Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 16, 2021; 9(29): 8763-8772
Published online Oct 16, 2021. doi: 10.12998/wjcc.v9.i29.8763
Midazolam dose is associated with recurrence of paradoxical reactions during endoscopy
Eun Hyo Jin, Ji Hyun Song, Jooyoung Lee, Jung Ho Bae, Su Jin Chung
Eun Hyo Jin, Ji Hyun Song, Jooyoung Lee, Jung Ho Bae, Su Jin Chung, Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul 06236, South Korea
Author contributions: Song JH contributed to conception and design; Jin EH did the analysis and interpretation of the data, drafting of the article; Lee J, Bae JH and Chung SJ did the critical revision of the article for important intellectual content; all authors approved the final version of the article.
Institutional review board statement: This study protocol conformed with the ethical guidelines of the 1975 Declaration of Helsinki and its subsequent revisions and was approved by the relevant institutional review board, No. H-1710-023-890.
Informed consent statement: Informed consent was not needed for this study.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: The presented data are anonymized and the risk of identification is low and the potential benefits of sharing these data outweigh the potential harms.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ji Hyun Song, MD, PhD, Professor, Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, 39F Gangnam Finance Center, 152 Teheran-ro, Gangnam-gu, Seoul 06236, South Korea. philomed@hanmail.net
Received: June 11, 2021
Peer-review started: June 11, 2021
First decision: June 25, 2021
Revised: June 26, 2021
Accepted: August 31, 2021
Article in press: August 31, 2021
Published online: October 16, 2021
Processing time: 126 Days and 5.1 Hours
Abstract
BACKGROUND

Midazolam is commonly used for sedation during gastrointestinal procedures. However, some patients experience paradoxical reactions characterized by excessive movement or excitement.

AIM

To investigate the rate of recurrence of paradoxical reactions to midazolam during an upper endoscopy.

METHODS

We retrospectively reviewed 122152 sedative endoscopies among a total of 58553 patients at the Seoul National University Hospital, Healthcare System Gangnam Center, from July 2013 to December 2018. Among them, 361 patients with a history of paradoxical reaction during sedative upper endoscopy were enrolled. The characteristics of patients in the recurrent and non-recurrent groups were compared via multivariable analysis using logistic regression.

RESULTS

Paradoxical reactions occurred in 0.86% (1054/122152) of endoscopies, and in 1.51% (888/58553) of patients. Among the 361 subjects with previous paradoxical reactions in sedative endoscopies, 111 (30.7%) experienced further paradoxical reactions. Univariable analysis revealed that the total midazolam dose used was higher in the recurrent group (6.74 ± 2.58 mg) than in the non-recurrent group (5.49 ± 2.04 mg; P < 0.0001). Patients were administered a lower dose of midazolam than previous doses: 1 mg less in the recurrent group and 2 mg less in the non-recurrent group. Multivariable analysis showed that the midazolam dose difference was an independent risk factor for recurrent paradoxical reaction (odds ratio: 1.213, 95%CI: 1.099-1.338, P = 0.0001).

CONCLUSION

The rate of recurrence of paradoxical reactions is significantly associated with midazolam dosage. The dose of midazolam administered to patients with previous paradoxical reactions should be less than that previously used.

Keywords: Gastroscopy; Endoscopy; Conscious sedation; Midazolam; Flumazenil

Core Tip: A paradoxical reaction refers to an unexpectedly increased excitement and excessive movement, as opposed to the anxiolytic or sedative effect of midazolam. This is the first study to investigate the recurrence rate of paradoxical reactions to midazolam during upper endoscopy under sedation. We report that the rate of recurrence of paradoxical reactions is significantly associated with the dose of midazolam administered. To avoid the recurrence of such reactions, we recommend reducing the total dose of midazolam administered to patients with previous paradoxical reactions by ≥ 2 mg compared to the dose previously used.