Dr. Marcelo Amato discusses clinical trials, various methods and outcomes of lung recruitment strategies.
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From Nihon Kohden OrangeMed
Marcelo Amato: In-Line Suction App of the NKV-550 - Ma
Introduction and Background Reference:
Recruitment maneuvers (RMs) are a low-cost intervention that involves briefly applying high airway pressure to open collapsed lung tissue and keep it open. The goal is to increase the surface area available for gas exchange and improve ventilation distribution throughout the lungs. RMs are often used in patients with acute respiratory distress syndrome (ARDS), a serious condition that can be associated with high in-hospital mortality rates.
ARDS (acute respiratory distress syndrome)
ARDSnet and PEEP are both related to the care of patients with
ARDSnet The Acute Respiratory Distress Syndrome Network (ARDSnet) is a contract program established in 1994 by the National Heart, Lung, and Blood Institute (NHLBI) to test strategies for improving ARDS patient care. The ARDSnet protocol is a protective ventilation strategy that uses a table-based approach to set positive end-expiratory pressure (PEEP) and inspired oxygen fraction (FiO2). The protocol also uses a stress index to monitor PEEP by analyzing the shape of the inspiratory airway opening pressure curve. The ARDSnet ARMA study is a pivotal clinical trial that established the current standard of care for mechanical ventilation.
PEEP Positive end-expiratory pressure (PEEP) is used to prevent lung collapse and can increase oxygenation. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury, but they can also cause circulatory depression and lung injury from overdistention. Most patients requiring mechanical ventilation for ARDS receive PEEP of 5 to 12 cm of water.
PEEP EIT PEEP EIT, or electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration, is a method used to optimize PEEP for patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation. The goal is to improve respiratory system mechanics and reduce the risk of ventilator-induced lung injury (VILI).
Dr. Laurent Brochard - Setting positive end-expiratory pressure: does the 'best compliance' concept really work?
Summary: The traditional 'best compliance' strategy for determining optimal PEEP settings in ARDS carries risks and overlooks some key physiological aspects. The advent of new technologies and methods presents more reliable strategies to assess recruitment and overdistention, facilitating personalized approaches to PEEP optimization.
Presentation by Dr. Marcelo Amato:
(transcribed)
"This is a study that we randomized patients to two different approaches: one was the typical ARDSnet and the other was PEEP titration based on EIT, which is going to give us a PEEP titration very similar to the best compliance. There are some situations in which they are clearly different, but not all. In most of the cases, they are going to coincide. But this is something just to follow up on in the discussion that you see when you compare the two.
This is the low PEEP FiO2 table. Before randomization, every single patient was titrated according to ARDSnet and also according to the EIT. But then, the patients were randomized and then they follow one approach or the other. It's interesting to see that if you if you are in the ARDSnet and then you are going to have your PEEP titration, sometimes you increase PEEP, but sometimes you have to decrease your PEEP level, as we are discussing. So it's not necessarily a high peep. In fact, the average here is just one centimeter above than the average, so it's about the same.
But this is something really interesting: If you are using EIT, you come with a higher PEEP for obese. It's quite obvious because they have much less over-distension. Then the crossing point is going to to show you a better PEEP. This is the patients before randomization. Driving pressure was the same in both groups, but then, 24 hours later there was a difference in four centimeters of water, that was sustained along the time. So compliance got better and driving pressure got four centimeters less.
Now we are changing our philosophy a little bit. Which is: we titrated PEEPs every two days in the patients, and to our surprise, the need for PEEP doesn't decrease along the days. It's just two centimeters of water-- this is this small drop here. So, it looks like the need for PEEP is anatomical, it's not from the disease. Another clue that this is true is that in surgical patients that have normal lungs, the need for PEEP was precisely the same as covid patients -- just two centimeters on average less. So most of the PEEP that you need is just because you are lying down supine and you have anatomical chest wall, belly fatiness, and everything. So, it's not coming from the disease. This is something that we are discussing doing.
This is the drop in driving pressure, after randomization, if you follow this peep titration. So, in every single patient you decrease a little bit you're driving pressure, because you are trying to find the sweet spot for every patient. But if the patient is a recruiter you have a much larger drop, but still you're not causing harm. If you're using the ARDSnet this is here, and this is a little bit lower here. So then, I think, just to stress the point that the recruitability is very important if you're using the ARDSnet or some convention, because you then you really are going to cause an increase in driving pressure for the non-recruiters, and the recruiters they can go with a higher PEEP without too much trouble.
