Bronchiolitis Reanalysis: Hypertonic Saline Does Not Reduce LOS

Marcia Frellick

April 20, 2016

A reanalysis of two meta-analyses on the benefit of nebulized hypertonic saline (HS) for infants comes to an opposite conclusion and finds that it does not reduce length of stay (LOS) in infants with bronchiolitis.

The two previous analyses were hampered by an outlier population, according to the authors of the new analysis, who also point out that there was an imbalance in day of illness at presentation between treatment groups in positive trials.

Once the differences were accounted for, they say, the data do not support hypertonic saline's effect in reducing LOS for acute viral bronchiolitis in a typical US population.

The study was published online April 18 in JAMA Pediatrics.

These results should put an end to the confusion that has surrounded the issue over the years, according to Ricardo Quinonez, MD, chief of the Division of Pediatric Hospital Medicine at Children's Hospital of San Antonio in Texas, who was not involved in the study.

"This study slams the door shut on hypertonic saline as a way to decrease [LOS] for kids with bronchiolitis," he told Medscape Medical News.

The authors, led by Corinne G. Brooks, MD, from the Leadership in Preventive Medicine and Pediatrics Residencies at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, note bronchiolitis is one of the most common illnesses resulting in hospital admission in infants in the United States.

Current practice guidelines in the United States do not recommend any medications for bronchiolitis therapy in young children. The latest guideline from the American Academy of Pediatrics says that only supportive care, including oxygen and hydration, is strongly recommended.

Dr Quinonez said, given these latest results, "at least in the US, where our [LOS] is already less than 3 days, there's just no evidence that hypertonic saline will help decrease [LOS] any further. Because that was the stated use for hypertonic saline, in that regard, there's really no indication for it in the hospital setting anymore."

He added, "What we're going to have to do in the future is realize that this is a highly benign illness and although some kids are probably going to require hospitalization for oxygen and for hydration, kids do well despite anything we do."

Efforts to reduce LOS should likely focus on "things we're more tolerant of," such as oxygen saturation, he said. "Right now we say anything below 90% is hypoxia.... [W]e might have to be more tolerant of lower saturations. That could significantly decrease [LOS]."

Alan Schroeder, MD, associate chief for research in the Division of Hospital Medicine and associate clinical professor at Lucille Packard Children's Hospital Stanford in California, agrees that changing the threshold for saturation needs exploration, as does the question of whether there should be a well-defined threshold for oxygenation at all.

"Pharmacologically, at this point, there's really nothing," he told Medscape Medical News. "Teaching physicians, nursing staff, and families to be comfortable with the idea that we just have to watch and wait is one of the biggest priorities now as we move forward with bronchiolitis care."

However, Dr Schroeder, who was not involved in the study, disagrees that the door should be closed completely on hypertonic saline.

"I think it's certainly possible that there are subgroups of patients with bronchiolitis who may benefit from hypertonic saline," he said. "If it only seems to work in studies where the [LOS] is long, then maybe the idea is it doesn't get you out of the hospital faster, but it might overall make you better faster.... But before we, as clinicians, embrace the therapy, we need to define those populations through well-done investigations."

Personally, he says, he does not order hypertonic saline. But for clinicians who have it in their protocol for bronchiolitis, he says, they should consider whether they now think it is evidence-based.

"I think that this study would show that it's probably not," he said.

Where Reanalysis Found Deficiencies

Among the evidence of outliers Dr Brooks and colleagues identified in the previous meta-analyses were two studies performed in the same center in China that had very different criteria for hospital discharge — 12 hours without respiratory symptoms — which was much stricter than in any other trial.

"They seem to wait until the kids are perfectly healthy until they send them home," Dr Schroeder said. "If you take the Chinese studies out of the equation, the effect is diminished quite significantly to the extent that the confidence interval does pass 0."

Among the 18 studies covered in the reanalysis, the authors also found differences in treatment groups in how sick people were at study enrollment, which tended to favor the treatment group.

"Patients presenting later in their illness were more likely to be allocated to the HS treatment arm in 6 of the 18 studies including most of the small positive studies, making [day of illness] imbalance a probable mechanism of bias representing small study effects," Dr Brooks and colleagues write.

The authors have disclosed no relevant financial relationships. Dr Quinonez is a member of the Medscape advisory board. Dr Schroeder is a contributor to Medscape.

JAMA Pediatr. Published online April 18, 2016. Full text

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