Dosing Strategy of Ramosetron to Prevent Postoperative Nausea and Vomiting and Development of Prediction Models Using Data Obtained From Randomized Controlled Trials: A Comparative Study.

PURPOSE: The study aimed to compare the postoperative nausea and vomiting (PONV) preventive effect of repeated administration of ramosetron with the standard treatment group and compare models to predict the incidence of PONV using machine-learning techniques. METHODS: A total of 261 patients scheduled for breast surgery were analyzed to evaluate the effectiveness of repeated intravenous administration of ramosetron. All patients were administered 0.3 mg ramosetron just before the end of surgery. For the repeated dose of ramosetron group, an additional dose of 0.3 mg was administered at 4, 22, and 46 hours after the end of the surgery. Postoperative nausea, vomiting, and retching were evaluated using the Rhodes Index of Nausea, Vomiting, and Retching at 6, 24, and 48 hours postoperatively. Previously published randomized controlled data were combined with the data of this study to create a new dataset of 1390 patients, and machine-learning-based PONV prediction models (classification tree, random forest, extreme gradient boosting, and neural network) was constructed and compared with the Apfel model. FINDINGS: Fifty patients (38.5%) and 60 patients (45.8%) reported nausea, vomiting, or retching 48 hours postoperatively in the standard and repeated-dose groups, respectively (P = 0.317, χ2 test). Median sensitivity, specificity, and accuracy of the Apfel model analyzed using the training set were 0.815, 0.344, and 0.495, respectively. IMPLICATIONS: The repeated administration of ramosetron did not reduce the incidence of PONV. The Apfel model had high sensitivity, however, its specificity and accuracy were lower than that in machine-learning-based models.

Ramosetron as an add-on therapy for refractory fibromyalgia: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments. METHODS: . In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D, and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10, and 28. Safety was continuously monitored throughout the study. RESULTS: . At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, p< 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, p< 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, p< 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events. CONCLUSIONS: . Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.

A suspected case of serotonin syndrome induced by palonosetron and ramosetron administration.

Serotonin syndrome occurs when serotonin (5-hydroxytryptamine, 5-HT) levels increase and is accompanied by symptoms of mental status changes, neuromuscular abnormalities, and autonomic hyperactivity. Serotonin receptor 3 antagonists, such as palonosetron or ramosetron, are commonly used for their antiemetic effects during general anesthesia. However, overdosage of these drugs carries a risk of serotonergic toxicity as they increase serum serotonin levels due to inhibition of serotonin reuptake. Serotonin syndrome caused by 5-HT3 antagonists is thought to be caused by the synergistic effects of high doses of serotonergic drugs or the combination of two or more serotonergic drugs with different mechanisms of action. The incidence of serotonin syndrome is unknown because it is a rare condition that cannot be selected for in randomized clinical trials. Therefore, physicians must focus on the clinical manifestations of the syndrome and manage patients before the condition becomes life-threatening.

Effect of dexamethasone and ramosetron on the prevention of postoperative nausea and vomiting in low-risk patients: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Several studies have investigated the effect of antiemetics on postoperative nausea and vomiting (PONV) in high-risk groups. However, few studies have investigated the effect of antiemetics in patients at low risk of developing PONV. METHODS: In this prospective, randomized, double-blinded trial, 177 patients undergoing surgery under general anesthesia were randomly allocated to three groups. Patients allocated to group C (control group) received 2 mL of intravenous 0.9% saline, those allocated to group R (ramosetron group) received 0.3 mg of intravenous ramosetron, and those allocated to group DR (ramosetron plus dexamethasone group) received 5 mg of intravenous dexamethasone and 0.3 mg of intravenous ramosetron. RESULTS: Finally, 174 patients completed the study, and the types of surgeries were orthopedic (n = 80), rhinologic (n = 47), urologic (n = 29), and others (n = 18). The incidence of PONV up to 48 h postoperatively was significantly lower in group DR than in group C. The incidence of PONV up to 0-1 h postoperatively was significantly lower in groups R and DR than in group C. The usage pattern of rescue antiemetics was consistent with the incidence of PONV. The percentage of patients requiring rescue analgesics 0-1 h postoperatively was significantly lower in groups R and DR than in group C. CONCLUSIONS: The combination of dexamethasone and ramosetron demonstrated a superior effect in preventing PONV for 48 h after surgery under general anesthesia than saline in patients at low risk of developing PONV. Compared with saline injections, ramosetron injections yielded better outcomes for the incidence of PONV and the use of rescue antiemetics and rescue analgesics 0-1 h postoperatively. TRIAL REGISTRATION: Clinical trial registration number: criskorea@korea.kr, KCT0006749.

