Hello, and welcome to today's Journal Club Critical Care Medicine webcast. This webcast, hosted and supported by the Society of Critical Care Medicine, is part of the Journal Club Critical Care Medicine series. This webcast features two articles that appear in the July 2023 issue of Critical Care Medicine. This webcast is being recorded. The recording will be available to registrants on demand within five business days. All you need to do is simply log into mysccm.org and navigate to the My Learning tab. Hello and my name is Tony Gerlach. I'm a clinical pharmacist at Ohio State University Medical Center in Columbus, Ohio, and I will be serving as the moderator for today's webcast. Thank you for joining us. Just a few housekeeping items before we get started. There will be a question and answer session at the conclusion of both presentations. To submit questions throughout the presentation, type into the questions box located on your control panel. If you have a comment to share during the presentations, you may also use the question box as well. You will also have the opportunity to participate in a survey interactive poll. When you see the poll, simply click on the bubble next to your choice. And finally, everyone joining us for today's webcast will receive a follow-up email that will include an evaluation. Please take five minutes to complete the evaluation as your feedback is greatly appreciated. Please note the disclaimer stating that the content to follow is for educational purposes only. And now I'd like to introduce today's presenters. First is Professor Ravi Taiwapathy, who is a staff specialist in the Intensive Care Unit and Director of Intensive Care Research at Frankston Hospital, Frankston, and Director of Intensive Care at Peninsula Private Hospital. Ravi has worked for more than four years as a fellow in ECMO and Intensive Care at Glenfield Hospital. He published several research papers on neonatal, pediatric, and adult ECMO. He is one of the investigators of the CSER trial that compared conventional ventilation to ECMO for the treatment of severe acute respiratory failure in adults. And he's currently investigating PRISMA Login Plus, a novel low-flow E-Core device. Our second speaker is Dr. Steve Lin, who is an emergency physician and scientist at St. Michael's Hospital. He is an associate professor and clinician scientist in the Division of Emergency Medicine, Department of Medicine, with appointments at the Institute of Health Policy Management and Evaluation, and the Institute of Medical Science at the University of Toronto. He is also an adjunct professor in the Department of Physics at Ryerson University. Steve's translational research program aims to improve resuscitation and outcomes in cardiac arrest patients. Steve is an ACLS Medical Director and Instructor at the Heart and Stroke Foundation of Canada and is currently the Medical Director of the ACLS Education Program at Unity Health Toronto. Thank you for joining us today. Now I'll turn the presentation over to Ravi. Thank you, Tony, for that kind introduction for me. And I would also like to thank the Society of Critical Care Medicine for providing me this opportunity to talk to you all about the recent article that we published in Critical Care Medicine. The article that I'm going to be presenting today is on evaluating one of the upcoming therapies of patients with severe respiratory failure admitted to intensive care units using a device called HEMOLUN. This is a low-flow extracorporeal carbon dioxide removal device. I have no potential conflicts of interest to declare with this presentation. And to start my presentation, I want to inform you that recent data suggests that reducing tidal volumes as well as driving pressures on mechanical ventilation was known to improve survival in patients with ARDS and other forms of acute lung injury. However, this strategy of low volume and low driving pressure ventilation can lead to hypercapnic acidosis in some patients. And there are a number of low-flow extracorporeal carbon dioxide removal devices that are available to treat or correct this hypercapnic acidosis that is seen with low tidal volume ventilation. The problem with these devices are that there are substantial differences in their carbon dioxide removal capacities as well as their safety profiles. So not all devices are the same, and that leads to the complexity of using these devices for such an indication. The question that I want to pose to you here is, should acute hypercapnic acidosis as defined by a carbon dioxide level of more than 50 millimeters of mercury with acidosis be treated or actively corrected in patients with ARDS? I wait for a few seconds for you to complete this poll, and then I'll move on with my next slide. All right, that is an interesting poll, which I didn't quite anticipate. So it's equally distributed, but that's what I see. All right, moving on to the next slide in the talk, recent data suggests that hypercapnic acidosis is harmful. There are many studies that have confirmed or suggested this association, and a few of them were published from my group too. So if this hypercapnia and associated acidosis is harmful or is associated with adverse events, then it is logical to think that we should actively correct or treat this hypercapnic acidosis. Now, there are a few studies that were conducted using randomized control designs to see whether such a correction of