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BACKGROUND: Postoperative nausea and vomiting (PONV) are common complications after surgery. Neurokinin-1 (NK1) receptor antagonists have been shown to be safe and effective for the prevention and treatment of PONV in humans. Rolapitant is a potent, selective NK1 receptor antagonist that is rapidly absorbed, has a remarkably long half-life (up to180 hours), and appears to have a low potential for drug–drug interactions. We evaluated the dose response for rolapitant for the prevention of PONV in subjects at high risk for this condition, and rolapitant's effects on preventing delayed PONV were explored up to 5 days after surgery. METHODS: A randomized, multicenter, double-blind, dose-ranging study of rolapitant was conducted with placebo and active control groups. Six hundred nineteen adult women undergoing open abdominal surgery were randomly assigned in equal ratios to 1 of 6 study arms: oral rolapitant in 5-mg, 20-mg, 70-mg, or 200-mg doses; IV ondansetron 4 mg; or placebo, stratified by history of PONV or motion sickness. The primary study endpoint was absence of emetic episodes, regardless of use of rescue medication, at 24 hours after extubation. RESULTS: Groups assigned to rolapitant 20-mg, 70-mg, and 200-mg had a higher incidence of no emesis in comparison with placebo at 24 hours after surgery. A linear relationship between rolapitant dose and primary outcome was seen. The probability of an emetic episode was significantly lower in the rolapitant 70-mg and 200-mg groups in comparison with placebo (P ≤ 0.001 based on the log-rank test). No significant differences were noted between rolapitant and the active control (ondansetron) at 24 hours after surgery, but there was a higher incidence of no emesis (regardless of rescue medication use) in the rolapitant 200- and 70-mg groups at 72 and 120 hours, respectively. CONCLUSION: Rolapitant is superior to placebo in reducing emetic episodes after surgery and reduces the incidence of vomiting in a dose-dependent manner. No differences in side effect profile were observed between rolapitant and placebo.

This randomized, double-masked, placebo-controlled, multicenter trial was conducted in 9 countries to assess the safety and efficacy of 2 doses of intravenous ondansetron (8 and 16 mg) for the control of opioid-induced nausea and vomiting. A total of 2574 nonsurgical patients who presented with pain requiring treatment with an opioid analgesic agent participated in this trial. The most common presenting painful condition was back or neck pain, reported by approximately one third of patients. A total of 520 patients (317 females, 203 males) developed nausea or vomiting after opioid administration and were randomly assigned to receive a single dose of 1 of 3 study treatments: placebo (n = 94), ondansetron 8 mg (n = 215), or ondansetron 16 mg (n = 211). Ondansetron 8 and 16 mg led to complete control of emesis in 134 of 215 patients (62.3%) and 145 of 211 patients (68.7%), respectively. Results with both doses were significantly better than those seen with placebo (43 of 94 patients [45.7%]). Complete control of nausea was achieved in 6.8% of placebo patients, 14.8% of ondansetron 8-mg-treated patients, and 19.4% of ondansetron 16-mg treated patients; only ondansetron 16 mg was significantly better than placebo (P = 0.007). Significantly more patients who received ondansetron 8 mg than patients who received placebo were satisfied/very satisfied with their antiemetic treatment, as assessed by 4 patient-satisfaction questions. Significantly more patients who received ondansetron 16 mg compared with placebo were satisfied/very satisfied on 2 of 4 satisfaction questions. In conclusion, based on the observed incidence of opioid-induced nausea and vomiting in this study, it may be more appropriate to treat symptoms on occurrence rather than administering antiemetic agents prophylactically. The results of this study demonstrate that intravenous ondansetron in doses of 8 or 16 mg is an effective antiemetic agent for the control of opioid-induced nausea and vomiting in nonsurgical patients requiring opioid analgesia for pain.

