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Hypertonic saline indications for bronchiolitis lack evidence for clear guidance

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Accumulation of evidence key in determining clinical guidelines

For pediatricians looking for answers on how best to provide treatment for their patients, nothing can be more frustrating than two randomized clinical trials (RCTs) with contradictory results. When we consider study design and risk of bias, these two RCTs appear to be well designed and well implemented. Differences in populations, interventions, controls, and outcome measures may also result in study results being different; however, examination of these two studies shows no obvious reasons for their results to differ because of these factors. It remains to be seen whether the way in which albuterol was used in reference to hypertonic saline has an effect on the outcome.

Evaluating the efficacy of hypertonic saline in the treatment of bronchiolitis is not an easy task. Evidently, it is difficult to base treatment decisions on the result of a single study. The summary of a systematic review from 2013 in the Cochrane Database is that there is probably not a role for hypertonic saline for patients with bronchiolitis treated in the emergency department, but it may be helpful for inpatients by decreasing their length of hospital stay by 1.15 days.

These two trials point us to the importance of using scientifically developed systematic reviews and meta-analyses to get the best sense of optimal treatment for children. From our read of the current systematic review (which now will need to be updated) and our read of these two individual trials, we would not start using hypertonic saline in the emergency department on a routine basis. However, nebulized hypertonic saline may have a role to play for children hospitalized with bronchiolitis.

Dr. Sim Grewal is in the division of pediatric emergency medicine at the University of Alberta in Edmonton. Dr. Terry P. Klassen is part of Translating Emergency Knowledge for Kids at the Manitoba Institute of Child Health, and is in the department of pediatrics at the University of Manitoba, both in Winnipeg. Neither physician reported any relevant financial disclosures. These comments have been adapted from an editorial accompanying the studies in JAMA Pediatrics (JAMA Pediatr. 2014 26 May [doi: 10.1001/jamapediatrics.2014.423]).


 

FROM JAMA PEDIATRICS

The therapeutic value of hypertonic saline in treating bronchiolitis in young children remains unclear, based on the findings of two randomized controlled trials with conflicting results.

While one found no significant improvements in outcomes between hypertonic and normal saline, the other found a lower risk of hospitalization in children receiving hypertonic saline.

"Based on the results of this and other studies, the administration of a single dose of 3% hypertonic saline in the acute care setting does not appear to be more effective than normal saline in improving short-term respiratory distress in bronchiolitis," reported Dr. Todd Florin of Cincinnati Children’s Hospital Medical Center and his associates in the first study (JAMA Pediatr. 2014 May 26 [doi: 10.1001/jamapediatrics.2013.5306]).

Dr. Florin’s team equally randomized 62 children under age 24 months to receive 4 mL of either 3% hypertonic saline or normal saline within 90 minutes after receiving standard therapy for bronchiolitis, which included nasal suctioning and a single dose of nebulized albuterol. The children had all presented to the emergency department of Children’s Hospital of Philadelphia during one of two consecutive bronchiolitis seasons, from November to April in 2010 and 2011.

All children were assessed using the Respiratory Distress Assessment Instrument (RDAI) 1 hour after treatment and then 2 hours after treatment for those being discharged or still in the ED at that time. Based on the Respiratory Assessment Change Score (RACS) – which uses the RDAI score and a standardized change in respiratory rate to assess respiratory status changes – the normal saline group showed clinically significant improvement (a RACS of –3) after an hour, whereas the hypertonic saline group did not.

There was no significant difference in the median RDAI scores, heart rate, oxygen saturation, hospitalization rate, or child’s breathing or feeding status (based on parental perception) between the two groups.

Yet the hospitalization rate was lower in the hypertonic saline group of the other study, which used similar protocols in a larger population, reported Dr. Susan Wu of Children’s Hospital Los Angeles and her associates, also in JAMA Pediatrics (JAMA Pediatr. 2014 May 26 [doi: 10.1001/jamapediatrics.2014.301].

Their participants included 408 children under age 24 months presenting with bronchiolitis at two different children’s hospital EDs between March 2008 and April 2011. All patients received 2.5 mg of nebulized albuterol, after which 197 children received 4 mL of normal saline and 211 children received 4 mL of 3% hypertonic saline, each inhaled up to three times. Children admitted received their assigned saline (always premedicated with albuterol sulfate) every 8 hours until discharge.

While 42.6% of the normal saline patients were admitted to the hospital, only 28.9% of the hypertonic saline patients were admitted (P = .01), for an adjusted odds ratio of 0.49 and a number needed to treat of 8 to prevent one hospitalization. "Other statistically significant predictors of admission included site, male sex, patient weight, baseline respiratory rate, and baseline oxygen saturation," the authors reported.

Among those admitted, the length of stay was 3.16 days for the hypertonic saline participants and 3.92 days for the normal saline participants, but the difference was not significant (P = .24). No significant difference was found in the RDAI score, which decreased in both groups. The RACS was calculated using the same methods as in the Florin study for 366 cases, but no significant differences in the mean RACS scores existed between the two groups after adjustment for RDAI baseline scores.

Dr. Wu and her team recommended that future research "investigate the optimal dosing and administration regimen and the patient-level factors that may affect response to hypertonic saline."

The Florin et al. study was funded by an Academic Pediatric Association Young Investigator Award. The Wu et al. study was funded by the Thrasher Research Fund and the department of pediatrics, University of Southern California Keck School of Medicine, Los Angeles. The authors of both studies declared that they had no relevant financial disclosures.

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