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      Efficacy and safety of ramosetron versus ondansetron for postoperative nausea and vomiting after general anesthesia: a meta-analysis of randomized clinical trials

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          Abstract

          Background

          Postoperative nausea and vomiting is a common side effect of general anesthesia. In this study, we performed a meta-analysis on the efficacy and safety of ramosetron versus ondansetron in the prevention of postoperative nausea and vomiting using the most recently published randomized controlled clinical studies.

          Methods

          PubMed and EMBASE were searched for randomized controlled clinical trials comparing the efficacy and safety of ramosetron and ondansetron. The meta-analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Oxford, UK). Dichotomous outcomes are presented as the relative risk (RR) with a 95% confidence interval (CI).

          Results

          A total of 898 patients from nine selected studies were treated with antiemetics after surgery, including 450 patients who received ondansetron 4 mg and 448 patients who received ramosetron 0.3 mg. The meta-analysis showed no statistically significant difference between the two groups with regard to prevention of postoperative nausea (PON) during different time periods in the 48 hours after surgery. When comparing the efficacy of ramosetron and ondansetron in the prevention of postoperative vomiting (POV), at various time intervals in the 24 hours after surgery, ramosetron was significantly more efficient than ondansetron: 0–6 hours (RR 0.46, 95% CI 0.24–0.92; P=0.03), 0–24 hours (RR 0.72, 95% CI 0.52–1.00; P=0.05), and 6–24 hours (RR 0.51, 95% CI 0.31–0.84; P=0.008). At other time periods between 24 and 48 hours after surgery, ramosetron did not show better efficacy than ondansetron. When comparing the safety profiles of ramosetron and ondansetron, fewer side effects were recorded in the ramosetron group (RR 0.65, 95% CI 0.47–0.91; P=0.01).

          Conclusion

          Our meta-analysis demonstrates that ramosetron was more effective than ondansetron in the prevention of early POV (0–24 hours) with fewer recorded side effects. However, our study did not reveal any statistically significant differences in efficacy between ramosetron and ondansetron in the prevention of PON or late POV (at 24–48 hours).

          Most cited references21

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          Pathophysiological and neurochemical mechanisms of postoperative nausea and vomiting.

          Clinical research shows that postoperative nausea and vomiting (PONV) is caused primarily by the use of inhalational anesthesia and opioid analgesics. PONV is also increased by several risk predictors, including a young age, female sex, lack of smoking, and a history of motion sickness. Genetic studies are beginning to shed light on the variability in patient experiences of PONV by assessing polymorphisms of gene targets known to play roles in emesis (serotonin type 3, 5-HT3; opioid; muscarinic; and dopamine type 2, D2, receptors) and the metabolism of antiemetic drugs (e.g., ondansetron). Significant numbers of clinical trials have produced valuable information on pharmacological targets important for controlling PONV (e.g., 5-HT3 and D2), leading to the current multi-modal approach to inhibit multiple sites in this complex neural system. Despite these significant advances, there is still a lack of fundamental knowledge of the mechanisms that drive the hindbrain central pattern generator (emesis) and forebrain pathways (nausea) that produce PONV, particularly the responses to inhalational anesthesia. This gap in knowledge has limited the development of novel effective therapies of PONV. The current review presents the state of knowledge on the biological mechanisms responsible for PONV, summarizing both preclinical and clinical evidence. Finally, potential ways to advance the research of PONV and more recent developments on the study of postdischarge nausea and vomiting (PDNV) are discussed.
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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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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                23 April 2015
                : 9
                : 2343-2350
                Affiliations
                Department of Anesthesiology, General Hospital of Jinan Military Command, Jinan, People’s Republic of China
                Author notes
                Correspondence: Chengjie Gao, Department of Anesthesiology, General Hospital of Jinan Military Command, 25 Shifan Road, Jinan, Shandong 250031, People’s Republic of China, Email gaochjmd@ 123456yeah.net
                Article
                dddt-9-2343
                10.2147/DDDT.S80407
                4410833
                a8bd2873-b772-4d25-9d57-b50c505162a3
                © 2015 Gao et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                ramosetron,ondansetron,postoperative nausea and vomiting,general anesthesia,meta-analysis

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