Diphenhydramine as an Adjunctive Sedative in Patients on Chronic Opioids

Phase 4

Completed

Conditions: Colonoscopy
Adjunct Anesthesia Medication

Interventions: Drug: Placebo
Drug: Diphenhydramine

Registration Number: NCT01967433

Lead Sponsor: University of Oklahoma

Brief Summary: To access the efficacy of adding diphenhydramine as adjunct to improve sedation and to reduce the amount of standard sedatives used during colonoscopy in patients on chronic opioids.

Detailed Description: Specific Aims:

The primary aim of our study is to determine if addition of Diphenhydramine to Fentanyl and Midazolam will decrease the dose of Fentanyl and Midazolam used during colonoscopy in individuals on chronic opioids. Secondarily we will be looking at quality of sedation, duration of colonoscopy, time to reach cecum and adverse effects (hypoxia defined as O2 saturation less than 89% lasting for more than 30 seconds, hypotension defined as systolic BP less than 90 mmhg and use of reversal agents i.e Naloxone or Flumazenil).

Day of Procedure:

After consent is obtained the medical records of the patients will be reviewed and demographic information, co-morbidities, current medication will be extracted and recorded.

On the day of colonoscopy Alcohol use disorder inventory (AUDIT) will be used to screen for alcohol abuse. AUDIT was developed by World Health Organization and has been validated over a period of 2 decades. It consist of 10 questions, each question is scored 0-4 on the basis of subjects alcohol use. It takes about 2-4 minutes to complete. A score 10 or greater is highly specific or alcohol use.

Subjects will be checked in and prepared according to routine protocols of the VA medical center. Participants will be randomly assigned to receive either 50 mg of diphenhydramine or 10 ml of 0.9% sodium chloride. On the day of colonoscopy randomization will be performed by an independent investigator who is a pharmacist at VA medical center using the website http://www.randomization.com. She will also prepare and dispense medication. Each endoscopy team will consist of an attending gastroenterologist, gastroenterology fellow and two nurses. Medications will be administered by one of the nurses under the direct supervision of the physician.

At the start of procedure baseline vitals will be recorded as per our unit's policy. Research medication will be administered 3 minutes prior to administration of other medications. Neither the patient nor the medical staff including the endoscopist will be aware of the contents of the vial. Conscious sedation will be achieved using a combination of intravenous midazolam and fentanyl as standard sedative. Rarely, additional diphenhydramine will be given, on the basis of the judgment of the endoscopist. During the procedure vital signs including oxygen saturation will be monitored at 3-5 minute interval. Procedure related complications, including hypotension, desaturation and cardiac arrhythmia will be managed according to our endoscopy unit policy and protocols.

Following the procedure, the nurse and the fellow or the attending will individually rate the quality if sedation on a ten-point Likert scale. Qualitative assessment will also be made (Under-sedated, adequately sedated, or over-sedated).

Recovery time will be recorded.

Day Following the Colonoscopy Twenty-four hour discharge a follow up call will be made and the patients will be asked to evaluate the level of sedation on a 10-point scale (1, inadequate; 10 completely without discomfort); pain (1, no pain; 10 severe pain), and amnesia (10, no memory of the procedure; 1 complete memory).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Patients aged 18-64 years undergoing screening, surveillance, diagnostic and therapeutic colonoscopy
Patient on chronic opioids defined as at least 5 mg of morphine or its equivalent at least 3 days per week for more than 3 months

Exclusion Criteria

Inability to execute informed consent
Allergy to Diphenhydramine, fentanyl or midazolam
Known or suspected pregnancy
Endoscopic procedure without sedation
Patient scheduled to have other endoscopic procedures on the same day
Prior alimentary tract surgery
Severe cardiopulmonary disease (ASA IV)
Monoamine Oxidase Inhibitors (MOI) use within 2 weeks of procedure

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	0.9% sodium chloride 10 ml IV 3 minuted prior to administration of other sedatives
Diphenhydramine	Diphenhydramine	Diphenhydramine 50 mg IV 3 minutes prior to administration of other sedatives

Primary Outcome Measures

Name	Time	Method
Dosage of Fentanyl	From induction (first dose of sedative) to end of procedure	Moderate sedation (using the American Society of Anesthesiologists definition of maintaining purposeful response to verbal or tactile stimulation, adequate ventilation requiring no airway protection, and maintenance of cardiovascular function) was then achieved using incremental doses of the combination of intravenous midazolam (1 mg) and fentanyl (25 μg) given every 2 to 3 minutes. To minimize any crossover, additional diphenhydramine was not permitted.

Secondary Outcome Measures

Name	Time	Method
Quality of Sedation	During the colonoscopy and 24 hours after discharge	Quality of sedation will be accessed by the nurse and the physician at the end of procedure. Name: 10 point visual analogue scale Minimum score: 1 (worse) Maximum score: 10 (better)
Number of Participants With Adverse Events	From induction (first dose of sedative) to discharge	Following adverse events will be recorded: (1)Hypoxia defined as O2 saturation less than 89% lasting for more than 30 seconds, (2)hypotension defined as systolic BP less than 90 mmhg and (3)use of reversal agents i.e Naloxone or Flumazenil
Duration of Procedure	Time from induction (first dose of sedative) to discharge	Induction period (time from first dose of fentanyl to scope insertion), procedural time (time from scope insertion to scope out), and recovery time (time from scope out to discharge) were recorded by the nursing staff in their standard documentation.
Dosage of Midazolam	From induction (first dose of sedative) to end of procedure	Moderate sedation (using the American Society of Anesthesiologists definition of maintaining purposeful response to verbal or tactile stimulation, adequate ventilation requiring no airway protection, and maintenance of cardiovascular function) was then achieved using incremental doses of the combination of intravenous midazolam (1 mg) and fentanyl (25 μg) given every 2 to 3 minutes. To minimize any crossover, additional diphenhydramine was not permitted.
24 Hour Follow up Amnesia Score	At about 24 after the procedure	Patient were also asked to rate amnesia on a 10 point scale 24 after discharge. minimum= 0 (worse) maximum =10 (better)
24 Hour Follow up Pain Score	About 24 hours after the procedure	At 24 hr follow up patients were asked to rate the level of pain during the procedure using 10 point scale. 10 point visual analogue scale minimum= 0 (better) maximum =10 (worse)