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      Comparative efficacy of ramosetron and ondansetron in preventing postoperative nausea and vomiting: An updated systematic review and meta-analysis with trial sequential analysis

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          Abstract

          Background

          Postoperative nausea and vomiting is a distressing complication of surgery, and 5-HT 3 receptor antagonists are often prescribed to prevent it. Ondansetron is the agent typically administered to prevent postoperative nausea and vomiting. Although ramosetron has a longer duration of action than ondansetron, it remains unclear whether ramosetron is the more effective medication. We performed an updated meta-analysis on the comparative efficacy of ramosetron and ondansetron in preventing postoperative nausea and vomiting.

          Methods

          We searched six databases for all trials that randomly assigned patients to ramosetron or ondansetron groups. The primary outcome was postoperative nausea or vomiting in the early, late, and next-day periods. The secondary outcomes were side effects of the medications. We used the random-effects model to combine the results. Trial sequential analyses were performed to correct for repetitive testing in the updated meta-analysis.

          Results

          Twenty-seven randomized controlled trials with 3,811 patients were included in the meta-analysis. The combined results of ramosetron vs. ondansetron efficacy in preventing postoperative nausea and vomiting were as follows: Risk ratio [95% confidence interval] = 0.82 [0.69–0.98] for early postoperative nausea, 0.76 [0.65–0.89] for late postoperative nausea, 0.69 [0.57–0.84] for next-day postoperative nausea, 0.78 [0.63–0.98] for early postoperative vomiting, 0.57 [0.45–0.72] for late postoperative vomiting, and 0.61 [0.43–0.86] for next-day postoperative vomiting. Dizziness was significantly lower in ramosetron groups than in ondansetron groups (risk ratio [95% confidence interval] = 0.81 [0.66–0.98]). Trial sequential analysis revealed that the results for late postoperative nausea, late postoperative vomiting, and next-day postoperative nausea were conclusive.

          Conclusions

          Ramosetron is more effective in preventing late postoperative nausea, late postoperative vomiting, and next-day postoperative nausea than ondansetron. The incidence of dizziness may be lower in patients receiving ramosetron than in patients receiving ondansetron.

          Trial registration

          University hospital Medical Information Network Clinical Trials Registry: UMIN000022980

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          Most cited references33

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          Ramosetron, a 5-HT3 receptor antagonist for the control of nausea and vomiting.

          Ramosetron is a selective serotonin 5-HT3 receptor antagonist with an affinity higher than that of the previously available drugs ondansetron, granisetron and tropisetron. Ramosetron was shown in pharmacological assays to inhibit activities mediated by 5-HT3 receptors, such as emesis caused by cisplatin. In clinical trials, ramostreon was at least as effective as the reference "setrons" against nausea and vomiting induced by chemotherapy or surgical interventions, but the efficacy was well maintained during a 48-h period, so that efficacy was significantly higher with ramosetron in terms of nausea and vomiting 6-48 h after treatment. Hence, ramosetron represents a good alternative over previously available drugs for the prophylaxis and treatment of chemotherapy-induced and postoperative nausea and vomiting. Data in children also support the efficacy of ramosetron, which is well tolerated by both child and adult patients.
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            Comparison of ramosetron with ondansetron for prevention of postoperative nausea and vomiting in patients undergoing gynaecological surgery.

