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The issue of postoperative nausea and vomiting (PONV) remains important in surgical practice, contributing to patient distress, slower recovery, and increased use of healthcare resources. Many surgical patients report it to be a worse problem than pain. Numerous findings of research indicate that PONV significantly affects patients' well-being and is among the important determinants of patient satisfaction with perioperative care. Numerous investigations have confirmed the efficacy of combining pharmacological interventions indicating that PONV is a clinical complication that is in principle avoidable. Nonetheless, PONV continues to be bothersome for too many patients. Thus, perhaps the biggest challenge across the field is to achieve a uniformly high standard of PONV management using the currently available resources. Although a risk-adapted approach has been advocated in the past, the current trend incorporated in clinical guidelines support a more liberal approach of multimodal antiemetic prevention. The current article emphasizes pros and cons of the various approaches to PONV prophylaxis and depicts most promising strategies to achieve a "PONV-free hospital.", Competing Interests: Declaration of Competing Interest PK acted as clinical investigator in clinical trials on PONV and received patient-related fees to conduct the studies. He is also the coauthor of the cited consensus statements on PONV published by the Society of Ambulatory Anesthesia (SAMBA) and American Society for Enhanced Recovery (ASER)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Postoperative nausea and vomiting (PONV) occurs commonly in surgical patients despite widespread prophylactic antiemetic use. Rescue options are currently limited. 5HT3 antagonists are most frequently used for prophylaxis, but if they fail, additional doses are not effective as rescue medication. Intravenous (IV) amisulpride, a well-studied D2/D3 antagonist, has been shown in trials to prevent PONV. This study was designed to determine if amisulpride could be used to treat established PONV in patients at low-to-moderate risk of PONV who had not received any prior prophylaxis., Methods: Men and women aged over 18 years were permitted to enroll if they were to undergo general inhalational anesthesia, expected to last at least 1 hour, for an outpatient or inpatient surgical procedure. Patients who then suffered PONV were randomized equally to 1 of 3 single-dose IV regimens: placebo or 5 or 10 mg amisulpride. The primary end point was complete response, defined as no emesis in the period 30 minutes to 24 hours after study drug treatment and no use of rescue medication in the entire 24-hour period., Results: One thousand nine hundred eighty-eight patients were enrolled preoperatively, of whom 560 were randomized to a treatment arm. Complete response occurred in 39 of 181 patients (21.5%) in the placebo group compared to 60 of 191 patients (31.4%; P = .016) and 59 of 188 patients (31.4%; P = .016) in the amisulpride 5 and 10 mg groups, respectively. The adverse event profile of amisulpride at either dose was similar to placebo., Conclusions: IV amisulpride at 5 and 10 mg was safe and efficacious in the treatment of established PONV in surgical patients undergoing general anesthesia with no prior PONV prophylaxis.

Background: Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis., Methods: Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery., Results: Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects., Conclusions: APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.

Rationale: Buspirone, a partial 5HT(1A) agonist and D₂ and D₃ antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown., Objective: To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV., Methods: A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0 mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥ 4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable)., Results: A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0 % (90 % confidence interval [CI] 37.5-60.5 %). With buspirone, that incidence ranged from a mean of 40.8 % (29.3-52.4 %) in the 1 mg arm to 58.0 % (46.5-69.5 %) in the 0.3 mg arm (P > 0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures., Conclusion: We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PONV.

