title: A comparison of the combination of aprepitant and dexamethasone versus the combination of ondansetron and dexamethasone for the prevention of postoperative nausea and vomiting in patients undergoing craniotomy.
abstract: BACKGROUND
  Postoperative nausea and vomiting (PONV) occur commonly after craniotomy. In patients receiving prophylaxis with ondansetron and dexamethasone, vomiting occurred in 45% of patients at 48 hours. In addition to causing patient discomfort, the physical act of vomiting may increase intracranial pressure or cerebral intravascular pressure, jeopardizing hemostasis and cerebral perfusion. Aprepitant is a neurokin-1 receptor antagonist with a long duration of action and no sedative side effect. In a large multicenter study in patients undergoing abdominal surgery, aprepitant was significantly more effective than was ondansetron in preventing vomiting at 24 and 48 hours postoperatively. We hypothesized that the combination of aprepitant with dexamethasone will decrease the incidence of postoperative vomiting when compared with the combination of ondansetron and dexamethasone in patients undergoing craniotomy under general anesthesia.
  
  
  METHODS
  Patients scheduled to undergo craniotomy under general anesthesia were enrolled in this prospective, double-blind, randomized study. Patients were randomized to receive oral aprepitant 40 mg (or matching placebo) 1 to 3 hours before induction of anesthesia or ondansetron 4 mg IV (or placebo) within 30 minutes of the end of surgery. All patients received dexamethasone 10 mg after induction of anesthesia. The anesthetic technique was standardized. Data were collected at regular intervals by blinded personnel for 48 hours after surgery. Statistical analysis was performed using Wilcoxon's ranked sum test and χ(2) test. P < 0.05 was considered statistically significant.
  
  
  RESULTS
  One hundred four patients completed the study. The cumulative incidence of vomiting at 48 hours was 16% in the aprepitant group and 38% in the ondansetron group (P = 0.0149). The incidence of vomiting was also decreased in the aprepitant group at 2 hours (6% vs. 21%, P = 0.0419) and 24 hours (14% vs. 36%, P = 0.0124). From 0 to 48 hours, there was no difference between the aprepitant and ondansetron groups in the incidence of nausea (69% vs. 60%), nausea scores, need for rescue antiemetics (65% vs. 60%), complete response (no PONV and no rescue, 22% vs. 36%), or patient satisfaction with the management of PONV.
  
  
  CONCLUSIONS
  The combination of aprepitant and dexamethasone was more effective than was the combination of ondansetron and dexamethasone for prophylaxis against postoperative vomiting in adult patients undergoing craniotomy under general anesthesia. However, there was no difference between the groups in the incidence or severity of nausea, need for rescue antiemetics, or in complete response between the groups.
authors.affiliation: Duke University Medical Center, Box 3094, Durham, NC 27710, USA. habib001@mc.duke.edu
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Habib
authors.forename: John C
authors.initials: JC
authors.lastname: Keifer
authors.forename: Cecil O
authors.initials: CO
authors.lastname: Borel
authors.forename: William D
authors.initials: WD
authors.lastname: White
authors.forename: Tong J
authors.initials: TJ
authors.lastname: Gan
mesh_terms: D000328:Adult; D000077608:Aprepitant; D003399:Craniotomy / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D017294:Ondansetron; D020250:Postoperative Nausea and Vomiting / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies
chemical_list: D009025:Morpholines; D000077608:Aprepitant; D017294:Ondansetron; D003907:Dexamethasone