Intraoperative 5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older adults undergoing hip fracture surgery: a single-center retrospective study.

PURPOSE: Postoperative delirium (POD) occurs commonly in older adults, resulting in unfavorable outcomes. Several recent clinical studies have suggested that 5-hydroxytryptamine 3 (5-HT3) receptor antagonists can treat and prevent POD. In this retrospective study, the association between 5-HT3 receptor antagonists and POD was investigated in older adults who underwent hip fracture surgery. METHODS: The electronic medical records of older adults aged ≥ 65 years who underwent hip fracture surgery between January 2011 and June 2018 were reviewed retrospectively. Multivariable logistic regression analysis was used to investigate the association between 5-HT3 receptor antagonists and the occurrence of POD. In addition to the incidence of POD, anesthesia-, surgery-, and patient-related factors related to POD were evaluated. RESULTS: Of the 1025 patients included, 813 (79.3%) were administered 5-HT3 receptor antagonists intraoperatively; 471 (45.9%) were administered ramosetron, and 342 (33.4%) were administered palonosetron. POD was identified in 242 patients (23.6%). Ramosetron and palonosetron reduced the POD incidence by 53% (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.32‒0.71; P < 0.001) and 41% (OR 0.59; 95% CI 0.39‒0.89; P = 0.011), respectively. Additionally, age, American Society of Anesthesiologists physical status class 4, and male were confirmed as risk factors for POD. CONCLUSION: Intraoperative 5-HT3 receptor antagonists may be associated with a reduced risk of POD and can be considered one of the preventive strategies for POD in older adults undergoing hip fracture surgery.

Efficacy of Serotonin Type 3 Receptor Antagonist Ramosetron on Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)-Like Symptoms in Patients with Quiescent Inflammatory Bowel Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

Patients with quiescent inflammatory bowel disease (IBD) frequently suffer diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms, such as abdominal pain or stool irregularities. Here, we assessed the effect of ramosetron, a serotonin type 3 (5-HT3) receptor antagonist, on IBS-D-like symptoms in patients with quiescent IBD. Seventy patients with quiescent IBD, who met the Rome III diagnostic criteria for IBS-D, were randomly assigned to receive either ramosetron (5 µg; n = 35) or a placebo (n = 35) orally once daily for 4 weeks. The primary endpoint was the responder rate for global assessment of relief from overall IBS-D-like symptoms. The responder rates for relief of abdominal pain/discomfort and improvement of bowel habits were also evaluated. The responder rate for relief from overall IBS-D-like symptoms at the final evaluation point was significantly higher in the ramosetron group (35.5%) than in the placebo group (11.4%) (p = 0.037). The responder rate for improvement of bowel habits was significantly higher in the ramosetron group (38.7%) than in the placebo group (14.3%) (p = 0.028). The reduction of stool frequency was significantly greater in the ramosetron group than in the placebo group (p = 0.044). Ramosetron is effective for relief of overall IBS-D-like symptoms in patients with quiescent IBD.

A Comparative Clinical Study of Methylprednisolone with Ondansetron versus Ramosetron in Preventing Postoperative Nausea and Vomiting in Patients Undergoing Middle-Ear Surgeries.

