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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 -
Frontiers in Pharmacology 2022Hyperemesis gravidarum is a serious pregnancy complication that affects approximately 1% of pregnancies worldwide. To determine whether the use of ondansetron during...
Hyperemesis gravidarum is a serious pregnancy complication that affects approximately 1% of pregnancies worldwide. To determine whether the use of ondansetron during pregnancy is associated with abnormal pregnancy outcomes. PubMed, Cochrane Library, CINAHL, Embase, CNKI, CBM, WANFANG, and ClinicalTrials.gov were searched for citations published in any language from inception to 15 December 2021. Eligible studies included any observational study. Odds ratio (OR) and 95% confidence interval (CI) were used as indicators to examine the association between ondansetron and abnormal pregnancy outcomes. Twenty articles from 1,558 citations were included. Our preliminary analysis showed that compared with the unexposed group, the use of ondansetron during pregnancy may be associated with an increased incidence of cardiac defects (OR = 1.06, 95% CI: 1.01-1.10), neural tube defects (OR = 1.12, 95% CI: 1.05-1.18), and chest cleft (OR = 1.21, 95% CI: 1.07-1.37). Further sensitivity analysis showed no significant association between ondansetron and cardiac defects (OR = 1.15,95% CI: 0.94-1.40) or neural tube defects (OR = 0.87,95% CI: 0.46-1.66). When controversial studies were eliminated, the results for the chest defects disappeared. Simultaneously, we found that the use of ondansetron was associated with a reduced incidence of miscarriage (OR = 0.53, 95% CI: 0.31-0.89). Ondansetron was not associated with orofacial clefts (OR = 1.09,95% CI: 0.95-1.25), spinal limb defects (OR = 1.14,95% CI: 0.89-1.46), urinary tract deformities (OR = 1.06,95% CI: 0.97-1.15), any congenital malformations (OR = 1.03,95% CI: 0.98-1.09), stillbirth (OR = 0.97,95% CI: 0.83-1.15), preterm birth (OR = 1.22,95% CI: 0.80-1.85), neonatal asphyxia (OR = 1.05,95% CI: 0.72-1.54), or neonatal development (OR = 1.18,95% CI: 0.96-1.44) in our primary analysis. In our analysis, using ondansetron during pregnancy was not associated with abnormal pregnancy outcomes. Although our study did not find sufficient evidence of ondansetron and adverse pregnancy outcomes, future studies including the exposure period and dose of ondansetron, as well as controlling for disease status, may be useful to truly elucidate the potential risks and benefits of ondansetron.
PubMed: 36120333
DOI: 10.3389/fphar.2022.951072 -
Journal of Cardiothoracic and Vascular... Nov 2022TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) is carried out in various clinical settings, with an increasing importance, and sedation usually is required to perform it.... (Meta-Analysis)
Meta-Analysis Review
TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) is carried out in various clinical settings, with an increasing importance, and sedation usually is required to perform it. Several sedative agents are available, and the authors aimed to compare the cardiovascular and respiratory safety of the strategies used for sedation in TEE through a systematic review with network meta-analysis (NMA). The MEDLINE, CENTRAL, EMBASE, and PsycInfo databases were searched in December 2020 for randomized clinical trials (RCTs) comparing sedation strategies for patients undergoing TEE. The authors assessed variations in systolic blood pressure (SBP), heart rate (HR), and peripheral oxygen saturation (SpO), along with the incidences of hypotension, bradycardia, and desaturation. A random-effect meta-analysis was performed. Nine RCTs (N = 881 patients) with 20 active arms (5 dexmedetomidine; 4 propofol; 4 midazolam; 3 midazolam + opioid; 2 ketamine + propofol; 1 midazolam + ondansetron; 1 midazolam + metoclopramide) and 1 placebo arm were included. Dexmedetomidine was associated with decreases in SBP (mean difference [MD] = -18.78 mmHg; 95% CI [-26.27 to -11.28]) and HR (MD = -11.15 beats/min; 95% CI [-16.15 to -6.15]). Dexmedetomidine significantly reduced the HR compared with ketamine + propofol (-16.90 beats/min; 95% CI: -33.21 to -0.58]) and midazolam + opioid (-24.15 beats/min; 95% CI: -42.67 to -5.63). Midazolam was found to reduce SBP (-12.09 mmHg; 95% CI: -20.43 to -3.74) and was shown to reduce SpO compared with the placebo (-1.00%; 95% CI -1.74 to -0.26). Based on the NMA, the drugs with a higher likelihood of decreasing both SBP and HR were dexmedetomidine and midazolam. All of the drugs led to a small decrease (only statistically significant for midazolam) in SpO, with the systematic use of supplemental O in some trials. The risks of hypotension, bradycardia, or desaturation were not significantly different among the evaluated drugs.
