Intravenous Amisulpride Improves PONV Control After Failed Antiemetic Prophylaxis

Introduction

Amisulpride is a selective dopamine D2/D3 receptor antagonist that has been used as an oral antipsychotic. Recent studies have demonstrated that low-dose intravenous amisulpride is an effective antiemetic for postoperative nausea or vomiting(PONV) prevention.

Aim 

To evaluate the efficacy and safety of intravenous amisulpride as rescue treatment for established postoperative nausea or vomiting in patients who experienced PONV despite receiving prophylactic antiemetic therapy. 

Patient Profile

• Adult patients (≥18 years) undergoing elective open or laparoscopic surgery under general inhalational anaesthesia. 
• Patients considered at moderate or high risk of PONV based on recognized risk factors (e.g., female gender, nonsmoking status, history of PONV or motion sickness, expected postoperative opioid use).

Methods

• Multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase III trial. 
• A total of 2,285 patients were enrolled, of these, 702 patients who developed PONV within 24 hours despite prophylaxis were randomized and received study medication.
• Patients experiencing a qualifying PONV episode were randomized in a 1:1:1 ratio to receive: 
  1. Amisulpride 5 mg IV
  2. Amisulpride 10 mg IV
  3. Matching placebo
• Primary Endpoint: Complete response, defined as no vomiting/retching and no rescue antiemetic use during the 24 hours following treatment (excluding emesis within the first 30 minutes). 
• Secondary Endpoints
  1. Incidence of vomiting
  2. Rescue medication use
  3. Nausea severity and burden
  4. Significant nausea (score ≥4)
  5. Time to treatment failure
  6. Length of PACU and hospital stay
• Safety was assessed through adverse-event monitoring, laboratory testing, and follow-up for seven days after treatment.

Results

Primary Outcome (Figure 1)

• The 10 mg amisulpride group achieved a significantly higher complete response rate than placebo (41.7% vs 28.5%; p=0.006)
• The odds ratio for complete response with 10 mg amisulpride vs placebo was 1.80 (95% CI: 1.22–2.64; P = 0.006).
• At each prespecified interim assessment (2, 4, and 6 hours), the complete response rate was approximately 20% higher with amisulpride 10 mg than with placebo.
• Patients receiving 10 mg amisulpride achieved a significantly greater complete response rate than those receiving placebo, with an absolute difference of 13.2%.

Figure 1 : Complete response

 

Secondary Endpoints (Figure 2)

• Both amisulpride doses significantly reduced vomiting episodes compared with placebo, with the greatest reduction observed with 10 mg
• Patients receiving amisulpride 10 mg required significantly less rescue antiemetic therapy.
• Amisulpride 10 mg significantly reduced moderate-to-severe nausea.
• Neither dose significantly reduced the incidence of any nausea compared with placebo.

Figure 2: Secondary Endpoints 

 

 

 

 

 

 

 

 

 

 

 

*Significant nausea was defined as a nausea score ≥4.

• Time to treatment failure was significantly prolonged with amisulpride 10 mg compared with placebo (median 443 vs 120 minutes; HR 0.63, P < 0.001), indicating sustained control of postoperative nausea & vomiting symptoms.
• Patients treated with amisulpride 10 mg had a numerically shorter PACU stay following treatment than those receiving placebo, with mean durations of 140.9 and 175.5 minutes, resp. 
• The mean hospital stay after dosing was reduced from 56.3 hrs in the placebo group to 50.3 hrs in the amisulpride 10 mg grp.

Safety 

The safety profile of intravenous amisulpride was comparable to placebo, with no clinically relevant safety concerns identified.

Table 1 : Safety Profile of Intravenous Amisulpride Compared with Placebo

Safety Outcome	Placebo	Amisulpride          5 mg	Amisulpride 10 mg
Patients with ≥1 adverse event	48.1%	42.2%	43.0%
Serious adverse events	2.1%	2.5%	1.3%
Deaths	0	0	0

Conclusion

• A single intravenous dose of 10 mg amisulpride was safe and significantly more effective than placebo for the rescue treatment of postoperative nausea and vomiting in patients who failed standard prophylaxis. 
• The treatment improved complete response rates, reduced vomiting and rescue medication use, prolonged time to treatment failure. Intravenous amisulpride therefore represents an effective rescue antiemetic option for established PONV after failed prophylaxis.

Reference

Anesthesiology. 2019;130(2):203–212.