Background: One of the most troublesome complications after middle-ear surgeries has been postoperative nausea and vomiting (PONV). A notable decrease in PONV has been observed with the use of 5-hydroxytryptamine type 3 receptor antagonists and glucocorticoids. Aim: This study aimed to evaluate the effectiveness of the combination of intravenous methylprednisolone and ondansetron with ramosetron alone in preventing PONV in patients undergoing middle-ear surgeries. Settings and Design: This was a prospective, randomized, double-blind study that comprised sixty patients in the age group of 18-60 years belonging to the American Society of Anesthesiologists (ASA) physical status classification I or II and undergoing middle-ear surgery. Materials and Methods: With the help of computer-generated randomization table, sixty patients in the age group of 18-60 years belonging to ASA physical status classification I or II and undergoing middle-ear surgery were randomly allotted to receive a combination of methylprednisolone 40 mg (given at the beginning of surgery) and ondansetron 4 mg (given near the end of surgery) (Group MO, n = 30) or ramosetron 0.3 mg (near the end of surgery) (Group R, n = 30). In both the groups, the incidence of PONV was studied. Statistical Analysis: Chi-square test or Fisher's exact test was utilized to analogize the categorical variables. Independent t-test was utilized to analogize the continuous variables. Results: In the first 2 h after the surgery, the difference between the two groups regarding the incidence of PONV was insignificant. Between 2 h and 24 h, the incidence of nausea was lowered significantly in the group MO compared to the group R (P = 0.01). Between 24 h and 48 h, the incidence of nausea was more in group R compared to the combination therapy group, which was statistically significant. Conclusion: The combination therapy is better than ramosetron alone for the prevention of PONV after middle-ear surgery. Therefore, we advocate a combination of methylprednisolone and ondansetron for prophylaxis for PONV in middle-ear surgeries.

A Randomised Controlled Trial to Compare the Effect of Ramosetron and Ondansetron in Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Gynaecological Procedures.

Background and objective The antiemetic drug is one of the most common armamentariums in an anaesthesiologist's pharmacopoeia to prevent postoperative nausea and vomiting (PONV). PONV is one of the usual side effects after general anaesthesia, especially in female patients (21%) and after laparoscopic surgery (60%). This study aimed to compare the efficacy of ondansetron with ramosetron. Methodology After institutional ethical clearance and informed written consent, one hundred female patients scheduled for laparoscopic gynaecological surgeries were selected for this prospective, double-blinded, randomised interventional study. These patients were further subdivided into two equal groups (50 in groups R and O). Group R received ramosteron 0.3mg, and group O received ondansetron 8mg 30 minutes before the end of surgery. Patients were assessed between 0-2, 2-6, 6-12 and 12-24 hrs in the postoperative period. The primary objective of this study was to compare the effect of a single dose of ramosetron (0.3mg) with a single dose of ondansetron (8mg) for the prevention of PONV after general anaesthesia in laparoscopic surgeries. The secondary goal was to record the time of occurrence of the first episode of PONV, the need for rescue antiemetics, patient satisfaction scores, and to look for any side effects. Results This study shows no significant difference in the reduction of PONV incidence between group O and group R in the first 24 hours of the postoperative period. The overall incidence of PONV was significantly higher in the early postoperative (0-6 hrs) than in the late postoperative period (6-24 hrs), i.e., 51% and 13%, respectively. The requirement of rescue antiemetic was higher in group O than in group R but not statistically significant. In our study, both groups had similar patient satisfaction scores. Headache was the most common side effect and was noted in 9% of the patient population. Conclusion We conclude that ramosetron is as effective as ondansetron in preventing the incidence and severity of PONV up to 24 hours postoperatively.

Heart-Rate-Corrected QT Interval Response to Ramosetron during Robot-Assisted Laparoscopic Prostatectomy: A Randomized Trial.

