Dataset Information

Effect of Nebulized Hypertonic Saline Treatment in Emergency Departments on the Hospitalization Rate for Acute Bronchiolitis: A Randomized Clinical Trial.

ABSTRACT:

Importance

Acute bronchiolitis is the leading cause of hospitalization among infants. Previous studies, underpowered to examine hospital admission, have found a limited benefit of nebulized hypertonic saline (HS) treatment in the pediatric emergency department (ED).

Objective

To examine whether HS nebulization treatment would decrease the hospital admission rate among infants with a first episode of acute bronchiolitis.

Design, setting, and participants

The Efficacy of 3% Hypertonic Saline in Acute Viral Bronchiolitis (GUERANDE) study was a multicenter, double-blind randomized clinical trial on 2 parallel groups conducted during 2 bronchiolitis seasons (October through March) from October 15, 2012, through April 15, 2014, at 24 French pediatric EDs. Among the 2445 infants (6 weeks to 12 months of age) assessed for inclusion, 777 with a first episode of acute bronchiolitis with respiratory distress and no chronic medical condition were included.

Interventions

Two 20-minute nebulization treatments of 4 mL of HS, 3%, or 4 mL of normal saline (NS), 0.9%, given 20 minutes apart.

Main outcomes and measures

Hospital admission rate in the 24 hours after enrollment.

Results

Of the 777 infants included in the study (median age, 3 months; interquartile range, 2-5 months; 468 [60.2%] male), 385 (49.5%) were randomized to the HS group and 387 (49.8%) to the NS group (5 patients did not receive treatment). By 24 hours, 185 of 385 infants (48.1%) in the HS group were admitted compared with 202 of 387 infants (52.2%) in the NS group. The risk difference for hospitalizations was not significant according to the mixed-effects regression model (adjusted risk difference, -3.2%; 95% CI, -8.7% to 2.2%; P = .25). The mean (SD) Respiratory Distress Assessment Instrument score improvement was greater in the HS group (-3.1 [3.2]) than in the NS group (-2.4 [3.3]) (adjusted difference, -0.7; 95% CI, -1.2 to -0.2; P = .006) and similarly for the Respiratory Assessment Change Score. Mild adverse events, such as worsening of cough, occurred more frequently among children in the HS group (35 of 392 [8.9%]) than among those in the NS group (15 of 384 [3.9%]) (risk difference, 5.0%; 95% CI, 1.6%-8.4%; P = .005), with no serious adverse events.

Conclusions and relevance

Nebulized HS treatment did not significantly reduce the rate of hospital admissions among infants with a first episode of acute moderate to severe bronchiolitis who were admitted to the pediatric ED relative to NS, but mild adverse events were more frequent in the HS group.

Trial registration

clinicaltrials.gov Identifier: NCT01777347.

SUBMITTER: Angoulvant F

PROVIDER: S-EPMC6583778 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAirway 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.ObjectivesTo assess the effects of nebulised hypertonic (≥ 3%) saline solution in infants with acute bronchiolitis.Search methodsWe 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 criteriaWe 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 analysisTwo 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 resultsWe 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' conclusionsNebulised 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:Acute bronchiolitis is the commonest cause of hospitalisation in infancy. Currently management consists of supportive care and oxygen. A Cochrane review concluded that, "nebulised 3 % saline may significantly reduce the length of hospital stay". We conducted a systematic review of controlled trials of nebulised hypertonic saline (HS) for infants hospitalised with primary acute bronchiolitis.Searches to January 2015 involved: Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Embase; Google Scholar; Web of Science; and, a variety of trials registers. We hand searched Chest, Paediatrics and Journal of Paediatrics on 14 January 2015. Reference lists of eligible trial publications were checked. Randomised or quasi-randomised trials which compared HS versus either normal saline (+/- adjunct treatment) or no treatment were included. Eligible studies involved children less than 2 years old hospitalised due to the first episode of acute bronchiolitis. Two reviewers extracted data to calculate mean differences (MD) and 95 % Confidence Intervals (CIs) for length of hospital stay (LoS-primary outcome), Clinical Severity Score (CSS) and Serious Adverse Events (SAEs). Meta-analysis was undertaken using a fixed effect model, supplemented with additional sensitivity analyses. We investigated statistical heterogeneity using I(2). Risk of bias, within and between studies, was assessed using the Cochrane tool, an outcome reporting bias checklist and a funnel plot.Fifteen trials were included in the systematic review (n?=?1922), HS reduced mean LoS by 0.36, (95 % CI 0.50 to 0.22) days, but with considerable heterogeneity (I(2)?=?78 %) and sensitivity to alternative analysis methods. A reduction in CSS was observed where assessed [n?=?516; MD -1.36, CI -1.52, -1.20]. One trial reported one possible intervention related SAE, no other studies described intervention related SAEs.There is disparity between the overall combined effect on LoS as compared with the negative results from the largest and most precise trials. Together with high levels of heterogeneity, this means that neither individual trials nor pooled estimates provide a firm evidence-base for routine use of HS in inpatient acute bronchiolitis.

