High-dose inhaled nitric oxide shortens hospital stay in infants with bronchiolitis

Infants with bronchiolitis who received 150 ppm inhaled nitric oxide plus standard supportive treatment had shorter hospital stays and improved respiratory outcomes, according to results published in Annals of the American Thoracic Society.

“Overall, the reductions [in time to fit for discharge, time to reach a sustained oxygen saturation greater than or equal to 92% on room air and time to hospital discharge] were approximately twofold for the 150 ppm nitric oxide (NO) group compared with standard supportive treatment (SST) alone, while the 85 ppm group responded as did the SST group,” Aviv Goldbart, MD, associate professor and head of the department of pediatrics at Soroka Medical Center, and colleagues wrote.

“The significant improvement in the various measured parameters in the 150 ppm group compared with the control group represents clinically meaningful responses to bronchiolitis treatment for the infants,” Goldbart and colleagues added.

In a prospective, multicenter, double-blind, randomized controlled trial, Goldbart and colleagues analyzed 89 infants with acute bronchiolitis to determine the safety and efficacy of inhaled NO (iNO) plus SST against SST alone.

As Healio previously reported, an intermittent high dose of iNO increased the percentage of methemoglobin in infants with bronchiolitis compared with standard oxygen therapy.

To assess the treatment options against one another, researchers randomly assigned infants to one of three treatment groups: 150 ppm NO plus SST (n = 29), 85 ppm NO plus SST (n = 32) and oxygen/air plus SST (control treatment; n = 26). For a maximum of 5 days, infants received the treatment four times daily in 40-minute increments, according to researchers.

Researchers primarily assessed the time to reach “fit for discharge,” which meant reaching a sustained oxygen saturation of at least 92% on room air and a clinical score less than or equal to 5. They also looked at time to reach both these endpoints separately and time to hospital discharge.

Researchers found hazard ratios for the various time to event outcomes through a Cox proportional hazards regression model, and the number of recorded adverse events, treatment-related or serious, determined the safety of iNO.

Looking at time to achieve “fit for discharge,” infants given 150 ppm NO plus SST had a significant reduction in this time compared with those given 85 ppm NO plus SST (HR = 2.11; 95% CI, 1.03-4.31) and those in the control group (HR = 2.32; 95% CI, 0.44-1.81). Researchers found that between the low-dose iNO group and the control group, this time did not significantly differ.

Compared with both the low-dose iNO group and the control group, those in the high-dose group also showed reduced time to hospital discharge (low-dose group, HR =2.01; 95% CI, 1.01-3.99; control group, HR = 2.28; 95% CI, 1.03-5.06) and reduced time to sustained oxygen saturation of at least 92% on room air (low-dose group, HR = 2.15; 95% CI, 0.98-4.71; control group, HR = 2.62; 95% CI, 1.05-6.53).

Again, researchers found no significant differences in time to hospital discharge between the low-dose iNO group and the control group.

In terms of time to reach a clinical score less than or equal to 5, there were no differences among treatment groups.

The highest percentage of adverse events was in those given 85 ppm iNO (n = 20; 62.5%), followed by those given 150 ppm iNO (n = 18; 62.1%) and those given SST alone (n = 13; 50%). The infections and infestations organ class, comprised of bronchiolitis, pneumonia, otitis media and urinary tract infection, demonstrated the largest incidence rates across all treatment groups (150 ppm, 28%; 85 ppm, 25%; SST, 19%).

Researchers reported five serious adverse events but deemed them not related to treatment, which suggests that iNO was well tolerated in this cohort.

Further, all treatment groups had similar discontinuation rates based on adverse events and no clinically significant changes in respiratory rates or heart rates following treatment.

“Our results point to a need to accelerate a more definitive study of high-dose iNO for treatment of moderate to severe bronchiolitis,” Goldbart and colleagues wrote.