hypercapnic acidosis when low or ultra-low tidal volume ventilation was used in patients with the ARDS. Now, the two studies that I want to point out today are the extravagant study that was published in the Intensive Care Medicine Journal in 2013, and the REST study that was published in JAMA in 2021. Now, the studies, although had the same aim, they had quite differences in the results. The extravagant study showed that there was no significant benefit in terms of increase in ventilator free days when this extracorporeal carbon dioxide removal was used in conjunction with mechanical ventilation. However, they found that in a subgroup of patients where their PF ratios were less than 150, the use of such an extracorporeal carbon dioxide removal device increased the ventilator free days. Now, when REST trial targeted the same population of patients where a PF ratio of less than 150 was used as an entry criteria, they found that there was a reduction in ventilator free days, which was signaling a potential harm with this type of intervention. Now, there are many reasons for the differences in these two trials. I will not go into the details because that's not the focus of the talk today, but important to note that the problems or the differences in these two studies are that the case selection was somewhat different. More importantly, the type of device that was tested in these two different studies are totally different in the sense one used the arteriovenous configuration with a higher flow rate of 1.2 to 1.3 liters in the extravent study and in the REST study, it was a low flow device that was used and patients that were recruited into the REST trial were much more hypoxic than the extravent studies. In addition to these things, the familiarity and the device management also varied significantly in both these trials and these may have contributed to the differences. Now, I would like to put another question for polling, which tells or which asks whether we should do a randomized control trial before we understand the device completely. In other words, understanding the device is not just turning the device on and turning the device off, but to really know what the device does in terms of how effective it is, what is the safety profile, and more importantly, to know what is the right group of patients that could potentially benefit from such a device. So there are four options there. The first two options say that we should do an early randomized control trial to test a device and the other two options say that we would wait for better understanding of the device before we do a randomized control evaluation. All right, so it looks like many people feel that the device is better evaluated by an early randomized control trial and that's fine. Okay, let's move on to the next question, the next slide. So what I personally feel is the device should be evaluated to an extent that we know the ins and outs of the device as well as the right group of patients who could benefit most from a particular device. And for that, we would need some amount of experience with using that device before we can test such a device in the randomized control way. As the society of critical care model says, right care for the right care right now, I feel the right device needs to be selected for the right patient and that will take some time. And this article is perhaps a step towards knowing more about a device that could be tested in randomized control trials as well as assist in routine case selection for a day-to-day case management tool. Now, in this study, our aim was to investigate the use of a single extracorporeal carbon dioxide removal device called the hemo lung in patients with acute respiratory failure. And more importantly, we wanted to identify factors that are independently associated with the patient's survival. The objectives included to present the clinical characteristics of the patients with acute lung injury treated with hemo lung and to assess the efficacy and safety of hemo lung in clearing the carbon dioxide and reducing the mechanical ventilatory supports. Furthermore, we wanted to assess the safety of this device and we wanted to compare the characteristics of patients who died in intensive care versus those who survived to better understand the characteristics of survival and to use those characteristics in a multivariable regression analysis to identify the independent factors that are associated with ICM survival. So, this is a retrospective, multi-center, multinational study that included patients treated with hemo lung for acute respiratory failure. And the data was collected between April 2013 to June 2021, so about eight years or so, from 55 centers across the world. And the inclusion criteria for including a patient into the study was to have the patient's respiratory failure as an acute, due to an acute cause, and the data should be part of the ALung registry and the discharge status should be known for those patients who are in the registry. And obviously, we excluded the patients who had chronic lung conditions because they are a different group of people and that would increase the heterogeneity of our sample. The outcomes were that we chose the physiological variables as the pH and CO2 improvement within the first 36 hours of initiating hemo lung therapy. And the secondary outcomes included reduction in mechanical ventilatory supports as evidenced by a reduction