IMPORTANCE: In 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.
OBJECTIVE: To 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 SOURCES: MEDLINE 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 SELECTION: Randomized 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 SYNTHESIS: Data abstraction was performed per PRISMA guidelines. Fixed- and random-effects, variance-weighted meta-analytic models were used.
MAIN OUTCOMES AND MEASURES: Pooled 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.
RESULTS: A 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 RELEVANCE: Nebulized NS may be an active treatment for acute viral bronchiolitis. Further evaluation should occur to establish whether it is a true placebo.
A meta-analysis was performed to analyze the efficacy of 3% hypertonic saline (HS) in bronchiolitis. Pubmed and MEDLINE databases were searched for relevant articles. A total of 2 authors selected the articles according to the inclusion criteria and then data were carefully extracted. Weighted mean difference (WMD) with 95% confidence interval (95% CI) values were used to pool continuous data, including length of stay and clinical severity score (CSS). Relative risk (RR) with 95% CI was calculated to determine the association between 3% HS and re-admission. The pooled data revealed that infants treated with 3% HS exhibited shorter durations of hospitalization compared with those treated with normal saline (NS; WMD=-0.43; 95% CI=-0.70, -0.15). Subgroup analysis examining the combination of HS or NS with additional medication demonstrated that 3% HS with epinephrine significantly decreased the length of hospital stay, with a WMD=-0.62 (95% CI=-0.90, -0.33). The results indicated a lower CSS score in the 3% HS group compared with the NS group (SMD=-0.80; 95% CI=-1.06, -0.54). The pooled outcome indicated a beneficial effect of 3% HS on decreasing re-admission rates compared with NS (RR=0.93; 95% CI=0.70, 1.23). No potential publication bias was observed (Begg's, P=0.133; Egger's, P=0.576). In conclusion, 3% HS was demonstrated to be a more successful therapy compared with NS for infants with bronchiolitis.
As concerns over health care-related harms and costs continue to mount, efforts to identify and combat medical overuse are needed. Although much of the recent attention has focused on health care for adults, children are also harmed by overuse. Using a structured PubMed search and manual tables of contents review, we identified important articles on pediatric overuse published in 2015. These articles were evaluated according to the quality of the methods, the magnitude of clinical effect, and the number of patients potentially affected and were categorized into overdiagnosis, overtreatment, and overutilization. Overdiagnosis: Findings included evidence for overdiagnosis of hypoxemia in children with bronchiolitis and skull fractures in children suffering minor head injuries. Overtreatment: Findings included evidence that up to 85% of hospitalized children with radiographic pneumonia may not have a bacterial etiology; many children are receiving prolonged intravenous antibiotic therapy for osteomyelitis although oral therapy is equally effective; antidepressant medication for adolescents and nebulized hypertonic saline for bronchiolitis appear to be ineffective; and thresholds for treatment of hyperbilirubinemia may be too low. Overutilization: Findings suggested that the frequency of head circumference screening could be relaxed; large reductions in abdominal computed tomography testing for appendicitis appear to have been safe and effective; and overreliance on C-reactive protein levels in neonatal early onset sepsis appears to extend hospital length-of-stay.
In 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.
OBJECTIVE:
To 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 SOURCES:
MEDLINE 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 SELECTION:
Randomized 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 SYNTHESIS:
Data abstraction was performed per PRISMA guidelines. Fixed- and random-effects, variance-weighted meta-analytic models were used.
MAIN OUTCOMES AND MEASURES:
Pooled 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.
RESULTS:
A 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 RELEVANCE:
Nebulized NS may be an active treatment for acute viral bronchiolitis. Further evaluation should occur to establish whether it is a true placebo.