Purpose: To compare the efficacy and safety of oral ondansetron with i.v. granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy. Patients and Methods: Chemotherapy-naive patients with histologically confirmed malignancies were randomized to receive a single 24 mg ondansetron hydrochloride tablet plus a 50 ml i.v. infusion of normal saline, or a single 10 µg/kg (50 ml) i.v. infusion of granisetron plus a placebo tablet in this multicenter, double-blind, parallel-group trial. Study drug was administered 30 min prior to a single i.v. infusion of cisplatin (50-75 mg/m 2 ), given over a period of  three h. Concurrent administration of corticosteroids was not allowed. Efficacy measurements included the number of emetic episodes, need for rescue medication, and patient assessments of nausea and appetite. Complete response (CR) was defined as no emetic episodes, rescue, or withdrawal; major response was defined as one or two

UNLABELLED Two identical, randomized, double-blind, placebo-controlled studies enrolled 2061 adult surgical outpatients at high risk of postoperative nausea and vomiting (PONV) to compare i.v. ondansetron 4 mg with droperidol 0.625 mg and droperidol 1.25 mg for the prevention of PONV. The antiemetic drugs or placebo were administered i.v. 20 min before the induction of anesthesia with a barbiturate compound, followed by maintenance with N2O/isoflurane/enflurane. Nausea, emetic episodes, adverse events, and patient satisfaction were analyzed for the 0 to 2 h and 0 to 24 h postoperative periods. In the 0 to 2 h postoperative period, there was a complete response (no emesis or rescue antiemetic) in 46% of subjects given placebo (P < 0.05 versus antiemetic groups), in 62% given ondansetron, in 63% given droperidol 0.625 mg, and in 69% given droperidol 1.25 mg (P < 0.05 versus ondansetron). In the 0 to 24-h postoperative period, there were no significant differences in complete response between the ondansetron and droperidol 0.625 or 1.25 mg groups; all groups remained superior to placebo. The proportion of patients without nausea during the 0 to 24 h postoperative period was greater in the antiemetic groups compared with the placebo group; however, droperidol 1.25 mg was more effective than ondansetron 4 mg or droperidol 0.625 mg (43% vs 29% or 29%, respectively). Headache incidence was higher in the ondansetron group compared with either droperidol group. Patient satisfaction scores did not differ significantly among antiemetic treatment groups, although all were superior to placebo. In conclusion, all antiemetic treatment regimens were superior to placebo for the prevention of PONV in the immediate postoperative period; however, droperidol 1.25 mg was more efficacious than ondansetron during the early recovery period (0-2 h). There were no significant differences between ondansetron and either droperidol dose for emesis prevention during the 0 to 24 h postoperative period. IMPLICATIONS More than 2000 patients at high risk of postoperative nausea and vomiting were given either placebo, ondansetron 4 mg, or droperidol 0.625 mg or 1.25 mg i.v. before the administration of general anesthesia. After surgery, the incidence of nausea, vomiting, medication side effects, and patient satisfaction were evaluated for 24 h. Droperidol 0.625 or 1.25 mg i.v. compared favorably with ondansetron 4 mg i.v. for the prevention of postoperative nausea and vomiting after ambulatory surgery.

The use of opioids for postoperative analgesia may be limited by side effects such as nausea and vomiting. Because ondansetron, a selective serotonin type 3 (5-hydroxytryptamine [5-HT3]) antagonist, is effective for chemotherapy and general anesthesia-induced nausea and vomiting, we hypothesized that it may also be effective for opioid-induced nausea and vomiting. ASA physical status I-III patients undergoing regional anesthesia were eligible for the study. Those who requested an antiemetic after postsurgical opioid administration were randomized to receive a single dose of ondansetron (0.1 mg, 4 mg, or 16 mg intravenously [I.V.]) or placebo in a double-blind fashion. Emetic episodes, nausea and pain ratings, and adverse events were recorded for 24 h after study drug administration. Patient satisfaction scores were obtained 24 h after study drug infusion. A significantly (P < 0.05) larger proportion of patients treated with ondansetron 4 mg and 16 mg experienced no emetic episodes, received no rescue antiemetic, and completed the study compared with placebo. Nausea scores and patient satisfaction scores in the ondansetron 16-mg group were significantly (P < 0.05) more favorable than in the placebo group. Postsurgical pain scores did not differ among groups. The incidence of adverse events was similarly low across groups. The results of this study support our hypothesis that I.V. ondansetron is effective for postsurgical opioid-induced nausea and vomiting.

