Remimazolam and Postoperative Nausea and Vomiting in High-risk Patients

NCT ID: NCT04861337

Last Updated: 2024-01-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

552 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-19

Study Completion Date

2023-04-22

Brief Summary

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This trial aims to explore whether the intraoperative use of remimazolam can reduce the incidence of postoperative nausea and vomiting (PONV) in high-risk patients. According to the Apfel's simplified score, patients with 3 or more of the following factors are at high risk of postoperative nausea and vomiting (PONV), i.e., women, non-smokers, history of PONV, and postoperative use of opioids.

Detailed Description

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Postoperative nausea and vomiting (PONV) is a common adverse event after general anesthesia. The incidence of PONV within 2 hours after surgery was approximately 14% in patients undergoing laparoscopic gynecological procedure and it could be about 22%-33% within 24 hours and as high as 80% in high-risk patients. Even with prophylaxis and treatment, such as 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, the incidence of PONV is still about 7%-10%.

PONV is an important clinical problem that impact the recovery of patients. Firstly, it can be a highly distress experience to patients and reduce their satisfaction with medical services. Secondly, PONV is associated with prolonged stay in the postanesthesia care unit and hospital, and increase medical expenditures. Thirdly, PONV increases the risk of reflux aspiration and lung infection.

Risk factors for PONV in adults include anxiety, opioid use, and inflammation. A cohort study showed that patients with anxiety before surgery have a 5-fold increase in the risk of PONV. Opioids are one of the main causes of PONV, and the incidence of PONV increases with the increasing dose of opioids. Inflammation is also considered to be a potential molecular mechanism leading to PONV. Animal studies have shown that surgery can cause inflammation throughout the body and central nervous system, and stimulate the "vomiting center" , which leads to PONV.

Several clinical studies reported that midazolam decreased PONV. In a meta-analysis included 12 randomized trials (841 patients), the use of midazolam during the perioperative period reduced the risk of PONV by about 55%. Another Meta-analysis involving 16 randomized controlled studies also reported similar results. The use of midazolam during the perioperative period reduced the risk of PONV by approximately 45%.

The mechanism by which benzodiazepines reduce PONV is not fully understood, but may include the following. Benzodiazepines can reduce the incidence of anxiety and reduce the severity of anxiety. On the other hand, studies have shown that the use of remimazolam enhances the analgesic effect of remifentanil and may reduce the dose of opioids. Another aspect is benzodiazepines may suppress the inflammatory response.

Remimazolam is an ultra-short-acting benzodiazepine sedative. It has a more predictable fast onset, short duration of sedative action, and rapid recovery profile, but there is no clinical study on whether remimazolam has an effect on the incidence of PONV. The investigators speculate that remimazolam as a supplement anesthetic during general anesthesia can reduce the incidence of PONV.

Conditions

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Postoperative Nausea and Vomiting Benzodiazepine High-risk Patients

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Remimazolam Group

Remimazolam infusion is initiated after induction of general anesthesia at a rate of 0.25 mg/kg/h and stopped 15 minutes before the end of surgery.

Group Type EXPERIMENTAL

Remimazolam

Intervention Type DRUG

Remimazolam is infused at a rate of 0.25 mg/kg/h from end of anesthesia induction until 15 minutes before the end of surgery.

Placebo Group

Placebo (0.9% saline) infusion is initiated after induction of general anesthesia at the same rate as in the remimazolam group and stopped 15 minutes before the end of surgery.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Normal saline is infused at a rate same as in the remimazolam group from end of anesthesia induction until 15 minutes before the end of surgery.

Interventions

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Remimazolam

Remimazolam is infused at a rate of 0.25 mg/kg/h from end of anesthesia induction until 15 minutes before the end of surgery.

Intervention Type DRUG

Placebo

Normal saline is infused at a rate same as in the remimazolam group from end of anesthesia induction until 15 minutes before the end of surgery.

Intervention Type DRUG

Other Intervention Names

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Remimazolam group Placebo group

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years old;
2. Scheduled to undergo elective surgery under general anesthesia;
3. Judged to be at high risk of postoperative nausea and vomiting. According to the Apfel's simplified score, patients with 3 or more of the following factors are at high-risk: women, non-smokers, history of PONV, postoperative use of opioids.

