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Pharmaceuticals (Basel, Switzerland) Dec 2022Hypotension induced by spinal anaesthesia is a common clinical complication associated with multiple perioperative adverse events. We conducted a systemic review and... (Review)
Review
Hypotension induced by spinal anaesthesia is a common clinical complication associated with multiple perioperative adverse events. We conducted a systemic review and meta-analysis to confirm whether ondansetron could alleviate hypotension following spinal anaesthesia. PubMed, Embase, Web of Science, and Cochrane Library were searched to identify eligible randomised controlled trials from their respective database inception dates to 30 September 2022. The primary outcome of the meta-analysis was the incidence of hypotension after spinal anaesthesia. The risk of bias in the included studies was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB 2.0). Grading of Recommendations, Assessment, Development, and Evaluation was applied to assess the level of certainty. A total of 25 studies were included in this research. The meta-analysis revealed that ondansetron significantly decreased the incidence of hypotension (RR = 0.65, 95% CI 0.53−0.80, p < 0.01, I2 = 64%) and bradycardia. In addition, patients treated with ondansetron had a reduced need for vasopressors administration. This study suggests that ondansetron may be recommended as a prophylaxis for hypotension and bradycardia following spinal anaesthesia; the level of evidence was moderate with a high level of heterogeneity.
PubMed: 36559039
DOI: 10.3390/ph15121588 -
Anaesthesia Feb 2015Several studies have investigated the presence of a drug interaction between tramadol and ondansetron that reduced the efficacy of tramadol postoperatively. Most of... (Meta-Analysis)
Meta-Analysis Review
Several studies have investigated the presence of a drug interaction between tramadol and ondansetron that reduced the efficacy of tramadol postoperatively. Most of these studies were small and the results inconsistent, so we performed a systematic review and meta-analysis of randomised controlled trials comparing the cumulative dose of tramadol administered by patient-controlled analgesia within the first 24 h after surgery between subjects receiving tramadol alone and those who received tramadol with ondansetron. Six studies, with a total of 340 participants, met the selection criteria and were included in the meta-analysis. There was an increased tramadol requirement in patients receiving ondansetron. The standardised mean difference in tramadol requirements, expressed in terms of standard deviations (95% CI), was 1.03 (0.54-1.53) (p < 0.001) at 4 h, 0.66 (0.06-1.25) (p = 0.03) at 8 h, 0.86 (0.41-1.31) (p < 0.001) at 12 h and 0.45 (0.01-0.90) (p = 0.046) at 24 h postoperatively, where the mean pooled standard deviations were 79.5, 157.7, 238.1 and 289.4 mg at 4, 8, 12 and 24 h, respectively. There was a significant linear time effect over the 24 h, indicating that the effect of ondansetron on tramadol consumption diminished with time. The results support the presence of a drug interaction between tramadol and ondansetron in the early postoperative period that potentially decreases the effectiveness of tramadol.
Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Antiemetics; Drug Interactions; Humans; Ondansetron; Pain, Postoperative; Postoperative Nausea and Vomiting; Postoperative Period; Randomized Controlled Trials as Topic; Tramadol; Treatment Outcome
PubMed: 25490944
DOI: 10.1111/anae.12948 -
Canadian Geriatrics Journal : CGJ Mar 2019Post-operative delirium (POD) is associated with higher rates of functional decline and death. Ondansetron is a serotonin antagonist which could represent a therapeutic... (Review)
Review
BACKGROUND
Post-operative delirium (POD) is associated with higher rates of functional decline and death. Ondansetron is a serotonin antagonist which could represent a therapeutic or preventive option in POD.
METHODS
A systematic review of MEDLINE, EMBASE, CENTRAL, and PsychINFO was performed. Three randomized controlled trials (RCTs) met inclusion criteria (intervention of ondansetron compared to a control group).
RESULTS
Two RCTs examined ondansetron for the treatment of POD in patients after cardiac or post-trauma surgery in the ICU. Studies assessed either a one-time dose or doses for 3 days of ondansetron or haloperidol IV. They suggested similar reductions in average delirium scores and rates in both interventions, although one study suggested ondansetron to be associated with higher rates of rescue haloperidol use. One RCT examined prophylactic ondansetron versus placebo IV, for five days postoperatively, to prevent POD in orthopedic patients. There were significantly fewer delirious patients in the ondansetron group. In general, studies had major methodological limitations and were very heterogenous in study tools, interventions used, and populations studied.
CONCLUSIONS
Ondansetron may be an effective agent for the prevention or treatment of POD, but studies are few and of poor quality, thus making the conclusions tenuous. Further large RCTs are needed.
PubMed: 31501677
DOI: 10.5770/cgj.22.266 -
PloS One 2017Postoperative nausea and vomiting is a distressing complication of surgery, and 5-HT3 receptor antagonists are often prescribed to prevent it. Ondansetron is the agent... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparative efficacy of ramosetron and ondansetron in preventing postoperative nausea and vomiting: An updated systematic review and meta-analysis with trial sequential analysis.
BACKGROUND
Postoperative nausea and vomiting is a distressing complication of surgery, and 5-HT3 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.
