Continued midazolam versus diphenhydramine in difficult-to-sedate patients: a randomized double-blind trial.
OBJECTIVE
Current guidelines recommend diphenhydramine in patients undergoing endoscopy who are not adequately sedated with a benzodiazepine and opioid combination. Because this practice has not been adequately assessed, we performed a randomized, double-blind trial comparing diphenhydramine with continued midazolam in such patients.


METHODS
Patients undergoing elective colonoscopy with moderate sedation were eligible. Sedation was measured with the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score with adequate sedation defined as 3 on a 0- to 5-point scale. Patients not adequately sedated with midazolam 5 mg and fentanyl 100 μg were randomly assigned to diphenhydramine 25 mg versus continued midazolam 1.5 mg. Adequacy of sedation was assessed 3 minutes after each study medication dose. If MOAA/S was 4 to 5, study medication was repeated, to a maximum of 3 doses. The primary endpoint was adequate sedation.


RESULTS
The planned enrollment of 200 patients (100 in each study group) was attained. Adequate sedation was achieved less often with diphenhydramine than midazolam (27% vs 65%, difference = -38%; 95% CI, -50% to -24%; P < .0001). After study medications were completed, more patients required additional medication for sedation or analgesia with diphenhydramine versus midazolam (84% vs 68%, P = .008), whereas the time to discharge from the recovery unit was similar (134 vs 129 minutes). Treatment effect was consistent across subgroups including age ≤55, substance abuse, benzodiazepine use, opioid use, and psychiatric medication use.


CONCLUSIONS
Endoscopists performing moderate sedation should continue midazolam rather than switching to diphenhydramine in patients who do not achieve adequate sedation with usual doses of midazolam and an opioid. (Clinical trial registration number: NCT01769586.).
Yale School of Medicine, New Haven, Connecticut, USA.
Hamita
H
Sachar
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Nipaporn
N
Pichetshote
Yale School of Medicine, New Haven, Connecticut, USA.
Kavitha
K
Nandigam
Yale School of Medicine, New Haven, Connecticut, USA.
Keta
K
Vaidya
Yale School of Medicine, New Haven, Connecticut, USA; VA Connecticut Healthcare System, West Haven, Connecticut, USA.
Loren
L
Laine
D018686:Anesthetics, Intravenous / Q000627:therapeutic use; D003113:Colonoscopy / Q000379:methods*; D016292:Procedural Sedation / Q000379:methods*; D004155:Diphenhydramine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D008297:Male; D008874:Midazolam / Q000008:administration & dosage*; D008875:Middle Aged
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D004155:Diphenhydramine; D008874:Midazolam; D005283:Fentanyl