Objectives: A prophylactic anti-emetic strategy should depend on the number of nausea and vomiting risk factors. This study was undertaken to evaluate the practices of postoperative nausea and vomiting (PONV) prevention practices among obstetrician-gynaecologists, anaesthetists., Study Design: A prospective, self-administered questionnaire survey was emailed to all Club d'Anesthésie Réanimation Obstétricale (Caro) members (French Obstetric and Gynaecology Anaesthetists' Association)., Methods: The questionnaire had closed-ended questions to evaluate each Caro member's prophylactic anti-emetic practices. Questions concerned demographic datas, prophylactic anti-emetic drugs administered to the patients with or without well known risk factors for developing PONV, the existence of protocol to prevent PONV in their own department of anaesthesiology and their awareness of the existence of French Society of Anaesthesia and Intensive Care (Sfar) PONV prevention guidelines 2007., Results: Of 115 questionnaires, 66 respondents (57%) returned the questionnaires. Most of the respondents (74%) worked in a university hospital. Forty-two percent practiced exclusively in obstetric-gynaecology department. Fifty-six percent were anaesthetists for more than 20 years. Eighty-five percent of the physicians were well-informed about the SFAR's PONV prevention guidelines. Thirty seven percent of respondents assessed Apfel score systematically for all their patients. The percentages, which didn't calculate the probability of PONV with Apfel score or calculated only in cases of PONV history or travel sickness were 18% and 45% respectively. In cases of two or more risk factors, 63% used droperidol, dexamethasone and ondansetron in double or triple combinations., Conclusions: Although most surveyed practitioners were well informed about the new guidelines concerning PONV prevention, 27% not follow these guidelines regarding the administration of anti-emetic drugs. The calculation of Apfel score in the preoperative period must be also strengthened., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Despite major advances, emesis remains a major problem in the context of cancer chemotherapy and in the postoperative period. A better understanding of the relevant neurocircuitry, especially the central pattern generator responsible for emesis and the central role of substance P, led to the development of a new class of antiemetics: the neurokinin-1 (NK1) receptor antagonists. Aprepitant is the first NK1 receptor antagonist approved for use in postoperative nausea and vomiting, but several other compounds are currently being investigated for their potential as antiemetics in the postoperative and cancer chemotherapy settings.

Objective: Compared with the 5HT(3) antagonist ondansetron, the NK(1) antagonist aprepitant has been shown in two double-blind trials to provide greater protection against postoperative vomiting and comparable or greater control of nausea. Post hoc analyses of pooled data from these trials were performed to more fully characterize the efficacy profile of aprepitant in terms of nausea and use of rescue therapy., Research Design and Methods: Patients (n = 1599) scheduled for major surgery under general anesthesia (primarily gynecological surgery) were assigned to receive a preoperative dose of aprepitant 40 mg PO, 125 mg PO, or ondansetron 4 mg IV. in two randomized, double-blind, clinical trials., Main Outcome Measures: Post-surgery vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale)., Results: In the 24 hours after surgery, aprepitant 40 mg was more effective than ondansetron for all five endpoints evaluated: (1) no significant nausea (56.4% vs. 48.1%); (2) no nausea (39.6% vs. 33.1%); (3) no vomiting (86.7% vs. 72.4%); (4) no nausea and no vomiting (38.3% vs. 31.4%); and (5) no nausea, no vomiting, and no use of rescue (37.9% vs. 31.2%) (p < 0.035 for the odds ratio for each comparison). Numerically more patients receiving aprepitant 125 mg also achieved these endpoints compared with ondansetron., Conclusions: These post hoc analyses confirm the favorable efficacy profile of aprepitant for the prevention of post operative nausea and vomiting.

Background: The neurokinin(1) antagonist aprepitant is effective for prevention of chemotherapy-induced nausea and vomiting. We compared aprepitant with ondansetron for prevention of postoperative nausea and vomiting., Methods: Nine hundred and twenty-two patients receiving general anaesthesia for major abdominal surgery were assigned to receive a single preoperative dose of oral aprepitant 40 mg, oral aprepitant 125 mg, or i.v. ondansetron 4 mg in a randomized, double-blind trial. Vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale) were documented for 48 h after surgery. Primary efficacy endpoints were complete response (no vomiting and no use of rescue therapy) 0-24 h after surgery and no vomiting 0-24 h after surgery. The secondary endpoint was no vomiting 0-48 h after surgery., Results: Aprepitant at both doses was non-inferior to ondansetron for complete response 0-24 h after surgery (64% for aprepitant 40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lower bound of 1-sided 95% CI > 0.65), superior to ondansetron for no vomiting 0-24 h after surgery (84% for aprepitant 40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P < 0.001), and superior for no vomiting 0-48 h after surgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125 mg, and 66% for ondansetron; P < 0.001). The distribution of peak nausea scores was lower in both aprepitant groups vs ondansetron (P < 0.05)., Conclusions: Aprepitant was non-inferior to ondansetron in achieving complete response for 24 h after surgery. Aprepitant was significantly more effective than ondansetron for preventing vomiting at 24 and 48 h after surgery, and in reducing nausea severity in the first 48 h after surgery. Aprepitant was generally well tolerated.

