Well, it's a pleasure being here today. My name's Ravi Kamani, and I'm going to talk today about PALIC-2, the Pediatric Acute Lung Injury Consensus Conference, the second edition, which focused on pediatric ARDS, a new definition, as well as clinical management guidelines. I'll begin by saying I have no real disclosures which are relevant for my talk, although all my disclosures are listed here. And this project is a follow-up project to PALIC-1. The first PALIC was convened between 2012 and 2015 and really co-founded here by Neil Thomas, Philippe Jouvet, and Doug Wilson. And we really owe them a lot of debt and gratitude. They brought together 27 experts from eight countries to create the first pediatric-specific definition of ARDS. And we generated 151 recommendations in nine different sections and topic areas. And PALIC-2 really built off of PALIC-1. Organizing committee was myself, Guillaume Emerud, and Yolanda Lopez-Fernandez. We complemented this with methodologists, Melba Mbeya, who was a part of the original PALIC, as well as two new methodologists, some experts in implementation science, as well as librarians. In addition, what you'll see is that the original sections from PALIC-1 were represented in PALIC-2 with new members, which are highlighted there in red. And in addition, two entirely new sections were created for PALIC-2, one that focused on informatics, data, and decision support, and another which focused on resource-limited settings or developing regions. In total, the PALIC-2 process encompassed about twice as many people as PALIC-1, including members from 15 countries, six continents. About 40% of our participants were women, and 36% were young investigators. We also had a respiratory therapist, a nurse, as well as a physiotherapist and PhD researchers. And PALIC-2 has had a long story, starting in December 2019 when we first got together to talk about revising PALIC through the completion of the last meeting, which happened in March of 2022 in San Diego, where we presented the preliminary findings. And up until now, where we're presenting our final findings here in line with publication. And our process followed a very detailed outline as put forward by the Institute of Medicine. We had our executive committee, which oversaw the whole process, as well as a guideline panel that was divided into several subgroups, those 11 subgroups, that together we identified the topics of interest, generated the relevant PICO questions in each of those subsections, summarized the evidence and additional information by doing a detailed literature review in each of those areas, extracted the data using standardized extraction forms, and then used those to judge the certainty of the body of evidence. After that, these were crafted into specific recommendations with strength of the recommendations as given by the GRADE methodology. Subsequently, we worded those recommendations and developed manuscripts. In total, we have 146 final recommendations, which have, again, just been published here in Pediatric Critical Care Medicine. 18 of these recommendations are definition statements. 34 are clinical practice guidelines that went through rigorous review with the Institute of Medicine-based approach with a grading of the evidence. 62 fell into the good practice or policy statement area. And then 32 fall into this research statement area. These have been published here in Pete's Critical Care Medicine with an executive summary as well as a supplemental issue, which contains additional manuscripts, the 11 sections as well as a detailed methodology manuscript with all of the evidence to decision tables, which form the basis for the recommendations. Now, I encourage you to please read all these manuscripts, but what I will do here in the next 10 minutes or so is just highlight some of the high-level changes that we made, and then you'll hear from a few of the individual experts from some of the additional sections that will go into much more detail about some specifics in each of their sections and important areas. So the first here is focused on the PARDS definition, and you'll note that there are many things that are the same as the previously proposed PALICC definition, age, timing, origin of edema, and chest X-ray findings or chest imaging findings with new opacities, either unilateral or bilateral. These are consistent with the first PALICC definition. We've added some clarity that the chest imaging should not be due primarily to atelectasis or pleural effusion. But there are some new elements to the definition, including a delayed risk stratification that would occur greater than or equal to four hours after the initial diagnosis. So a patient may meet criteria for PARDS if they meet the either invasive ventilation criteria with an oxygenation index greater than four or an oxygen saturation index greater than five, or on NIV with a PF ratio less than or equal to 300 or an SF ratio of less than or equal to 250. And you'll see we rounded that number up for simplicity and ease. But then we recommend a stratification occur at least four hours after the original diagnosis. And we've simplified the strata from mild, moderate, and