Topics: Antiemetics; Benzimidazoles; Humans; Ondansetron; Postoperative Nausea and Vomiting
PubMed: 28977021
DOI: 10.1371/journal.pone.0186006 -
Scientific Reports Nov 2023Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: a systematic review and meta-analysis of randomized clinical trials.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal. Augmentation of 5-HT3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin; Receptors, Serotonin, 5-HT3; Treatment Outcome; Randomized Controlled Trials as Topic; Obsessive-Compulsive Disorder; Drug Therapy, Combination
PubMed: 38012263
DOI: 10.1038/s41598-023-47931-x -
BMC Medicine Dec 2016Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.
METHODS
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.
RESULTS
After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.
CONCLUSIONS
Most 5-HT receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.
TRIAL REGISTRATION
This study was registered at PROSPERO: ( CRD42013003564 ).
Topics: Adult; Antiemetics; Antineoplastic Agents; Drug Therapy, Combination; Glucocorticoids; Humans; Nausea; Network Meta-Analysis; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 28007031
DOI: 10.1186/s12916-016-0761-9 -
Medicine May 2015Newly developed neurokinin-1 receptor (NK-1R) antagonists have been recently tried in the prevention of postoperative nausea and vomiting (PONV). This systematic review... (Meta-Analysis)
Meta-Analysis Review
Newly developed neurokinin-1 receptor (NK-1R) antagonists have been recently tried in the prevention of postoperative nausea and vomiting (PONV). This systematic review and meta-analysis was conducted to explore whether NK-1R antagonists were effective in preventing PONV.The PRISMA statement guidelines were followed. Randomized clinical trials (RCTs) that tested the preventive effects of NK-1R antagonists on PONV were identified by searching EMBASE, CINAHL, PubMed, and the Cochrane Library databases followed by screening. Data extraction was performed using a predefined form and trial quality was assessed using a modified Jadad scale. The primary outcome measure was the incidence of PONV. Meta-analysis was performed for studies using similar interventions. Network meta-analysis (NMA) was conducted to compare the anti-vomiting effects of placebo, ondansetron, and aprepitant at different doses.Fourteen RCTs were included. Meta-analysis found that 80 mg of aprepitant could reduce the incidences of nausea (3 RCTs with 224 patients, pooled risk ratio (RR) = 0.60, 95% confidence interval (CI) = 0.47 to 0.75), and vomiting (3 RCTs with 224 patients, pooled RR = 0.13, 95% CI = 0.04 to 0.37) compared with placebo. Neither 40 mg (3 RCTs with 1171 patients, RR = 0.47, 95% CI = 0.37 to 0.60) nor 125 mg (2 RCTs with 1058 patients, RR = 0.32, 95% CI = 0.13 to 0.78) of aprepitant showed superiority over 4 mg of ondansetron in preventing postoperative vomiting. NMA did not find a dose-dependent effect of aprepitant on preventing postoperative vomiting.Limited data suggested that NK-1R antagonists, especially aprepitant were effective in preventing PONV compared with placebo. More large-sampled high-quality RCTs are needed.
Topics: Antiemetics; Aprepitant; Dose-Response Relationship, Drug; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Ondansetron; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 25984662
DOI: 10.1097/MD.0000000000000762 -
Frontiers in Pharmacology 2023Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of...
Cancer is a neoplastic transformation that affects tissue. Among the many complications associated with cancer treatment, managing the distressing side effects of chemotherapy-induced nausea and vomiting (CINV) is of main concern. Ondansetron is a selective serotonin 5-HT3 receptor antagonist that has emerged as an essential medication against CINV in adult cancer patients. Ondansetron efficacy and tolerability have made it a primary medication in CINV prophylaxis and treatment regimens. The study aims to offer a detailed overview of ondansetron's effectiveness, safety, and impact on patients' lives, ultimately contributing to the ongoing research to enhance the quality of cancer care. On 4 September 2023, a search was conducted of the ClinicalTrials.gov database using the search terms "cancer," "ondansetron," and "Zofran." Inclusion and exclusion criteria were defined to select relevant clinical trials. Included trials were completed with results and interventional studies that assessed the preventive effects of ondansetron on CINV in adult cancer patients. A total of 23 clinical trials were identified, with only 13 of them focusing on investigating the preventive effects of ondansetron on CINV in adult cancer patients. The collective findings from these trials showed an effective management of CINV using ondansetron. Through a comprehensive overview of clinical trials, the use of ondansetron in adult cancer patients represents a significant improvement in CINV management.
PubMed: 38074143
DOI: 10.3389/fphar.2023.1310455 -
Clinical Pharmacology and Therapeutics May 2022Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to...
Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically-based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1,000 simulated women who were 2 days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.005 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.
Topics: Female; Humans; Infant; Breast Feeding; Lactation; Milk, Human; Ondansetron; Postpartum Period
PubMed: 35076931
DOI: 10.1002/cpt.2530 -
The Cochrane Database of Systematic... May 2016Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum.
OBJECTIVES
To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy.
MAIN RESULTS
Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth.
AUTHORS' CONCLUSIONS
On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.
Topics: Acupuncture Therapy; Adrenal Cortex Hormones; Antiemetics; Female; Humans; Hydrocortisone; Hyperemesis Gravidarum; Metoclopramide; Ondansetron; Placebo Effect; Prednisolone; Pregnancy; Promethazine; Pyridoxine
PubMed: 27168518
DOI: 10.1002/14651858.CD010607.pub2