Effect of the Antihistamine Injection to Prevent Paradoxical Reaction During Sedative Endoscopy

Effect of an Adjunctive Sedative for the Patients With Histories of Paradoxical Reaction to Midazolam During Sedative Endoscopy

This single-blind prospective study is aimed to investigate the effect of antihistamine as an adjunctive sedative for the patients with histories of severe paradoxical reaction to midazolam during sedative endoscopy. Participating patients are to receive antihistamine intravenously in addition to midazolam. The primary outcome is the reduction of paradoxical reaction in the antihistamine combination group. The secondary outcome is to compare sedation quality, performance quality, reduction of total midazolam dose will be analyzed between antihistamine combination and midazolam only group.

Study Overview

• Status: Unknown
• Conditions: Endoscopy
• Intervention / Treatment: Drug: Chlorpheniramine and midazolam; Drug: Midazolam

Detailed Description

The present study will be conducted at Seoul National University Hospital Gangnam center between May 2019 and April 2020. Participants who have histories of paradoxical reaction to sedative endoscopy in medical record gave consent on the day of the endoscopy and were assigned to receive the combination of chlorpheniramine (4-6mg) with midazolam(1-10mg) Meanwhile, the patients do not want the use of chlorpheniramine and were assigned to midazolam alone as routine clinical practice. Research medication (chlorpheniramine) was administered 2 to 3 minutes before the administration of midazolam outside of endoscopy room. The blinded endoscopist and assistant nurse are going to perform induction for moderate sedation using incremental doses of the intravenous midazolam (1-2 mg) given every 2 minutes. The endoscopists and assistant nurses will assess the occurrence of severe paradoxical reaction (Grade 3) and other major quality outcomes (procedure/intubation time, sedation quality, completeness of procedure [10 Key image documentation], the satisfaction of procedure, side effects). The endoscopists and nurses will individually rate outcome measure using a 5-point Likert scale.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Healthcare System Gangnam Center, Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previous histories of the paradoxical reaction during a sedative endoscopic examination

Exclusion Criteria:

• inability to execute informed consent
• allergic to antihistamine agent
• pregnancy
• severe cardiopulmonary disease
• prior administration of antihistamine on the same day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: antihistamine combination; Participants in this group will get combination chlorpheniramine and midazolam injection for sedative endoscopy.	Drug: Chlorpheniramine and midazolam; Administration of chlorpheniramine injection as an adjunctive sedative during sedative endoscopy.
Placebo Comparator: midazolam; Participants in this group will get only midazolam injection for sedative endoscopy	Drug: Midazolam; Administration of midazolam as a sedative during sedative endoscopy as routine clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of severe paradoxical reaction (>= level 3)	(1) irrational talking or increased talkativeness such as mumbling to himself/herself; (2) restlessness or loss of cooperation such as resisting the insertion of endoscope or trying to bite the scope; (3) excessive movement requiring repositioning such as jerking or swinging movements of the arms and legs or trying to draw out the scope or mouthpiece; and (4) hostile action such as trying to strike the endoscopists or attending nurses.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
procedure/intubation time	procedural time (time from scope insertion to scope out) Intubation time (time from scope insertion to upper esophagus)	1 day
Dose of midazolam	total amount of benzodiazepine	1 day
completeness of procedure	photo documentation of key anatomical area	1 day
Satisfaction for Quality of sedation	5-point Likert scale : endoscopists and assistant nurses; Strongly unsatisfied; Unsatisfied; Neither satisfied nor unsatisfied; Satisfied; Strongly satisfied	1 day
Satisfaction for the procedure	5-point Likert scale for pain and sedation: patients; Strongly unsatisfied; Unsatisfied; Neither satisfied nor unsatisfied; Satisfied; Strongly satisfied	1 day
adverse events	hypoxia, arrythmia, low blood pressure and administration of antidote	1 day

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Publications and helpful links

General Publications

• Sachar H, Pichetshote N, Nandigam K, Vaidya K, Laine L. Continued midazolam versus diphenhydramine in difficult-to-sedate patients: a randomized double-blind trial. Gastrointest Endosc. 2018 May;87(5):1297-1303. doi: 10.1016/j.gie.2017.01.028. Epub 2017 Jan 31.
• Nusrat S, Madhoun MF, Tierney WM. Use of diphenhydramine as an adjunctive sedative for colonoscopy in patients on chronic opioid therapy: a randomized controlled trial. Gastrointest Endosc. 2018 Oct;88(4):695-702. doi: 10.1016/j.gie.2018.04.2342. Epub 2018 Apr 22.
• Tae CH, Kang KJ, Min BH, Ahn JH, Kim S, Lee JH, Rhee PL, Kim JJ. Paradoxical reaction to midazolam in patients undergoing endoscopy under sedation: Incidence, risk factors and the effect of flumazenil. Dig Liver Dis. 2014 Aug;46(8):710-5. doi: 10.1016/j.dld.2014.04.007. Epub 2014 Jun 2.
• Tu RH, Grewall P, Leung JW, Suryaprasad AG, Sheykhzadeh PI, Doan C, Garcia JC, Zhang N, Prindiville T, Mann S, Trudeau W. Diphenhydramine as an adjunct to sedation for colonoscopy: a double-blind randomized, placebo-controlled study. Gastrointest Endosc. 2006 Jan;63(1):87-94. doi: 10.1016/j.gie.2005.08.015.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): April 14, 2020
• Study Completion (Anticipated): April 14, 2020

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 7, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2020
• Last Update Submitted That Met QC Criteria: April 15, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: midazolam; paradoxical reaction
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Midazolam; Chlorpheniramine
• Other Study ID Numbers: H-1093-054-1017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No