This study was another meta-analysis. You know meta-analysis they are very tricky because depending on your selection criteria, you put a lot of weight in a few studies and you ignore many of them conveniently (or not). But this other meta-analysis, after the publication of the ARDS trial, is still showing that recruitment maneuver and high PEEP is favorable. I think it's important for you when presenting the recruitment maneuver too that if you look at the literature very carefully it's still an occupies. You cannot say that the ARDS trial changed everything-- is it's a kind of biased approach, because you're putting too much emphasis on one single study that was done in a very peculiar way.
Let me just show you one more thing because came to my mind. Let's let's just summarize what we have as mechanical ventilation trials. It's interesting because not all these studies are considering the meta-analysis. In '95 we publish a physiological study. '98 it was the New England. Then we had these three studies comparing high versus low tidal volume right. Then we have the ARDSnet. Then we have the alveolar that was testing high versus low peep FiO2 table. Then we have all these studies here that were testing also high versus low peep. And then finally, we had these three other studies art, epivent and farlop, and this live which was a french study from Jean-Jacques Ruby. He was testing the personalized approach. So they they are trying to find diffuse ARDS, they use a higher PEEP. It's interesting to think about like this: that here we propose the multiplicity of mechanisms, then all these trials were testing low tidal volume.
This was a big success so this story was was a big success. Although, here, we said oh, "protective strategy is good." All studies said, "protective strategy increases mortality." I know because in our hospital we started to use high tidal volume again. And then the ARDSnet said, "okay, now you decrease it." But from this point on there only confusion. It's interesting because, I think the question is not set yet, I think we should not say that the ARDS trial eliminated all other things. I'm not going to talk about the ARDS, but I would like to just show this. Look at this: Just to understand how mechanical ventilation is confused, this is (a study) from 95 to year 2000. Our study was showing improved mortality when reducing tidal volume. But then look at all of those studies--they were showing opposite results.
And finally, then the ARDSnet came. It's just to say I think we forgot about this. But, you know, mechanical ventilation is very difficult because what you plan to do is not what happened exactly in the trial. So i think we have to keep some some criticism about it.
What I would like to show you is this. This is the study from Bob that was also positive. But what I would like to show here is the following. This story about the high PEEP studies never produced a positive study. However, this study was performed in our institution, and it's interesting that very few people quote this paper. We have 300 patients. We randomize to a high peep and low peep strategy after is the post-operative cardiac patients. It's not precisely ARDS but they have a very low pf ratio they they have a pf ratios around 200 or less. Then they stay in the ICU, typically under mechanical ventilation for 24-48 hours. We use the recruitment maneuver going up to 45. This was this was (I don't remember if it was two minutes) So typically these patients they had EIT image, so you don't see any dorsal ventilation. Then after the maneuver, you have this. Then we had a positive result because we decreased the pulmonary complications significantly and we decreased the length of stay. So, it was a moderate recruitment manuever. I would say in terms of pressure is moderate, but in terms of time it was two minutes. Very good assessment to not have hemodynamic problems. You see, we always try to have the blood pressure above 80 to start. You have a drop, but then you recover you never reach below 60. This is the control group.
In experimental studies there are an abundance of situations in which you show that if you compare open language versus ARDSnet there is a big difference. No question about this. We have also some results on cytokines, we have some human studies showing that you have less inflammation.
What I would like to show is the following: This study came from the results of the new Epivent study. So this study used esophageal pressure to titrate PEEP, trying to reach slightly positive transpulmonsry pressure. It's interesting that this approach gives you exactly the same PEEP as EIT. Every time you have the crossing point between collapse and over-distension, we have a transpulmonary pressure between zero and plus two. This study was negative, but once they did a pos-hoc analysis comparing the patients which were on the target in terms of transpulmonary pressure they had a positive result.
I'm just trying to say that the literature if you look carefully there are signals that there is still some room for improvement.
I think the problem is that we are we are kind of of doing this very naive strategies. "Let's increase PEEP by a new table." Or, like the express study, "let's increase PEEP until reaching a plateau pressure of 28." These some strategies that doesn't they don't have any good rationale. So i'm just trying to defend the idea that..."
"...we should keep the recruitment maneuver in the ventilator because if you look at carefully I think there is still some issues that we have to resolve."
The idea of this recruitment maneuver is to detect this type of animal or this type of patient so you increase PEEP and then has a beautiful response. As compared with this animal or this patient that was already recruited and then maybe has a viral pneumonia. Then it's not going to gain anything. This I what we would like to to have.
I would like just to make brief review on the methods here. Customary method is the EIT method that we use: we titrate PEEP, and we try to find the crossing point between collapse and over-distension extended. Custom method is is is a kind of analysis that we do that we can use in the long term. For instance, let's suppose that I did a PEEP titration, and let's suppose that I do many maneuvers with the patient. Six hours later, I can still calculate how much collapse and over-distension this patient has with EIT. This is what I call extended Acosta approach. We estimate collapse and over-distention not only during the titration, but for a long period of time.
