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Nebulized Hypertonic Saline for Bronchiolitis - Why Can't Researchers Get It Right? :

April 19, 2016

Among infants hospitalized for bronchiolitis, does administration of nebulized hypertonic saline decrease length of stay compared to nebulized normal saline?

I'm getting a little dizzy watching the pendulum swing back and forth on benefits of nebulized hypertonic saline for bronchiolitis. What gives?

Source: Silver AH, Esteban-Cruciani N, Azzarone G, et al. 3% Hypertonic Saline Versus Normal Saline in Inpatient Bronchiolitis: A Randomized Controlled Trial. Pediatrics.2015;136(6):1036-1043; doi:10.1542/peds.2015-1037. See AAP Grand Rounds commentary by Dr. Daniel Lesser (subscription required).

PICO Question: Among infants hospitalized for bronchiolitis, does administration of nebulized hypertonic saline decrease length of stay compared to nebulized normal saline?

Question type: Intervention

Study design: Randomized controlled

What gives, mostly, is that many randomized controlled trials of hypertonic saline for bronchiolitis were not planned carefully, particularly with regard to reducing bias. Bias is an important consideration in every study, of course, but it becomes most important when an outcome of interest is a bit subjective. When that is the case, anything that risks biasing the interpretation of that outcome runs a great chance of reaching false conclusions.

With bronchiolitis treatment studies, including the study by Silver et al, the primary question being asked is whether nebulized 3% saline, compared to placebo, shortens duration of hospitalization. Of course, it's tough to be entirely objective about this, and most studies, including Silver's, relied on the attending physician to make a judgment about when to discharge. Clearly that decision is difficult to standardize, particularly with multiple attending physicians involved. Within the limitations of the outcome measure, the Silver study was larger than most (about 200 infants total) and also more careful with study design than most. The study did not find a benefit in length of stay or 7-day readmission rates.

The second quagmire with all these studies is the application of meta-analytical techniques to combine results of multiple studies. For hypertonic saline treatment of bronchiolitis, 3 meta-analyses have been performed relatively recently. One is a Cochrane Review last updated in 2013 showing that treatment "may significantly reduce the length of hospital stay among infants hospitalised with non-severe acute viral bronchiolitis and improve the clinical severity score in both outpatient and inpatient populations." The treatment groups had median hospitalization about 1 day less than the control groups. Pretty impressive, right?

Next was a study published in Pediatrics last year, by the same lead author of the Cochrane Review above, now updated with newer studies and concluding that treatment was "safe and potentially effective." Now the duration of hospitalization was down to about half a day less in the treatment groups. Hmm.

Enter the latest meta-analysis by Maguire, also published in 2015. I'll let the abstract conclusion summarize: "There is disparity between the overall combined effect on [length of stay] 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 [hypertonic saline] in inpatient acute bronchiolitis."

In other words, we have 2 problems when interpreting studies related to nebulized hypertonic saline treatment of bronchiolitis. First, the better-planned and larger trials seem to be more likely to show less benefit from treatment, and second, the individuals trials differ too much in study design to allow for meaningful analysis by a pooled method like meta-analysis.

I don't get involved in routine management of bronchiolitis patients, but if I did I wouldn't bother with nebulized hypertonic saline therapy unless someone comes up with very striking evidence showing benefit.

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