D2受体在PONV中的作用提供了一定的支持。

原始文献来源

Ahlström SE, Bergman PH, Jokela RM, Olkkola KT, Kaunisto MA, Kalso EA. Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia. Acta Anaesthesiol Scand. 2023 May 8. doi: 10.1111/aas.14261.

英文原文

 Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia

Background: The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model.

Methods: This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2–24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes.

Results: The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0–2 h and 23% at 2–24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the postanaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71–0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1x10-5). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028).

Conclusions: Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV. 

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