Comparison of the Efficacy of Ondansetron and Aprepitant for the Prevention of Postoperative Nausea and Vomiting: A Double Blinded Randomized Control Trial in Patients Undergoing Mastectomy/Thyroidectomy

INTRODUCTION: General anaesthesia is a pharmacological depression of the neurological system that results in temporary loss of response to various external stimuli. Postoperative nausea and vomiting (PONV) is an unpleasant side effect of general anaesthesia. They together are the second most common complaints reported. The causative factors of PONV are varied which includes patient related, operative and anaesthesia related factors. Post operative nausea and vomiting (PONV), despite the advances in anaesthetic care is still a problem, following certain types of surgery in the high risk population. Presently, the overall incidence of PONV varies with the types of operative procedures and with the patient groups and is approximately 25 to 30%. A simple score to predict PONV was devised by Apfel et al. The risk factors included are : women, previous history of travel sickness or PONV, non-smokers, and those who receive opioids postoperatively Depending on the Apfel risk score, the PONV incidence was precicted as 10% for a score of 0, 21% for a score of 1, 39% for a score of 2, 61% for a score of 3 and 79% for a score of 4. The incidence of PONV following mastectomy is reported to be 60 to 80%when no prophylactic antiemetic is given, but it can still be as high as 20 to 30% despite the administration of ondansetron. Similarly, patients undergoing various thyroid surgical procedures have a high percentage of PONV because most of them are women and due to several surgical causes. PONV is frequently listed by patients as the most distressing concern in the post operative period, sometimes even exceeding the pain of surgery. The growing awareness to improve patient satisfaction has prompted to strive for a post operative period free of nausea and vomiting. Aprepitant belongs to the class of Neurokinin 1 receptor antagonist. It is highly selective for neurokinin receptors and its half life is long. It is demonstrated to be effective against emesis induced by opioids and chemotherapeutic drugs. In patients having open abdominal surgical procedures and craniotomy, studies have shown that aprepitant had more antiemetic effect than ondansetron in preventing vomiting in the postoperative period. This study was an effort to compare the antiemetic efficacy of ondansetron and aprepitant in women undergoing mastectomy and thyroidectomy. AIM OF THE STUDY: The aim of this study is to compare the efficacy of ondansetron and aprepitant in the prevention of postoperative nausea and vomiting in women undergoing mastectomy and thyroidectomy. OBJECTIVES: 1. To compare the antiemetic efficacy of ondansetron and aprepitant in the prevention of postoperative vomiting in female patients undergoing mastectomy / thyroidectomy. 2. To evaluate the severity of postoperative nausea, number of episodes of vomiting, timing of the first vomiting episode and use of rescue antiemetics in thyroidectomy and mastectomy patients receiving ondansetron or aprepitant as antiemetic. 3. To assess if the patients satisfaction in the management of postoperative nausea and vomiting improves with this intervention. PATIENTS AND METHODS: SETTING OF THE STUDY: This study was carried out in the department of Anaesthesiology, Christian Medical College and Hospital, Vellore, which is a tertiary care hospital. The subjects were selected from among those patients posted for elective surgery by the department of Endocrine surgery. STUDY DESIGN: The two groups in this study were group 1 who received injection ondansetron and capsule placebo and group 2 who received capsule aprepitant and injection placebo. The protocol is as follows. This is a double blinded, randomized clinical control trial, approved by the ethics and research committee of our institution. Inclusion Criteria: 1. ASA (American Society of Anaesthesiology) physical status 1 and 2, 2. Female patients, 3. Age 18 to 65 years, 4. Scheduled for thyroidectomy / mastectomy. EXCLUSION CRITERIA: 1. Patients who are receiving antiemetics, 2. Patients on steroid medication, 3. Patients on drugs known to cause emesis currently or in the immediate past, 4. Patients with known hypersensitivity to ondansetron or aprepitant, 5. Pregnant and nursing mothers. A few days before the surgery, the details of the study were explained to the eligible patients and a detailed information sheet was given to them. On the day before the surgery, an informed consent was obtained from those who were willing to participate in the study. The randomization schedule was a computer generated random sequence, done by the biostatistician who was not involved with the study. On the day of the surgery, patients were randomized to receive one of the 2 antiemetic treatments: oral aprepitant 40 mg capsule within 3 hours of the anticipated induction of anaesthesia or injection ondansetron 8 mg I.V (4 ml) towards the end of surgery and 2 more doses in the ward at 8 hourly intervals. Double blinding was done with matching placebos. A pharmacist who was not involved in the study prepared aprepitant 40 mg capsules, placebo matching aprepitant capsules, injection ondansetron 8 mg (4 ml) vials and matching saline placebo vials. The anaesthesia technique included optimal premedication and standard anaesthetic agents. The patient was shifted to the post anaesthesia care unit, monitored for 1 hour and later shifted to the ward. Other antiemetic medications were prohibited prophylactically within 24 hours of surgery. Only rescue therapy was offered on patient request, persistant nausea or an emetic episode. The type of rescue medication was left to the discretion of the post operative care provider. The duration of anaesthesia and timing of all the emetic episodes and rescue medications given post operatively were recorded. An independent investigator unaware of the patient’s randomization collected the data. Using a verbal rating scale, patients graded nausea from 0 (no nausea) to 10 (nausea as bad as it could be) at 0-2, 2-12 and 12-24 hours after the operation. Nausea was defined as an uncomfortable feeling that leads to a tendency to vomit. Retching was defined as an effort to vomit which is not under voluntary control and that does not cause expulsion of stomach contents. Vomiting was defined as a expulsion of stomach contents. An emetic episode was described as a single retch or vomit or any number of continuous vomits or retches. STATISTICAL METHODS: The primary outcome in this study is the occurrence of vomiting. Chi square test was used to compare this outcome variable between the two groups to determine the statistical significance. Similarly, the secondary outcomes in study which includes severity of postoperative nausea, number of episodes of vomiting and use of rescue antiemetics are compared between the two groups using chi-square tests. The other parameters like the duration of anaesthesia and the timing of the first vomiting episode were compared between the two groups using Mann-Whitney non parametric test. Data analysis was performed using the software SPSS 14.0 and Microsoft Office Excel 2007. RESULTS: The two groups in this study are group 1 who received injection ondansetron and capsule placebo and group 2 who received capsule aprepitant and the placebo injection. The protocol is as follows. GROUP 1 - Cap. placebo within 1 hour preoperatively and Inj. Ondansetron 4 ml (8 mg) in the post operative period every 8 hours - 3 doses. (1st dose was given in theatre at the end of surgery & the next 2 doses were given in the ward). GROUP 2 - Cap.Aprepitant within 1 hour preoperatively (along with the pre medication) and Inj.placebo 4 ml in the post operative period every 8 hours - 3 doses (1st dose was given in theatre at the end of surgery & the next 2 doses were given in the ward). In this study there were 62 patients in group 1 and 63 patients in group 2 making a total of 125 patients. Out of this 125 patients, 5 patients were excluded from the study after randomisation, since they required unanticipated intensive care or high dependency unit admissions or required intraoperative steroids which will influence the assessment of antiemetic efficacy. CONCLUSIONS: A single dose of oral aprepitant has comparable effects to injection ondansetron administered eighth hourly in preventing PONV, the severity of nausea, number of rescue antiemetics and the time to first emetic episode in the 24 hour postoperative period.