Remimazolam and Postoperative Nausea and Vomiting in High-risk Patients
Remimazolam and Postoperative Nausea and Vomiting in High-risk Patients
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.
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.
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.