Influence of midazolam-related genetic polymorphism on conscious sedation during upper gastrointestinal endoscopy in a Korean population

Jae Yong Park,Hyun Kang,Sang Wook Lee,Jae Gyu Kim,Beom Jin Kim,Jeong Wook Kim,In-Jin Jang

doi:10.1038/s41598-019-52517-7

Jae Yong Park, Hyun Kang + Show 5 more

Open Access

https://doi.org/10.1038/s41598-019-52517-7

Copy DOI

Abstract

Genetic polymorphism can result in abnormal pharmacodynamics that subsequently leads to the individual variance in sedative effects and adverse reactions. The aim of this study was to elucidate the association between midazolam-related genetic polymorphism and sedative effects, including adverse reactions, under conscious sedation during upper gastrointestinal endoscopy. We prospectively enrolled 100 eligible patients undergoing upper gastrointestinal endoscopy. The efficacy of the sedation, adverse reactions, plasma concentration of midazolam and 1-hydroxymidazolam were investigated as well as the genetic polymorphism of MDR1 and CYP3A5. The correlation between genetic polymorphism and sedative effects was assessed. Regarding MDR1 gene, the plasma concentration of midazolam was greater in patients with CGC haplotype (P = 0.012), while it was lower in patients with CAC haplotype (P = 0.005) than in those with other haplotypes. However, genetic polymorphism of neither MDR1 nor CYP3A5 correlated with the plasma concentration of 1-hydroxymidazolam. CGT haplotype of MDR1 was significantly correlated with sedation grade after midazolam administration (P = 0.042). In contrast, genetic polymorphism of CYP3A5 was not correlated with sedation grade. There was no association between genetic polymorphism of MDR1 or CYP3A5 and selected adverse reactions related to midazolam. Genetic polymorphism of MDR1 influences the concentration of midazolam and the sedation grade. However, it is not associated with adverse reactions such as paradoxical response and retrograde amnesia.

Highlights

Upper gastrointestinal (GI) endoscopy is a common and essential procedure performed for diagnostic or therapeutic purposes in patients with GI symptoms[1,2]
The present study examined the association between the genetic polymorphism of genes involved in midazolam metabolism and various responses to midazolam in conscious sedation during UGI endoscopy
The presence of CGC or CAC haplotype of MDR1 was significantly associated with the plasma concentration of midazolam

Summary

Introduction

Upper gastrointestinal (GI) endoscopy is a common and essential procedure performed for diagnostic or therapeutic purposes in patients with GI symptoms[1,2]. Sedation can reduce the patient’s fear of the procedure through anxiolytic effect and transient amnesia which allows the patients to undergo an endoscopy in a comfortable state. Among various types of sedative drugs available, midazolam is the most widely used drug for conscious sedation in GI endoscopy[5]. This is due to its several advantages such as a short half-life, fast onset of sedation, and strong anterograde amnesia effect[6]. Predictive factors of adverse reactions to midazolam during GI endoscopy, including paradoxical response and retrograde amnesia, are unclear[7]. The aim of this study was to elucidate the association between midazolam-related genetic polymorphism and sedative effects, including adverse reactions, under conscious sedation during upper GI endoscopy

Objectives

Methods

Results

Conclusion