Ramosetron, often used to prevent postoperative nausea and vomiting, might cause heart-rate-corrected (QTc) interval prolongation, as might robot-assisted laparoscopic prostatectomy (RALP), which requires a steep Trendelenburg position and CO2 pneumoperitoneum. This study aimed to determine how ramosetron administration affects the QTc interval in patients treated with RALP. Fifty-six subjects were randomly assigned to ramosetron (n = 28) or control (n = 28) groups. The ramosetron group received 0.3 mg of ramosetron after anesthetic induction, whereas the control group received normal saline. The QTc interval was measured before and after induction; after 5, 30, and 60 min of being placed in the Trendelenburg position; immediately after being returned to a supine position; and at the end of surgery. Linear mixed models were used to compare QT intervals between groups. QTc intervals did not differ significantly between groups over time (Pgroup×time = 0.111). However, they increased significantly in both groups after placement in the Trendelenburg position compared with before induction (Ptime < 0.001). This increase in QTc continued until the end of surgery in both groups. Based on these findings, ramosetron can be safely administered for the prevention of postoperative nausea and vomiting among patients undergoing RALP.

Effects of ramosetron orally disintegrating tablets on the prophylaxis of post-discharge nausea and/or vomiting in female patients undergoing day surgery under general anesthesia: a randomized controlled trial.

BACKGROUND: This study was performed to evaluate the effectiveness of ramosetron orally disintegrating tablets (ODTs) in preventing post-discharge nausea and/or vomiting (PDNV) in female patients following outpatient surgery under general anesthesia. METHODS: This multicenter randomized study included three South Korean tertiary hospitals. Before surgery, 138 patients were randomly allocated into two groups. In the ramosetron group, ramosetron ODT 0.1 mg was administered after discharge in the morning of postoperative days 1 and 2. Metoclopramide 10 mg was administered as a rescue antiemetic (capped at 30 mg per day). In the control group, patients were administered only metoclopramide 10 mg when nausea and/or vomiting occurred. The primary outcome was the incidence of nausea during 24 h after discharge. RESULTS: We found significant differences in the incidence (13% vs. 33%, P = 0.008) and severity (P = 0.011) of nausea between the ramosetron and the control groups during 24 h after discharge. In addition, the rate of rescue antiemetic (metoclopramide) administration during 24 h after discharge was lower in the ramosetron group (6%) than in the control group (18%) (P = 0.033). Patient satisfaction score was higher in the ramosetron group than in the control group (P < 0.001). CONCLUSION: Ramosetron ODT reduces the incidence and severity of postoperative nausea after discharge during the first 24 h and may be a valuable option for the prevention of PDNV in female patients after day surgery under general anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04297293 . Registered on 05 March 2020.

Antiemetic Prophylaxis with Ramosetron for Postoperative Nausea and Vomiting in Patients Undergoing Microvascular Decompression : A Prospective, Randomized Controlled Trial.

OBJECTIVE: This prospective, randomized, double-blinded trial aimed to evaluate the efficacy and safety of prophylactic ramosetron administration against postoperative nausea and vomiting (PONV) in patients undergoing microvascular decompression (MVD). METHODS: In this study, 100 patients undergoing MVD were randomly allocated to the control (normal saline, 2 mL) or ramosetron (ramosetron, 0.3 mg) groups at the end of surgery. The incidence and severity of PONV, need for rescue antiemetics, patient satisfaction score, duration of hospital stay, and the occurrence of adverse events were evaluated 48 hours post-surgery. RESULTS: Data obtained from 97 patients were included in the final analysis. The incidence of PONV was significantly lower in the ramosetron group than in the control group throughout the 48-hour postoperative period (29.2% vs. 51.0%, p=0.028). A similar trend was observed with regard to PONV severity (p=0.041). The need for rescue antiemetics, satisfaction score, duration of hospital stays, and the occurrence of adverse events did not significantly differ between the groups. CONCLUSION: Prophylactic ramosetron administration reduced the incidence and severity of PONV in patients undergoing MVD without causing serious adverse events. Thus, ramosetron use may improve patient recovery following MVD.