Project description:IntroductionBronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus. Being a common reason for hospitalisation, it affects 13-17% of all hospitalised children younger than 2 years. Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance and oxygen supplementation when needed, is recommended. However, non-evidence-based diagnostic and therapeutic approaches, including the use of inhaled bronchodilators, nebulised epinephrine, and nebulised and systemic steroids, are common. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. We aim to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis.Methods and analysisThis will be a randomised, double-blinded, parallel-group, controlled trial. Children younger than 2 years who are hospitalised due to bronchiolitis will be recruited from at least three paediatric departments in Poland. Bronchiolitis is defined as an apparent viral respiratory tract infection associated with airway obstruction that is manifested by at least one of following symptoms: tachypnoea, increased respiratory effort, crackles and/or wheezing. A total of 140 children will be randomised (1:1) to receive either hypertonic saline nebulisation (5 mL, three times a day) or normal saline at the same dose. The primary outcome measure will be the duration of hospitalisation.Ethics and disseminationThe Bioethics Committee of the Lower Silesia Medical Chamber in Wroclaw approved the study protocol (4/PNDR/2023). Caregivers will receive oral and written information about the study and written informed consent will be obtained by the study physicians. The findings of the study will be submitted to a peer-reviewed journal, and abstracts will be submitted to relevant national and international conferences.Trial registration numberClinicalTrials.gov Registry (NCT06069336).

Project description:ImportanceIn therapeutic trials for acute viral bronchiolitis, consistent clinical improvement in groups that received nebulized normal saline (NS) as placebo raises the question of whether nebulized NS acts as a treatment rather than a placebo.ObjectiveTo measure the short-term association of nebulized NS with physiologic measures of respiratory status in children with bronchiolitis by analyzing the changes in these measures between the use of nebulized NS and the use of other placebos and the changes before and after nebulized NS treatment.Data sourcesMEDLINE and Scopus were searched through March 2019, as were bibliographies of included studies and relevant systematic reviews, for randomized clinical trials evaluating nebulized therapies in bronchiolitis.Study selectionRandomized clinical trials comparing children 2 years or younger with bronchiolitis who were treated with nebulized NS were included. Studies enrolling a treatment group receiving an alternative placebo were included for comparison of NS with other placebos.Data extraction and synthesisData abstraction was performed per PRISMA guidelines. Fixed- and random-effects, variance-weighted meta-analytic models were used.Main outcomes and measuresPooled estimates of the association with respiratory scores, respiratory rates, and oxygen saturation within 60 minutes of treatment were generated for nebulized NS vs another placebo and for change before and after receiving nebulized NS.ResultsA total of 29 studies including 1583 patients were included. Standardized mean differences in respiratory scores for nebulized NS vs other placebo (3 studies) favored nebulized NS by -0.9 points (95% CI, -1.2 to -0.6 points) at 60 minutes after treatment (P < .001). There were no differences in respiratory rate or oxygen saturation comparing nebulized NS with other placebo. The standardized mean difference in respiratory score (25 studies) after nebulized NS was -0.7 (95% CI, -0.7 to -0.6; I2 = 62%). The weighted mean difference in respiratory scores using a consistent scale (13 studies) after nebulized NS was -1.6 points (95% CI, -1.9 to -1.3 points; I2 = 72%). The weighted mean difference in respiratory rate (17 studies) after nebulized NS was -5.5 breaths per minute (95% CI, -6.3 to -4.6 breaths per minute; I2 = 24%). The weighted mean difference in oxygen saturation (23 studies) after nebulized NS was -0.4% (95% CI, -0.6% to -0.2%; I2 = 79%).Conclusions and relevanceNebulized NS may be an active treatment for acute viral bronchiolitis. Further evaluation should occur to establish whether it is a true placebo.

