Effect of palonosetron and the association palonosetron/aprepitant on the incidence of postoperative nausea and vomiting in high-risk oncological patients

Abstract

1. Background - Nausea and vomiting are amongst the most distressing symptoms in the postoperative setting. Its etiology is multifactorial and is associated with a number of risk factors that can be related or unrelated to the patients history. Examples of patient-related factors include age, gender, weight and history of postoperative nausea and vomiting, while surgery-related factors are duration of surgery, anesthetic medication, type of surgery and postoperative pain. The main instrument used by anesthesiologists to estimate the risk of symptom occurrence is the Apfel score which includes 4 variables and attributes one point for each. The variables are: female gender, non-smokers, previous postoperative nausea and vomiting and use of opioids after surgery. Each point increases 20% the probability of adverse event ranging from 10 to 80% considering that those who score 0 on the scale already have a 10% chance. To prevent such complications physicians utilize antiemetic medication that act on specific physiopathological pathways. These pathways include the chemoreceptor trigger zone and the vomiting centre located in the medulla oblongata. Both receive peripheral and central input involving serotonine, dopamine, acetylcholine, histamine and neurokinines receptors. This study takes in to account recent studies and guidelines for treatment of nausea and vomiting, especially those concerning the blockade of neurokinin 1 receptor with Aprepitant. The study investigates new possibilities of treatment associating the classic serotonin receptors (5-HT3) antagonist to Aprepitant. 2. Objectives - Assess the effect of the association palonosetron/dexamethasone and aprepitant on the reduction of postoperative nausea and vomiting in patients with high risk for these symptoms undergoing oncological mastectomy.3. Methods - The study is a prospective, double-blind, randomized clinical trial of women patients, classified as ASA I or II, undergoing oncological mastectomy admitted in the ''Instituto do Câncer do Estado de São Paulo''. The patients will be randomly selected through the program ''list randomizer'' available in the website www.random.org . Then, they'll be divided in to two groups of approximately 42 people. One group will receive 120mg of aprepitant orally 60 minutes before surgery, then, during the procedure, 8mg of palonosetron and 4mg of dexamethasone intravenously. The other group will receive placebo orally 60 minutes before surgery, then, during the procedure, 8mg of palonosetron and 4mg of dexamethasone. Inclusion factors will be Apfel 3 or 4 patients, total intravenous anesthesia and literate patients. Exclusion factors will be combined anesthesia, ASA III or IV, history of allergies to any of the medications used and neurological deficits and/or psychiatric disturbances. After the procedure the patients will be analyzed for nausea trough the Linkert scale, and for pain trough verbal descriptor scale and visual analog scale. (AU)