The Effect of Ramosetron on Remifentanil in Preventing Emergence Cough from Sevoflurane Anesthesia in Female Patients.

BACKGROUND: Remifentanil reduces cough during extubation. Ramosetron, a 5-HT3 receptor antagonist, is a potent antiemetic. Regarding the antitussive property of 5-HT receptor agonists, ramosetron can mediate the cough reflex by increasing the remifentanil requirement. This study evaluated the effect of ramosetron on the optimal effect-site concentration (Ce) of remifentanil for preventing emergence cough from sevoflurane anesthesia in female patients. METHODS: Forty-seven randomly selected female patients undergoing laparoscopic cholecystectomy received either ramosetron 0.3 mg (n = 23) or the same volume of normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce using target-controlled infusion in 50% of patients (EC50) and 95% of patients (EC95) were assessed using Dixon's up-and-down or isotonic regression method with a bootstrapping approach. RESULTS: Using Dixon's up-and-down method, the EC50 of remifentanil in the control group (1.33 ± 0.38 ng/mL) was comparable to that of ramosetron group (1.50 ± 0.69 ng/mL) (P = 0.615). Using isotonic regression analysis, the EC50 (83% confidence interval) did not differ between the two groups (1.17 [0.86-1.43] ng/mL and 1.13 [0.68-1.56] ng/mL in control and ramosetron groups). However, the EC95 (95% confidence interval) was significantly lower in the control group than in the ramosetron group (1.90 [1.45-1.96] ng/mL and 2.92 [2.35-2.97] ng/mL). CONCLUSION: Remifentanil Ce for preventing emergence cough was higher in the ramosetron group than in the control group. It may indicate the lowering effect of ramosetron on the antitussive activity of remifentanil.

Effect of ramosetron, a 5-HT3 receptor antagonist on the severity of seizures and memory impairment in electrical amygdala kindled rats.

The entorhinal cortex (EC) plays a pivotal role in epileptogenesis and seizures. EC expresses high density of serotonergic receptors, especially 5-HT3 receptors. Cognitive impairment is common among people with epilepsy. The present study investigated the role of 5-HT3 receptor on the severity of seizures and learning and memory impairment by electrical kindling of amygdala in rats. The amygdala kindling was conducted in a chronic kindling manner in male Wistar rats. In fully kindled animals, ramosetron (as a potent and selective 5-HT3 receptor antagonist) was microinjected unilaterally (ad doses of 1, 10 or 100 µg/0.5 µl) into the EC 5 min before the novel object recognition (NOR) and Y-maze tests or kindling stimulations. Applying ramosetron at the concentration of 100 µg/0.5 µl (but not at 1 and 10 µg/0.5 µl) reduced afterdischarge (AD) duration and increased stage 4 latency in the kindled rats. Moreover, the obtained data from the NOR test showed that treatment by ramosetron (10 and 100 µg/0.5 µl) increased the discrimination index in the fully kindled animals. Microinjection of ramosetron (10 and 100 µg/0.5 µl) in fully kindled animals reversed the kindling induced changes in the percentage of spontaneous alternation in Y-maze task. The findings demonstrated an anticonvulsant role for a selective 5-HT3 receptor antagonist microinjected into the EC, therefore, suggesting an excitatory role for the EC 5-HT3 receptors in the amygdala kindling model of epilepsy. This anticonvulsive effect was accompanied with a restoring effect on cognitive behavior in NOR and Y-maze tests.

Levosulpiride and Ramosetron for the Prevention of Postoperative Nausea and Vomiting in Laparoscopic Surgery: A Prospective Randomized Double-blind Study.