The introduction of serotonin 5-HT3 receptor antagonists into clinical practice allowed for a dramatic improvement in the management of nausea and vomiting. Despite this, postoperative and chemotherapy-induced emesis remains a significant, unresolved issue in many patients even when a combination of antiemetic drugs is used. Numerous neurotransmitters have been implicated in triggering emesis; however, the tachykinin substance P, by virtue of its localisation within both the gastrointestinal vagal afferent nerve fibres and brainstem emetic circuitry, and its ability to induce vomiting when administered intravenously, is thought to play a key role in emetic responses. Because substance P is the most likely endogenous ligand for the neurokinin-1 (NK1) receptor, the development of nonpeptide NK1 receptor antagonists led scientists to evaluate these compounds as antiemetics. The five NK1 receptor inhibitors that have been studied initially in humans are: vofopitant (GR-205171), CP-122721, ezlopitant (CJ-11974), MK-869 (L-754030) and its prodrug L-758298. Except for monotherapy in acute cisplatin-induced emesis, this new class of drugs has proven to be highly effective in the control of both chemotherapy-induced nausea and vomiting, and postoperative nausea and vomiting. No major adverse event was reported in the preliminary trials. Further investigation is mandatory in order to assess the optimal treatment regimen and to make sure the wide spectrum activity of the NK1 receptor inhibitors does not cause significant adverse effects in the context of the treatment of nausea and vomiting.

Study Objective: To identify the maximally effective dolasetron dose (i.e., maximum efficacy with minimum adverse events) for prevention of postoperative nausea and vomiting (PONV) using the statistical power generated in a pooled patient sample from three large, nearly identical clinical trials., Design: Three randomized, multicenter, placebo-controlled, double-blinded trials., Setting: Trials 1, 2, and 3 enrolled patients at 10, 25, and 17 hospitals and/or surgical centers, respectively., Patients: A total of 1,946 ASA physical status, I, II, and III patients. Trials 1 and 2 enrolled only female patients (n = 916) undergoing gynecologic surgery. Trial three enrolled 722 females (approximately 70% gynecologic surgeries) and 308 males (approximately 46% orthopedic surgeries) undergoing a variety of surgical procedures., Interventions: All surgical procedures used balanced general anesthesia. Patients received 12.5, 25, 50, or 100 mg of the antiemetic, dolasetron, near the end of anesthesia., Measurements and Main Results: Efficacy endpoints were identical and measured for 24 hours: complete response (no vomiting or rescue medication) and maximum nausea, reported using a 100-mm visual analog scale (VAS). Safety was assessed using adverse event reports, laboratory and electrocardiographic data, and vital signs. All four dolasetron doses produced significant increases in complete response and decreases in maximum VAS nausea compared with placebo (p < 0.01). No increased efficacy was observed with dolasetron doses higher than 12.5 mg. Safety was similar between each dolasetron dose and placebo., Conclusion: Dolasetron 12.5 mg, given near the end of anesthesia, is the maximally effective dose studied for preventing postoperative nausea and vomiting.

In this double-blind, randomized, parallel group study, we have investigated the antiemetic activity of the potent and selective NK1 receptor antagonist GR205171 25 mg i.v. compared with placebo in the treatment of established postoperative nausea and vomiting (PONV) in patients after major gynaecological surgery performed under general anaesthesia. The incidence of PONV in the study population was 65%. Thirty-six patients were treated with placebo or GR205171 (18 patients per group). GR205171 produced greater control of PONV than placebo over the 24-h assessment period. The stimuli for emesis after PONV are multifactorial and the efficacy of GR205171 in this study supports the broad spectrum potential for NK1 receptor antagonists in the management of postoperative emesis. GR205171 was well tolerated and no adverse events were reported that would preclude the further development of this agent.

