Combination Antiemetic Regimen for Prevention of PONV in Breast Surgery Patients

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).