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The Cochrane Database of Systematic... Oct 2020Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects.
OBJECTIVES
• To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded.
DATA COLLECTION AND ANALYSIS
A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo.
MAIN RESULTS
We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353.
AUTHORS' CONCLUSIONS
We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).
Topics: Adult; Anesthesia, General; Antiemetics; Drug Therapy, Combination; Female; Humans; Male; Network Meta-Analysis; Placebos; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 33075160
DOI: 10.1002/14651858.CD012859.pub2 -
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 -
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 -
Current Medical Research and Opinion May 2021Postoperative nausea and vomiting (PONV) is a common complication following surgery, and may be one of the most distressing parts of the surgical journey. With... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Postoperative nausea and vomiting (PONV) is a common complication following surgery, and may be one of the most distressing parts of the surgical journey. With combination pharmacological therapy recommended for PONV prophylaxis, this systematic review and meta-analysis evaluates whether perioperative palonosetron and dexamethasone is more efficacious than palonosetron administered alone.
METHODS
We searched CENTRAL; EMBASE; CINAHL; Google Scholar; Web of Science citation index; the US clinical trials register; UK clinical trials register; Australia and New Zealand Clinical trials register; and conference abstracts for major anaesthesia conferences in the last three years.We included randomized controlled trials that compared adult patients undergoing surgery who received palonosetron and dexamethasone, against those who received palonosetron.
RESULTS
A total of 12 studies (1152 patients) were included. Medium-grade evidence showed that the palonosetron and dexamethasone combination significantly reduced 24-hour rescue anti-emetic requirement (RR: 0.59, 95% confidence interval (CI): 0.41-0.86). There was however no significant difference in the 6-hour (RR: 0.82, 95% CI: 0.61-1.09) and 24-hour PONV incidences (RR: 0.60, 95% CI: 0.33-1.10). Similarly, PONV incidences after 24 h did not differ between groups (RR:0.82, 95% CI: 0.59-1.14). Headache and dizziness were the most common side-effects reported.
CONCLUSIONS
Combination prophylaxis with palonosetron and dexamethasone reduces post-operative anti-emetic requirement, although is not associated with a significant difference in PONV. There was considerable heterogeneity in the studies, and trial sequential analysis indicates that further studies are needed to strengthen the clinical evidence.
Topics: Adult; Anesthesia; Antiemetics; Dexamethasone; Humans; Palonosetron; Postoperative Nausea and Vomiting
PubMed: 33617380
DOI: 10.1080/03007995.2021.1893677 -
Journal of Personalized Medicine Dec 2022This updated systematic review and meta-analysis with trial sequential analysis aimed to compare the efficacy of the perioperative administration of palonosetron with... (Review)
Review
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.
PubMed: 36675743
DOI: 10.3390/jpm13010082 -
PloS One 2021To determine the effectiveness of pharmacologic interventions for preventing postoperative nausea and vomiting (PONV) in patients undergoing thyroidectomy. (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To determine the effectiveness of pharmacologic interventions for preventing postoperative nausea and vomiting (PONV) in patients undergoing thyroidectomy.
DESIGN
Systematic review and network meta-analysis (NMA).
DATA SOURCES
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar.
ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
Randomized clinical trials that investigated the efficacy of pharmacologic interventions in preventing PONV in patients undergoing thyroidectomy were included. The primary endpoints were the incidences of postoperative nausea and vomiting (PONV), postoperative nausea (PON), postoperative vomiting (POV), use of rescue antiemetics, and incidence of complete response in the overall postoperative phases. The secondary endpoints were the same parameters assessed in the early, middle, and late postoperative phases. The surface under the cumulative ranking curve (SUCRA) values and rankograms were used to present the hierarchy of pharmacologic interventions.
RESULTS
Twenty-six studies (n = 3,467 patients) that investigated 17 different pharmacologic interventions were included. According to the SUCRA values, the incidence of PONV among the overall postoperative phases was lowest with propofol alone (16.1%), followed by palonosetron (27.5%), and with tropisetron (28.7%). The incidence of PON among the overall postoperative phases was lowest with propofol alone (11.8%), followed by tropisetron and propofol combination (14%), and ramosetron and dexamethasone combination (18.0%). The incidence of POV among the overall postoperative phases was lowest with tropisetron and propofol combination (2.2%), followed by ramosetron and dexamethasone combination (23.2%), and tropisetron alone (37.3%). The least usage of rescue antiemetics among the overall postoperative phases and the highest complete response was observed with tropisetron and propofol combination (3.9% and 96.6%, respectively).