Background: Postoperative nausea and vomiting (PONV) continues to be common complication of anesthesia and surgery in spite of availability of so many antiemetic drugs and regimens for prevention. This study compared Ramosetron and Levosulpiride in terms of efficacy for PONV prevention after laparoscopic surgery. Aim: To compare the efficacy of intravenous (i.v.) Levosulpiride 25 mg with i.v. Ramosetron 0.3 mg in preventing PONV. Setting: S. D. M. College of Medical Sciences and Hospital, Sattur, Dharwad from November 2018 to June 2020. Design: It is a prospective randomized double-blind study. Statistical Analysis: All the data were collected, tabulated, and expressed as mean ± standard deviation. Data were analyzed using IBM Statistical Package for the Social Sciences (SPSS 22.0 Evaluation version). Unpaired sample t-test and Chi-square test have been used for the quantitative and qualitative data, respectively. A P value of 0.05 was considered statistically insignificant. Materials and Methods: This prospective randomized, double-blind study was conducted in 200 patients undergoing laparoscopic surgery falling under the inclusion criteria are numbered and every nth patient selected by systemic random sampling procedure and allocated into two groups of 100 each, group Levosulpiride (Group L) and group Ramosetron (group R) study drugs givenwithin 30 min induction of anesthesia. Group L will receive LEVOSULPIRIDE 25 mg i.v. Group R will receive RAMOSETRON 0.3 mg i.v. Results: The incidence of vomiting in the Levosulpiride group and in the Ramosetron groupduring 0-4 h (20% vs. 30%, P = 0.1110), 4-8 h (4% vs. 5%, P = 0.7450), 8-12 h (5% vs. 4% P = 0.7210) and 12-24 h (0% vs. 0%). The incidence of nausea and overall PONV and the use of rescue antiemetic was not significantly different during all time intervals. The severity of nausea was not different between the two groups. Difference in the efficacy of Levosulpiride and Ramosetron was statistically insignificant (P > 0.05) in the prevention of PONV. Conclusion: Levosulpiride 25 mg or Ramosetron 0.3 mg given intravenously to prevent PONV inpatients undergoing elective laparoscopic surgery under general anesthesia are equally effective in controlling PONV.

A randomized controlled trial of the effect of ramosetron on postoperative restoration of bowel motility after gynecologic laparoscopic surgery.

OBJECTIVE: To investigate the effect of ramosetron after gynecological laparoscopic surgery on the recovery of bowel function. METHODS: A prospective randomized controlled trial conducted at Kyung Hee University hospital, South Korea, from August 2016 to September 2017. Patients were randomized to receive either 10 mg dexamethasone before induction of anesthesia (control group C), followed by intravenous administration of patient-controlled analgesia (IV-PCA) or 2 ml normal saline before induction of anesthesia and 0.6 mg ramosetron (study group R) administered with IV-PCA. RESULTS: A total of 88 patients were enrolled. Times to first flatus (group C 23.98 ± 6.31 vs. group R 27.14 ± 9.56 h; P = 0.148) and first defecation (group C 36.16 ± 16.04 vs. group R 43.41 ± 20.01 h; P = 0.138) showed no statistically significant differences. No significant differences were observed in the frequency of postoperative nausea and vomiting (PONV) and demand for additional analgesics. Multiple linear regression for analysis of factors affecting time to first flatus revealed no significant results. CONCLUSION: Ramosetron did not delay bowel movement recovery after gynecologic laparoscopic surgery and was as effective as dexamethasone in regulating PONV. Ramosetron can be used with IV-PCA without concerns about delay in recovery of bowel function. CLINICALTRIALS: gov registration number: NCT02849483.

Comparison of the Effectiveness of Palonosetron and Ramosetron in Preventing Postoperative Nausea and Vomiting: Updated Systematic Review and Meta-Analysis with Trial Sequential Analysis.