Exclusion Criteria

1. Refuse to participate;
2. Previous history of schizophrenia, epilepsy, Parkinson's disease or myasthenia gravis;
3. Severe liver dysfunction (Child-Pugh class C);
4. Severe renal dysfunction (dialysis required);
5. Patients of the American Society of Anesthesiologists (ASA) grade 4 and above;
6. Emergency surgery;
7. Continuously taking benzodiazepines for more than 1 week before surgery;
8. Any other circumstances that are considered unsuitable for study participation by attending physicians or investigators.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dong-Xin Wang

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dong-Xin Wang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

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Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing Hospital of the Ministry of Health

Beijing, Beijing Municipality, China

Site Status

Beijing YouAn Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Fuwai Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Tongji Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Site Status

Wuhan Puai Hospital

Wuhan, Hubei, China

Site Status

Suzhou Municipal Hospital

Suzhou, Jiangsu, China

Site Status

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, China

Site Status

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

Hangzhou, Zhejiang, China

Site Status

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Countries

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China

References

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Geng ZY, Liu YF, Wang SS, Wang DX. Intra-operative dexmedetomidine reduces early postoperative nausea but not vomiting in adult patients after gynaecological laparoscopic surgery: A randomised controlled trial. Eur J Anaesthesiol. 2016 Oct;33(10):761-6. doi: 10.1097/EJA.0000000000000491.

Reference Type BACKGROUND
PMID: 27307217 (View on PubMed)

Dewinter G, Staelens W, Veef E, Teunkens A, Van de Velde M, Rex S. Simplified algorithm for the prevention of postoperative nausea and vomiting: a before-and-after study. Br J Anaesth. 2018 Jan;120(1):156-163. doi: 10.1016/j.bja.2017.08.003. Epub 2017 Nov 23.

Reference Type BACKGROUND
PMID: 29397124 (View on PubMed)

Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MT, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramer MR; Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014 Jan;118(1):85-113. doi: 10.1213/ANE.0000000000000002.

Reference Type BACKGROUND
PMID: 24356162 (View on PubMed)

Li CJ, Wang BJ, Mu DL, Hu J, Guo C, Li XY, Ma D, Wang DX. Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery. Br J Surg. 2020 Jan;107(2):e123-e132. doi: 10.1002/bjs.11354.

Reference Type BACKGROUND
PMID: 31903588 (View on PubMed)

Joo J, Park S, Park HJ, Shin SY. Ramosetron versus ondansetron for postoperative nausea and vomiting in strabismus surgery patients. BMC Anesthesiol. 2016 Jul 22;16(1):41. doi: 10.1186/s12871-016-0210-5.

Reference Type BACKGROUND
PMID: 27449404 (View on PubMed)

Pym A, Ben-Menachem E. The effect of a multifaceted postoperative nausea and vomiting reduction strategy on prophylaxis administration amongst higher-risk adult surgical patients. Anaesth Intensive Care. 2018 Mar;46(2):185-189. doi: 10.1177/0310057X1804600207.

Reference Type BACKGROUND
PMID: 29519221 (View on PubMed)

Burkhardt T, Czorlich P, Mende KC, Treitz A, Kiefmann R, Westphal M, Schmidt NO. Postoperative Nausea and Vomiting Following Craniotomy: Risk Factors and Complications in Context of Perioperative High-dose Dexamethasone Application. J Neurol Surg A Cent Eur Neurosurg. 2019 Sep;80(5):381-386. doi: 10.1055/s-0039-1685194. Epub 2019 May 10.

Reference Type BACKGROUND
PMID: 31075810 (View on PubMed)

Laufenberg-Feldmann R, Muller M, Ferner M, Engelhard K, Kappis B. Is 'anxiety sensitivity' predictive of postoperative nausea and vomiting?: A prospective observational study. Eur J Anaesthesiol. 2019 May;36(5):369-374. doi: 10.1097/EJA.0000000000000979.