CONCLUSION
Propofol and tropisetron alone and in combination, and the ramosetron and dexamethasone combination effectively prevented PONV, PON, POV in patients undergoing thyroidectomy, with some heterogeneity observed in this NMA of full-text reports. Their use minimized the need for rescue antiemetics and enhanced the complete response.
TRIAL REGISTRATION NUMBER
CRD42018100002.
Topics: Antiemetics; Drug Therapy, Combination; Humans; Network Meta-Analysis; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Thyroidectomy; Treatment Outcome
PubMed: 33428643
DOI: 10.1371/journal.pone.0243865 -
Computational and Mathematical Methods... 2022Postoperative nausea and vomiting (PONV) is a typical and unpleasant physical symptom that occurs in patients after surgery, and it may be one of the most challenging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is a typical and unpleasant physical symptom that occurs in patients after surgery, and it may be one of the most challenging elements of the recovery process. PONV can be caused by a variety of factors, including surgery itself, anesthesia, or medications. Palonosetron is a medication that is now licensed by the Food and Drug Administration for the treatment of this ailment. The efficacy of palonosetron in reducing physical symptoms in patients following surgery was investigated in this meta-analysis and comprehensive review.
METHODS
Following a quick search of databases such as CENTRAL, EMBASE, CINAHL, Google Scholar, the Science quotation index's Web site, the United States clinical trial check-in, the United Kingdom clinical trial check-in, the New Zealand clinical trial check-in, and the Australia check-in, as well as outlines of major anesthesia meetings held in the previous five years, we were able to get a good start on our research. Growing adults who had surgery and were given other drugs were compared to individuals who did get palonosetron in randomized controlled trials.
RESULTS
A total of 8324 participants were recruited in 10 different clinical studies. It has been shown that palonosetron may significantly reduce the 24-hour PONV incidence and 95% confidence interval (CI) 0.41-0.86. When comparing the 6-hour and 48-hour time periods, the incidences of experiencing PONV were neither statistically different (RR: 0.82, 95% confidence interval: 0.61-1.09) or considerably different (RR: 0.60, 95% confidence interval: 0.33-1.10). Following in a similar vein, there was no significant difference between the groups in the occurrence of PONV after 48 hours (RR: 0.82, 95 percent CI: 0.59-1.14). The most often reported side effects of the medicine were headaches and dizziness, which were the most common. Regardless of the drug used, the difference in adverse reactions was not statistically significant.
CONCLUSION
When it comes to the prevention of early PONV, it has been shown that palonosetron is more effective than other medications. Palonosetron, on the other hand, has been demonstrated to be more effective than other medications in preventing vomiting after laparoscopic surgery.
Topics: Adult; Anesthesia; Antiemetics; Humans; Laparoscopy; Palonosetron; Postoperative Nausea and Vomiting
PubMed: 35387223
DOI: 10.1155/2022/7474053 -
European Journal of Clinical... Nov 2021Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients' quality of life. Recently, studies have shown... (Meta-Analysis)
Meta-Analysis
PURPOSE
Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients' quality of life. Recently, studies have shown inconsistent antiemetic effects of two common 5-hydroxytryptamine 3 receptor antagonists, namely, palonosetron and granisetron. Therefore, we conducted a meta-analysis to evaluate the effectiveness of palonosetron versus granisetron in preventing CINV.
METHODS
Relevant studies were obtained from PubMed, Embase, and Cochrane databases. The primary outcome was the complete response (CR) rate. Secondary outcomes were headache and constipation events.
RESULTS
In total, 12 randomized controlled trials and five retrospective studies were reviewed. Palonosetron was consistently statistically superior to granisetron in all phases in terms of the CR rate (acute phases: odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.06-1.54; delayed phases: OR = 1.38, 95% CI = 1.13-1.69; and overall phases: OR = 1.37, 95% CI = 1.17-1.60). Moreover, a non-significant difference was found between the two groups in terms of the headache event, but the occurrence of the constipation event was lower in the granisetron group than in the palonosetron group.
CONCLUSION
Palonosetron showed a higher protective efficacy in all phases of CINV prevention, especially in delayed phases, and no relatively severe adverse effects were observed.
