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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Endoscopy

Intervention / Treatment
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* Drug: Chlorpheniramine and midazolam
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paradoxical reaction, midazolam