Introduction

In high-risk surgical patients, postoperative nausea and vomiting (PONV) occurs in up to 60 to 80% without prophylaxis. Current guidelines recommend combining antiemetics with different mechanisms of action for the prevention of PONV. Amisulpride, a dopamine D₂/D₃ receptor antagonist, had previously shown antiemetic efficacy and a favorable safety profile, prompting evaluation as part of combination prophylaxis.

Aim

To determine whether a single intravenous 5 mg dose of amisulpride, administered in combination with a standard non-dopaminergic antiemetic, is more effective than placebo in preventing PONV in high-risk surgical patients.

Method

Study Design

Patient Profile

• Aged >18 years undergoing elective surgery, open or laparoscopic, under volatile general anaesthesia, expected to last for atleast 1 hour
• Having 3 or 4 established PONV risk factors: female sex, previous history of PONV or motion sickness, non-smoker and expected use of postoperative opioids for analgesia
• With adequate cardiac, hepatic and renal function and having serum potassium of atleast 3 mmol/l

Treatment Strategy

• The study was conducted at 29 sites in France, Germany, and the United States
• Cohort comprised 1,147 adult surgical patients 
• Patients were randomised to receive either IV amisulpride 5 mg plus a standard antiemetic (most commonly ondansetron or dexamethasone), or placebo plus a standard antiemetic at induction of general anesthesia
• Outcomes were assessed during the first 24 hours after surgery

Endpoints

Primary Endpoint

Secondary Endpoints

• Incidence of emesis
• Incidence and severity of nausea
• Significant nausea (score ≥4 on an 11-point scale)
• Rescue medication use

Safety Endpoint

Results

• A total of 572 patients received amisulpride and 575 received placebo
• Baseline characteristics of both groups were comparable
• Ondansetron was given as a standard antiemetic in approximately 50% and the remaining received dexamethasone
• Complete response was achieved in higher proportion of patients in the amisulpride group vs placebo as seen in Figure 1. 

Figure 1. Complete response rates

 

• The comparison of other outcomes is shown in Figure 2.
• Amisulpride group exhibited lower incidence of emesis, nausea and use of rescue medication

Figure 2. Comparison of other outcomes

• The rate of AEs was comparable between the groups
• Safety outcomes were comparable between groups, with no clinically relevant increase in QT prolongation, extrapyramidal symptoms, or sedation

Conclusion

• A single 5 mg intravenous dose of amisulpride, when added to a standard antiemetic regimen, significantly reduced postoperative nausea and vomiting in high-risk surgical patients. 
• The treatment was well tolerated and demonstrated a safety profile comparable to placebo, supporting its use as part of combination PONV prophylaxis.

Anesthesiology. 2018 June;128(6):1099–1106. Doi:10.1097/ALN.0000000000002133.