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Randomized controlled trial examining the usefulness and safety of midazolam continuous intravenous infusion and pethidine hydrochloride in small intestine endoscope (NHOG-MDZ-GFCF)

Randomized controlled trial examining the usefulness and safety of midazolam continuous intravenous infusion and pethidine hydrochloride in small intestine endoscope (NHOG-MDZ-GFCF)

76

The most frequent indication for small bowel endoscopy is so-called unexplained gastrointestinal bleeding (OGIB), and the usefulness of small bowel endoscopy has also been confirmed in cases of small bowel stenosis, tumors, inflammatory bowel disease, etc. One problem with small bowel balloon endoscopy is that it is more painful than other endoscopic procedures.There is little literature on sedation for small bowel endoscopy. Generally, sedation with intermittent intravenous midazolam and pethidine hydrochloride as an analgesic are used, but the effect is not sufficient, and a standard administration method has not been established. The development of more appropriate sedation methods will reduce patient suffering, improve outcomes, and enhance safety.

This study is a prospective randomized controlled trial by 15 centers of the National Hospital Organization Gastroenterology Research Group. Currently, midazolam is administered intermittently, with additional doses given repeatedly during body movement, resulting in fluctuating blood levels and occasional oversedation. Continuous intravenous midazolam infusion can maintain a constant effective blood concentration and is expected to provide sufficient sedation and analgesia with only the addition of pethidine hydrochloride during body movement. In this study, we compared the efficacy and safety of "continuous intravenous midazolam plus pethidine hydrochloride" ( "new group") with those of "intermittent intravenous midazolam plus pethidine hydrochloride" ( "standard group"). 76 patients were randomized between May 2020 and September 2021.

No serious adverse events were reported.

Of the 76 patients enrolled, 39 were assigned to the new group and 37 to the standard group. The number of patients in the analysis population (FAS, PPS, and safety analysis population) was 74 in total: 38 in the new group and 36 in the standard group (Did not receive allocated intervention n=2). The primary endpoint of proportion of adequate sedation (mean ( standard deviation)) was 0.637 (0.315) for the new group and 0.609 (0.272) for the standard group, with an estimated difference (new group - standard group) of 0.024, 95% CI = -0.111 to 0.160, p = 0.721. The proportion of body movements requiring treatment interruption was 7.9% (3/38) in the new group and 25.0% (9/36) in the standard group, p = 0.091. In terms of surgeon satisfaction, 76.3% (29/38) of the new group and 77.8% (28/36) of the standard group reported adequate sedation on the day of the examination, p = 1.000, and 89.5% (34/38) of the new group and 97.2% (35/36) of the standard group reported patient satisfaction with the same sedation, p = 0.392. The percentage of test discontinuation was 5.3% (2/38) in the new group and 2.8% (1/36) in the standard group, p = 1.000. Median (range) pethidine dose per hour (mg/hr) was 52.2 (28.6 to 112.5) in the new group and 48.9 (27.2 to 116.7) in the standard group, p = 0.287. The median (range) of midazolam doses per hour (mg/hr) was 8.4 (1.1-21.7) in the new group and 5.7 (1.6-19.1) in the standard group, p = 0.003.

In this study, we compared the efficacy and safety of "continuous intravenous midazolam plus pethidine hydrochloride" (new group) with those of "intermittent midazolam plus pethidine hydrochloride" (standard group) in small bowel endoscopy. The new group tended to have less body movement, but was not superior to the standard group. Given the acceptable safety profile of both groups and the paucity of similar studies, continuous infusion may be considered an option for sedation in some patient populations.

Nov. 01, 2023

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs031200018

Sakakibara Yuko

National Hospital Organization Osaka National Hospital

2-1-14, Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan

sakakibara.yuko.cp@mail.hosp.go.jp

Sakakibara Yuko

National Hospital Organization Osaka National Hospital

2-1-14, Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan

+81-6-6942-1331

sakakibara.yuko.cp@mail.hosp.go.jp

Complete

April. 20, 2020

Interventional

randomized controlled trial

double blind

active control

parallel assignment

treatment purpose

(1) Patients with small intestine endoscopy and treatment for more than 1 hour
(2) Patients with ECOG PS 0-2
(3) Patients who are over 20 years old at the time of obtaining consent
(4) Patients whose written consent was obtained by the patient's own free will

(1) American Society of Anesthesiologists physical status classification (ASA-PS) 4 or more patients
(2) Patients with heart failure (New York Heart Association: NYHA) grade 4
(3) Respiratory failure (Fletcher-Huge-jones classification) Grade 5 patients
(4) Child-Pugh classification grade C patients
(5) Women who are or may be pregnant
(6) Patients who are allergic to the drugs used
(7) Patients taking HIV protease inhibitor, efavirenz, and cobicistat-containing drugs
(8) Patients with myasthenia gravis and acute narrow-angle glaucoma
(9) In the event that the investigator or research investigator determines that participation in this study is not appropriate

Both

OGIB, Small bowel stenosis, small bowel tumor, inflammatory bowel disease

Midazolam single intravenous + pethidine hydrochloride combination
Midazolam continuous intravenous infusion + pethidine hydrochloride combination

OGIB, small intestine, inflammatory bowel disease, small intestine endoscope

Midazolam single intravenous, Midazolam continuous intravenous infusion

Proper sedation rate

1) Proportion of body movements that require testing / treatment interruption
2) Satisfaction level (surgeon, research subject)
3) Amount of midazolam and pethidine hydrochloride used
4) Proportion of serious adverse events
5) Proportion of test suspension including presence or absence of additional drugs

+81-52-951-1111

Jan. 24, 2020

none