Less dogma, less arguments, less arguments, less misfortunes.

—Voltaire, Treaty on Tolerance, 1763.

Interest in noninvasive ventilation (NIV) for the management of acute respiratory distress syndrome (ARDS) has been questioned ever since its first implementation in ICUs. Physiologically, NIV enables recruitment of under-ventilated alveoli, increases functional residual capacity, and reduces intrapulmonary shunt. In addition, NIV unloads inspiratory muscles, which alleviates dyspnea and reduces the work of breathing (1).

Studies in adult patients underline the expectations and fears associated with the application of NIV in respiratory failure. In 1998, Antonelli et al (2) found that NIV reduced the duration of ventilation and the number of serious complications related to conventional ventilation. However, multicenter studies suggested that NIV was successful in only half of the patients with acute hypoxemic respiratory failure (3). The LUNG SAFE study also underlined that this mode of ventilation could significantly increase ICU mortality among the most severe patients (i.e., those with Pao2/Fio2 < 150 mm Hg) (4). Thus, despite encouraging preliminary results mostly observed by comparison to historical cohorts, use of NIV in patients with severe ARDS has generated controversy. The main point of debate relates to the selection of patients who are more or less likely to improve with NIV. Indeed, most randomized controlled trials (RCTs) in this field have not had a large enough sample size to be able to address this issue.

This debate has also extended to pediatric ARDS (pARDS), but with less evidence. For example, the 2015 First Pediatric Acute Lung Injury Consensus Conference (PALICC-1) recommendations were based on RCTs in adults, and 13 observational studies in children (5). These pediatric cohort studies—whether prospective or retrospective—included heterogeneous populations of mild-to-moderate pARDS. Moreover, physiologic features in the children, notably lower lung compliance and functional residual capacity, and decreased tolerance to high respiratory loads emphasized the need for more age-specific evidence (5).

In 2019, Khemani et al (6) reported the results of the 2016–2017 pARDS Incidence and Epidemiology (PARDIE) study, which included 744 children from 145 PICUs in 27 countries. Nearly one-quarter (160/708 patients with complete data) of PARDIE population was initially managed with NIV. As in adults (2), NIV-failure rate reached 50%. An alert point for pediatric intensivists was that comparisons of mortality in NIV-failing patients was as follows: 5% in children who were maintained on NIV alone versus 25% in those who subsequently needed intubation (mortality 17% in the overall cohort). An additional key message from this observational research related to the determination of patient severity. For example, optimal discrimination in severity occurred if the PALICC-1 definition was used at 6 hours after pARDS diagnosis. This 6-hour window provides a limited opportunity in which a NIV trial can be used and a dynamic evaluation of oxygen requirement can be made. Of note, this 6-hour trial and evaluation is included in the 2023 Second Pediatric Acute Lung Injury Consensus Conference recommendations for pARDS management (7). The 2016–2017 PARDIE observational study provides a unique opportunity for evaluating pARDS management recommendations because it is a well-curated, prospectively collected dataset. However, the dataset does relate to practice over 6 years ago. That being said, many of us in the field have been waiting for the new report by Emeriaud et al (8) in this issue of Pediatric Critical Care Medicine, since it may help us to better understand NIV in pARDS.

The newly reported study (8) was a planned ancillary study of the PARDIE dataset, which included a distribution in pARDS severity of 23% mild, 37% moderate, and 40% severe. There three points to highlight in the PARDIE data. First, there is the clear usefulness of multicenter observational studies to inform clinical practice, as highlighted in recent PICU research summaries from United States and United Kingdom research networks (9–11). Second, Emeriaud et al (8) have used multiple statistical approaches to limit and reduce potential biases from uncontrolled confounding. For example, to control for “confounding by indication,” a propensity score analysis was performed with rigorous adjustment for confounding factors. Such an approach should minimize the likelihood of incorrectly attributing outcomes, notably mortality, to NIV. Third, there is of course the 6 years interval between now, 2023, and when the PARDIE dataset was completed. Our view is that this is long, but there has not been any major innovations or change in ARDS management.

Overall, we believe that the PARDIE-NIV work has kept its promise and challenges some central “dogma” in contemporary practice. Emeriaud et al (8) now show us that in comparison with invasive ventilation use of NIV is not associated with greater hazard of mortality, whatever the pARDS severity grouping. In the multivariable analysis, the authors were not able to identify patients most likely to be successfully managed with NIV; but, conversely, they highlighted explanatory factors associated with a greater risk of NIV failure. A Venn diagram in the paper details all possible combinations in terms of response rate to NIV from these three risk factors, that is, immunosuppression, severe hypoxemia, and nonrespiratory pediatric logistic organ dysfunction score greater than 2, which suggests the need for vigilant monitoring of those with these diagnosis when managed using NIV. More precisely, one group of high-risk patients stands out: immunocompromised children with organ failure. However, this message should be tempered, as mortality in this group did not appear to be any better in primarily intubated patients. As observed by others, this group of patients is particularly vulnerable, whatever the ventilatory strategy (12).

Last, but not least, the new PARDIE study also challenge the commonly held view that delay in intubation caused by initially using NIV is associated with greater hazard of mortality. In fact, in the NIV failure group, the duration of NIV prior to intubation (for each hr) was not correlated with mortality. Nevertheless, as the authors cautiously point out, the sample size may be insufficient to make this assertion, and a delay of up to 6 hours for evaluation may be an appropriate compromise in practice. The authors do mention in their discussion the risk of “NIV-induced lung injury.” The design of the PARDIE observational study, and the short NIV duration in the NIV failure group, does not help us with this question.

In conclusion, the new PARDIE-NIV work is a real “game changer” for pediatric critical care practitioners. In pARDS patients, we now have some basis for using a time-limited (i.e., 6 hr) NIV trial before transitioning to invasive mechanical ventilation. This work also provides us with an agenda for future work, such as use of monitoring transdiaphragmatic pressure, tidal volume, or the work of breathing, to best guide the identification of NIV-failure during the time-limited trial.

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