Then I would like to talk a little bit about this recruitment to inflation ratio, because maybe lots of people they are going to ask you "how does your method compare with this method proposed by lauren brochar?" Because people in toronto they are suggesting this method. Then our method, that is our our tool which is kind of compliance gain, that we built in the ventilator.
By the way this was a an idea from Bob, so Bob should be here. This idea, you're going to see that this method has a very good physiological background. So, this is the the EIT method. Just to review: we do decremental PEEP trial, and instead of just assessing the compliance (like PEEP typically do in the ventilator) we try to find this crossing point between collapse and over-distension. The blue is over-distension. You see, it does not coincide with the best compliance always, why this i think for two or three reasons. One of them is that the EIT is here, and so there is very little representation of the apical lung regions. so we are taking just the big slice-- the most over distended lung (which is this), and the most collapsed ones. So you are taking the extremes of the lung, and then the compliance curve is more or less. I'm taking the average of the O lung, so sometimes they do not coincide precisely. I think EIT is very sensitive to over-distension, so typically this crossing point is a little bit below the maximum compliance.
Something that is very beautiful to see: What happens if my patient is obese? You're going to see. First of all, we have done lots of validation studies comparing CT versus EIT, and they match very well. Lots of studies, so you really can believe in these results in terms of percent of lung mass that is collapsed. In this study that we did to understand the benefit of this recruitment in the Nihon Kohden ventilation, we again tested how much the EIT was matching with CT, just to be sure that we can publish this study in a good journal. Again, we had perfect match between CT and EIT. This is the estimation based on EIT. And you see that it's matching very well with the CT results. In fact, we had a very good correlation between both methods. These are these peaks that we studied. So, the collapse estimated by CT in the x-axis and estimated by EIT.
So, why we did this? Because this we did for five animals and then but the whole study we performed in 12 animals. Then we can guarantee that the what we are presenting as the EIT results represent really what we you would see by CT.
Ok, what happened if i have an obese patient? Just to understand a little bit the philosophy of the Acosta method and the recruitability assessment. It's interesting that we can reproduce obese patients in pigs by doing this we just put some weight on the belly. I have exactly the same result as an obese patient. And then, this curve shifts to this curve. I like this very much because look at what happened. You see there is a perfect shift. Compliance gets the same maximum value. It's just because you shift everything to higher PEEP levels but you see you can use 14 of PEEP now with very little over-distension. This is the beauty of this method that is capturing this. If i had an esophageal balloon i would capture precisely this i would capture that the plural pressures increased by precisely the same amount.
I like these results because this make me very confident that we can really use high PEEP in obese patients. You're not causing any over-distension, and you are keeping transpulmonary pressures in a very similar levels. The shift is also observed when doing trendellenburg, and I like at this. Look this is the crossing point here is 11 . Just by doing this the crossing point is 16. Because now it's not an obese patient, but all the belly is on top of the lung. So, same results: esophageal pressures are going to increase by the same amount.
So then, when i see this in EIT, I know that we are we are we are doing precisely this: We are trying to keep the transpulmonary pressure at the minimum point that I don't have too much collapse and not much over-distension. Then for these patients, one of the ideas (and this is something that we can think for the future) Lauren Brochar started to do this kind of plug meetings, maybe you are aware about. The plug meetings is a kind of very nice initiative in which they are trying to do multi-center physiological studies. Which i like very much because you're collecting data not to prove that a randomized treatment is better than another. But to collect information in a multi-center fashion.
For instance, I participated in this study with the same patients the covid patients and what we did is that I was trying to checking these patients if this maneuver proposed by lauren brocha they could help us. The maneuver is something like this what he's proposing is okay you go from a PEEP of 6 you increase to 16 and then you suddenly decrease to 6. You can see here that the respiratory rate was decreased. It's important not have any auto PEEP. this is the only reason why they do this and then how this maneuver works the maneuver is something like this: You take this drop and then you can say, "look my PEEP decreased by 10 centimeters my end-expiratory lung volume decreased 1000 ml." But the compliance of the patient was just 30. You calculated the compliance here,at some peak level. Compliance of the patient was just 30. So if my compliance is 30, and I had the 10 centimeters of water changing PEEP, and if everything is linear if compliance is linear all over the pv curve, I should have a drop in end-expiratory lung volume of 300 MLS. But, I had the 1000 so this drop was 1000, you see. So then this means that my lung decreased much more than what was predicted by compliance. So then there was some what they call recruitment volume.
