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Original Investigation |

Association Between Hypertonic Saline and Hospital Length of Stay in Acute Viral Bronchiolitis A Reanalysis of 2 Meta-analyses

Corinne G. Brooks, MD, MS1; Wade N. Harrison, MPH2; Shawn L. Ralston, MD, MS3
[+] Author Affiliations
1Leadership in Preventive Medicine and Pediatrics Residencies, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
2Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
3Children’s Hospital at Dartmouth-Hitchcock, Lebanon, New Hampshire
JAMA Pediatr. 2016;170(6):577-584. doi:10.1001/jamapediatrics.2016.0079.
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Importance  Two previous meta-analyses of nebulized hypertonic saline (HS) on hospital length of stay (LOS) in acute viral bronchiolitis have suggested benefit. Neither study fully addressed the issue of excessive heterogeneity in the cohort of studies, indicating that it may be inappropriate to combine such dissimilar studies to estimate a common treatment effect.

Objective  To reanalyze the existing data set for sources of heterogeneity to delineate the population most likely to benefit from HS.

Data Sources  We used the previously analyzed cohort of randomized trials from 2 published meta-analyses comparing HS with normal saline (or, in 1 case, with standard of care) in infants hospitalized for bronchiolitis. We also repeated the search strategy used by the most recent Cochrane Review in the Medline database through September 2015.

Study Selection  Eighteen randomized clinical trials of HS in infants with bronchiolitis reporting LOS as an outcome measure were included.

Data Extraction and Synthesis  The guidelines used for abstracting data included LOS, study year, setting, sample size, type of control, admission/discharge criteria, adjunct medications, treatment frequency, mean day of illness at study enrollment, mean severity of illness scores, and mean age.

Main Outcomes and Measures  Weighted mean difference in LOS and study heterogeneity as measured by the I2 statistic.

Results  There were 18 studies included of 2063 infants (63% male), with a mean age of 4.2 months. The mean LOS was 3.6 days. Two main sources of heterogeneity were identified. First, the effect of HS on LOS was entirely sensitive to the removal of one study population, noted to have a widely divergent definition of the primary outcome. Second, there was a baseline imbalance in mean day of illness at presentation between treatment groups. Controlling for either of these factors resolved the heterogeneity (I2 = reduced from 78% to 45% and 0%, respectively) and produced summary estimates in support of the null hypothesis (that HS does not affect LOS). There was a weighted mean difference in LOS of −0.21 days (95% CI, −0.43 to +0.02) for the sensitivity analysis and +0.02 days (95% CI, −0.14 to +0.17) for studies without unbalanced treatment groups on presentation.

Conclusions and Relevance  Prior analyses were driven by an outlier population and unbalanced treatment groups in positive trials. Once heterogeneity was accounted for, the data did not support the use of HS to decrease LOS in infants hospitalized with bronchiolitis.

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Figure 1.
Mean Difference in Length of Stay (LOS) Between Hypertonic Saline and Normal Saline Treatment Groups

The overall and sensitivity analyses, excluding outlier population, are shown here. Weights are from random effects analysis.

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Figure 2.
Funnel Plot With Pseudo 95% CIs
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Figure 3.
Mean Difference in Length of Stay (LOS) Between Hypertonic Saline (HS) and Normal Saline Treatment Groups

The subgroup analysis by imbalance in day of illness (DOI) at presentation is shown here. Weights are from random effects analysis.

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Figure 4.
Mean Differences in Length of Stay (LOS) and Illness Duration Between Hypertonic Saline (HS) and Normal Saline (NS)Treatment Groups

Subgroup analysis postulating a threshold response for LOS of 3 days or more. A, Admission to discharge. No correction for imbalance in day of illness at presentation. B, First symptoms to discharge. Corrected for imbalance in day of illness at presentation. WMD indicates weighted mean difference. Weights are from random effects analysis.

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