Reference Type BACKGROUND
PMID: 30865002 (View on PubMed)

de Boer HD, Detriche O, Forget P. Opioid-related side effects: Postoperative ileus, urinary retention, nausea and vomiting, and shivering. A review of the literature. Best Pract Res Clin Anaesthesiol. 2017 Dec;31(4):499-504. doi: 10.1016/j.bpa.2017.07.002. Epub 2017 Jul 8.

Reference Type BACKGROUND
PMID: 29739538 (View on PubMed)

Horn CC, Wallisch WJ, Homanics GE, Williams JP. Pathophysiological and neurochemical mechanisms of postoperative nausea and vomiting. Eur J Pharmacol. 2014 Jan 5;722:55-66. doi: 10.1016/j.ejphar.2013.10.037. Epub 2013 Oct 26.

Reference Type BACKGROUND
PMID: 24495419 (View on PubMed)

Gan TJ, Belani KG, Bergese S, Chung F, Diemunsch P, Habib AS, Jin Z, Kovac AL, Meyer TA, Urman RD, Apfel CC, Ayad S, Beagley L, Candiotti K, Englesakis M, Hedrick TL, Kranke P, Lee S, Lipman D, Minkowitz HS, Morton J, Philip BK. Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. Anesth Analg. 2020 Aug;131(2):411-448. doi: 10.1213/ANE.0000000000004833.

Reference Type BACKGROUND
PMID: 32467512 (View on PubMed)

Grant MC, Kim J, Page AJ, Hobson D, Wick E, Wu CL. The Effect of Intravenous Midazolam on Postoperative Nausea and Vomiting: A Meta-Analysis. Anesth Analg. 2016 Mar;122(3):656-663. doi: 10.1213/ANE.0000000000000941.

Reference Type BACKGROUND
PMID: 26332858 (View on PubMed)

Ahn EJ, Kang H, Choi GJ, Baek CW, Jung YH, Woo YC. The Effectiveness of Midazolam for Preventing Postoperative Nausea and Vomiting: A Systematic Review and Meta-Analysis. Anesth Analg. 2016 Mar;122(3):664-676. doi: 10.1213/ANE.0000000000001062.

Reference Type BACKGROUND
PMID: 26516802 (View on PubMed)

Barends CRM, Absalom AR, Struys MMRF. Drug selection for ambulatory procedural sedation. Curr Opin Anaesthesiol. 2018 Dec;31(6):673-678. doi: 10.1097/ACO.0000000000000652.

Reference Type BACKGROUND
PMID: 30124543 (View on PubMed)

Horiguchi Y, Ohta N, Yamamoto S, Koide M, Fujino Y. Midazolam suppresses the lipopolysaccharide-stimulated immune responses of human macrophages via translocator protein signaling. Int Immunopharmacol. 2019 Jan;66:373-382. doi: 10.1016/j.intimp.2018.11.050. Epub 2018 Dec 5.

Reference Type BACKGROUND
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Wesolowski AM, Zaccagnino MP, Malapero RJ, Kaye AD, Urman RD. Remimazolam: Pharmacologic Considerations and Clinical Role in Anesthesiology. Pharmacotherapy. 2016 Sep;36(9):1021-7. doi: 10.1002/phar.1806. Epub 2016 Sep 1.

Reference Type BACKGROUND
PMID: 27496519 (View on PubMed)

Brice DD, Hetherington RR, Utting JE. A simple study of awareness and dreaming during anaesthesia. Br J Anaesth. 1970 Jun;42(6):535-42. doi: 10.1093/bja/42.6.535. No abstract available.

Reference Type BACKGROUND
PMID: 5423844 (View on PubMed)

Hines S, Steels E, Chang A, Gibbons K. Aromatherapy for treatment of postoperative nausea and vomiting. Cochrane Database Syst Rev. 2018 Mar 10;3(3):CD007598. doi: 10.1002/14651858.CD007598.pub3.

Reference Type BACKGROUND
PMID: 29523018 (View on PubMed)

Other Identifiers

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2020-429

Identifier Type: -

Identifier Source: org_study_id

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