This updated systematic review and meta-analysis with trial sequential analysis aimed to compare the efficacy of the perioperative administration of palonosetron with that of ramosetron in preventing postoperative nausea and vomiting (PONV). A total of 17 randomized controlled trials comparing the efficacy of the perioperative administration of palonosetron to that of ramosetron for preventing PONV were included. The primary outcomes were the incidences of postoperative nausea (PON), postoperative vomiting (POV), and PONV, which were measured in early, late, and overall phases. Subgroup analysis was performed on the basis of the administration time of the 5-HT3 receptor antagonist and divided into two phases: early phase and the end of surgery. A total of 17 studies with 1823 patients were included in the final analysis. The incidence of retching (relative risk [RR] = 0.525; 95% confidence interval [CI] = 0.390 to 0.707) and late POV (RR = 0.604; 95% CI = 0.404 to 0.903) was significantly lower in the palonosetron group than in the ramosetron group. No significant differences were demonstrated in the incidence of PON, PONV, complete response, use of antiemetics, and adverse effects. Subgroup analysis showed that palonosetron was superior to ramosetron in terms of early PON, late PON, overall POV, and use of rescue antiemetics when they were administered early; in terms of retching, regardless of the timing of administration. Ramosetron was superior to palonosetron in terms of early PON when they were administered late. The prophylactic administration of palonosetron was more effective than that of ramosetron in preventing the development of retching and late POV. In this meta-analysis, no significant differences in PONV prevention between the two drugs were demonstrated. Further studies are required to validate the outcomes of our study.

Microbiological and Physicochemical Stability of Fentanyl, Oxycodone, Hydromorphone, Ketorolac, Ramosetron, and Ondansetron for Intravenous Patient-controlled Analgesia: An In Vitro Study.

BACKGROUND: Postoperative patient-controlled analgesia provides pain relief, encourages early mobilization, and results in a shortened hospital stay. Patient-controlled analgesia involves the mixing of different types of drugs. When using patient-controlled analgesia, it is important to confirm the microbiological and physicochemical stability of each drug in a mixture to guarantee that the drug is delivered to the patient in an unaltered form. OBJECTIVES: To confirm the microbiological and physicochemical stability of various drug mixtures for intravenous patient-controlled analgesia. STUDY DESIGN: An in vitro protocol to examine the microbiological and physicochemical stability of the most commonly used postoperative intravenous patient-controlled analgesia mixtures at our institution. SETTING: In vitro laboratory study. METHODS: Each mixture contained a total of 4 drugs: fentanyl 400 µg, ketorolac 30 mg, either hydromorphone 4 mg or oxycodone 10 mg, and either ramosetron 0.3 mg or ondansetron 10 mg. Each mixture was placed in a portable patient-controlled analgesia system containing 0.9% saline and stored at a constant temperature of 24°C for 96 hours. Physical properties (color, transparency, and sedimentation) were observed with the naked eye and optical microscopy. Sterility testing was performed to assess microbiological contamination in the drug mixture during the 96-hour study period. The pH of each mixture was evaluated for up to 96 hours after mixing. The concentration of each drug was evaluated by high-performance liquid chromatography every 24 hours until 96 hours after mixing. RESULTS: All mixtures appeared visibly transparent, and no sediments were visible under the microscope. Bacterial or fungal growth was not observed in any of the samples after 14 days of incubation. The pH variations in all mixtures were maintained within 0.25 over the 96-hour study period. The concentration of drugs, except ketorolac, ranged from 90-110% of the initial concentration up to 96 hours after mixing. In the mixtures with a pH of 4.21-4.39, the concentration of ketorolac significantly decreased at 24 hours and 48 hours. LIMITATIONS: Confirmation of the stability of drugs in vitro does not automatically ensure that the pharmacokinetics and pharmacodynamics of the drugs are not altered in vivo. CONCLUSION: With the exception of ketorolac, the drugs used in the intravenous patient-controlled analgesia drug mixtures in this study were physicochemically stable up to 96 hours after mixing. The concentration of ketorolac decreased in more acidic mixtures.

Synthesis and Development of Indole Based 5-HT3 Receptor Antagonists as Anti-Emetic Drugs in Oncology: An Update.

