Combination Antiemetic Regimen for Prevention of PONV in Breast Surgery Patients
Condition: Postoperative Nausea and Vomiting
MeSH terms: Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to compare the efficacy of the use of oral aprepitant in
      combination with intravenous ondansetron and dexamethasone with the efficacy provided by the
      use of oral aprepitant and dexamethasone for preventing vomiting during the first 24-48 hours
      after breast surgery.
    

Detailed description: 
      Postoperative nausea and vomiting (PONV) is one of the most common complications associated
      with surgery. The overall incidence of PONV is reported to be about 25-30% with specific
      surgeries having an incidence up to 70-80%.1-5 Although PONV is typically not life
      threatening, patients dread the sensation of nausea and the serious effects of retching and
      vomiting. PONV in the surgical patient can cause wound dehiscence, electrolyte imbalance,
      increased intraocular pressure, increased intracranial pressure, aspiration, esophageal
      rupture, and loss of vision due to retinal detachment. 6-11 In several studies, investigators
      found that patients rank vomiting as the most undesirable common side effect after surgery.
      PONV is costly in economic terms and is a reason day surgery patients must be admitted in the
      hospital for an overnight stay.12, 13 It is estimated that a patient who experiences an
      episode of vomiting costs an additional $300 based on emesis basins, supplies, gowns,
      bedding, additional medications, and nursing/physician time.14-20

      In general, PONV is highest in women (with a 2-3 times increased risk) and particularly after
      procedures such as gynecological surgery, laparoscopy, thyroidectomy and breast surgery.5,
      21-35 A study by Sinclair and group found that patients undergoing breast augmentation
      experienced an 8-10 fold higher incidence of PONV than patients undergoing other types of
      plastic surgery.26 Similar incidences were found in other studies of 48% to 68% of PONV in
      patients undergoing mastectomies, breast reconstruction, and implantation.36-40

      The hospitalization of patients undergoing breast cancer surgery has significantly decreased
      by 40% between 1993 and 2003. Many surgeries are now being performed on an outpatient basis
      according to the Agency for Healthcare Research and Quality (AHRQ), with 96% of lumpectomies,
      86% of partial mastectomies and 22% of complete mastectomies scheduled as ambulatory
      surgeries.41 Carroll and group found that 35% of outpatients suffered from nausea and
      vomiting after they left the surgical center.42 Therefore, the resulting problem is not only
      the high incidence of nausea and vomiting in this specific group of patients but the post
      discharge nausea and vomiting (PDNV) that will occur when these patients are at home and
      without direct medical oversight.

      Although still unclear, it is postulated that the etiology of postoperative nausea and
      vomiting is the central mechanism involving stimulation of the chemoreceptor trigger zone
      (CTZ) located bilaterally at the floor of the fourth ventricle in the area postrema. The CTZ
      is sensitive to toxins and other substances in the blood and cerebrospinal fluid. The CTZ
      also receives sensory signals from the gastro-intestinal tract. The are three major central
      nervous system (CNS) areas involved with PONV which all have specific emetogenic receptors.
      Blockade of these receptors is postulated to be the mechanism of action of the commonly used
      antiemetics. The agents' antagonist activity may be at one or more receptors with different
      binding affinities and acting at different emetic neuroreceptors. The multifactorial etiology
      of PONV involving multiple receptors is believed to be the reason one single agent is not
      100% effective. The administration of an agent working on one receptor type will typically
      reduce the PONV incidence by 30%. Use of a combination of antiemetic agents acting on
      different receptor sites will further reduce the incidence. This combination has shown
      greater efficacy than a single agent alone. Although this regimen has improved outcomes it
      has not eliminated the problem of PONV and patients needing rescue therapy post surgery
      occurs frequently. It would appear reasonable to assume that the use of more than 2
      antiemetics would further reduce the incidence of PONV.43 However; published evidence of
      greater than 2 agents is scarce. Therefore, the main objective of our proposal is to study a
      combination antiemetic regimen (3 agents vs. 2 agents) in females scheduled for breast
      surgery, a patient population considered at high risk for postoperative vomiting. The
      selected agents will cover different receptors based on the hypothesized PONV multifactorial
      etiology with stimulation of several factors. It is unknown which of these receptors may be
      stimulated and by which stimuli (anesthetic, surgery, or patient factors).
    

Intervention name(s): Aprepitant, Dexamethasone, Ondansetron; Aprepitant, Dexamethasone, Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Aprepitant oral 40mg one dose, dexamethasone IV 4mg one dose, ondansetron 4 mg one dose; Aprepitant 40mg oral one time, dexamethasone IV 4mg one time placebo one time
Other intervention name(s): Emend=aprepitant; Emend=aprepitant
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Ondansetron; Aprepitant; Fosaprepitant; BB 1101
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: PONV; breast surgery; prevention; antiemetics