FROM JAMA PEDIATRICS
The results of two previously published meta-analyses supporting a shortening of hospital length of stay following the use of hypertonic saline in infants with acute viral bronchiolitis are unreliable, according to a study published in JAMA Pediatrics.
Hypertonic saline should not be expected to shorten the length of hospital stay for those with acute viral bronchiolitis in typical hospital settings in the United States, Dr. Corinne G. Brooks of the Leadership in Preventive Medicine and Pediatrics Residencies at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and her associates concluded.
The investigators reached this conclusion after reanalyzing data from the 18 randomized clinical trials using hypertonic saline in infants with bronchiolitis reporting hospital length of stay as an outcome measure in the two previously published meta-analyses, after finding no additional data sources through a literature search. The studies included 2,063 infants (63% male), with a mean age of 4.2 months and a mean length of stay of 3.6 days ( JAMA Pediatr. 2016 Apr 18. doi: 10.1001/jamapediatrics.2016.0079 ).
Dr. Brooks explained the rationale behind the study by pointing out that the previously published analyses failed to address and account for the large amount of study heterogeneity in the assessed cohort of studies, necessitating a reanalysis of the full data set to investigate factors with the potential to introduce such heterogeneity.
The reanalysis produced two significant findings, which collectively accounted for all of the heterogeneity between the assessed studies. First, one of the study populations was determined to be a significant outlier with very different criteria for discharge and substantially longer expected hospital length of stay. Because the statistical significance of the weighted mean difference in hospital length of stay attributable to the use of hypertonic saline was sensitive to the removal of this study population, heterogeneity was found to resolve to moderate to acceptable levels. Second, an important baseline difference between the treatment arms in day of illness at study enrollment was found. Patients presenting later in their illness were more likely to be allocated to the hypertonic saline treatment arm in 6 of the 18 studies assessed, most of which were small positive studies. Therefore, this difference accounted for a systematic bias favoring treatment groups.
Based on their reanalysis of the available data, Dr. Brooks and her associates said that the appearance of a meaningful reduction in the length of hospital stay for infants with acute viral bronchiolitis was a direct result of the inappropriate combination of studies with clinically significant differences in outcome definitions, and the previously unnoticed systematic bias in treatment group allocation.
No external funding was provided. None of the authors reported any conflicts of interest.
