title: Antiemetics added to phenylephrine infusion during cesarean delivery: a randomized controlled trial.
abstract: OBJECTIVE
  To estimate whether the addition of metoclopramide or its combination with ondansetron to a prophylactic phenylephrine infusion provides improved intraoperative nausea and vomiting prophylaxis compared with phenylephrine infusion alone.
  
  
  METHODS
  Women scheduled for elective cesarean delivery were randomized to one of three groups: placebo (placebo plus placebo); metoclopramide (metoclopramide 10 mg plus placebo); or combination (metoclopramide 10 mg plus ondansetron 4 mg). The first study drug was administered before spinal placement and the second was administered after cord clamping. Spinal anesthesia was standardized. The primary outcome was intraoperative nausea and vomiting.
  
  
  RESULTS
  Three-hundred patients completed the study in two centers. Intraoperative nausea and vomiting occurred in 49%, 31%, and 23% of patients in the placebo, metoclopramide, and combination groups, respectively (P<.001). There was a significant difference between the two centers in exteriorization of the uterus (93% compared with 39%; P<.001) and intraoperative nausea and vomiting rates (47% compared with 20%; P<.001). In a multivariable model adjusting for center, exteriorization of the uterus, age, and hypotension, intraoperative nausea and vomiting were significantly lower in the metoclopramide and combination groups compared with placebo (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.24--4.42; P=.001 and OR 4.06, 95% CI 2.06--7.97; P<.001, respectively). Postoperative nausea and vomiting were reduced with the combination compared with placebo at 2 hours (39% compared with 20%; P<.017), but not at 2-6 hours or at 6-24 hours.
  
  
  CONCLUSIONS
  Metoclopramide with ondansetron reduced intraoperative nausea and vomiting and early postoperative nausea and vomiting compared with placebo. Metoclopramide alone also decreased intraoperative but not postoperative nausea and vomiting. Surgical factors contributed to a significant difference in intraoperative nausea and vomiting between the two centers.
authors: Departments of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada; and Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors: Ashraf S
authors: AS
authors: Habib
authors: Ronald B
authors: RB
authors: George
authors: Dolores M
authors: DM
authors: McKeen
authors: William D
authors: WD
authors: White
authors: Unyime S
authors: US
authors: Ituk
authors: Sohair A
authors: SA
authors: Megalla
authors: Terrence K
authors: TK
authors: Allen
mesh_terms: D000328:Adult; D000775:Anesthesia, Spinal / Q000009:adverse effects; D000932:Antiemetics / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002585:Cesarean Section; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control*; D008787:Metoclopramide / Q000627:therapeutic use*; D009325:Nausea / Q000209:etiology / Q000517:prevention & control; D017294:Ondansetron / Q000627:therapeutic use*; D010656:Phenylephrine / Q000627:therapeutic use; D011247:Pregnancy; D014839:Vomiting / Q000209:etiology / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D002316:Cardiotonic Agents; D010656:Phenylephrine; D017294:Ondansetron; D008787:Metoclopramide
references: Balki M, Carvalho JC. Intraoperative nausea and vomiting during cesarean section under regional anesthesia. Int J Obstet Anesth 2005;14:230–41.
references: Ngan Kee WD, Khaw KS, Ng FF. Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section. Br J Anaesth 2004;92:469–74.
references: Habib AS. A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia. Anesth Analg 2012;114:377–90.
references: Chestnut DH, Vandewalker GE, Owen CL, Bates JN, Choi WW. Administration of metoclopramide for prevention of nausea and vomiting during epidural anesthesia for elective cesarean section. Anesthesiology 1987;66:563–6.
references: Lussos SA, Bader AM, Thornhill ML, Datta S. The antiemetic efficacy and safety of prophylactic metoclopramide for elective cesarean delivery during spinal anesthesia. Reg Anesth 1992;17:126–30.
references: Stein DJ, Birnbach DJ, Danzer BI, Kuroda MM, Grunebaum A, Thys DM. Acupressure versus intravenous metoclopramide to prevent nausea and vomiting during spinal anesthesia for cesarean section. Anesth Analg 1997;84:342–5.
references: Mishriky BM, Habib AS. Metoclopramide for nausea and vomiting prophylaxis during and after Caesarean delivery: a systematic review and meta-analysis. Br J Anaesth 2012;108:374–83.
references: Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, et al.. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441–51.
references: Danelli G, Zangrillo A, Nucera D, Giorgi E, Fanelli G, Senatore R, et al.. The minimum effective dose of 0.5% hyperbaric spinal bupivacaine for cesarean section. Minerva Anestesiol 2001;67:573–7.
references: Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A. The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med 2009;360:2528–35.
references: Allen TK, George RB, White WD, Muir HA, Habib AS. A double-blind, placebo-controlled trial of four fixed rate infusion regimens of phenylephrine for hemodynamic support during spinal anesthesia for cesarean delivery. Anesth Analg 2010;111:1221–9.
references: Ngan Kee WD, Khaw KS, Ng FF, Lee BB. Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2004;98:815–21.
references: Siddiqui M, Goldszmidt E, Fallah S, Kingdom J, Windrim R, Carvalho JC. Complications of exteriorized compared with in situ uterine repair at cesarean delivery under spinal anesthesia: a randomized controlled trial. Obstet Gynecol 2007;110:570–5.
references: Viney R, Isaacs C, Chelmow D. Intra-abdominal irrigation at cesarean delivery: a randomized controlled trial. Obstet Gynecol 2012;119:1106–11.
references: Habib AS, Gan TJ. Evidence-based management of postoperative nausea and vomiting: a review. Can J Anaesth 2004;51:326–41.