Recruited volume. You may think the other way around: If i increase my 10 centimeters of water, I should have an increasing volume of just 300. But I got 1000. This is because I recruited a lot of alveoli. The idea of this method so then you calculate this recruited volume divided by the expected one and I have this big number so this patient is very well recruitable. This is the recruitment to inflation ratio. A high number means that this recruited volume is much larger than what is predicted by compliance.
I think our maneuver is much better. I think it's much more once you understand the rationale, I think it makes much more sense. This idea was not mine--this idea came from Bob. The maneuver is doing the following: We just put pressure control, we increase PEEP, and then you go down. But the nice thing is that when you look at the EIT signal (which is the platysmograph of the EIT) you observe two very nice features. First, if I compare 15 of people before and 15 of PEEP afterwards, I have an increase in end expiratory lung volume. Which is precisely what Dr. Laurent Brochard is trying to measure (he's trying to measure this gain). But look what is what happened with the tidal volume: It also increased. I think the nice thing about this maneuver is now I comparing the same PEEP before and afterwards, and then these increasing compliance has to be proportional to the amount of recruitment that you got. This is also proportional, but this is also proportional. I think the problem of Laurent Brochard is that he was trying to compare this PEEP with a different PEEP. Then this is not linear, because you are not at the same PEEP level. Then you are mixturing your have a mix of gaining compliance and over-distension and then it gets complicated.
By doing this going up and down you eliminate the over distension problem and then the gaining compliance has to be proportional to the gain in recruitment.
This is what we are going to prove now, because we did the CT and EITT analysis. When the comparison is performed at the same peak level the compliancy gain is linearly related to the aeration gain and linearly relation related to recruitment that you observing the city so if your your compliance improves by 30 percent very likely you recruited 30 of the units so you go you overstand and then you go down nothing happen. This is a typically non-recruitable patient, very recruitable. The going down is very different from the going up. And decent recruitment.
Let's see on the on the tool on the Nihon Kohden Gentle Lung Tool. This is airway pressure. This is compliance. This is a typical non-recruitable patient, because compliance went down. I finish here exactly at the same point. This is a typically non-recruitable patient and the Tool is going to tell me compliancy gain zero. Now, compare with this airway pressure going up and down compliance goes down a little bit and then, boom, jumps. This is a very recruitable patient. The gain in compliance, here is 10, here is 20. So, a big gain in compliance. At the same PEEP level (you should always compare the same PEEP level). Then, wow, this patient is very recruitable. The EIT you see this image: green "gain in compliance." Again in the EIT you see I see the same signal that we have in the ventilator because we are doing almost the same. It's just proximal sensor versus non-proximal sensor.
Now, let's see the results. First of all: gain in compliance. With these animals, we tried to have a a model like a viral pneumonia. Every time we tried to do a model that is non-recruitable, I got some injury in the other lung, and then the animal was recruitable. It was it was very difficult to have a no a completely non-recruitable model. I tried to put some plugs in the airways, but then sometimes the plug would dislodge. Then we decided to do something a little bit simpler: which is the recruitable one is the normal animal with some injury. The non-recruitable was a animal that I had previously recruited and was on ideal PEEP. Then after having been in the ideal PEEP, I tried to do a recruitment maneuver on top of this and see if I have any further recruitment. This was the idea. If the animal was was at a five of PEEP, very recruitable. So compliance again calculated by the ventilator was more than 100. If the animal was previously recruited and I could I could prove it on the CT that all the units were already open, no signal of gain.
I like this graph very much--look at this. Compliancy gain at the same PEEP. This is exactly what the ventilator give us one: hundred percent gain. Forty percent gain. This is collapse reversal on the CT. You see, aall the animals on ideal PEEP are here, and all the other animals are here. I can see that, for instance, if I have at least 10 percent more units aerated in the lung, I need to have more than 35 percent. We can later on play with better thresholds, but I think this is a good threshold to use clinically. So every time you have at least 35 percent of compliancy again, you have at least 10 percent more units in the lung. And how much is your reduction in driving pressure? More than three centimeters of water.
Then this is the final result. This is my last slide. I like because this is the proof of concept: If you have a big compliancy gain, you are really recruiting anatomically. More than 10% of units get open. And this represents a reduction of three centimeters of water in driving pressure, which is clinically relevant according to the driving pressure paper. Each centimeter is four percent lower mortality. We are decreasing mortality theoretically by twelve percent.
This is the final result of all of these two. Forget about gaining volume let's present only gaining compliance. We don't need the driving pressure with that. I don't know maybe we can present in this way because we can do this correlation. We can say, oh you gain 50 percent of compliance so potentially you can reduce your driving pressure by x. You can do this calculation. If you're using the same you are not doing recruitment and choosing the best. This one i took from the maneuver not from the PEEP titration. I took from the maneuver.
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