Project description:OBJECTIVE:Three-percent hypertonic saline (HTS) is a hyperosmotic therapy used in pediatric traumatic brain injury to treat increased intracranial pressure and cerebral edema. It also promotes plasma volume expansion and cerebral perfusion pressure, immunomodulation, and anti-inflammatory response. We hypothesized that HTS will improve concussive symptoms of mild traumatic brain injury. METHODS:The study was a prospective, double-blind, randomized controlled trial. Children, 4 to 7 years of age with a Glasgow Coma Scale score greater than 13, were enrolled from a pediatric emergency department following closed-head injury upon meeting Acute Concussion Evaluation criteria with head pain. Patients were randomized to receive 10 mL/kg of HTS or normal saline (NS) over 1 hour. Self-reported pain values were obtained using the Wong-Baker FACES Pain Rating Scale initially, immediately following fluids, and at 2 to 3 days of discharge. The primary outcome measure was change in self-reported pain following fluid administration. Secondary outcome measures were a change in pain and postconcussive symptoms within 2 to 3 days of fluid administration. We used an intention-to-treat analysis. RESULTS:Forty-four patients, ranging from 7 to 16 years of age with comparable characteristics, were enrolled in the study; 23 patients (52%) received HTS, and 21 (48%) received NS. There was a significant difference (P < 0.001) identified in the self-reported improvement of pain following fluid administration between the HTS group (mean improvement = 3.5) and the NS group (mean improvement = 1.1). There was a significant difference (P = 0.01) identified in the self-reported improvement of pain at 2 to 3 days after treatment between the HTS group (mean improvement = 4.6) and the NS group (mean improvement = 3.0). We were unable to determine a difference in other postconcussive symptoms following discharge. CONCLUSIONS:Three-percent HTS is more effective than NS in acutely reducing concussion pain in children.

Project description:ImportanceWhile intravenous magnesium decreases hospitalizations in refractory pediatric acute asthma, it is variably used because of invasiveness and safety concerns. The benefit of nebulized magnesium to prevent hospitalization is unknown.ObjectiveTo evaluate the effectiveness of nebulized magnesium in children with acute asthma remaining in moderate or severe respiratory distress after initial therapy.Design, setting, and participantsA randomized double-blind parallel-group clinical trial from September 26, 2011, to November 19, 2019, in 7 tertiary-care pediatric emergency departments in Canada. The participants were otherwise healthy children aged 2 to 17 years with moderate to severe asthma defined by a Pediatric Respiratory Assessment Measure (PRAM) score of 5 or greater (on a 12-point scale) after a 1-hour treatment with an oral corticosteroid and 3 inhaled albuterol and ipratropium treatments. Of 5846 screened patients, 4332 were excluded for criteria, 273 declined participation, 423 otherwise excluded, 818 randomized, and 816 analyzed.InterventionsParticipants were randomized to 3 nebulized albuterol treatments with either magnesium sulfate (n = 410) or 5.5% saline placebo (n = 408).Main outcomes and measuresThe primary outcome was hospitalization for asthma within 24 hours. Secondary outcomes included PRAM score; respiratory rate; oxygen saturation at 60, 120, 180, and 240 minutes; blood pressure at 20, 40, 60, 120, 180, and 240 minutes; and albuterol treatments within 240 minutes.ResultsAmong 818 randomized patients (median age, 5 years; 63% males), 816 completed the trial (409 received magnesium; 407, placebo). A total of 178 of the 409 children who received magnesium (43.5%) were hospitalized vs 194 of the 407 who received placebo (47.7%) (difference, -4.2%; absolute risk difference 95% [exact] CI, -11% to 2.8%]; P = .26). There were no significant between-group differences in changes from baseline to 240 minutes in PRAM score (difference of changes, 0.14 points [95% CI, -0.23 to 0.50]; P = .46); respiratory rate (0.17 breaths/min [95% CI, -1.32 to 1.67]; P = .82); oxygen saturation (-0.04% [95% CI, -0.53% to 0.46%]; P = .88); systolic blood pressure (0.78 mm Hg [95% CI, -1.48 to 3.03]; P = .50); or mean number of additional albuterol treatments (magnesium: 1.49, placebo: 1.59; risk ratio, 0.94 [95% CI, 0.79 to 1.11]; P = .47). Nausea/vomiting or sore throat/nose occurred in 17 of the 409 children who received magnesium (4%) and 5 of the 407 who received placebo (1%).Conclusions and relevanceAmong children with refractory acute asthma in the emergency department, nebulized magnesium with albuterol, compared with placebo with albuterol, did not significantly decrease the hospitalization rate for asthma within 24 hours. The findings do not support use of nebulized magnesium with albuterol among children with refractory acute asthma.Trial registrationClinicalTrials.gov Identifier: NCT01429415.