Hello, my name is Alex Prota. I am a professor of pediatrics and division chief of pediatric critical care medicine at Duke University Medical Center. My assignment today is to discuss with you where I deviate from the PARDS guidelines. These are my disclosures, none of which are relevant to today's talk. You should already know that the PALIC-PARDS definition and guidelines were published in 2015. That was the work of 27 experts from eight countries. You should also know that the PARDS 2.0 guidelines are being published contemporaneously with this Congress. These are much more inclusive guidelines and definitions created by 56 experts from 15 countries with representation from resource-limited settings, Asia, Africa, and South America at this time, and a much less skewed gender distribution among experts. I will use this general setup for the remaining of the talk, where I will present a particular PARDS guideline, present some data as to why I or someone would deviate from that guideline, and then whether or not the PARDS 2.0 guidelines address that specific concern. The first point I want to bring up is the choice of tidal volume in the management of PARDS. The original PARDS guidelines recommended the use of tidal volumes in or below the range of physiologic tidal volumes, such as 5 to 8 mLs per kilogram, or even lower tidal volumes of 3 to 6 mLs per kilogram for patients with poor respiratory system compliance. It should be noted that the choice of reduced tidal volumes stems largely from the adult literature. For instance, in the study by Marcel Amato in 1998, where a protective strategy employing reduced tidal volumes and high PEEP resulted in lower mortality compared to a conventional strategy using higher tidal volumes. This was followed by two negative studies comparing a lower tidal volume and a conventional tidal volume strategy. And it was not until a few years later, with the ARMA study, that the ARSNet work group showed a survival advantage for patients being ventilated with 6 mLs per kilo tidal volume compared to 12 mLs per kilo tidal volume. But why were some of these studies positive and some were negative? Well, this is largely dependent on the degree of separation between the two experimental arms as it relates to tidal volume. For instance, in the Stewart and Bruchard study, there was relative proximity between the 6 mL per kilo and 10 mL per kilo tidal volume between the two groups, whereas in the Amato study and the ARMA study, there was a great separation between the low tidal volume groups in 5 to 6 mLs per kilo and the high tidal volume groups at about 11, 12 mLs per kilo. The relationship between tidal volume and mortality in pediatric ARDS is much more nebulous. This is a meta-analysis conducted by the Dutch group involving observational studies in ARDS. Just to orient you to the next few slides, these are forest plots of the various studies showing different cut points for tidal volume, such as less than 7 mLs per kilo or more than 7 mLs per kilo or less than 8 mLs per kilo and more than 8 mLs per kilo as it relates to the primary outcome mortality. And you can see that with a 7 mL per kilo cut point for tidal volume, there is no difference in mortality. And the same is true for 8 mLs per kilo. Interestingly, when one chooses a cut point of 10 mLs per kilo, there is also not influence in mortality, and there is also not a correlation of 12 mLs per kilo with mortality. So taking this to extremes, when we compare patients that receive ventilation with less than 7 mLs per kilo tidal volume or more than 10 mLs per kilo tidal volume, that does not seem to influence mortality at all. And there is no association of mortality with 7 and 12 mLs per kilo tidal volume. Robby Kamani and colleagues published a single-center study assessing the effect of tidal volume on mortality in nearly 300 children with PARDS. Tidal volume on day one was inversely associated with mortality. In other words, patients ventilated with a tidal volume less than 6 mLs per kilogram had the highest mortality, whereas patients ventilated with tidal volumes greater than 10 mLs per kilo had a lower mortality. Of course, this is an association, and tidal volume here is probably a surrogate marker for disease severity in that some patients with the higher tidal volumes had the lower lung injury scores, whereas patients with more severe lung injury were ventilated with lower tidal volumes. But it's clear that there are patients with PARDS that can be ventilated with high tidal volumes and do just fine. So perhaps the point of discussion should not be necessarily which tidal volume one is employing, but as derived eloquently by Marcel Amato and colleagues, perhaps one should be focusing more on the driving pressure. This is a complex slide that I'm not going to spend a lot of time discussing, other than the fact that when one increases peak inspiratory pressure by maintaining the driving pressure constant, there is no change, no increment in mortality, and that mortality starts to increase when one starts to ventilate patients with driving pressures above 15 centimeters of water. So I have, on occasion, deviated from the PALICC original guidelines and have ventilated patients with PARDS with tidal volumes greater than 8 mLs per kilo, usually in the zone of 9, 10 mLs per kilo, for patients that require additional ventilation and in whom those tidal volumes can be accomplished with relatively low driving pressures of 10, 12. PALICC 2.0 does not necessarily address that, although it introduces the concept of driving pressure as a consideration. It still recommends now a tidal volume range of 6 to 8 mLs per kilogram and recommends that tidal volumes below 6 mLs per kilogram should be used, especially if one is needing to control plateau pressure and driving pressure limits. And they caution about the use of very