Diphenhydramine as an Adjunctive Sedative in Patients on Chronic Opioids

Colonoscopy Clinical Trial

Official title:

Use of Diphenhydramine as an Adjunctive Sedative for Colonoscopy in Patients Chronically on Opioids

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01967433
• Other study ID #: DAASIPCO
• Status: Completed
• Phase: Phase 4
• Start date: December 2013
• Est. completion date: July 2018

Study information

• Verified date: March 2020
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: July 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Adjunct Anesthesia Medication
• Colonoscopy

Intervention

Drug:
• Diphenhydramine

• Placebo

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
University of Oklahoma

Country where clinical trial is conducted

United States, 

References & Publications (11)

Abraham NS, Fallone CA, Mayrand S, Huang J, Wieczorek P, Barkun AN. Sedation versus no sedation in the performance of diagnostic upper gastrointestinal endoscopy: a Canadian randomized controlled cost-outcome study. Am J Gastroenterol. 2004 Sep;99(9):1692-9. — View Citation

Bergeron P, Enns J, Delima L, Dupuis JY, Wynands JE. Effects of routine premedication for cardiac catheterization on sedation, level of anxiety and arterial oxygen saturation. Can J Cardiol. 1995 Mar;11(3):201-5. — View Citation

Cook PJ, Flanagan R, James IM. Diazepam tolerance: effect of age, regular sedation, and alcohol. Br Med J (Clin Res Ed). 1984 Aug 11;289(6441):351-3. — View Citation

Hirsh I, Vaissler A, Chernin J, Segol O, Pizov R. Fentanyl or tramadol, with midazolam, for outpatient colonoscopy: analgesia, sedation, and safety. Dig Dis Sci. 2006 Nov;51(11):1946-51. Epub 2006 Sep 29. — View Citation

Hofmeister EH, Egger CM. Evaluation of diphenhydramine as a sedative for dogs. J Am Vet Med Assoc. 2005 Apr 1;226(7):1092-4. — View Citation

Husain Z, Hussain K, Nair R, Steinman R. Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug. Cardiol J. 2010;17(5):509-11. — View Citation

Keeffe EB, O'Connor KW. 1989 A/S/G/E survey of endoscopic sedation and monitoring practices. Gastrointest Endosc. 1990 May-Jun;36(3 Suppl):S13-8. — View Citation

Peña LR, Mardini HE, Nickl NJ. Development of an instrument to assess and predict satisfaction and poor tolerance among patients undergoing endoscopic procedures. Dig Dis Sci. 2005 Oct;50(10):1860-71. — View Citation

Roach CL, Husain N, Zabinsky J, Welch E, Garg R. Moderate sedation for echocardiography of preschoolers. Pediatr Cardiol. 2010 May;31(4):469-73. doi: 10.1007/s00246-009-9622-z. Epub 2010 Jan 3. — View Citation

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. — View Citation

Zubarik R, Ganguly E, Benway D, Ferrentino N, Moses P, Vecchio J. Procedure-related abdominal discomfort in patients undergoing colorectal cancer screening: a comparison of colonoscopy and flexible sigmoidoscopy. Am J Gastroenterol. 2002 Dec;97(12):3056-61. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dosage of Fentanyl	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.	From induction (first dose of sedative) to end of procedure
Secondary	Quality of Sedation	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)	During the colonoscopy and 24 hours after discharge
Secondary	Duration of Procedure	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.	Time from induction (first dose of sedative) to discharge
Secondary	Number of Participants With Adverse Events	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	From induction (first dose of sedative) to discharge
Secondary	24 Hour Follow up Pain Score	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)	About 24 hours after the procedure
Secondary	Dosage of Midazolam	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.	From induction (first dose of sedative) to end of procedure
Secondary	24 Hour Follow up Amnesia Score	Patient were also asked to rate amnesia on a 10 point scale 24 after discharge. minimum= 0 (worse) maximum =10 (better)	At about 24 after the procedure