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Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis.Birth Defects Research Aug 2020Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital... (Meta-Analysis)
Meta-Analysis
Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta-analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case-control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB-based meta-analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00-1.23; p < .05; n = 6 studies; I = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00-1.49; p < .05; n = 4 studies; I = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19-1.84; p < .01; n = 5 studies; I = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and "respiratory system anomalies."
Topics: Abnormalities, Drug-Induced; Antiemetics; Cleft Lip; Cleft Palate; Female; Humans; Ondansetron; Pregnancy
PubMed: 32420702
DOI: 10.1002/bdr2.1705 -
European Journal of Pediatrics Jul 2020This review aimed to meta-analyze evidence of efficacy and safety of one single dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis.... (Meta-Analysis)
Meta-Analysis
This review aimed to meta-analyze evidence of efficacy and safety of one single dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis. Database searches of MEDLINE (PubMed), Scopus (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up to November 2019 were performed. Only randomized clinical trials versus placebo were considered. Fixed and random effect models were used for the analyses of pooled data. Thirteen randomized clinical trials (2146 patients) were finally included. One single dose of ondansetron showed to produce (1) higher chance of vomiting cessation within 8 h (RR 1.41, 95% CI 1.19-1.68; low-quality evidence); (2) lower chances of oral rehydration therapy failure (RR 0.43, 95% CI 0.34-0.55; high-quality evidence), intravenous hydration needs (RR 0.44, 95% CI 0.34-0.57; high-quality evidence), and hospitalization rates within 8 h (RR 0.49, 95% CI 0.32-0.75; high-quality evidence); and (3) no statistically significant differences in return visits to emergency department (RR 1.14, 95% CI 0.74-1.76; high-quality evidence) compared with placebo. Further studies are necessary to better assess long term efficacy and safety of ondansetron in this context.Conclusions: Mixed evidence was found via few studies about the efficacy and safety of a single dose of ondansetron in the pediatric population.What is known:• Ondansetron use for vomiting in pediatric acute gastroenteritis is increasing worldwide.• Actual convictions come from studies evaluating one and more than one dose of the drug.What is new:• This is the first review to collect data about the effects of one single dose of ondansetron on strong and temporally homogeneous clinical outcomes.• This study supports the use of one dose of ondansetron in pediatric acute gastroenteritis.• Further studies are necessary to assess its long-term efficacy and safety.
Topics: Acute Disease; Adolescent; Antiemetics; Child; Drug Administration Schedule; Gastroenteritis; Humans; Models, Statistical; Ondansetron; Treatment Outcome; Vomiting
PubMed: 32382791
DOI: 10.1007/s00431-020-03653-0 -
The Journal of Emergency Medicine Apr 2020It is common practice for emergency physicians to give parenteral opioids for acute pain, however, some treating physicians have concerns that using parenteral opioids...
Should Antiemetics be Given Prophylactically with Intravenous Opioids While Treating Acute Pain in the Emergency Department?: Clinical Practice Paper Approved by American Academy of Emergency Medicine Clinical Guidelines Committee.
BACKGROUND
It is common practice for emergency physicians to give parenteral opioids for acute pain, however, some treating physicians have concerns that using parenteral opioids can lead to nausea and vomiting when used alone. Therefore, antiemetics are often given prophylactically with opioids for nausea and vomiting in the emergency department (ED). This systematic review evaluates the use of prophylactic antiemetics with parenteral opioids for the treatment of acute pain in the ED.
METHODS
A 10-year literature search using keywords was performed in PubMed for English-language human studies. Abstracts were screened to identify high-quality studies, which then underwent a more rigorous structured review. The recommendations are made based on the literature review.
RESULTS
Eight articles met criteria for structured review and citation in this article. These include one review article, two randomized controlled trials, three prospective observational trials, one retrospective study, and one pre- and post-intervention trial.
CONCLUSIONS
Based on the literature review, routine use of prophylactic antiemetics are not indicated with administration of parenteral opioids for treatment of acute pain in the ED, as nausea and vomiting are infrequent side effects. The recent literature clearly demonstrates that there are potential undesirable side effects from the use of antiemetics when using opioids. However, one subgroup of patients, those with a known history of nausea and vomiting after opioid use or a history of travel sickness, may benefit from the use of prophylactic antiemetic when being treated with parenteral opioids.
Topics: Acute Pain; Analgesics, Opioid; Antiemetics; Emergency Medicine; Emergency Service, Hospital; Humans; Metoclopramide; Observational Studies as Topic; Ondansetron; Retrospective Studies; United States; Vomiting
PubMed: 32216978
DOI: 10.1016/j.jemermed.2019.12.024 -
Pediatrics Apr 2020Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use. (Meta-Analysis)
Meta-Analysis
CONTEXT
Several antiemetics have been used in children with acute gastroenteritis. However, there is still controversy over their use.
OBJECTIVE
To determine the effectiveness and safety of antiemetics for controlling vomiting in children with acute gastroenteritis.
DATA SOURCES
Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Latin America and the Caribbean Literature on Health Sciences, and gray literature, until December 2018.
STUDY SELECTION
We selected randomized clinical trials comparing metoclopramide, ondansetron, domperidone, dexamethasone, dimenhydrinate, and granisetron.
DATA EXTRACTION
Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model.
RESULTS
Twenty-four studies were included (3482 children). Ondansetron revealed the largest effect in comparison to placebo for cessation of vomiting (odds ratio = 0.28 [95% credible interval = 0.16 to 0.46]; quality of evidence: high) and for hospitalization (odds ratio = 2.93 [95% credible interval = 1.69 to 6.18]; quality of evidence: moderate). Ondansetron was the only intervention that reduced the need for intravenous rehydration and the number of vomiting episodes. When considering side effects, dimenhydrinate was the only intervention that was worse than placebo.
LIMITATIONS
Most treatment comparisons had low- or very low-quality evidence, because of risk of biases and imprecise estimates.
CONCLUSIONS
Ondansetron is the only intervention that revealed an effect on the cessation of vomiting, on preventing hospitalizations, and in reducing the need for intravenous rehydration. Ondansetron was also considered a safe intervention.
Topics: Acute Disease; Antiemetics; Child; Child, Preschool; Dexamethasone; Diarrhea; Dimenhydrinate; Domperidone; Fluid Therapy; Gastroenteritis; Granisetron; Hospitalization; Humans; Infant; Metoclopramide; Network Meta-Analysis; Ondansetron; Randomized Controlled Trials as Topic; Regression Analysis; Vomiting
PubMed: 32132152
DOI: 10.1542/peds.2019-3260 -
Asian Journal of Anesthesiology Sep 2019Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been...
Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been averted. Patients describe it as a highly unpleasant experience, while clinicians are concerned due to its adverse effects such as increased oxygen consumption. In this article, we present a summary of the pathophysiological mechanisms involved in postoperative shivering (POS), risk factors, and inadvertent effects. The major objective of this article was to review the existing literature on the effi ciency of various drug interventions as a prophylactic measure against POS. Since α2-adrenergic, opioid, anticholinergic, and serotonergic pathways are thought to play a role in the pathogenesis of POS, a wide variety of drugs has been investigated in this regard. Although the methodological diversity of the study designs and regimens does not support drawing defi nite conclusions, there is evidence indicating a benefi cial effect of dexmedetomidine, ketamine, tramadol, meperidine, dexamethasone, nefopam, granisetron, and ondansetron in the prevention of POS. The purpose of this review is to provide a thorough insight on various drug options and to serve as an aid for clinicians for careful analysis of the advantages and disadvantages of each regimen to decide which regimen will be ideally suited for the medical profi le of each patient.
Topics: Adrenergic alpha-2 Receptor Agonists; Humans; Nefopam; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Shivering; Tramadol
PubMed: 31842530
DOI: 10.6859/aja.201909_57(3).0002 -
The Journal of Pediatrics Nov 2019To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the...
OBJECTIVES
To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the acute care setting.
STUDY DESIGN
Using keywords, 799 studies published up from December 1954 to February 2018 were extracted from MEDLINE via Pubmed, Embase via OVID, CINAHL via EBSCO, and Cochrane Controlled Trials Registry. Studies were evaluated for inclusion and exclusion by 2 independent reviewers using predetermined inclusion and exclusion criteria.
RESULTS
The search yielded 84 studies for full review, of which 54 were included in the systematic review. Studies were subsequently separated into 1 group of 6 case series studies containing quantitative data on sumatriptan, ondansetron, phenothiazines, prokinetic agents, carbohydrate, isometheptene, and aprepitant; 1 one group consisting only of qualitative studies containing expert recommendations.
CONCLUSIONS
Ondansetron has the most quantitative and qualitative evidence to support its inclusion in pediatric emergency department protocols as a rescue therapy. Sumatriptan and aprepitant are potential candidates for inclusion as abortive therapies. Qualitative data from retrospective studies and case reports are not applicable to a larger patient population. This report informs a need for controlled, prospective cohort studies and randomized, controlled trials to optimize current management protocols and to develop new medical interventions.
Topics: Child; Critical Care; Disease Management; Humans; Vomiting
PubMed: 31540764
DOI: 10.1016/j.jpeds.2019.06.057 -
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 -
The Cochrane Database of Systematic... Sep 2019Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for...
BACKGROUND
Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population.
OBJECTIVES
Primary objective1. To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of deliriumSecondary objectivesTo assess the following:1. effects of pharmacological interventions on delirium-free and coma-free days; days with coma; delirium relapse; duration of mechanical ventilation; intensive care unit (ICU) and hospital length of stay; mortality; and long-term outcomes (e.g. cognitive; discharge disposition; health-related quality of life); and2. the safety of such treatments for critically ill adult patients.
SEARCH METHODS
We searched the following databases from their inception date to 21 March 2019: Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO using the Ovid platform. We also searched the Cochrane Library on Wiley, the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/PROSPERO/), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. We performed a grey literature search of relevant databases and websites using the resources listed in Grey Matters developed by the Canadian Agency for Drugs and Technologies in Health (CADTH). We also searched trial registries and abstracts from annual scientific critical care and delirium society meetings.
SELECTION CRITERIA
We sought randomized controlled trials (RCTs), including quasi-RCTs, of any pharmacological (drug) for treatment of delirium in critically ill adults. The drug intervention was to be compared to another active drug treatment, placebo, or a non-pharmacological intervention (e.g. mobilization). We did not apply any restrictions in terms of drug class, dose, route of administration, or duration of delirium or drug exposure. We defined critically ill patients as those treated in an ICU of any specialty (e.g. burn, cardiac, medical, surgical, trauma) or high-dependency unit.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified studies from the search results; four review authors (in pairs) performed data extraction and assessed risk of bias independently. We performed data synthesis through pairwise meta-analysis and network meta-analysis (NMA). Our hypothetical network structure was designed to be analysed at the drug class level and illustrated a network diagram of 'nodes' (i.e. drug classes) and 'edges' (i.e. comparisons between different drug classes from existing trials), thus describing a treatment network of all possible comparisons between drug classes. We assessed the quality of the body of evidence according to GRADE, as very low, low, moderate, or high.
MAIN RESULTS
We screened 7674 citations, from which 14 trials with 1844 participants met our inclusion criteria. Ten RCTs were placebo-controlled, and four reported comparisons of different drugs. Drugs examined in these trials were the following: antipsychotics (n = 10), alpha agonists (n = 3; all dexmedetomidine), statins (n = 2), opioids (n = 1; morphine), serotonin antagonists (n = 1; ondansetron), and cholinesterase (CHE) inhibitors (n = 1; rivastigmine). Only one of these trials consistently used non-pharmacological interventions that are known to improve patient outcomes in both intervention and control groups.Eleven studies (n = 1153 participants) contributed to analysis of the primary outcome. Results of the NMA showed that the intervention with the smallest ratio of means (RoM) (i.e. most preferred) compared with placebo was the alpha agonist dexmedetomidine (0.58; 95% credible interval (CrI) 0.26 to 1.27; surface under the cumulative ranking curve (SUCRA) 0.895; moderate-quality evidence). In order of descending SUCRA values (best to worst), the next best interventions were atypical antipsychotics (RoM 0.80, 95% CrI 0.50 to 1.11; SUCRA 0.738; moderate-quality evidence), opioids (RoM 0.88, 95% CrI 0.37 to 2.01; SUCRA 0.578; very-low quality evidence), and typical antipsychotics (RoM 0.96, 95% CrI 0.64 to1.36; SUCRA 0.468; high-quality evidence).The NMAs of multiple secondary outcomes revealed that only the alpha agonist dexmedetomidine was associated with a shorter duration of mechanical ventilation (RoM 0.55, 95% CrI 0.34 to 0.89; moderate-quality evidence), and the CHE inhibitor rivastigmine was associated with a longer ICU stay (RoM 2.19, 95% CrI 1.47 to 3.27; moderate-quality evidence). Adverse events often were not reported in these trials or, when reported, were rare; pair-wise analysis of QTc prolongation in seven studies did not show significant differences between antipsychotics, ondansetron, dexmedetomidine, and placebo.
AUTHORS' CONCLUSIONS
We identified trials of varying quality that examined six different drug classes for treatment of delirium in critically ill adults. We found evidence that the alpha agonist dexmedetomidine may shorten delirium duration, although this small effect (compared with placebo) was seen in pairwise analyses based on a single study and was not seen in the NMA results. Alpha agonists also ranked best for duration of mechanical ventilation and length of ICU stay, whereas the CHE inhibitor rivastigmine was associated with longer ICU stay. We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days, days with coma, physical restraint use, length of stay, long-term cognitive outcomes, or mortality. No studies reported delirium relapse, resolution of symptoms, or quality of life. The ten ongoing studies and the six studies awaiting classification that we identified, once published and assessed, may alter the conclusions of the review.
Topics: Antipsychotic Agents; Critical Illness; Delirium; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 31479532
DOI: 10.1002/14651858.CD011749.pub2 -
JBI Database of Systematic Reviews and... Oct 2019The objective of this review was to synthesize the best available evidence on the effectiveness and harms of pharmacological interventions for the treatment of delirium...
OBJECTIVE
The objective of this review was to synthesize the best available evidence on the effectiveness and harms of pharmacological interventions for the treatment of delirium in adult patients in the intensive care unit (ICU) after cardiac surgery.
INTRODUCTION
Patients who undergo cardiac surgery are at high risk of delirium (incidence: 50-90%). Delirium has deleterious effects, increasing the risk of death and adversely affecting recovery. Clinical interventional trials have been conducted to prevent and treat postoperative delirium pharmacologically including antipsychotics and sedatives. These trials have provided some evidence about efficacy and influenced clinical decision making. However, much reporting is incomplete and provides biased assessments of efficacy; benefits are emphasized while harms are inadequately reported.
INCLUSION CRITERIA
Participants were ≥ 16 years, any sex or ethnicity, who were treated postoperatively in a cardiothoracic ICU following cardiac surgery and were identified as having delirium. Any pharmacological intervention for the treatment of delirium was included, regardless of drug classification, dosage, intensity or frequency of administration. Outcomes of interest of this review were: mortality, duration and severity of delirium, use of physical restraints, quality of life, family members' satisfaction with delirium management, duration/severity of the aggressive episode, associated falls, severity of accidental self-harm, pharmacological harms, harms related to over-sedation, ICU length of stay, hospital length of stay (post ICU), total hospital length of stay, need for additional intervention medication and need for rescue medication. Randomized controlled trials were considered first and in their absence, non-randomized controlled trials and quasi-experimental would have been considered, followed by analytical observational studies.
METHODS
A search was conducted in PubMed, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, Epistemonikos, Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, Clinical Trials in New Zealand, and ProQuest Dissertations and Theses to locate both published and unpublished studies. There was no date limit for the search. A hand search for primary studies published between January 1, 2012 and November 17, 2018 in relevant journals was also conducted. Only studies published in English were considered for inclusion. Two reviewers independently assessed the methodological quality using standardized critical appraisal instruments from JBI and McMaster University. Quantitative data were extracted using the standardized JBI data extraction tool. A meta-analysis was not performed, as there was too much clinical and methodological heterogeneity in the included studies. Results have been presented in a narrative form. Standard GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) evidence assessment of outcomes has been reported.
RESULTS
Three RCTs investigating morphine versus haloperidol (n = 53), ondansetron versus haloperidol (n = 72), and dexmedetomidine versus midazolam (n = 80) were included. Due to heterogeneity and incomplete reporting, a meta-analysis was not feasible. Overall, the methodological quality of these studies was found to be low. Additionally, this review found reporting of harms to be inadequate and superficial for all three studies and did not meet the required standards for harms reporting, as defined by the CONSORT statement extension for harms.
CONCLUSIONS
It was not possible to draw any valid conclusions regarding the effectiveness of morphine vs haloperidol, ondansetron vs haloperidol or dexmedetomidine vs midazolam in treating delirium after cardiac surgery. This is due to the low number of studies, the poor methodological quality in conducting and reporting and the heterogeneity between the studies.
Topics: Accidental Falls; Antipsychotic Agents; Cardiac Surgical Procedures; Delirium; Family; Hospital Mortality; Humans; Hypnotics and Sedatives; Intensive Care Units; Length of Stay; Quality of Life; Severity of Illness Index
PubMed: 31449136
DOI: 10.11124/JBISRIR-D-18-00010 -
Industrial Psychiatry Journal 2018Alcohol use disorders (AUDs) is an important public health concern as estimates of the prevalence of AUD range at 4%-6% in the Indian population. Currently, there is... (Review)
Review
Alcohol use disorders (AUDs) is an important public health concern as estimates of the prevalence of AUD range at 4%-6% in the Indian population. Currently, there is limited literature on the pharmacotherapeutic interventions for AUD in the Indian setting. It is imperative to identify the possible variations in their effects from Western studies, and hence the current review was attempted to perform a comprehensive evaluation and critical appraisal of the methodology of the evidence on pharmacological strategies of relapse prevention of AUD in the Indian setting. A total of 18 studies were included in the review. Disulfiram was the most common pharmacological agent to be studied. The initial literature before 2000 focused primarily on disulfiram, whereas the studies in the next decade compared it to acamprosate and naltrexone and emerging interest in anticraving agents such as baclofen and topiramate had been noted over the past few years. No studies were available on newer agents such as ondansetron, selective serotonin reuptake inhibitors or formulations such as depot and implants. Deterrent agents were found to be better when compared to anticraving agents in terms of abstinence and relapse, whereas the latter were more effective for control of craving. Among the pharmacological agents studied, the greatest evidence exists for disulfiram for relapse prevention which could be due to affordability of disulfiram and social support in the Indian context. The chief methodological limitations include the lack of randomized trials and objective measures for assessing abstinence.
PubMed: 31359967
DOI: 10.4103/ipj.ipj_79_17