Get with the latest ARDS guideline

Until recently, the American Thoracic Society had last issued guidance on acute respiratory distress syndrome (ARDS) in 2017, back when the condition wasn't even a household name.

The experts tasked with updating the society's guidelines found a lot of new data to incorporate, on steroids, neuromuscular blockers, extracorporeal membrane oxygenation (ECMO), and more. Their resulting recommendations were published by the American Journal of Respiratory and Critical Care Medicine online on Nov. 30, 2023, and in print in January.

Sarina Sahetya, MD, MHS, corresponding author of the guidelines and a pulmonary and critical care specialist and assistant professor of medicine at Johns Hopkins in Baltimore, recently discussed what's changed and why.

Q: What motivated this guideline update?

A: The initial guidelines were completed in 2017, and they were always meant to be a living document that could continue to be updated as more evidence was generated in the field of ARDS. Since 2017, there have been a number of landmark trials and new evidence generated, so it was always on the radar to update at some point. And then of course, in 2020, we had the COVID pandemic, and clinicians everywhere were faced with an influx of patients who had acute respiratory distress syndrome, and there was really a need to more urgently make sure the guidelines reflected the latest state of the evidence and were as up to date as possible. That's when a group of us got together and decided we need to update them now so that we could help guide people at the bedside.

Q: COVID-19 inspired a lot of research into ARDS. Did the results affect the guidance?

A: The way guidelines are done, we have to look at all the trials that have been completed to date. When we started doing the literature searches, not a lot of additional trials had been completed in ARDS and COVID. When we were writing the paper, we tried to acknowledge, OK, here are some areas where some trials came out after the pooled evidence for the guideline was put together. But in general, most of the trials that were included were completed before the pandemic. The pandemic really created an environment where we wanted to be able to provide guidance, but very few of the included trials were COVID-specific.

Q: The new recommendations were mostly conditional. Why is that?

A: A strong recommendation means that pretty much everyone who has ARDS should get the recommended intervention. … A conditional recommendation means there's a lot more nuance. That may mean that the evidence suggests benefit but it's not overwhelming. For example, the recommendation that people with ARDS should receive steroids is conditional because there's a lot of heterogeneity in how these steroid trials have been done. … Some use prednisone, some use dexamethasone, some use hydrocortisone. Each of the different trials used different doses of the steroid. Each of the trials used different durations of the steroid. When we put it together, we see this consistent signal that there's a benefit to steroids in ARDS, but we can't actually tell you what's the best regimen.

Also, a lot of these trials didn't have the resources or funding to look at long-term outcomes. What are the downsides of steroids? Maybe an increased risk for infection, higher sugars. But there's also concern that it could have longer effects on your muscle strength or cognition. … The conditional recommendation says we see an important signal for improving mortality, but we don't know exactly how you should execute this and we don't know if there are downsides that the evidence just hasn't shown us yet. … You can apply your judgment at the bedside for your patient to personalize therapy.

Q: What are the important takeaways from the other new recommendations?

A: We have a conditional recommendation that patients with moderate to severe ARDS, so a P/F ratio less than 150, should receive higher versus lower PEEP [positive end-expiratory pressure]. Again, that was a conditional recommendation because all the trials that were included in the meta-analysis generated that signal of mortality benefit, but it's very difficult to say everyone should get one specific PEEP strategy because all the tested PEEP strategies were so different.

We have a conditional recommendation that people with very severe ARDS should be considered for ECMO. That is consistent with the literature that there's benefit, but we know ECMO is a very high-intensity and invasive intervention, and it's very resource-intensive, and resources are scarce in some places, especially during the pandemic. So it is essential to be thoughtful about a candidate who might have risk factors for increased harm and/or may not benefit from ECMO referral. That is important to think about when you're operationalizing.