severe into mild moderate as one group or severe as the other group. And this was largely based on the epidemiologic data that supported that the severe group appeared to be quite a different phenotype than the mild and moderate group that oftentimes there was little differentiation, especially towards clinical outcomes between mild and moderate. And as a consequence, we've lumped those together. But we have specifically pulled out this NIV PARDS group to highlight that in fact, they too have severity, that there could be mild and moderate NIV PARDS or severe NIV PARDS. We've also introduced this concept of possible PARDS, which is different from the at-risk for PARDS group. In the original PALICC definition, the at-risk for PARDS group encompassed a large number of patients that were on, let's say, nasal interfaces, for example, like nasal NIV. And in the possible PARDS stratification, now we've acknowledged that many of these patients actually probably do have ARDS, but we could not diagnose it because we maybe are less confident in the amount of oxygen that's being delivered, for example. So this possible PARDS group includes patients that are on high-flow nasal cannula or nasal modes of non-invasive ventilation, in addition to patients that may be missing lung imaging, for example, in resource-limited settings. Now, there have been some other important updates, specifically in areas of mechanical ventilation, which I'll talk about here next. The tidal volume recommendations are that we should be using physiologic tidal volumes between six to eight mLs per kilo in all patients with PARDS and avoid supraphysiologic tidal volumes, but that tidal volumes less than six mLs per kilo should be used, if they're needed, to stay below the suggested plateau in driving pressure limits, which I'm gonna talk about here in a second. And we also suggest a lower limit of tidal volume, four mLs per kilo, that you should start to use more and more caution. We've added a bit more clarity in the inspiratory pressure section here. So the first recommendation is unchanged, that in the absence of transpulmonary pressure, we suggest limiting plateau pressure to less than or equal to 28 centimeters of water, allowing for a slightly higher plateau pressure for patients with reduced chest wall compliance. But now we've added these two additional relevant recommendations, one about driving pressure. And although there's no clear trial data about driving pressure, we do suggest the same limit of 15 centimeters of water measured under static conditions that has been proposed based upon adult studies. And that we also recommend using a lung protective ventilation bundle that bundles together things like tidal volume, PEEP, inspiratory pressure limitation. We do have a few more recommendations with respect to PEEP, based largely on a multitude of strong observational studies that suggest that we should be using PEEP levels that are at least in line with the low PEEP, high FiO2 table from ARDSNet. And so we do recommend that our PEEP levels should generally be maintained in line with this. Although we do say that when adjusting PEEP levels to achieve proposed oxygenation or ventilation targets, that we pay attention to other factors, including hemodynamics and compliance, that's a separate recommendation. And that it's always important to pay attention to avoiding exceeding the plateau pressure or driving pressure limits that have been suggested as I previously alluded to. We have some new recommendations with respect to non-invasive respiratory support. We do suggest a time limited trial of NIV, whether that be CPAP or BiPAP, if there are no clear indications that the patient needs to be intubated at that time. And that if patients are on NIV and don't show signs of clinical improvement within the first six hours here, we then we suggest that they should be intubated in fact. And this includes patients that are at greater risk for complications from invasive ventilation, such as those with immunodeficiency. There's increasing data that seems to be emerging that we should not necessarily be withholding intubation or delaying intubation in this population. And that particularly for patients that have severe NIV PARDS or severe other organ dysfunction, that the move to intubation should perhaps be done more quickly. Now, the definition allows for the possibility of high flow nasal cannula in this possible PARDS group. But in fact, in the non-invasive respiratory support section, it's unclear when we should be using high flow nasal cannula in patients that are either at risk or have possible PARDS. And this is an area for sure for future investigation. There was some clear data from randomized trials and resource limited settings about different modalities of non-invasive respiratory support that would support the use of CPAP, for example, over high flow nasal cannula, CPAP or high flow nasal cannula, excuse me, over standard oxygen therapy in patients at risk for PARDS. Although if CPAP is being used, that it should be done under clear physician oversight. And that in resource limited settings in particular, the use of CPAP over high flow