Clinical trial NCT04861337: Remimazolam and Postoperative Nausea and Vomiting in High-risk Patients
Official title: Effect of Remimazolam on Incidence of Postoperative Nausea and Vomiting Following General Anesthesia in High-risk Patients: a Multicenter, Double-blinded, Placebo-controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Nausea and Vomiting
Benzodiazepine
High-risk Patients
Keywords: Postoperative nausea and vomiting
Benzodiazepines
High-risk patients
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2021-04-27
Enrollment: 552
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of postoperative nausea and vomiting (PONV) within 24 hours following surgery
timeFrame: Up to 24 hours after surgery
Secondary outcomes:
measure: Incidence of PONV within 48 hours after surgery
timeFrame: Up to 48 hours after surgery
measure: Incidence of complications within 30 days after surgery
timeFrame: Up to 30 days after surgery
measure: Subjective sleep quality score within 3 days after surgery
timeFrame: Up to 3 days after surgery
measure: Incidence of emergence delirium (ED)
timeFrame: Up to 30 minutes after surgery or during the stay in PACU
measure: Incidence of delirium within 3 days after surgery
timeFrame: Up to 3 days after surgery
measure: Length of stay in hospital after surgery
timeFrame: Up to 30 days after surgery
Other outcomes:
measure: Incidence of intraoperative awareness
timeFrame: Up to 24 hours after surgery
measure: Incidence of dreaming during general anesthesia
timeFrame: Up to 24 hours after surgery
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital of the Ministry of Health
state: Beijing
city: Beijing
country: China
facility: Beijing YouAn Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Fuwai Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of HUST
state: Hubei
city: Wuhan
country: China
facility: Wuhan Puai Hospital
state: Hubei
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
state: Jiangsu
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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