from the JAMA Network this is JAMA clinical reviews interviews and ideas about Innovations in Medicine Science and clinical practice here's your host welcome to this JAMA clinical reviews podcast I am Dr David Simel associate editor for JAMA in this podcast we will be discussing guidelines for the care of patients with acute respiratory distress syndrome commonly referred to as ards the new guidelines were released on June 16 2023 by the European Society of intensive care medicine released online in the journal intensive care medicine to address this topic we are pleased to be joined by Dr Derek Angus who is the chair of critical care medicine at the University of Pittsburgh School of Medicine Dr Angus is also a senior editor at JAMA and the author of The Clinical guidelines synopsis that appears in JAMA in the July 23rd 2023 issue Dr Angus thanks for joining us today you're welcome David well let's start with definitions which is how we like to begin things on our clinical guideline synopsis ards is non-cardiogenic pulmonary edema where the patient is mechanically ventilated and requires at least five centimeters water of positive end expiratory pressure which we call peep so as a physician who's not a specialist in intensive care medicine that definition has always felt arbitrary to me primarily because as patients have deteriorating oxygen we often have an informed suspicion that they already have ards but they're just not intubated yet and don't meet the peep definition how did the guidelines group handle that so let's be clear a guidelines committee isn't in charge of coming up with a new definition but it's pretty hard to know how to use the guidelines or interpret the guidelines unless you know how you're going to Define and diagnose who has aired yes and who doesn't have abs and what you described there are the current criteria for diagnosing ideas and you are right that there's a degree of arbitriness to them what is not arbitrary is the conceptual biomechanistic definition of area so really for decades now we've all been pretty comfortable with the idea that what airds is is the umbrella term A syndrome for all these moments when some sort of injury either coming in from outside like pneumococcal species coming into the lung into the Airways or some sort of toxin in the blood perfusing the pulmonary vasculature something causes an injury to the lung that causes this so-called non-cardiogenic pulmonary edema and we get a thickening of the space between the capillary and the alveolus we get damaged the lining of the alveolus and we get fluid in the alveolar Sac where there should have been air and all of that compromises particularly oxygen transfer gas exchange in general but particularly the ability to oxygenate and compromises lung functions so that's not arbitrary having said that trying to operationalize that at the bedside it's not easy and there's been a debate for decades how can you make sure that it's not due to cardiac failure how can you rule out cardiacs to cause upon edema how do you know there is actually pulmonary edema how do you know it's acute and so on and so the current definition has been around for a decade or so and it's actually a leaner definition than some of the older definitions which involved using the swan gas catheter to rule out cardiac causes of pulmonary edema but because ards was for so long the focus of clinicians taking care of patients who had this problem in ventilated patients the current definition was still focused only on patients who were on the ventilator and they were trying to standardize the peep because they were really interested in having a reliable measure of the degree of hypoxemia and you can't measure that unless you have a strong measure of what you think the oxygen content is in the alveolus so you can get an A gradient all that to say the current definition is actually a pretty good reliable and consistent definition for patients who are intubated this underlying process of injured lung developing palmedema surely that could happen before the patient is intubated and the answer is totally yes and so what did the guidelines committee do well they alluded to something which we also remarked on which is someone needs to update the definition and the criteria and that definitely has to happen that wasn't the job of the guidelines committee but they did want to be hamstrung by the technical definition that restricted RDS to just those patients who are on the ventilator so long-winded story they also talked about the term acute hypoxemic respiratory failure not otherwise explained by pre-existing lung disease or heart disease the advantage of this is it gave them permission to look at what are the strategies someone might use when they're encountering a patient either before they're intubated to try to avoid them even having to be intubated or in the many parts of the world with less access to Modern intensive care where there may not even be access to a ventilator and so it was a smart move by the guidelines committee to use this broader term acute hypoxemia respiratory failure and then enlarge their literature services for exploring the evidence around the best things to do in the patient who isn't yet intubated let's say I've got a patient though with acute hypoxemic respiratory failure and their hypoxemia is progressing the guidelines suggest some mechanical parameters for the tidal volume and Peep and you alluded to peep as part of the definition many of our listeners like me aren't intensivists so could you just review