In the Journals

Nebulized normal saline may serve as active treatment in acute viral bronchiolitis

A recent meta-analysis published in JAMA Pediatrics suggests that nebulized normal saline may be considered an active treatment as opposed to a placebo in studies evaluating therapies for acute viral bronchiolitis in young children.

“In most randomized clinical trials, nebulized normal saline is used as the placebo, which is logical given that normal saline is also used as the vehicle for nebulization of the active treatment. However, consistent improvement above expected rates in patients receiving placebo has been noted across bronchodilator trials,” the researchers wrote. “The waxing and waning nature of bronchiolitis may explain these findings, but given the strong trend toward improvement, it is also possible that nebulized normal saline is acting as an effective treatment.”

To further investigate this question, the researchers identified 29 randomized clinical trials involving 1,583 patients that compared children aged 2 years or younger with bronchiolitis who were treated with nebulized normal saline. Studies with a treatment group receiving an alternative placebo were also included for comparison of normal saline with other placebos. The researchers then examined pooled estimates of the association with respiratory scores, respiratory rates and oxygen saturation within 60 minutes of treatment for nebulized normal saline compared with another placebo and change before and after nebulized normal saline.

In the meta-analysis, three studies involved comparison of nebulized normal saline with a non-nebulized placebo. Results showed that standardized mean differences in respiratory scores favored the normal saline group over the other placebo group by –0.9 points (95% CI, –1.2 to –0.6) at 60 minutes after therapy, with no major differences observed in respiratory rate or oxygen saturation between the normal saline vs. other placebo groups.

Twenty-five studies offered data on composite respiratory scores for patients receiving nebulized normal saline. In the meta-analysis, the researchers found that the standardized mean difference in respiratory score after nebulized normal saline was –0.7 (95% CI, –0.7 to –0.6; I2 = 62%).

The Respiratory Distress Assessment Index (RDAI), which was the most commonly used score and the only score used often enough to perform a subgroup analysis preserving scale, was used in 13 studies. In an analysis of these studies, the weighted mean difference in RDAI after nebulized normal saline was –1.6 points (95% CI, –1.9 to –1.3; I2 = 72%).

Additionally, the weighted mean difference after nebulized normal saline was –5.5 breaths per minute (95% CI, –6.3 to –4.6; I2 = 24%) in the 17 studies providing information on respiratory rates and the weighted mean difference in oxygen saturation after nebulized normal saline was –0.4% (95% CI, –0.6 to –0.2; I2 = 79%) in the 23 studies that offered data on oxygen saturation.

Sensitivity analyses that removed outliers or studies at high risk for bias did not substantively alter the point estimates but did reduce heterogeneity in some cases.

“This meta-analysis suggests that nebulized normal saline could be an active treatment for acute viral bronchiolitis rather than an inert placebo,” they wrote. “Further evaluation of nebulized normal saline vs. sham nebulization and/or oral placebo should occur to establish whether or not nebulized normal saline is a true placebo. Future study designs should factor in the potential treatment effect of nebulized normal saline on short-term outcomes.” – by Melissa Foster

Disclosures: The authors report no relevant financial disclosures.

A recent meta-analysis published in JAMA Pediatrics suggests that nebulized normal saline may be considered an active treatment as opposed to a placebo in studies evaluating therapies for acute viral bronchiolitis in young children.

“In most randomized clinical trials, nebulized normal saline is used as the placebo, which is logical given that normal saline is also used as the vehicle for nebulization of the active treatment. However, consistent improvement above expected rates in patients receiving placebo has been noted across bronchodilator trials,” the researchers wrote. “The waxing and waning nature of bronchiolitis may explain these findings, but given the strong trend toward improvement, it is also possible that nebulized normal saline is acting as an effective treatment.”

To further investigate this question, the researchers identified 29 randomized clinical trials involving 1,583 patients that compared children aged 2 years or younger with bronchiolitis who were treated with nebulized normal saline. Studies with a treatment group receiving an alternative placebo were also included for comparison of normal saline with other placebos. The researchers then examined pooled estimates of the association with respiratory scores, respiratory rates and oxygen saturation within 60 minutes of treatment for nebulized normal saline compared with another placebo and change before and after nebulized normal saline.

In the meta-analysis, three studies involved comparison of nebulized normal saline with a non-nebulized placebo. Results showed that standardized mean differences in respiratory scores favored the normal saline group over the other placebo group by –0.9 points (95% CI, –1.2 to –0.6) at 60 minutes after therapy, with no major differences observed in respiratory rate or oxygen saturation between the normal saline vs. other placebo groups.

Twenty-five studies offered data on composite respiratory scores for patients receiving nebulized normal saline. In the meta-analysis, the researchers found that the standardized mean difference in respiratory score after nebulized normal saline was –0.7 (95% CI, –0.7 to –0.6; I2 = 62%).

The Respiratory Distress Assessment Index (RDAI), which was the most commonly used score and the only score used often enough to perform a subgroup analysis preserving scale, was used in 13 studies. In an analysis of these studies, the weighted mean difference in RDAI after nebulized normal saline was –1.6 points (95% CI, –1.9 to –1.3; I2 = 72%).

Additionally, the weighted mean difference after nebulized normal saline was –5.5 breaths per minute (95% CI, –6.3 to –4.6; I2 = 24%) in the 17 studies providing information on respiratory rates and the weighted mean difference in oxygen saturation after nebulized normal saline was –0.4% (95% CI, –0.6 to –0.2; I2 = 79%) in the 23 studies that offered data on oxygen saturation.

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Sensitivity analyses that removed outliers or studies at high risk for bias did not substantively alter the point estimates but did reduce heterogeneity in some cases.

“This meta-analysis suggests that nebulized normal saline could be an active treatment for acute viral bronchiolitis rather than an inert placebo,” they wrote. “Further evaluation of nebulized normal saline vs. sham nebulization and/or oral placebo should occur to establish whether or not nebulized normal saline is a true placebo. Future study designs should factor in the potential treatment effect of nebulized normal saline on short-term outcomes.” – by Melissa Foster

Disclosures: The authors report no relevant financial disclosures.