Moving beyond race and ethnicity to understand the effect of inhaled nitric oxide on bronchopulmonary dysplasia prevention

Abstract

In their study, Blaisdell et al conclude that diuretics do not "substantially improve the respiratory status of the infant born extremely premature." 1 I disagree with this interpretation. The main outcome measure of the study was "change in the respiratory status," defined on the basis of 5 very broad categories ("deceased," "endotracheal tube," "continuous positive airway pressure or nasal cannula >2 liters per minute," "nasal cannula <2 LPM," and "no support"; their Table II) that are not sensitive enough to detect the incremental improvement that may result from the use of diuretics. For example, improvement in lung compliance, which is supposed to be the primary beneficial effect, 2-4 could result in decreases in the peak inspiratory pressure required to ventilate the patients but not necessarily to extubation because the latter may be necessary for other reasons (eg, apnea). Thus, this improvement would be counted as a "failure" under the study criteria. Similarly, a significant decrease in the fraction of inspired oxygen would be counted as "failure" if the patient remained intubated or on continuous positive airway pressure. The authors interpret the fact that the treated group required increased respiratory support after the diuretics were started either as unnecessary care or as failure of the diuretic therapy. A more plausible explanation would be that these patients required more support because they were more premature and had been considerably sicker since birth (their Table I). Thus, in the beginning of the treatment, they already had injury (eg, barotrauma and/or oxygen toxicity) that cannot be expected to be reversed by the use of diuretics. Lastly, considering that the participating centers were not following a common protocol, it is possible that some of the results might have been influenced by the different practices regarding invasive ventilation and oxygen therapy, both of which are known causes of morbidity. I believe that the findings of the study do not warrant any change in the use of diuretics.

Bronchopulmonary dysplasia

“…A reduction in rate of this outcome was found in the African American population but not the white or Hispanic groups 196 . This observation may be regarded as hypothesis-generating and an appropriate basis for further prospective randomized controlled trials 197 .…”

Early Hypoxic Respiratory Failure in Extreme Prematurity: Mortality and Neurodevelopmental Outcomes

“…Finally, definition of race was based on maternal self-identification. 45 Furthermore, iNO exposure duration may be brief in some of these neonates, and although propensity modeling was done in these neonates, all confounding factors may not have been adjusted. Also, because most grade III/IV IVHs occur during the first 3 days of life, especially in infants with HRF, the exposure to iNO and IVH could be incidental.…”

Inhaled nitric oxide use in neonates: Balancing what is evidence-based and what is physiologically sound

“…The impact of these variables on the observed treatment effect was not considered. Without a thorough understanding of the interplay of race/ethnicity and these other exposures, we risk therapeutic misuse of iNO in the preterm population [78]. Thus, while the findings of RiNOP are hypothesis-generating, further prospective, randomized clinical trials are necessary to evaluate the observed treatment effect [79].…”