To assess changes in the electrocardiogram (ECG) associated with intraoperative infusion of adenosine in patients undergoing open abdominal gynecological surgery.One hundred and sixty-six patients undergoing gynecological surgery were randomly assigned to receive one of four doses of adenosine infusion (25, 50, 100, or 200 μg/kg/min) or matching placebo. Study drug administration was started at skin incision and discontinued at end of surgery. A standardized general anesthetic regimen was used and adjusted based on hemodynamic and bispectral index values. Heart rate and rhythm variables, and PR, QRS, QT, and QTc intervals were recorded from 12-lead ECGs before anesthesia and immediately after patient arrival in the postanesthesia care unit. In addition, a rhythm strip was obtained during administration of the loading dose of the study drug. ECG variables were compared within and between groups. Incidence of ECG and hemodynamic abnormalities was recorded.One hundred and fifty-one subjects had a full set of electrocardiographic data: placebo (n = 38), group adenosine 25 μg/kg/min (n = 31), group adenosine 50 μg/kg/min (n = 29), group adenosine 100 μg/kg/min (n = 28), and group adenosine 200 μg/kg/min (n = 25). Statistically significant postoperative QTc prolongation was observed in all study groups when compared with baseline except for the adenosine 200 μg/kg/min group. However, these changes from baseline were not different among the groups. There were also no significant differences in PR, QRS, and QT intervals between the treatment groups.There was no difference in QTc prolongation following intraoperative administration of adenosine infusion compared with placebo during isoflurane general anesthesia. However, QTc prolongation is common following general anesthesia.

Background Adenosine regulates pain transmission by actions at spinal, supraspinal, and peripheral sites. A few studies have suggested that administration of adenosine might be associated with anesthetic- and analgesic-sparing effects. The primary aim of this multicenter study was to determine the dose-response profile of adenosine with respect to perioperative analgesia. Methods Women undergoing major gynecologic surgery were enrolled. Subjects were randomly assigned to receive one of four doses of adenosine (25, 50, 100, or 200 microg x kg x min) or matching placebo. A dose-escalation cohort approach was followed. Study drug administration was started in the operating room at the time of skin incision and discontinued at the end of surgery. The anesthetic technique was standardized. Postoperative analgesia was provided with a standardized morphine patient-controlled analgesia system. Data were collected in the hospital and after discharge daily through postoperative day 7. Results A total of 166 subjects received treatment with study drug: 125 received adenosine and 41 received placebo. Except for height, there were no differences between treatment groups with respect to demographic or baseline characteristics. Cumulative opioid use during the initial 24-h period after extubation was not significantly different between treatment groups. There were also no differences between treatment groups with respect to cumulative anesthetic use, intraoperative opioid requirements, pain scores, sedation, time to readiness for discharge from the postanesthesia care unit, time to readiness for discharge from the hospital, opioid-related symptom distress scores, patient satisfaction with pain control, and occurrence of adverse events. Conclusions There were no differences between placebo and adenosine with respect to efficacy and safety for perioperative analgesia.

Study Objectives: To compare repeat intravenous (IV) dosing of ondansetron 4 mg with placebo for the treatment of postoperative nausea and vomiting (PONV) in patients for whom prophylactic, preoperative ondansetron 4 mg IV was inadequate Design: Randomized, double-blind, placebo-controlled study. Setting: Ten outpatient surgical centers in the United States. Patients: 2,199 male and female ASA physical status I, II, and III patients ≥12 years old scheduled to undergo outpatient surgical procedures and receive nitrous oxide-based general anesthesia. Interventions: Ondansetron 4 mg IV was administered to all patients before induction of general anesthesia. Patients who experienced PONV or requested antiemetic therapy within 2 hours after discontinuation of inhaled anesthesia were randomized (1:1) to either a repeat IV ondansetron 4 mg dose or placebo. Measurements and Main Results: Of the 2,199 patients prophylactically treated with ondansetron 4 mg before anesthesia induction, 1,771 (80.5%) did not experience PONV or request antiemetic therapy during the 2 hours following discontinuation of anesthesia. Of the 428 patients who experienced PONV or requested antiemetic therapy during the same period, and were randomized to additional treatment (214 randomized to ondansetron, 214 randomized to placebo), the incidence of complete response (no emesis, no rescue medication, no study withdrawal) was similar for both ondansetron-randomized and placebo-randomized groups for the 2-hour (34% and 43%, respectively, p = 0.074) and 24-hour (28% and 32%, respectively, p = 0.342) postrandomization study periods. Repeat ondansetron dosing was not more effective than placebo in controlling either postoperative emesis or the severity/duration of postoperative nausea. The administration of an additional dose of ondansetron 4 mg postoperatively did not result in an increased incidence of adverse effects. Conclusions: In patients for whom preoperative prophylaxis with ondansetron 4 mg IV is not successful, a repeat dose of ondansetron 4 mg IV in the postanesthesia care unit does not appear to offer additional control of PONV.