the physiology here briefly and talk about how an intensivist sets up the ventilator in regards to a patient with acute respiratory distress syndrome so the ventilator is an amazing development it was definitely a real technological breakthrough in the 20th century faced with the polio epidemic people came out with round one event laters these so-called iron lungs these curas devices which tried to mimic the way we breathe by trying to help expand the lung to draw in a breath the modern ventilator doesn't do what the iron lung does the iron lung tries to mimic the way you or I breathe we take in a breath we actually expand our chest cage and create negative pressure inside the lung that's how we breathe we pool air in from the outside because we're creating a vacuum mechanical ventilators are on the outside and they push air in so during a breath an inspiration breath instead of what you learned in medical school about being at negative pressure or say negative two centimeters of water to get air flowing in they're pushing in with positive pressure and sometimes a lot more than two centimeters of water sometimes 20 30 or 40 centimeters of water to push the breath in now when they push that breath in for someone who was unable to adequately oxygenate and would otherwise have died the ventilator is incredibly life-saving but it's so non-physiologic that nearly every aspect of what we're doing can both be fantastic and detrimental at the same time so you have to decide how big should the breath be and since you're pushing it in with positive pressure you're concerned both about it being too big a breath and a breath it's under too much pressure which could be injurious equally at the end of the breath because the lung is injured Etc the lung can actually collapse down and so you try to keep the lung open at the end of the breath and that's what you use Peak for and then of course you have to say how much oxygen am I giving in oxygen is the lifeblood but oxygen itself can be toxic so when setting up the ventilator you have to decide how big should the breath be how many breaths should there be how much peep should be at the end of the breath and how much oxygen should I be giving all of these things have been the subject of all sorts of research both because if you do too much it can be problem and if you do too little it can be a problem in general we have moved from larger tidal volumes down to smaller tidal volumes and so the so-called six CC's per kilogram of Ideal predicted body weight has really been the standard erds management for about 20 years now since a landmark trial from the NIH showing a big drop in mortality and the presumption was that these larger breasts were in and of themselves by over distending the lung they were actually exacerbating the lung injury and actually putting the patient at greater risk of dying so you want to use smaller tidal volumes which also means a higher rate so you still get the same minute ventilation we've been trying the right peep forever we've tried to go with higher peep or lower peeps so-called best peep it's hard to say what's right the main thing to do is to not keep the peep unnecessarily high for too long so you need at least some people to keep the Airways open a little bit you can increase the peep if someone is having problems with oxygenation and then you should dial it back down again when the oxygenation is improving and remember the other problem with peep is that peep plus the positive Airway breath means the chest is a positive pressure which means the venous blood returning into the chest to fill the heart has trouble getting into the heart and so you can actually worsen shock and you can decrease the filling into the heart and so forth so in general we don't know the right peep but we know that we want to give enough peep to get adequate oxygenation but not more than that the other thing that people sometimes play around with if you're giving smaller tidal volume breaths we know that every so often in normal life we might take a big sigh or a yawn or a big breath and that might actually help purple penalveoli especially in an injured lung and so people spend a lot of time thinking about so-called recruitment Maneuvers or sigh breaths and at least at the time of the guidelines committee when they were writing their analysis there had been one large study conducted out of Brazil but actually recruiting patients in many different countries which was thinking that it would improve outcome by building in some recurrent so-called recruitment Maneuvers but actually that study suggested that these aggressive recruitment Maneuvers might even have been harmful possibly again because it increased the positive pressure even more causing cardiovascular collapse and so in the current guidelines they're not recommending the system the use of prolonged recruitment Maneuvers I gather then that what I should remember is lower of everything is better as long as it's working intensive care Road on a wave of Technologic innovation in the 70s and 80s and just brought more and more of everything and then we've definitely spent the last 20 or 30 years actually trying to pull back on a lot of the invasiveness so a guiding principle and intensive care is actually about being less intensive and being less invasive well let's say you've got this patient with ards and you've done your best you can with the title Vibes and the peep and the Recruitment and they're still having worsening hypoxemia the panel recommended pruning or turning the patient