Methods
This study was conducted with patients, American Society of Anesthesiologists physical status rating 1–2 and aged 20–60, who were scheduled to undergo laparoscopic gynaecologic surgery. Exclusion criteria were patients who were pregnant; weighed <45 or ≥100 kg; were smokers; and had a history of PONV, other serious medical ailment of the cardiovascular system, kidney, or liver, or a hepatic disorder. This study was approved by the Chung-Ang University Hospital Institutional Review Board and registered at the Australia-New Zealand Clinical Trials Registry (ACTRN12613000902796). The study objective, methods, and period, and the expected adverse events were explained to the patients before obtaining their consent for participation. Before surgery, the patients were also educated on the visual analogue scale (VAS), a tool by which nausea and pain are rated on a scale of 0 to 10, and the intravenous patient-controlled analgesia (IV-PCA), which would be used postoperatively.
The patients were divided into 2 groups using a random number generator in Microsoft Excel. The aprepitant group (group A) was given 40 mg of aprepitant with 30 mL of water orally, 90 min before anaesthesia induction. The patients were informed that the aprepitant was a premedication for their operation and were unaware that it was a study variable. All the patients in both groups received 0.2 mg of glycopyrrolate intramuscularly, and the standard monitoring methods, which included electrocardiography, non-invasive blood pressure assessment, and pulse oximetry, were initiated after the patients entered the operating room. First, 60-μg/kg midazolam and 2-mg/kg propofol were administered intravenously, followed by 0.6-mg/kg rocuronium after confirmation of the patients' loss of consciousness. Thereafter, intubation was performed. In the palonosetron group (group P), patients blinded to their group status received 0.075 mg of palonosetron intravenously immediately after endotracheal intubation, whereas the patients in group A received an equal volume of normal saline. An independent anaesthesia assistant who was not involved in either intraoperative or postoperative management prepared the study medications. Desflurane with oxygen/nitrous oxide in 0.5 FiO2 was administered at a 1.5–2 minimum alveolar concentration to maintain anaesthesia, and the ETCO2 was maintained at 35–40 mmHg. For postoperative pain management, nefopam (20 mg) was diluted in 100 mL of normal saline and administered intravenously for 30 min, 10 min before surgery. Using automated IV-PCA (Automed 3300; Ace Medical, Seoul, Republic of Korea), 20-μg/kg fentanyl was diluted in normal saline for a total volume of 100 mL, set at a 0.2-μg/kg bolus and a 15-min lockout interval. At the end of surgery, 0.004-mg/kg glycopyrrolate and 0.2-mg/kg pyridostigmine were administered intravenously to reverse any residual neuromuscular block after restoration of spontaneous breathing in all patients. All the anaesthetic procedures were performed by a single anaesthesiologist who was blinded to the patient group allocation.
PONV treatment completion was defined as a VAS nausea score <4 for 48 h after surgery or non-use of additional antiemetic drugs during this period. The VAS score was used to quantify the severity of nausea in the recovery room and 2, 6, 24, and 48 h after surgery. When a patient experienced nausea at a VAS score >4 with retching or vomiting, 10 mg of metoclopramide was administered intravenously. When symptoms did not improve at follow-up, 5 mg of dexamethasone was administered intravenously.
Postoperative pain management was standardised, and patients were trained to press the IV-PCA button when they experienced pain. The VAS score was used to represent the pain that patients experienced in the recovery room and 2, 6, 24, and 48 h after surgery, and their consumption of fentanyl in the IV-PCV was checked. If the VAS score was ≥4, an additional 50 μg of fentanyl was administered and recorded. Postoperative management and data collection were conducted according to the study protocol by another anaesthesiologist and a trained member of the research group, respectively, who were blinded to the patient groupings. The patients remained unaware of their group affiliation until study completion.
This study aimed to demonstrate that aprepitant is non-inferior to palonosetron in preventing PONV. A pilot study was conducted among 40 patients who received palonosetron, which reported a 35% incidence of PONV 48 h after surgery. When the non-superiority margin of aprepitant was set at 25% with an α value of 0.05 and statistical power of 80%, the required number of patients for each group was 46. Considering that <10% of the patients were lost to follow-up, a total of 100 patients were enrolled in the present study.
Repeated-measures analysis of variance was used for the statistical analysis. For continuous variables, a t test was used; for discrete variables, chi-square or Fisher exact tests were used. PASW Statistics version 18.0 (SPSS Inc., IBM Corporation, Chicago, IL, USA) was used for the analysis, and P < 0.05 was considered statistically significant.
BMC Anesthesiol. 2014;14(68) © 2014 BioMed Central, Ltd.
