Use of diphenhydramine as an adjunctive sedative for colonoscopy in patients on chronic opioid therapy: a randomized...

Chronic opioid use increases tolerance to sedatives. Diphenhydramine is recommended for difficult-to-sedate patients during endoscopic procedures. We hypothesized that the addition of diphenhydramine to midazolam and fentanyl would improve objective and subjective measures of procedural sedation.

This randomized, double-blind, placebo-controlled trial included patients on chronic opioids undergoing colonoscopy. Patients were randomized to receive 50 mg of diphenhydramine intravenously (n = 61) or placebo (n = 58), in addition to fentanyl and midazolam. Baseline characteristics, amount of fentanyl and midazolam, procedure times, and adverse events were recorded. Quality of sedation was assessed by the physician and nurse. Patients rated pain and amnesia on a 10-point scale.

There was no difference in amounts of fentanyl (125.4 ± 56.2 μg vs 126.9 ± 53.5 μg, P = .88) and midazolam (4.9 ± 2.1 mg vs 5 ± 1.9 mg, P = .79) used. The mean sedation scores from the physician (6.2 ± 1.1 vs 5.3 ± 1.2, P =.0002) and nurses (5.6 ± 1.5 vs 5.1 ± 1.4, P =.04) were statistically significant in favor of the diphenhydramine arm. Patient scores for pain (2.05 ± 2.17 vs 3.09 ± 3.95, P =.047) and amnesia (7.8 ± 3.4 vs 6.5 ± 3.8, P =.047) favored the group that received diphenhydramine. Qualitative assessment showed no significant difference between the groups. There was no difference in induction time (P = .86), procedure duration (P = .98), or recovery time (P = .16). Hypotensive episodes were more common in the placebo group (P = .027).

In patients on chronic opioid therapy, administration of diphenhydramine does not allow for lower doses of procedural sedatives but improves quality of sedation without increasing the number of adverse events. (Clinical trial registration number: NCT T01967433.).