face down for several hours a day which for someone who trained during my era is rather novel because everyone on a ventilator was flat on their back so it sounds simple and a non-invasive strategy to improve oxygenation but I know that's not so simple could you talk a little bit about that pruning great topic so the lung is where air and blood meet but air and blood don't meet evenly all the way through the lung thanks to gravity the heavy blood is at the bottom and light air is at the top and the lung isn't a perfect Cube or a perfect box and so pruning is doing is essentially recognizing that if you change which part of the lung is on the bottom then you change the relative proportion of West zones and so you're playing around with sort of the ideal matching of open alveoli that have air in them with alveoli that are getting a plentiful blood supply and if you can tweak the lungs through gravity to get a larger part of the lung with more effective essentially EQ matching then you can improve oxygenation that's the essence of it and lying on your back is in many ways not the ideal Arrangement and even turning sideways can sometimes help but certainly getting right the way onto your tummy is in many ways more advantageous now it's not true for everyone because the lung is injured heterogeneously and it doesn't always play out but for many patients who are having trouble with oxygenation you can get a remarkable boost in the ability to oxygenate Simply by Rolling them onto their stomach now simply by Rolling them onto your stomach these patients are incredibly ill they're intubated they've got lines in them if you roll them onto their stomach then you can't really see them what happens to all those lines what happens to their NG tube it can be very frightening and scary for the ICU nurses and the ICU dogs and so on and so although it sounds simple people have spent a long time trying to work out how to do it they've thought about trying to do it in like a striker frame strapping the patient into the bed and rolling them in reality though what has come out is with adequate training of the bedside team even in regular ICU beds it's pretty easy now once people are trained to roll patients over for up to several hours a day and you can roll them over for three or four hours roll them back for a while and do this sort of rotating back and forth and you just need to be careful and attentive to the fact that now some of you know you can't see the face properly make sure you don't pull lines out but that's what all the training is for and one real Landmark study from France shows that pruning had a massive effect on mortality simply because it avoided them having to massively turn up all the dials on the ventilator you could essentially use a gentler ventilation because you were getting much more effective gas exchange with pruning so pruning has really become a go-to move in anyone in whom there is ongoing recurrent problems with getting adequate oxygenation is pruning a strategy for the non-intubated patient with acute hypoxemic respiratory failure so pruning has been really widely adopted now for intubated patients during covet many patients even prior to being intubated even themselves found that they were more comfortable lying on their belly and there was a real movement to then say maybe we should prone the non-intubated covet patient there weren't any randomized Trials of this that really informed on it but there was quite a lot of anecdotal and observational evidence to suggest that pruning could be quite effective in non-intubated patients it's highly likely that the exactly the same principles that give the benefit in the intubated patient would also yield benefits in the non-intability patient the guidelines for the intubated patient address patient ventilator asynchrony and they advise us not to use routine neuromuscular blockage in ventilated patients could you describe what asynchrony is and what that experience is like for a patient if you remember I was mentioning that the ventilator is profoundly non-physiologic it's trying to push air into the chest and it also sets the rate at which it does it often patients are sedated and pretty sleepy and not too aware but if a patient is awake and they have a tube down their throat and the ventilator is shoving breath down their lungs that can feel very uncomfortable now there's a whole set of things that have happened in Ventilator design to try to have more disventilation that try to work with the patient take advantage of the patient's own respiratory efforts but patient ventilator asynchrony largely describes all those instances where you either consciously are almost buying an involuntary basis end up if you like bucking against the ventilator it's just it's an uncomfortable feeling and you engage in a variety of strategies to sort of fight with the ventilator and there is a thought that some of that in addition to being uncomfortable can also be injurious in and of itself it can actually exacerbate high pressure injury and so on inside the lung and so we're not fond of patients having patient ventilator asynchrony we think it cannot be nice for the patient in the short term and it could also be making the lung injury worse when the clinical situation deteriorates or the patient just isn't getting better the panel recommended referral for extra corporeal membrane oxygenation or ECMO now these recommendations have obviously been developed in light of all the new knowledge we've gained during the covid-19 pandemic and I think this