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
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Enrollment
- 552
- Locations
- 10
- Primary Endpoint
- Incidence of postoperative nausea and vomiting (PONV) within 24 hours following surgery
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years old;
- •Scheduled to undergo elective surgery under general anesthesia;
- •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
- •Refuse to participate;
- •Previous history of schizophrenia, epilepsy, Parkinson's disease or myasthenia gravis;
- •Severe liver dysfunction (Child-Pugh class C);
- •Severe renal dysfunction (dialysis required);
- •Patients of the American Society of Anesthesiologists (ASA) grade 4 and above;
- •Emergency surgery;
- •Continuously taking benzodiazepines for more than 1 week before surgery;
- •Any other circumstances that are considered unsuitable for study participation by attending physicians or investigators.
Arms & Interventions
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.
Intervention: Remimazolam (Drug)
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Incidence of postoperative nausea and vomiting (PONV) within 24 hours following surgery
Time Frame: Up to 24 hours after surgery
Nausea is diagnosed when the patient has gastrointestinal symptoms but does not vomit stomach contents. The severity of nausea is assessed using a digital subjective score scale (the scale ranges from 0 to 10, where 0 points represent no nausea, and 10 points represent the most severe nausea). Vomiting is diagnosed when the patient has gastrointestinal symptoms and retching or vomits gastric contents. Retching refers to the act of vomiting, but no stomach contents are vomited out.
Secondary Outcomes
- Subjective sleep quality score within 3 days after surgery(Up to 3 days after surgery)
- Incidence of emergence delirium (ED)(Up to 30 minutes after surgery or during the stay in PACU)
- Length of stay in hospital after surgery(Up to 30 days after surgery)
- Incidence of PONV within 48 hours after surgery(Up to 48 hours after surgery)
- Incidence of delirium within 3 days after surgery(Up to 3 days after surgery)
- Incidence of complications within 30 days after surgery(Up to 30 days after surgery)
Investigators
Dong-Xin Wang
Professor
Peking University First Hospital