Study Objective: To examine the safety and effectiveness of a range of single oral doses of dolasetron mesylate for the prevention of postoperative nausea and vomiting., Design: Randomized, double-blind, placebo-controlled trial., Setting: 32 hospitals., Patients: 789 female ASA physical status I, II, and III patients, ages 18 to 60 years, weighing between 45 and 100 kg, scheduled for major gynecologic surgery (including abdominal hysterectomy, gynecologic laparotomy, or vaginal hysterectomy) with general anesthesia., Interventions: 25, 50, 100, or 200 mg oral doses of dolasetron mesylate or placebo were administered 1 to 2 hours before induction of anesthesia. Efficacy was assessed for 24 hours postrecovery by measuring complete response (no emetic episodes, no rescue medication), total response (complete response with no nausea), time to first emetic episode or rescue, and patient visual analog scale evaluations of nausea severity and satisfaction with antiemetic therapy., Measurements and Main Results: Complete response rates for the 50, 100, and 200 mg dose groups were statistically greater than placebo (p < or = 0.018). Likewise, total response rates were statistically greater in the 50, 100, and 200 mg dose groups than in the placebo group (p = 0.012). Percentage of patients with no nausea and patient satisfaction scores were significantly higher for each dolasetron dose group than placebo (p < or = 0.047 and p < or = 0.004, respectively). Efficacy peaked at the 50 mg dose. The incidence of adverse events was similar in the placebo (30.1%) and dolasetron groups (29.4%). Headache was the most frequent treatment-related adverse event, with 2% to 5% incidence across groups. Incidence of adverse events did not increase with increasing dolasetron doses. Dose-related decreases in blood pressure at acute time points were not clinically significant., Conclusion: Single oral doses of dolasetron, administered 1 to 2 hours before induction of anesthesia, are safe and effective for preventing postoperative nausea and vomiting in this patient sample. Maximal antiemetic response was seen with the 50 mg oral dolasetron dose.

Study Objective: To compare the effectiveness of granisetron with placebo in the treatment of established postoperative nausea and vomiting (PONV)., Design: Randomized, placebo-controlled study., Setting: 34 hospitals in Europe, Scandinavia, and South Africa., Patients: 519 ASA physical status I, II, and III patients who developed PONV within 4 hours of the end of surgery performed with general anesthesia., Interventions: Patients received a single intravenous dose of granisetron 0.1 mg, 1 mg, or 3 mg, or placebo when symptoms of nausea or vomiting were experienced. Additional rescue medication could be given at the investigator's discretion if nausea and vomiting were not controlled., Measurements and Main Results: At all doses investigated, granisetron was significantly more effective (p < or = 0.001) than placebo in controlling vomiting: 38%, 46%, and 49% of patients receiving granisetron, 0.1 mg, 1.0 mg, and 3.0 mg, respectively, experienced no vomiting in the first 24 hours following drug administration, compared with 20% receiving placebo. There was a statistically significant linear relationship between vomiting control and granisetron dose (p < 0.001). Survival distributions of time to resolution of vomiting confirmed the statistically significant difference between patients receiving granisetron and those receiving placebo. Granisetron was well tolerated: the most common adverse experiences were pain, constipation, anemia, and headache, and the incidence of adverse experiences was not statistically significantly higher in any of the granisetron groups than in the placebo group., Conclusion: Granisetron was significantly more effective than placebo in all groups. Further studies in specific subgroups may be warranted.

We have studied 746 males and females undergoing general anaesthesia for any type of surgical procedure in a double-blind, controlled, randomized study. After experiencing at least one nausea and/or one emetic episode in the 6 h after recovery from anaesthesia, patients received either ondansetron 4 mg i.v. or metoclopramide 10 mg i.v. Patients were observed for postoperative nausea and vomiting (PONV) for 24 h after drug administration. Complete control of PONV was achieved more frequently in the ondansetron-treated patients compared with the metoclopramide-treated patients during the 24-h period (59% vs 41% (P < 0.001) and 44% vs 34% (P = 0.006) for emetic episodes and nausea, respectively). Furthermore, ondansetron was associated with greater patient satisfaction than metoclopramide (P < 0.001) with 49% and 32% of patients, respectively, very satisfied. The overall incidence of adverse events was similar in the ondansetron (7%) and metoclopramide (8%) groups. Ondansetron was as well tolerated and more effective than metoclopramide for all assessment criteria in the treatment of established PONV.

