Combination Antiemetic Regimen for Prevention of PONV in Breast Surgery Patients
Combination Antiemetic Regimen for Prevention of PONV in Breast Surgery Patients
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.
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).
Inclusion Criteria:

 All of the following criteria must be met for the potential subject to be eligible for
 participation:

 1. The subject is a female scheduled to undergo ambulatory breast surgery performed under
 general anesthesia

 2. The subject is expected to undergo general inhalation anesthesia.

 3. The subject presents with two of the three following high-risk factors associated with
 PONV (must be in their medical history in order to be eligible)

 -  She is a non-smoker.

 -  She has documented history of PONV and/or motion sickness.

 -  She is expected to receive intra-operative and postoperative opioid.

 4. The subject's American Society of Anesthesiologist physical status is ASA I-III

 5. The subject is between18 to 65 years of age.

 6. The subject is expected to be discharged from the hospital/surgical center on the same
 day as the surgery.

 7. The subject has provided written informed consent to participate in the study.

 If any of the following exclusion criteria are met, the potential subject is NOT eligible
 for participation:

 1. The subject has a history of allergic reaction to, intolerances of or
 contraindications for any of the study medications or required anesthetic agents.

 2. The subject has received or is expected to receive any excluded preoperative drug
 within 48 hours prior to induction; or is expected to receive any excluded
 intra-operative or postoperative medications.

 3. The subject is pregnant or lactating. (If the potential subject is pre-menopausal, a
 urine pregnancy test must be performed within 24 hours/1 day of study prior to the
 planned surgery time and confirmed negative in order for the potential subject to be
 enrolled).

 4. The subject is taking warfarin.

 5. The subject has a history of alcohol and/or drug abuse within 1 year of study
 medication, or has a positive screening or pre-study test for alcohol or drugs of
 abuse.

 6. The subject is expected to require the use of a nasogastric tube postoperatively.

 7. The subject has a diagnosed latex allergy.

 8. The subject has used oral aprepitant (Emend®) within the last 30 days.

 9. The subject has participated in a randomized study or has been exposed to any
 experimental drug within 30 days prior to enrollment of this study.

 Exclusion Criteria: