Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis.
ABSTRACT: To evaluate and compare the efficacy and safety of bronchodilators and steroids, alone or combined, for the acute management of bronchiolitis in children aged less than 2 years.Systematic review and meta-analysis.Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx, conference proceedings, and trial registers. Inclusion criteria Randomised controlled trials of children aged 24 months or less with a first episode of bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or combined, with placebo or another intervention (other bronchodilator, other steroid, standard care).Two reviewers assessed studies for inclusion and risk of bias and extracted data. Primary outcomes were selected by clinicians a priori based on clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and length of stay for inpatients. Direct meta-analyses were carried out using random effects models. A mixed treatment comparison using a Bayesian network model was used to compare all interventions simultaneously.48 trials (4897 patients, 13 comparisons) were included. Risk of bias was low in 17% (n = 8), unclear in 52% (n = 25), and high in 31% (n = 15). Only adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo: pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920 patients). Unadjusted results from a single large trial with low risk of bias showed that combined dexamethasone and adrenaline reduced admissions on day 7 (risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline alone or combined with steroids as the preferred treatments for outpatients (probability of being the best treatment based on admissions at day 1 were 45% and 39%, respectively). The incidence of reported harms did not differ. None of the interventions examined showed clear efficacy for length of stay among inpatients.Evidence shows the effectiveness and superiority of adrenaline for outcomes of most clinical relevance among outpatients with acute bronchiolitis, and evidence from a single precise trial for combined adrenaline and dexamethasone.
Project description:To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission.A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database.71 hospitals across England.We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life.In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR?=?61-209 days). The median length of stay was 1 day (IQR?=?0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR?=?1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR?=?2.5, 95% CI 1.7-3.7) and cerebral palsy (RR?=?2.4, 95% CI 1.5-4.0).Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis.
Project description:BACKGROUND:Airway oedema (swelling) and mucus plugging are the principal pathological features in infants with acute viral bronchiolitis. Nebulised hypertonic saline solution (? 3%) may reduce these pathological changes and decrease airway obstruction. This is an update of a review first published in 2008, and previously updated in 2010 and 2013. OBJECTIVES:To assess the effects of nebulised hypertonic (? 3%) saline solution in infants with acute bronchiolitis. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily, Embase, CINAHL, LILACS, and Web of Science on 11 August 2017. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 8 April 2017. SELECTION CRITERIA:We included randomised controlled trials and quasi-randomised controlled trials using nebulised hypertonic saline alone or in conjunction with bronchodilators as an active intervention and nebulised 0.9% saline, or standard treatment as a comparator in children under 24 months with acute bronchiolitis. The primary outcome for inpatient trials was length of hospital stay, and the primary outcome for outpatients or emergency department trials was rate of hospitalisation. DATA COLLECTION AND ANALYSIS:Two review authors independently performed study selection, data extraction, and assessment of risk of bias in included studies. We conducted random-effects model meta-analyses using Review Manager 5. We used mean difference (MD), risk ratio (RR), and their 95% confidence intervals (CI) as effect size metrics. MAIN RESULTS:We identified 26 new trials in this update, of which 9 await classification due to insufficient data for eligibility assessment, and 17 trials (N = 3105) met the inclusion criteria. We included a total of 28 trials involving 4195 infants with acute bronchiolitis, of whom 2222 infants received hypertonic saline.Hospitalised infants treated with nebulised hypertonic saline had a statistically significant shorter mean length of hospital stay compared to those treated with nebulised 0.9% saline (MD -0.41 days, 95% CI -0.75 to -0.07; P = 0.02, I² = 79%; 17 trials; 1867 infants) (GRADE quality of evidence: low). Infants who received hypertonic saline also had statistically significant lower post-inhalation clinical scores than infants who received 0.9% saline in the first three days of treatment (day 1: MD -0.77, 95% CI -1.18 to -0.36, P < 0.001; day 2: MD -1.28, 95% CI -1.91 to -0.65, P < 0.001; day 3: MD -1.43, 95% CI -1.82 to -1.04, P < 0.001) (GRADE quality of evidence: low).Nebulised hypertonic saline reduced the risk of hospitalisation by 14% compared with nebulised 0.9% saline among infants who were outpatients and those treated in the emergency department (RR 0.86, 95% CI 0.76 to 0.98; P = 0.02, I² = 7%; 8 trials; 1723 infants) (GRADE quality of evidence: moderate).Twenty-four trials presented safety data: 13 trials (1363 infants, 703 treated with hypertonic saline) did not report any adverse events, and 11 trials (2360 infants, 1265 treated with hypertonic saline) reported at least one adverse event, most of which were mild and resolved spontaneously. AUTHORS' CONCLUSIONS:Nebulised hypertonic saline may modestly reduce length of stay among infants hospitalised with acute bronchiolitis and improve clinical severity score. Treatment with nebulised hypertonic saline may also reduce the risk of hospitalisation among outpatients and emergency department patients. However, we assessed the quality of the evidence as low to moderate.
Project description:Admission of infants to hospital with bronchiolitis consumes considerable healthcare resources each winter. We report an analysis of hospital admissions in England over five decades.Data were analysed from the Hospital In-Patient Enquiry (HIPE, 1968-1985), Hospital Episode Statistics (HES, 1989-2011), Oxford Record Linkage Study (ORLS, 1963-2011) and Paediatric Intensive Care Audit Network (PICANet, 2003-2012). Cases were identified using International Classification of Diseases (ICD) codes in discharge records. Bronchiolitis was given a separate code in ICD9 (used in England from 1979). Geographical variation was analysed using Local Authority area boundaries. Maternal and perinatal risk factors associated with bronchiolitis and subsequent admissions for asthma were analysed using record-linkage.All-England HIPE and HES data recorded 468?138 episodes of admission for bronchiolitis in infants aged <1?year between 1979 and 2011. In 2011 the estimated annual hospital admission rate was 46.1 (95% CI 45.6 to 46.6) per 1000 infants aged <1?year. Between 2004 and 2011 the rates rose by an average of 1.8% per year in the all-England HES data, whereas admission rates to paediatric intensive care changed little (1.3 to 1.6 per 1000 infants aged <1?year). A fivefold geographical variation in hospital admission rates was observed. Young maternal age, low social class, low birth weight and maternal smoking were among factors associated with an increased risk of hospital admission with bronchiolitis.Hospital admissions for infants with bronchiolitis have increased substantially in recent years. However, cases requiring intensive care have changed little since 2004.
Project description:BACKGROUND:Acute bronchiolitis frequently causes infant hospitalization. Studies on different viruses or viral genomic load and disease severity or treatment effect have had conflicting results. We aimed to investigate whether the presence or concentration of individual or multiple viruses were associated with disease severity in acute bronchiolitis and to evaluate whether detected viruses modified the response to inhaled racemic adrenaline. METHODS:Nasopharyngeal aspirates were collected from 363 infants with acute bronchiolitis in a randomized, controlled trial that compared inhaled racemic adrenaline versus saline. Virus genome was identified and quantified by polymerase chain reaction analyses. Severity was assessed on the basis of the length of stay and the use of supportive care. RESULTS:Respiratory syncytial virus (83%) and human rhinovirus (34%) were most commonly detected. Seven other viruses were present in 8%-15% of the patients. Two or more viruses (maximum, 7) were detected in 61% of the infants. Virus type or coinfection was not associated with disease severity. A high genomic load of respiratory syncytial virus was associated with a longer length of stay and with an increased frequency of oxygen and ventilatory support use. Treatment effect of inhaled adrenaline was not modified by virus type, load or coinfection. DISCUSSION:In infants hospitalized with acute bronchiolitis, disease severity was not associated with specific viruses or the total number of viruses detected. A high RSV genomic load was associated with more-severe disease. CLINICAL TRIALS REGISTRATION:NCT00817466 and EudraCT 2009-012667-34.
Project description:Objective: To evaluate the effectiveness of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants. Methods: Four electronic databases (MEDLINE, EMBASE, CINAHL, and CENTRAL) were searched from their inception to February 28, 2017 for studies involving infants aged less than 24 months with bronchiolitis which assessed the use of epinephrine and corticosteroid combination therapy. The methodological quality of the included studies was assessed using the Cochrane Collaboration's Risk of Bias Tool. A random-effects meta-analysis was used to pool the effect estimates. The primary outcomes were hospital admission rate and length of hospital stay. Results: Of 1,489 citations identified, 5 randomized controlled trials involving 1,157 patients were included. All studies were of high quality and low risk of bias. Results of the meta-analysis showed no significant differences in the primary outcomes. Hospitalization rate was reduced by combinatorial therapy of epinephrine and corticosteroid in only one out of five studies, whereas pooled data indicated no benefit over epinephrine plus placebo. Clinical severity scores were significantly improved in all five RCTs when assessed individually, but no benefit was observed compared to epinephrine monotherapy when the data were pooled together. Pooled data showed that combination therapy was more effective at improving oxygen saturation level (mean difference: -0.70; 95% confidence interval: -1.17 to -0.22, p = 0.004). There was no difference in the risk of serious adverse events in infants treated with the combined epinephrine and corticosteroid therapy. Conclusions: Combination treatment of epinephrine and dexamethasone was ineffective in reducing hospital admission and length of stay among infants with bronchiolitis.
Project description:BACKGROUND:Rates of hospital admissions for bronchiolitis vary seasonally and geographically across England; however, seasonal differences by area remain unexplored. We sought to describe spatial variation in the seasonality of hospital admissions for bronchiolitis and its association with local demographic characteristics. METHODS:Singleton children born in English National Health Service hospitals between 2011 and 2016 (n=3 727 013) were followed up for 1?year. Poisson regression models with harmonic functions to model seasonal variations were used to calculate weekly incidence rates and peak timing of bronchiolitis admissions across English regions and clinical commissioning groups (CCGs). Linear regression was used to estimate the joint association of population density and deprivation with incidence and peak timing of bronchiolitis admissions at the CCG level. RESULTS:Bronchiolitis admission rates ranged from 30.9 per 1000 infant-years (95%?CI 30.4 to 31.3) in London to 68.7 per 1000 (95% CI 67.9 to 69.5) in the North West. Across CCGs, there was a 5.3-fold variation in incidence rates and the epidemic peak ranged from week 49.3 to 52.2. Admission rates were positively associated with area-level deprivation. CCGs with earlier peak epidemics had higher population densities, and both high and low levels of deprivation were associated with earlier peak timing. CONCLUSIONS:Approximately one quarter of the variation in admission rates and two-fifths of the variation in peak timing of hospital admissions for bronchiolitis were explained by local demographic characteristics. Implementation of an early warning system could help to prepare hospitals for peak activity and to time public health messages.
Project description:The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients.We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality.A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment.In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo.Clinicaltrials.gov NCT00604214 . Registered 24 January 2008.
Project description:Adoption of clinical respiratory scoring as a quality improvement (QI) tool in bronchiolitis has been temporally associated with decreased bronchodilator usage. We sought to determine whether documented use of a clinical respiratory score at the patient level was associated with a decrease in either the physician prescription of any dose of bronchodilator or the number of doses, if prescribed, in a multisite QI collaborative.We performed a secondary analysis of data from a QI collaborative involving 22 hospitals. The project enrolled patients aged 1 month to 2 years with a primary diagnosis of acute viral bronchiolitis and excluded those with prematurity, other significant comorbid diseases, and those needing intensive care. We assessed for an association between documentation of any respiratory score use during an episode of care, as well as the method in which scores were used, and physician prescribing of any bronchodilator and number of doses. Covariates considered were phase of the collaborative, hospital length of stay, steroid use, and presence of household smokers.A total of 1876 subjects were included. There was no association between documentation of a respiratory score and the likelihood of physician prescribing of any bronchodilator. Score use was associated with fewer doses of bronchodilators if one was prescribed (P = .05), but this association disappeared with multivariable analysis (P = .73).We found no clear association between clinical respiratory score use and physician prescribing of bronchodilators in a multicenter QI collaborative.
Project description:Objective:To systematically review the evidence around the effect of ambient levels of particulate and gaseous pollutants, and the risk of hospitalisation with bronchiolitis for infants under two years of age. Design:Systematic review of observational epidemiological studies including cohort, time series, case crossover and case control study designs. Data sources:Medline, Scopus, and Web of Science searched to November 2017 with no language restrictions. Eligibility criteria:Studies investigating impact of air pollution levels on particulate pollutants (diameter <2.5 ?m (PM2.5) or <10 ?m (PM10) and gaseous pollutants (nitrogen dioxide (NO2), sulphur dioxide (SO2), carbon monoxide (CO), ozone (O3)) on hospital admission for bronchiolitis. Main outcome measure:Risk of hospitalisation from bronchiolitis. Results:Eight studies were eligible for review. Long term exposure to PM2.5 may be associated with increased risk of hospitalisation for bronchiolitis. SO2 may also be associated with hospitalisation, but results for other pollutants are inconsistent between studies. In three of the five studies that showed a positive association between air pollutants and hospitalisation, measured concentrations were below World Health Organization (WHO) recommended levels. Conclusions:Certain particulate and gaseous pollutants may have a clinically relevant effect on hospital admissions for bronchiolitis in children below age two years old. Large cohort or time series studies are needed to examine this possible association. Protocol:The protocol can be found at PROSPERO (CRD42017080643).
Project description:Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS.The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling.Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p?=?0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p?=?0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan.Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.