Diphenhydramine as an Adjunctive Sedative in Patients on Chronic Opioids

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).

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)

- MOI use within 2 weeks of procedure