            Ramosetron is a new selective 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonist that reportedly has more potent antiemetic effects compared with other 5-HT(3) receptor antagonists. The purpose of this study was to evaluate the efficacy of ramosetron for the prevention of postoperative nausea and vomiting (PONV) with that of ondansetron or placebo in high-risk patients undergoing gynaecological surgery. In this prospective, randomized, double-blinded, placebo-controlled study, 162 healthy patients who were undergoing gynaecological operation under general anaesthesia using sevoflurane were enrolled. Patients were divided into three groups: the ramosetron group (0.3 mg i.v.; n=54), the ondansetron group (8 mg i.v.; n=54), and the placebo group (normal saline i.v.; n=54). The treatments were given before the end of surgery. The incidence of PONV, severity of nausea, and the use of rescue antiemetic requirements during the first 24 h after surgery were evaluated. The incidence of nausea was lower in the ramosetron (50%) and ondansetron (44%) groups compared with the placebo group (69%) (P<0.05). In addition, the incidence of vomiting was lower in both the ramosetron (17%) and the ondansetron (20%) groups than in the placebo group (44%) during the first 24 h after surgery (P<0.05). The visual analogue scale score for nausea was also lower in the ramosetron and ondansetron groups compared with the placebo group (P<0.05). The proportion of patients requiring rescue antiemetics was significantly lower with ramosetron (15%) when compared with the placebo group (41%) during the 24 h after surgery (P<0.05). However, there were no significant differences in the incidence of nausea and vomiting, severity of nausea, and required rescue PONV between the ramosetron and the ondansetron groups. Ramosetron 0.3 mg i.v. was as effective as ondansetron 8 mg i.v. in decreasing the incidence of PONV and reducing nausea severity in female patients during the first 24 h after gynaecological surgery.
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              Effect of ramosetron on patient-controlled analgesia related nausea and vomiting after spine surgery in highly susceptible patients: comparison with ondansetron.

              A prospective, randomized, double-blind clinical trial. To compare the effect of ramosetron with that of ondansetron on opioid-based IV patient-controlled analgesia (PCA) related postoperative nausea and vomiting (PONV) in highly susceptible patients after lumbar spine surgery. Optimal postoperative pain management is important to facilitate early mobilization after lumbar spine surgery. Opioid analgesia is associated with a high incidence of PONV. Among the currently available 5-hydroxytryptamine receptor 3 antagonists (5-HT3), ondansetron is being most widely used with unsatisfactory results regarding opioid-based IV PCA related PONV. Ramosetron is a newly developed 5-HT3 antagonist with higher receptor affinity and longer duration of action having theoretical advantage over ondansetron in this setting. However, data to support this view are lacking. All 94 female nonsmoker patients (aged 18-65 years) were randomly allocated into either ondansetron group (group O, n = 47) or ramosetron group (group R, n = 47). Fentanyl-based IV PCA was administered for 48 hours after surgery. Overall incidence and severity of nausea and incidence of vomiting were assessed for 48 hours after surgery. Secondary measures included: pain intensity and total amount of administered rescue analgesic. Patients' characteristics were similar between the groups. Overall incidence of nausea was similar between the groups; however, moderate to severe degree of nausea was significantly more in the group O (34%) than in the group R (13%) 6 to 24 hours after surgery. Overall incidence of vomiting and use of rescue antiemetic 6 to 24 hours after surgery was significantly lower in the group R (30% vs. 11% and 28% vs. 11%, respectively). Pain scores at 24 to 48 hours after surgery were significantly lower in the group R (31 +/- 25 vs. 13 +/- 15). Ramosetron was superior to ondansetron in terms of preventing vomiting and reducing the severity of nausea related to fentanyl-based IV PCA, with less adverse events, in patients with high susceptibility, undergoing lumbar spine surgery.
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                Author and article information

                Contributors
                Role: Data curationRole: InvestigationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 October 2017
                2017
                : 12
                : 10
                : e0186006
                Affiliations
                [1 ] Department of Anesthesiology, Kanagawa Children’s Medical Center, Minami-ku, Yokohama, Japan
                [2 ] Department of Anesthesiology and Critical Care Medicine, Kanazawa-ku, Yokohama City University Graduate School of Medicine, Yokohama, Japan
                International University of Health and Welfare School of Medicine, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0613-511X
                Article
                PONE-D-17-24552
                10.1371/journal.pone.0186006
                5627966
                28977021
                84424a22-7350-4643-9f9c-56ac34e839ce
                © 2017 Yokoi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 June 2017
                : 22 September 2017
                Page count
                Figures: 11, Tables: 3, Pages: 25
                Funding
                We received only the departmental funding. The funding source had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Abdominal Surgery
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Laparoscopy
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Nausea
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Nausea
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Vomiting
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Vomiting
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Vomiting
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Vomiting
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Gynecologic Surgery
                Research and Analysis Methods
                Database and Informatics Methods
                Database Searching
                Custom metadata
                All relevant data are within the paper and its Supporting Information file.

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