title: I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial.
abstract: BACKGROUND
  Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis.
  
  
  METHODS
  Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery.
  
  
  RESULTS
  Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects.
  
  
  CONCLUSIONS
  APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.
authors.affiliation: Department of Anaesthesia and Critical Care, University Hospital of Würzburg, Oberdürrbacher Str. 6, Würzburg 97080, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Kranke
authors.forename: L
authors.initials: L
authors.lastname: Eberhart
authors.forename: J
authors.initials: J
authors.lastname: Motsch
authors.forename: D
authors.initials: D
authors.lastname: Chassard
authors.forename: J
authors.initials: J
authors.lastname: Wallenborn
authors.forename: P
authors.initials: P
authors.lastname: Diemunsch
authors.forename: N
authors.initials: N
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Keh
authors.forename: H
authors.initials: H
authors.lastname: Bouaziz
authors.forename: M
authors.initials: M
authors.lastname: Bergis
authors.forename: G
authors.initials: G
authors.lastname: Fox
authors.forename: T J
authors.initials: TJ
authors.lastname: Gan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077582:Amisulpride; D000769:Anesthesia, Inhalation / Q000379:methods; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control*; D011184:Postoperative Period; D011229:Preanesthetic Medication / Q000379:methods; D013469:Sulpiride / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000932:Antiemetics; D018492:Dopamine Antagonists; D013469:Sulpiride; D000077582:Amisulpride
keywords: antiemetics; postoperative nausea and vomiting; randomized controlled trial; sulpiride/*analogues and derivatives, amisulpride