may be a good segue for us to address whether the recommendations for ards especially for ECMO generalized to all patients with ards or might they be specific to covet 19. you're right the panel made a lot of recommendations and sort of divided them into covid-19 specific or covid-19 non-specific I understand why they did that because there were many studies done in just covid-19 and then you ask yourself is it the same disease and the answer is I don't really know I don't even know if covid-19 is the same disease I think some of the studies done in year one of covid when it was all ancestral variants might not even apply to current covet that we've had so many mutations in the virus the underlying pathophysiology might not be different I would generally put this in the bucket of that's one of the problems with syndromes syndromes are useful for grouping certain things together but you may be grouping some things together that actually respond differently to different treatments so there's a lot of interest and actually the panel spent some time discussing this notion of sub final types or subtypes of airds it is quite plausible that some interventions work equally well for anyone with any kind of RDS while other interventions will only work in certain forms of RDS that's an area of ongoing research trying to understand other different subtypes of eridas but to your point around ECMO since ECMO is basically saying when the patient is in such trouble that the team can't even get adequate oxygenation even with the ventilator should you just take the whole thing offline take the lungs offline and use a separate device to provide oxygen while you give the lungs a chance to recover it's probably true that now that evidence for ECMO suggests that there are severely injured ards patients who if they really can't oxygenate they probably will benefit from ECMO that's probably true regardless of the cause of airds that's likely to be a reasonably wise recommendation for ards regardless of cause once the ards is so severe that regular ventilation cannot maintain even minimum adequate oxygenation Dr Angus during the pandemic patients with ards seem so sick with multiple comorbidities and it was hard to know whether the comorbidities made the ards worse or vice versa can you talk a little bit about the interplay between ards and all the comorbidities that we saw in our patients first of all the patients who get air Diaz may already have chronic illnesses that are very problematic such as bad underlying COPD or heart failure or ischemic heart disease and so forth secondly when they get ards they can get it along with several other acute organ dysfunctions like acute kidney injury or altered mental status coma Etc the thing we care about is having the patient survive and then survive with high quality of life it's a really pressing issue to ask the question when we report a high mortality rate with ards what is it about the air DS that's contributing to the mortality versus all the other things I'll be frank I don't think there's that many patients in modern intensive care who die a hypoxemic death that's only part of the picture the problem of multi-system organ failure is a complex one what we must do is try to not worsen the odds of death and some of these guidelines really speak to making sure that you don't make the injury worse with the ventilator but when patients get air DS if you provide perfect ventilation and fix the oxygenation and essentially take the lungs as a problem out of the equation that does not mean that the patient will necessarily survive there's still a huge amount of work to be done on thinking about all of the rest of the problem if it's the rest of sepsis or multicism organ failure or the underlying fact that they may already have very severe chronic organ insufficiency before we wrap up are there any further points that you would like to communicate to our listeners about ards so I think the only other thing I would say we took a study in Jama a few years ago on current practices from around the world in the care of areas it was a bit disappointing that the care was really variable although there's lots of uncertainty around some of the things that we do for erds and you spoke about the arbitraryness of the definitions there are some key take-home messages about things that you should try to do for every patient with RDS and those are many of the things that are in these guidelines trying to reconcile the fact that we have guidelines based on pretty robust evidence with the fact that practice is highly variable is obviously a source of dismay and so I'm quite interested in seeing ongoing efforts to work out how we can reduce unwanted variation it's probably not enough to just publish a guideline we need to think about how we disseminate the guidelines why are people not all following the practice did they read the paper and not agree with it or did they not read the paper so you know the ongoing challenge to try to make sure that every patient no matter where they're cared for is getting cared for by a team fully conversant with the latest literature so that's an ongoing challenge that I'm hoping to see continued progress in that space well thank you very much Dr Angus for this discussion and your insightful comments about this very important aspect of healthcare my pleasure Dave this episode was produced by Shelley Stephens at the JAMA Network to follow this and other Jama Network podcasts please visit us online at jamanetwork audio all one word.com thanks for listening