Topics: Analgesics, Opioid; Bradycardia; Dexmedetomidine; Echocardiography, Transesophageal; Humans; Hypnotics and Sedatives; Hypotension; Ketamine; Metoclopramide; Midazolam; Network Meta-Analysis; Ondansetron; Propofol
PubMed: 36028379
DOI: 10.1053/j.jvca.2022.07.003 -
Turkish Journal of Anaesthesiology and... Aug 2022Intraoperative shivering is quite common after regional anaesthesia, which not only increases the total body oxygen requirement but also causes discomfort to the...
Pharmacological Interventions for the Treatment and Control of Shivering in Adult Patients Undergoing Elective Surgery Under Regional Anaesthesia: A Systematic Review and Meta-Analysis.
Intraoperative shivering is quite common after regional anaesthesia, which not only increases the total body oxygen requirement but also causes discomfort to the patients. The aim of this systematic review is to determine the effectiveness of pharmacological agents administered intra-operatively for treating shivering in adult patients who are undergoing elective surgery under regional (i.e., central neuraxial) anaesthesia so that an optimal choice of an agent can be recommended for clinical application. A literature search was carried out using PubMed, Cochrane Library, CINAHL databases, and hand searches to identify relevant studies. After literature screening and information extraction, a systematic review was performed. Meta-analysis was performed for the primary outcome. The primary outcome was to evaluate the effectiveness of pharmacological agents used for the treatment and control of intraoperative shivering and the time taken to control shivering. The secondary outcome includes recurrence of shivering after pharmacological intervention and identification of common adverse effects related to them. In total, 10 studies (791 patients) were included. Common interventions were opioids, central α2 receptor agonist, and few other medications like magnesium sulfate, ondansetron, nefopam, and amitriptyline. Tramadol and dexmedetomidine were the most frequently documented drugs compared with other drugs to resolve shivering. The most effective drug with approximately 100% response rate was dexmedetomidine with the dose of 0.5 μg kg-1 intravenously given just after the appearance of shivering. Studies showed that tramadol is also an effective drug used to control shivering in most patients, and its effect is comparable with the pethidine.
PubMed: 35979970
DOI: 10.5152/TJAR.2021.20008 -
Supportive Care in Cancer : Official... Nov 2022To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients.
METHODS
We conducted a systematic review of randomized trials evaluating interventions to prevent acute CINV. Outcomes assessed were complete chemotherapy-induced vomiting (CIV) control, complete chemotherapy-induced nausea (CIN) control, complete CINV control, and discontinuation of antiemetics due to adverse effects.
RESULTS
The search identified 65,172 citations; 744 were evaluated at full-text, and 295 (25 pediatric) met eligibility criteria. In patients receiving highly emetogenic chemotherapy (HEC), complete CIV (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.05-1.44) and CIN (RR 1.34, 95% CI 1.10-1.62) control improved when olanzapine was added. The addition of a neurokinin-1 receptor antagonist (NK1RA) to a corticosteroid plus a serotonin-3 receptor antagonist (5HT3RA) also improved complete CIV (RR 1.11, 95% CI 1.08-1.14) and CIN (RR 1.05, 95% CI 1.01-1.08) control. Compared to granisetron/ondansetron, palonosetron provided improved complete CIV control when the 5HT3RA was given alone or when combined with dexamethasone. In patients receiving moderately emetogenic chemotherapy (MEC), dexamethasone plus a 5HT3RA improved complete CIV control compared to a 5HT3RA alone (RR 1.29, 95% CI 1.21-1.39). Only a single meta-analysis evaluating the safety outcome was possible.