An important group of antiemetic drugs used in the treatment of nausea and vomiting after chemotherapy containing an indole moiety in their structures, working as 5- hydroxytryptamine type 3 serotonin receptor antagonist (5-HT3). This study focuses on compounds bearing an indole core that present a 5-HT3 receptor antagonist activity, which have been successfully used as antiemetic drugs for reducing chemotherapy adverse secondary effects during cancer treatment. Their synthesis, biological activities, and some outstanding characteristics are discussed, providing a general outlook towards the development of more efficient antiemetic drugs.

Comparison of equipotent doses of Ramosetron, Ondansetron, and sub-hypnotic dose of Propofol for prevention of postoperative nausea and vomiting in laparoscopic cholecystectomy.

Background and Aims: For prevention of Postoperative nausea vomiting (PONV) in laparoscopic surgery, ramosetron is a selective 5-HT3 receptor antagonist with higher receptor affinity and slow dissociation than ondansetron. We compared these 2 drugs with propofol which has also shown antiemetic properties. The aim was to study ondansetron, ramosetron, and propofol with respect to incidence of PONV, its severity and the need for rescue antiemetic along with the side effects. Prospective, randomized, double blind study. Material and Methods: We compared antiemetic properties of ondansetron (4 mg i.v; n = 40) and ramosetron (0.3 mg i.v; n = 40) with propofol (0.5 mg/kg i.v; n = 40) on 120 ASA I/II patients scheduled for laparoscopic cholecystectomy. The side effects associated with study drugs, time to recovery from anesthesia, readiness for PACU discharge and patient satisfaction was also compared. Qualitative data variables are expressed by using frequency and percentage and quantitative data variables are expressed by using mean and SD. Quantitative data variables were compared using ANOVA test and others were compared by post hoc ANOVA Tukey's test. Results: Incidence of vomiting and need for rescue antiemetic was lowest with Ramosetron and highest in Propofol group. Time to recovery was more in Propofol group which was statistically significant. Readiness for PACU discharge was comparable in all the three groups. Conclusion: Subhypnotic dose of propofol requires more rescue antiemetic than Ondansetron and Ramosetron because of its short duration of action. Between Ondansetron and Ramosetron the latter is more effective in PONV prevention.

The effectiveness of ramosetron and ondansetron for preventing postoperative nausea and vomiting after arthroscopic rotator cuff repair: a randomized controlled trial.

BACKGROUND: Arthroscopic rotator cuff repair is a painful procedure, and treatment of emetic events associated with drugs used in the current multimodal pain management remains challenging. This study aimed to evaluate the effectiveness of ramosetron or ondansetron to relieve postoperative nausea and vomiting (PONV) and pain after arthroscopic rotator cuff repair. METHODS: In total, 122 consecutive patients undergoing arthroscopic rotator cuff repair were randomly allocated into three groups: ramosetron group (n = 39), ondansetron group (n = 43), and control group (n = 40). Then, 0.3 mg of ramosetron or 8 mg of ondansetron was administered intravenously at the end of surgery according to group. All patients received general anesthesia and multimodal pain management protocol including preemptive analgesic medication, fentanyl-based intravenous patient-controlled analgesia, and postoperative analgesic medication. Incidence of emetic events, rescue antiemetic requirements (10 mg of metoclopramide, IV), complete response, pain level, and side effects were recorded in three periods: 0-6, 6-24, and 24-48 h postoperatively. The severity of nausea and pain was evaluated using a visual analog scale. RESULTS: The ramosetron group tended to have a lower incidence and severity of nausea during the 6- to 24-h postoperative period and fewer rescue antiemetic drug requirements during the 0- to 48-h period than the control group, showing statistical significance. Additionally, the frequency of complete response of the ramosetron and ondansetron groups was significantly higher than that of the control group. No difference was found among the groups in the pain level except during the 0- to 6-h period. The two groups have a higher complete response during the 6- to 24-h period than the control group. CONCLUSIONS: Ramosetron use led to a lower incidence, mild severity of nausea, and reduced use of rescue antiemetic drug after arthroscopic rotator cuff repair during the 6- to 24-h postoperative period than the control. LEVEL OF EVIDENCE: Level I, randomized controlled trials, treatment study.