title: Paradoxical reaction to midazolam in patients undergoing endoscopy under sedation: Incidence, risk factors and the effect of flumazenil.
abstract: BACKGROUND
  The incidence, risk factors and management strategy of paradoxical reaction to midazolam during endoscopy are yet to be clarified.
  
  
  METHODS
  This single center prospective study included 4140 adult patients (2263 males, mean age of 57.7 ± 12.6) undergoing endoscopy under sedation with midazolam and pethidine between September 2011 and December 2011. The characteristics of patients with and without paradoxical reaction were compared. For patients who experienced paradoxical reaction and received flumazenil, their endoscopic images were reviewed to assess whether European Society of Gastrointestinal Endoscopy guidelines were met as quality indicator of endoscopy.
  
  
  RESULTS
  The incidence of paradoxical reaction was 1.4%. In multivariate analyses, male gender, unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of midazolam, and lower dose of pethidine were identified as independent risk factors for paradoxical reaction. Despite paradoxical reaction, endoscopic procedures were successfully completed in 93.3% of cases when flumazenil was administered. The rates of meeting quality indicator of endoscopy were 92.3% in patients receiving flumazenil for paradoxical reaction and 97.6% in patients without paradoxical reaction.
  
  
  CONCLUSIONS
  For patients with risk factors for paradoxical reaction, active use of pethidine with a dose reduction of midazolam might be helpful to prevent the occurrence of paradoxical reaction. Administration of flumazenil might be positively considered in cases of paradoxical reaction.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Chung Hyun
authors.initials: CH
authors.lastname: Tae
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ki Joo
authors.initials: KJ
authors.lastname: Kang
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: bhmin@skku.edu.
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Min
authors.affiliation: Biostatistics Team, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Joong Hyun
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Biostatistics Team, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Seonwoo
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jun Haeng
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Poong-Lyul
authors.initials: PL
authors.lastname: Rhee
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000931:Antidotes / Q000627:therapeutic use; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005442:Flumazenil / Q000627:therapeutic use; D006791:Hostility; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008614:Meperidine / Q000008:administration & dosage; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009294:Narcotics / Q000008:administration & dosage; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D000931:Antidotes; D006993:Hypnotics and Sedatives; D009294:Narcotics; D005442:Flumazenil; D008614:Meperidine; D008874:Midazolam
keywords: Endoscopy; Flumazenil; Midazolam; Paradoxical reaction