CONCLUSIONS
For patients receiving HEC, various antiemetic regimens improved CIV and CIN control. For patients receiving MEC, administration of a 5HT3RA plus dexamethasone improved CIV control. Analysis of antiemetic safety was constrained by lack of data.
Topics: Adult; Humans; Child; Antiemetics; Neoplasms; Nausea; Vomiting; Dexamethasone; Antineoplastic Agents
PubMed: 35953731
DOI: 10.1007/s00520-022-07287-w -
Turkish Journal of Obstetrics and... Jun 2022This investigation examined the efficacy of ondansetron (intervention) versus metoclopramide (control) in managing parturient females with hyperemesis gravidarum (HG),...
This investigation examined the efficacy of ondansetron (intervention) versus metoclopramide (control) in managing parturient females with hyperemesis gravidarum (HG), by pooling data from randomized controlled trials (RCTs) using a meta-analysis approach. From inception until January 2022, five information sources were screened: Cochrane Central Register of Controlled Trials, Google Scholar, Scopus, PubMed and Web of Science. Quality assessment was done through the Cochrane Risk of Bias (version 2) assessment tool. The mean difference (MD) with 95% confidence interval (CI) was used to summarize the continuous data in a fixed- or random-effects model, depending on the extent of between-study heterogeneity. Five RCTs were included, comprising a total of 695 patients (355 and 340 females were assigned to ondansetron and metoclopramide, respectively). Four RCTs had an overall "low" risk of bias, whereas one RCT had an overall "some concerns" due to lack of sufficient information about randomization. There was no significant difference between both groups regarding the pregnancy-unique quantification of emesis and nausea score [MD=0.23, 95% CI (-0.42, 0.88), p=0.49], length of hospital stay [MD=-0.17 days, 95% CI (-0.35, 0.02), p=0.08], the number of doses of drug received [MD=0.45, 95% CI (-0.08, 0.98), p=0.10], and duration of intravenous fluids [MD=-1.73 hours, 95% CI (-5.79, 2.33), p=0.40]. Among parturient females with HG, there was no substantial difference in efficacy between both agents. Nevertheless, ondansetron is favored over metoclopramide in view of its trending therapeutic efficacy and better safety profile.
PubMed: 35770443
DOI: 10.4274/tjod.galenos.2022.14367 -
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 -
Neuropsychopharmacology : Official... Mar 2022Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for...
Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.
Topics: Antipsychotic Agents; Humans; Perception; Schizophrenia; Sensory Gating; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35017671
DOI: 10.1038/s41386-021-01255-4 -
Journal of Perianesthesia Nursing :... Feb 2022Evaluate the efficacy of ondansetron in preventing shivering after spinal anesthesia in cesarean delivery. (Meta-Analysis)
Meta-Analysis
PURPOSE
Evaluate the efficacy of ondansetron in preventing shivering after spinal anesthesia in cesarean delivery.
DESIGN
Systematic review and meta-analysis METHODS: Following the PRISMA statement, PubMed, CINAHL, Cochrane, EMBASE, Google scholar and other grey literature databases were searched for eligible studies.
FINDINGS
The overall incidence of shivering after spinal anesthesia in cesarean delivery is 32%, with 24% in patients who received ondansetron compared to 40% in the placebo group. A total of 19 trials consisting of 1399 patients were evaluated. Compared to placebo, ondansetron is effective in reducing the incidence of shivering (RR, 0.47; 95% CI, 0.29 to 0.78; P = 0.003). The quality of evidence is low due to substantial heterogeneity, imprecision and suspected publication bias. Patients who received ondansetron are less likely to require rescue treatment for shivering (RR, 0.34; 95% CI, 0.15 to 0.76; P = 0.009). Also, ondansetron is associated with a lower incidence of hypotension necessitating vasopressor treatment, and nausea and vomiting with no effects on the incidence of bradycardia.
CONCLUSION
Ondansetron is effective in mitigating shivering after spinal anesthesia in cesarean delivery.