low tidal volumes below 4 mLs per kilogram. The next point I would like to make is about PEEP. The original PARDS guidelines were a bit nebulous and fairly non-prescriptive in regards to PEEP, suggesting that moderately elevated levels of PEEP between 10 and 15 cm of water should be used and that greater levels of PEEP greater than 15 cm of water may be needed in severe PARDS. But this doesn't really help us at the bedside. For instance, at Duke, we have a very robust respiratory therapist-driven mechanical ventilation protocol, so we needed to objectify the application of PEEP in patients with PARDS. And for that, we chose the low PEEP high FiO2 table from the ARDS network, which prescribes different PEEPs for different FiO2 requirements. This is not something that I intentionally deviate from, but I think the world does. And this is exemplified by this other work of Ravi Kimani and colleagues, showing throughout the entire spectrum of ARDS severity what PEEPs people actually use in relation to FiO2. So in green here, you'll see what is prescribed by the low PEEP FiO2 table from the ARDS network, showing that with lower FiO2 requirements, you have low PEEP. And with very high FiO2 requirements, you should use high PEEP. But in reality, very few times people deviated from a PEEP between 8 and 10 in pediatric ARDS. So there are patients with more severe hypoxemia that should be requiring much higher PEEPs that are treated with lower than indicated PEEPs. And this has significant repercussions. For instance, here, there is a graph of mortality on the right vertical axis in relationship to how far from the protocol one deviates. So if you are on protocol, mortality was pretty low. And the same is true. If you are applying more PEEP, that is prescribed by the low PEEP FiO2 table. But if you have a patient treated with PEEPs below the PEEP FiO2 table, that is associated with higher mortality. And the highest mortality is when PEEP is off by at least 5 centimeters of water, lower than what is prescribed by the PEEP FiO2 table. In other words, for patients that are on or better protocol, the survival is significantly higher than for those patients where PEEP is being applied at levels below what is prescribed by the PEEP FiO2 table. So how does PALIC 2.0 recommendations address the PEEP levels? PALIC 2.0 does so in a much more objective way. It has adopted the lower PEEP, higher FiO2 table from the ARDS network. So it's essentially what we have been doing in our units for the past few years. And it cautions about adjusting PEEP levels that will cause someone to exceed target plateau pressures or driving pressures. Another instance where I deviate from the PARDS guidelines has to do with high-frequency jet ventilation. The original PARDS guidelines did not recommend routine use of high-frequency jet ventilation in PARDS and would consider it for patients with severe air leak syndrome. Now this is a very local issue for us at Duke because we have a mechanical ventilation protocol that calls for the use of jet ventilation in patients under 8 kilograms in whom we cannot conventionally ventilate within certain driving pressures and plateau pressure curves. And we have been quite successful with that. These are data from Andy Miller, one of our lead respiratory therapists, showing the use of jet ventilator in children with PARDS in the moderate to severe range that could not be ventilated in a protective way by conventional ventilation. These patients showed effective improvement in ventilation with normalization of their pH and also lung recruitment and oxygenation, allowing for a weaning of FiO2 over the subsequent 24 to 72 hours. So how is jet ventilation addressed in PARDS 2.0? It actually isn't. So to my knowledge, there is no recommendation of jet ventilation in the new guidelines. The last point I want to make is about prone positioning. The original PARDS guidelines mentioned that prone positioning cannot be recommended as routine therapy and it should be considered as an option in cases of severe PARDS. Further study is warranted. We've known now for many years that proning patients improves oxygenation. This is a classic study from Luciano Caccinoni showing that an improvement in PaO2-FiO2 ratio when the patients are prone and worsening when they are supine again. And that is persistent throughout the first 10 days of the study. The original pediatric data were published by Martha Curley and her collaborators and involves 102 children randomized to prone and supine position. And this was a negative study showing lack of an advantage in ventilator-free days with the prone position compared to supine position. However, we now have pretty robust adult data with the PROSAVA study showing that prolonged and sustained and early prone positioning in adult ARDS has been associated with survival advantage. So prone positioning in children is easy. It is relatively safe. It is cheap and it has very little downside. So we have been employing prone positioning for our more severe patients with PARDS, especially those in whom we cannot achieve a safe, protective ventilation strategy with low FiO2 below 0.6. So we've been doing prone positioning consistently in our units for the more severe patients. So how does PARDS 2.0 address this issue? There are insufficient data to support or refute the use of prone positioning, and this is a conditional recommendation, and that the use of prone positioning may be considered in patients with PARDS and hypoxemia not responding to other interventions. They cannot make recommendations on the duration of prone positioning. So again, this is aligned with our current practice. And since we're coming up against time, I will stop here and thank you for your attention.

Pediatric Acute Respiratory Distress Syndrome

tidal volume

PEEP

high-frequency jet ventilation

prone positioning