in minute ventilation, respiratory rate, tidal volumes, and peak inspiratory pressure with the use of hemo lung within the first 36 hours. ICU discharge was the other secondary outcomes, and the safety and complication profile of these devices throughout the therapy was also chosen as a secondary outcome. We used descriptive statistics to provide an assessment of nominal statistical association. An assessment of nominal statistical association. And we used linear models to summarize the changes in values over time in terms of the pH, carbon dioxide, and other ventilatory settings from baseline to various time points that I'll show you in my subsequent slides. Finally, we used multivariable logistic regression models to identify the variables that are independently associated with survival to ICU discharge. Now, here are the results. Overall, we had about 259 patients in the registry during the study period. We excluded 69 of those patients because they were treated for chronic lung conditions, and we excluded a further 31 patients because the outcome data was not available. That left us with 159 patients with acute respiratory failure who were treated with this device. Now, this is a busy slide, and I don't expect you to read every line of it, but what I can suggest is that these patients were fairly young, with a median age of 55 years, and all these patients had significant hypercapnic acidosis as confirmed by a carbon dioxide value of 73.5 median and a pH of 7.23. Now, this is the slide that presents the primary outcome of the study, which is the improvement in pH and pCO2, and as you can see, there was a statistically as well as a clinically significant reduction in the carbon dioxide levels with the institution of this device, with a subsequent improvement in the pH as well as the device was instituted, confirming the efficacy of this device in clearing the carbon dioxide. When we looked at the secondary outcomes, there was a consistent reduction in minute ventilation across the time points that we studied. That was both statistically as well as clinically significant, as well as the peak inspiratory pressures. The tidal volumes were significantly lower at the eight hours since the institution of the hemo lung device, but subsequently there was no statistically significant reduction as compared to pre-hemo lung values. Similarly, the respiratory rate showed a reduction at the eight hours of instituting hemo lung therapy. When we looked at the data between survivors and the patients who died in intensive care, there were a few important characteristics that was available to us that could help in multivariable analysis, and these included the age of the patients. Patients who died in intensive care were much older, and also they had the diagnosis of COVID-19 respiratory failure. And furthermore, these patients were more hypoxemic with the requirement of higher oxygen and obviously a lower PF ratios too. Interestingly, the management of these patients also differed in the anticoagulation targets that were chosen. Patients who died did not have a recommended target of anticoagulation as per the manufacturer's instructions. So these may have contributed, but we have to be careful here to make strong assumptions because these are unadjusted data. When we looked at the complication profile of patients who died versus survived in terms of device-specific complications, like circuit thrombosis or other issues with the device, there was no significant difference between both the groups, and the blood product requirement also was not significant between patients who died to those who survived to the intensive care discharge. When we used the multivariable regression analysis model, there were some of the characteristics that came out to be independently associated with intensive care survival, and these include age of the patients over the top and the PF ratios as well as COVID-19 ARDS. Essentially, people who are younger had a higher survival, and that is not particularly surprising. But what is more interesting is PF ratios also are associated with independent survival. In other words, this study highlights the fact that patients who have a low PF ratio are unlikely to do well when this device is used to assist their respiratory failure. And this is one of the problems of the REST trial where they targeted patients with lower PF ratios. Had the results of a study like this were published or were made aware to the investigators, perhaps they may have chosen a different target of patients to be tested in a randomized control trial. COVID-19 ARDS obviously had an increased risk of mortality, and there are many reasons for it, and I'll not go through that at this stage. When we compared or when we assessed the robustness of this model for its discrimination, it showed a very good discrimination with the area under the curve of 0.83 or so, making that the discrimination of the model was quite good. So the strengths of this study are that this is the first study to date that specifically identified the independent association of variables that could predict survival in patients who are treated with extracorporeal carbon dioxide removal. And more importantly, this study investigated a single e-card device, and it chose to include patients only of respiratory failure due to acute conditions. And this significantly reduces the heterogeneity and gives a clear information in terms