Topics: Anesthesia, Spinal; Cesarean Section; Double-Blind Method; Female; Humans; Ondansetron; Pregnancy; Shivering; Vomiting
PubMed: 34836765
DOI: 10.1016/j.jopan.2021.05.007 -
The Cochrane Database of Systematic... Nov 2021About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK₁) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head-to-head comparisons do not allow comparison of all treatments versus another. OBJECTIVES: • In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting in network meta-analysis (NMA) - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy • In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting to treatment combinations including 5-HT₃ receptor antagonists and corticosteroids solely, in network meta-analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs).
SELECTION CRITERIA
We included RCTs including adults with any cancer receiving HEC or MEC (according to the latest definition) and comparing combination therapies of NK₁ and 5-HT₃ inhibitors and corticosteroids for prevention of CINV.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We expressed treatment effects as risk ratios (RRs). Prioritised outcomes were complete control of vomiting during delayed and overall phases, complete control of nausea during the overall phase, quality of life, serious adverse events (SAEs), and on-study mortality. We assessed GRADE and developed 12 'Summary of findings' tables. We report results of most crucial outcomes in the abstract, that is, complete control of vomiting during the overall phase and SAEs. For a comprehensive illustration of results, we randomly chose aprepitant plus granisetron as exemplary reference treatment for HEC, and granisetron as exemplary reference treatment for MEC.
MAIN RESULTS
Highly emetogenic chemotherapy (HEC) We included 73 studies reporting on 25,275 participants and comparing 14 treatment combinations with NK₁ and 5-HT₃ inhibitors. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 704 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with aprepitant + granisetron. Evidence from NMA (39 RCTs, 21,642 participants; 12 treatment combinations with NK₁ and 5-HT₃ inhibitors) suggests that the following drug combinations are more efficacious than aprepitant + granisetron for completely controlling vomiting during the overall treatment phase (one to five days): fosnetupitant + palonosetron (810 of 1000; RR 1.15, 95% confidence interval (CI) 0.97 to 1.37; moderate certainty), aprepitant + palonosetron (753 of 1000; RR 1.07, 95% CI 1.98 to 1.18; low-certainty), aprepitant + ramosetron (753 of 1000; RR 1.07, 95% CI 0.95 to 1.21; low certainty), and fosaprepitant + palonosetron (746 of 1000; RR 1.06, 95% CI 0.96 to 1.19; low certainty). Netupitant + palonosetron (704 of 1000; RR 1.00, 95% CI 0.93 to 1.08; high-certainty) and fosaprepitant + granisetron (697 of 1000; RR 0.99, 95% CI 0.93 to 1.06; high-certainty) have little to no impact on complete control of vomiting during the overall treatment phase (one to five days) when compared to aprepitant + granisetron, respectively. Evidence further suggests that the following drug combinations are less efficacious than aprepitant + granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): aprepitant + ondansetron (676 of 1000; RR 0.96, 95% CI 0.88 to 1.05; low certainty), fosaprepitant + ondansetron (662 of 1000; RR 0.94, 95% CI 0.85 to 1.04; low certainty), casopitant + ondansetron (634 of 1000; RR 0.90, 95% CI 0.79 to 1.03; low certainty), rolapitant + granisetron (627 of 1000; RR 0.89, 95% CI 0.78 to 1.01; moderate certainty), and rolapitant + ondansetron (598 of 1000; RR 0.85, 95% CI 0.65 to 1.12; low certainty). We could not include two treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron) in NMA for this outcome because of missing direct comparisons. Serious adverse events We estimated that 35 of 1000 participants experience any SAEs when treated with aprepitant + granisetron. Evidence from NMA (23 RCTs, 16,065 participants; 11 treatment combinations) suggests that fewer participants may experience SAEs when treated with the following drug combinations than with aprepitant + granisetron: fosaprepitant + ondansetron (8 of 1000; RR 0.23, 95% CI 0.05 to 1.07; low certainty), casopitant + ondansetron (8 of 1000; RR 0.24, 95% CI 0.04 to 1.39; low certainty), netupitant + palonosetron (9 of 1000; RR 0.27, 95% CI 0.05 to 1.58; low certainty), fosaprepitant + granisetron (13 of 1000; RR 0.37, 95% CI 0.09 to 1.50; low certainty), and rolapitant + granisetron (20 of 1000; RR 0.57, 95% CI 0.19 to 1.70; low certainty). Evidence is very uncertain about the effects of aprepitant + ondansetron (8 of 1000; RR 0.22, 95% CI 0.04 to 1.14; very low certainty), aprepitant + ramosetron (11 of 1000; RR 0.31, 95% CI 0.05 to 1.90; very low certainty), fosaprepitant + palonosetron (12 of 1000; RR 0.35, 95% CI 0.04 to 2.95; very low certainty), fosnetupitant + palonosetron (13 of 1000; RR 0.36, 95% CI 0.06 to 2.16; very low certainty), and aprepitant + palonosetron (17 of 1000; RR 0.48, 95% CI 0.05 to 4.78; very low certainty) on the risk of SAEs when compared to aprepitant + granisetron, respectively. We could not include three treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron, rolapitant + ondansetron) in NMA for this outcome because of missing direct comparisons. Moderately emetogenic chemotherapy (MEC) We included 38 studies reporting on 12,038 participants and comparing 15 treatment combinations with NK₁ and 5-HT₃ inhibitors, or 5-HT₃ inhibitors solely. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 555 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with granisetron. Evidence from NMA (22 RCTs, 7800 participants; 11 treatment combinations) suggests that the following drug combinations are more efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days): aprepitant + palonosetron (716 of 1000; RR 1.29, 95% CI 1.00 to 1.66; low certainty), netupitant + palonosetron (694 of 1000; RR 1.25, 95% CI 0.92 to 1.70; low certainty), and rolapitant + granisetron (660 of 1000; RR 1.19, 95% CI 1.06 to 1.33; high certainty). Palonosetron (588 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) and aprepitant + granisetron (577 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) may or may not increase complete response in the overall treatment phase (one to five days) when compared to granisetron, respectively. Azasetron (560 of 1000; RR 1.01, 95% CI 0.76 to 1.34; low certainty) may result in little to no difference in complete response in the overall treatment phase (one to five days) when compared to granisetron. Evidence further suggests that the following drug combinations are less efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): fosaprepitant + ondansetron (500 of 100; RR 0.90, 95% CI 0.66 to 1.22; low certainty), aprepitant + ondansetron (477 of 1000; RR 0.86, 95% CI 0.64 to 1.17; low certainty), casopitant + ondansetron (461 of 1000; RR 0.83, 95% CI 0.62 to 1.12; low certainty), and ondansetron (433 of 1000; RR 0.78, 95% CI 0.59 to 1.04; low certainty). We could not include five treatment combinations (fosaprepitant + granisetron, azasetron, dolasetron, ramosetron, tropisetron) in NMA for this outcome because of missing direct comparisons. Serious adverse events We estimated that 153 of 1000 participants experience any SAEs when treated with granisetron. Evidence from pair-wise comparison (1 RCT, 1344 participants) suggests that more participants may experience SAEs when treated with rolapitant + granisetron (176 of 1000; RR 1.15, 95% CI 0.88 to 1.50; low certainty). NMA was not feasible for this outcome because of missing direct comparisons. Certainty of evidence Our main reason for downgrading was serious or very serious imprecision (e.g. due to wide 95% CIs crossing or including unity, few events leading to wide 95% CIs, or small information size). Additional reasons for downgrading some comparisons or whole networks were serious study limitations due to high risk of bias or moderate inconsistency within networks.
AUTHORS' CONCLUSIONS
This field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematically researched and assessed. For people receiving HEC, synthesised evidence does not suggest one superior treatment for prevention and control of chemotherapy-induced nausea and vomiting. For people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK₁ and 5-HT₃ inhibitors when compared to treatments including 5-HT₃ inhibitors only. Rather, the results of our NMA suggest that the choice of 5-HT₃ inhibitor may have an impact on treatment efficacy in preventing CINV. When interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head-to-head comparisons, and that results of our NMA do not necessarily rule out differences that could be clinically relevant for some individuals.
Topics: Adult; Antiemetics; Antineoplastic Agents; Humans; Nausea; Network Meta-Analysis; Palonosetron; Randomized Controlled Trials as Topic; Vomiting
PubMed: 34784425
DOI: 10.1002/14651858.CD012775.pub2