Our strong recommendation was that patients should not receive prolonged lung recruitment maneuvers. The reason why it was a strong recommendation is because there was actually a consistent signal that people who received prolonged lung recruitment maneuvers, that's more than 30 cm H₂O of PEEP for greater than 60 seconds, had a higher risk of mortality. That was demonstrated in a randomized clinical trial that came out after the 2017 guidelines were published, so it was actually a change in recommendations between the 2017 and the 2024 guidelines. We strongly recommend it not be done because of the risks of patients having cardiac arrest or cardiac arrhythmias or hemodynamic effects from those high airway pressures. A good takeaway: Don't do this anymore.

Q: Could you talk about the recommendation to use neuromuscular blockers in early severe ARDS?

A: This is our controversial one. It's controversial for two reasons. One is because the largest trial to date of neuromuscular blockade—the ROSE trial, which was just published 2019—didn't show a benefit to neuromuscular blockade. Everyone remembers the trial that was just done and our recommendation seems opposite of that. But it's important to remember that we didn't just look at one trial, we looked at seven trials. … When you pull them together, looking at neuromuscular blockade versus placebo, there was a statistically significant effect, suggesting a lower mortality for patients with severe ARDS who received early neuromuscular blockade compared to deeply sedated patients who didn't.

Q: What's the second reason for controversy?

A: The second reason it's controversial is because around the same time we were making our guidelines, the European Society of Intensive Care Medicine came out with their own guidelines. In 2017, the clinical practice guideline was a joint venture between the American Thoracic Society and the European Society of Intensive Care Medicine. In 2023, the ATS and the European Society did their own guidelines separately. The one place where we disagreed is that we had a conditional recommendation for neuromuscular blockade and they actually had a strong recommendation against routine use of neuromuscular blockade.

Q: Why the difference?

A: It comes down a little bit to methodology. We included seven trials in our analysis to generate our evidence; the European group ended up including five trials. They found an effect that wasn't statistically significant on mortality. We had an effect that was statistically significant. … If you look at the way their question is phrased, [they say neuromuscular blockers] shouldn't be routinely used in all patients with moderate to severe ARDS. We agree with that. It should be in the patients who are most severely hypoxemic [PaO₂/FiO₂ ratio ≤100 mmHg], and it should be early in their course [<48 hours], and it should probably be in the patients that are most likely to be deeply sedated. When you read the headline soundbite, it feels like there's a big discrepancy. When you look at the details, it's a little bit more in line than it seems on the surface. Our effect estimate was almost the exact same, but their confidence interval was wider than our confidence interval.

Q: Is it hard to make decisions on recommendations that come down to a confidence interval?

A: It was hard in the sense of everyone was really thoughtful knowing that we were going to put something out there that many clinicians will take as the word, as what they should be doing at the bedside. That's why we tried really hard within the manuscript itself to add the nuance—when this should be applied or what population to think about it in. There were several meetings where we discussed these recommendations, both at the subcommittee level and then at a broader committee level, and we ultimately got to 100% consensus. We had a whole voting plan and we didn't end up having to do that. There was a lot of thought put in, a lot of discussion from experts in the field to try to generate something that is both useful and understandable to people who are actually caring for patients at the bedside.

Q: What else would you want bedside clinicians to take from the guidance?

A: It's important to understand that the strong recommendations are there for a reason, and those are the things that should be followed. The conditional recommendations are things that you should be thinking about and tailoring to the individual patient and that patient's preferences and unique characteristics for their disease presentation and also their lives. Everyone should understand that this is an exciting and evolving field, and clinical practice guidelines, because of the methodology, follow the evidence. We will always be trying to treat these guidelines as living documents that need to continually get updated as there are advances in the field.

Q: Is there a timeline for reviewing these guidelines again?

A: No specific timeline right now. There are a number of really important clinical trials that are in process. Two I can think of are related to steroids and mechanical ventilation strategies. I'm sure more that I don't know about yet are coming down the road. Once those are completed, and we have enough evidence to say, "It's time for an update," we'll certainly get on it.

One of the important advances that hopefully will be coming to the field is looking at these interventions in trials not just for all-comers with ARDS, but really understanding if there are biologic or physiologic differences in how people present with ARDS that mean they'll respond differently to these interventions. … I think that's an exciting future for the trials in the space, and if they're able to prove something, then it'll get incorporated in the next guidelines.