Study Objective: To evaluate a range of doses of intravenous (i.v.) dolasetron mesilate, in preventing postoperative nausea and vomiting (PONV)., Design: Double-blind, placebo-controlled, randomized, multicenter trial., Setting: Ten hospitals and/or surgical centers., Patients: 281 women undergoing gynecologic surgery with general anesthesia., Interventions: Patients received one of four single, i.v. doses of dolasetron mesilate (12.5 mg, 25 mg, 50 mg, and 100 mg) or placebo administered following cessation of anesthesia., Measurements and Main Results: Patients were monitored for 24 hours following study drug administration. The antiemetic efficacy of each dolasetron mesilate dose was evaluated by recording the number and timing of emetic episodes, and the effects on nausea were assessed by use of visual analog scales (VAS). Safety was assessed by adverse event reports, clinical laboratory tests, electrocardiographic (ECG) measurements, and monitoring vital signs. Complete responses (patients with no emetic episodes and no escape antiemetic medication requirements in 24 hours) were achieved by 54% in the 12.5-mg, 67% in the 25-mg, and 59% in both the 50-mg and 100-mg dolasetron mesilate dose groups, and by 43% in the placebo group. Nausea VAS assessments demonstrated that dolasetron-treated patients were significantly (p = 0.048) more likely to report no nausea (VAS score < 5 mm) than those in the placebo group. Adverse events reported generally were mild in intensity, and there were no clinically significant changes in laboratory tests, vital signs, or ECG parameters., Conclusions: Dolasetron was effective and well tolerated for the prevention of PONV in female patients undergoing gynecologic surgery with general anesthesia.

Purpose: To compare the efficacy, safety, and tolerability of dolasetron mesilate with placebo for the treatment of postoperative nausea and vomiting (PONV)., Methods: In a randomized, multicentre, double-blind, placebo-controlled study 337 adult patients undergoing surgery with general anaesthesia received one of four single, doses of dolasetron mesilate iv (12.5, 25, 50, or 100 mg) or placebo. Study medication was administered postoperatively when the patient reported nausea lasting 10 min or when one emetic episode occurred within two hours of the patient's arrival in the recovery room. Efficacy was assessed by the investigators over the 24-hr study period by recording the number and timing of emetic episodes, the severity of nausea, the timing of administration of escape antiemetic medications, and patients' and investigators' satisfaction with antiemetic therapy., Results: The study sample was predominately women, and the surgical procedures were primarily gynaecological. All dolasetron mesilate doses produced higher complete response rates than placebo (P < 0.05). Only approximately one-third of dolasetron patients required escape antiemetic medication compared with more than 50% of patients in the placebo group. Both patient and physician satisfaction with dolasetron treatment was high. The most common adverse event was mild or moderate headache for both placebo-treated patients and dolasetron-treated patients. Clinical laboratory results were unremarkable., Conclusion: Single doses of dolasetron mesilate iv, given after the first episode of PONV, were both effective and safe in this adult patient population.

In this randomized, double-blind, parallel group, placebo-controlled, dose-ranging study, we have compared three doses (0.1 mg, 1.0 mg and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron (Kytril), as prophylactic therapy for the prevention of postoperative nausea and vomiting. The aims were to determine the optimal dose of granisetron and to evaluate its safety profile. We studied 527 adult patients, undergoing elective open abdominal surgery or vaginal hysterectomy during general anaesthesia. Antiemetic prophylaxis with a single dose of granisetron 1.0 mg or 3.0 mg resulted in a significant reduction (P < 0.001 compared with placebo) in the numbers of patients experiencing postoperative vomiting, or nausea, or who achieved total control during the postoperative periods 0-6 h and 0-24 h. The two higher doses of granisetron (1.0 mg and 3.0 mg) provided effective prophylaxis against vomiting, with 78% and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63% and 62% in the first 24 h. This compares with 50% and 34% at 0-6 h and 0-24 h, respectively, in the placebo group. Granisetron was well tolerated and the optimum dose was 1.0 mg.