Topics: Antiemetics; Antineoplastic Agents; Granisetron; Humans; Nausea; Palonosetron; Quality of Life; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 33993343
DOI: 10.1007/s00228-021-03157-2 -
Cellular and Molecular Biology... Sep 2022Nausea and vomiting are known as side effects after surgery. Since serotonin antagonist drugs are widely used to prevent nausea and vomiting after surgery, the present... (Meta-Analysis)
Meta-Analysis
Evaluating the effect of anti-nausea drugs in IDO enzyme gene expression and preventing postoperative vomiting and nausea in patients undergoing general anesthesia: A Meta-analysis.
Nausea and vomiting are known as side effects after surgery. Since serotonin antagonist drugs are widely used to prevent nausea and vomiting after surgery, the present study was conducted to compare the effectiveness of this group's drugs, namely, ondansetron and palonosetron. On the other hand, recent studies have shown that the metabolites of the kynurenine pathway in the Suppression of the immune response play a role. Indoleamine 2,3 dioxygenase (IDO) is the main enzyme controlling this pathway. Therefore, the effect of these two drugs on IDO gene expression was evaluated. The present study is a systematic review with meta-analysis. The search was conducted in the Cochrane, PubMed, Clinical K, and CRD databases for randomized clinical trial articles that compared two drugs, palonosetron, and ondansetron, regarding nausea and vomiting in patients undergoing surgery with general anesthesia. In the end, eight studies were included in the meta-analysis. STATA13 statistical software was used to estimate the overall risk, relative risk, and data analysis. The results showed that the number of samples in all articles was 739. The analysis of the results between 0 and 24 hours showed that palonosetron reduces the incidence of nausea by 50% and the incidence of vomiting by 79% compared to ondansetron (p=0.001). Also, there was no difference between the IDO gene expression in the two drug groups (p>0.05). In general, the analysis of the results related to the effectiveness of palonosetron and ondansetron 24 hours after surgery with a dose of 0.075 mg of palonosetron versus 4 mg of ondansetron showed that palonosetron is more effective in reducing the incidence of nausea and vomiting in patients than ondansetron.
Topics: Humans; Anesthesia, General; Antiemetics; Gene Expression; Isoquinolines; Ondansetron; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Randomized Controlled Trials as Topic
PubMed: 36905254
DOI: 10.14715/cmb/2022.68.9.29 -
Frontiers in Public Health 2021The aim of this systematic review is to assess the published cost-effectiveness analyses of aprepitant for patients with chemotherapy-induced nausea and vomiting...
The aim of this systematic review is to assess the published cost-effectiveness analyses of aprepitant for patients with chemotherapy-induced nausea and vomiting (CINV). A systematic literature search was performed on PubMed, EMbase, the Cochrane Library, CNKI, WANFANG DATA, and CBM database. The date of publication is up to January 2019. Two reviewers independently reviewed titles, abstracts, and articles sequentially to select studies for data abstraction based on the inclusion and exclusion criteria. Disagreements were resolved and reviewers reached a consensus. The quality of the included studies was assessed according to the 24-item checklist of the consolidated health economic evaluation reporting standards (CHEERS). The costs reported by the included studies were converted to US dollars purchasing power parities (PPP) in the year 2019 using the CCEMG-EPPI-Certer Cost Converter. Thirteen articles were included based on the inclusion criteria for cost-effectiveness analysis and cost-utility analysis. Twelve studies were rated as good quality and one as a moderate quality based on the CHEERS checklist. Eight studies compared aprepitant plus 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone with the standard regimen (5-HT3RA and dexamethasone). It was concluded that aprepitant plus standard regimen was a cost-effective strategy for preventing CINV. Only one study that compared aprepitant plus 5-HT3RA with 5-HT3RA, concluded that the addition of aprepitant reduced the incidence of severe nausea, and it might also provide an economic benefit in the overall management. Four studies that compared aprepitant with other antiemetic drugs concluded that aprepitant is a cost-effective strategy for preventing CINV compared with metoclopramide. However, netupitan + palonosetron and olanzapine are cost-effective compared with aprepitant. This study is the first systematic evaluation of adding aprepitant to standard regimens for patients with CINV. Most economic evaluations of antiemetic medications are reported to be of good quality. Adding aprepitant to standard regimens is found to be a cost-effective strategy for preventing CINV.
Topics: Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Humans; Nausea; Vomiting
PubMed: 34513778
DOI: 10.3389/fpubh.2021.660514