nasal cannula might be preferred for patients that have possible PARDS. In the section on pulmonary ancillary therapies, there have not been major updates, some slight clarifications on the SpO2 targets, as well as the acceptable pH targets to remain within the driving pressure, plateau pressure and tidal volume ranges. We do not have a specific recommendation for or against prone positioning, and hopefully more data will be coming with the prospect clinical trial. We have similar recommendations for inhaled nitric oxide for its use in select populations, and the same with corticosteroids. And we do in fact, suggest against the routine use of surfactant. We have a series of good practice statements related to respiratory monitoring, many of which are similar, some of which are new to include new monitoring elements. Neuromuscular blockade is also suggested in certain situations of protective ventilation is not achieved with sedation alone. We have some new recommendations regarding fluids, nutrition, as well as packed red blood cell transfusion, and in general, have statements that align with many of the PANDEM recommendations for monitoring and titration of non-pulmonary support. We have updated the ECMO section with a few additional areas about evaluation, the type of ECMO therapy to be used, avoidance of hyperoxia and slow reductions in CO2, as well as the lung protective bundles and strategies to consider using while on ECMO. The new section on data and informatics, which highlights the importance of using electronic tools to screen critically ill patients to identify those that have ARDS, as well as using tools that will help with automatic monitoring of compliance with PALICC guidelines, for example, for lung protective ventilation, based largely on a series of trials showing improvements in outcomes in both adult patients, as well as some with pediatric patients. We've updated a number of good practice statements regarding follow-up, the initial approach to the follow-up plan for patients with ARDS, evaluation of health-related quality of life, physical, neurocognitive, emotional, family, and social function, as well as assessments of pulmonary function after they've left the hospital. And we've tried to synthesize a number of the treatment recommendations into a hopefully easy-to-digest schematic here, where those with good practice statements related to monitoring of respiratory effort, targeting sedation management, and adequate nutrition are applicable for the whole spectrum of pediatric ARDS patients, those on non-invasive, as well as invasive ventilatory support, that we have SpO2 targets and targeted fluid management, although there is low certainty of evidence in these areas. Our recommendations for the use of plateau and driving pressure limitation for those on invasive mechanical ventilation, as well as tidal volume targets, again, based upon oxygenation index severity. One to consider things like bi-level non-invasive ventilation and the use of intubation, although, again, low-level, very low-level uncertainty for many of these recommendations. The use of PEEP, which has more higher level of certainty, moderate level of certainty here from a number of observational studies. Use of neuromuscular blockade, inhaled nitric oxide, and then we cannot recommend for or against things like prone positioning, high-frequency oscillatory ventilation, or recruitment maneuvers in some of these patients on invasive mechanical ventilation. For ease of digestion, we've tried to summarize these into digestible tables that focused on activities like endotracheal intubation, mechanical ventilation bundles, the specific recommendations and where those recommendations lie, as well as good practice statements that might fall in line with those recommendations. The same can be held for the mechanical ventilation parameters, strategies and specific targets. Other approaches like prone positioning, surfactant, for example, escalation to ECMO, the specific recommendations, as well as the relevant good practice statements, components that are about general critical care, which as you can see, most aligned with good practice statements, as well as post-ICU follow-up. And then finally, we outline a number of research priorities related to mechanical ventilation monitoring, identification of new targets, let's say, for example, for tidal volume, as well as a number of other approaches that are in clear need for future research. I'll just conclude by saying PALIC-II is now complete. Please check out the new publications that are being released here with this meeting. This represents an update with more rigorous methodology, a large representative group of investigators involved in the project. We've consolidated and simplified the definition of ARDS, improved implementability, including for resource-limited settings, provided guidelines for both pulmonary and general management of critically ill patients with PARDS, and unfortunately, most of the recommendations had low or very low certainty of evidence. Thank you.

Ravi Kamani

PALIC-2

Pediatric Acute Lung Injury Consensus Conference

pediatric ARDS

clinical management guidelines