of the efficacy as well as the safety of the device. The other important aspect is that this is real-world data, and this confirms the physiological outcomes and the patient-centered outcomes that we studied that shows a significant benefit with the use of device in terms of improving the CO2 and correcting the pH when patients had acute hypercapnic respiratory failure. And such data, I believe, will provide significant clinical insights into the safety and efficacy of the device. And this study is a multi-center and multinational study, so it can be generalizable to other centers that are practicing e-card. And I believe that this will help in case selection for routine clinical practice as well as possible future randomness control. There are some limitations that are associated with the study, and some of them are that the retrospective nature of the study has potential bias for selection, and we have only included patients that were submitted to the registry, and it is likely that there are some patients who were not submitted to the registry, and thereby the results may not be really that accurate in terms of the overall outcomes. And we also had restrictions in the data that was available, and it was largely restricted to the first 36 hours on the blood gases as well as the ventilatory settings. And also the survival data was only limited to the intensive care unit discharge, and it would have been more helpful if we had more longer-term follow-up data too. To conclude, I would like to say that this article suggests that with the use of hemolung extracorporeal carbon dioxide removal device, there was a significant reduction in mechanical ventilatory support with an improvement in hypercapnic acidosis. And the factors that are independently associated with intensive care unit survival include a PF ratio of more than 100, the age of the patients, and non-COVID-19 CRDs. I conclude my presentation at this stage, and I would like to now turn it over to Dr. Stieve Lin to present. I thank you for your attention. Well, thank you so much, and again, thank you for the opportunity to present at this month's Journal Club. So the study that I'm presenting for Journal Club is called The Effect of Time-to-Treatment with Antiarrhythmic Drugs on Survival and Neurological Outcomes in Shock Refractory Out-of-Hospital Cardiac Arrest. There are a couple of disclosures I'd like to point out. On the co-PI of a pre-hospital epinephrine trial looking at various doses, the trial is called the Canrock Epinephrine Dose Optimal vs. Standard Evaluation Trial, and it's sponsored by the Canadian Institutes of Health Research, as well as I've previously received salary awards from CIHR and the Heart and Stroke Foundation of Canada. So it's been estimated that with every minute delay in defibrillation and CPR, the probability of surviving cardiac arrest decreases by about 7% to 10%. And again, in terms of definition, defibrillator shock alone that fails to terminate abnormal heart rhythms or abnormal heart activity in patients has been termed as shock refractory cardiac arrest, and current treatment guidelines recommend the use of lidocaine or amiodarone during resuscitation for shock refractory cardiac arrest. Now the data that we're looking at was derived from the North American Resuscitation Outcomes Consortium. Now this was a large North American consortium of 10 various sites within Canada and the United States, which collaborated to perform large pre-hospital clinical trials. The data that we're using for this study was derived from the Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest Trial, or the ALPS trial, that was published back in 2016. Now the population that was used here was looking at patients with persistent or recurrent VF or Pulseless V-Tach after more than one shock, those that had vascular access through an IO or IV, and then were randomized to either receive Amiodarone, Lidocaine, or Placebo, and the primary outcome was to survive the hospital discharge. Now this was a per-protocol analysis that was defined by the authors. Now they had randomized more than 3,000 patients, the groups were slightly different in terms of numbers. The Amiodarone group had 974 patients, Lidocaine 993 patients, and Placebo 1,059 patients. The conclusions were that overall, neither Amiodarone nor Lidocaine resulted in a significantly higher rate of survival than Placebo in patients with out-of-hospital cardiac arrest. What was interesting in this trial was that looking at the subgroup of bystander or witness cardiac arrest, there was a difference in terms of survival looking at Lidocaine and Amiodarone, which really posits us to think about whether there is the potential of timing that may have affected patient survival and their outcomes. So the objective of this study was to describe the relationship between time-to-treatment with antiarrhythmics in patients with out-of-hospital cardiac arrest and survival of hospital discharge and good neurological outcomes defined by the modified Rankin scale of 3 or less at hospital discharge. We wanted to explore whether the above relationship was modified by treatment type. Briefly, we used multivariable logistic regression to examine the association of treatment groups and time-to-treatment with survival outcomes. We used an exploratory interaction term between treatment and time-to-treatment, and that was tested in our models. In our adjusted analysis, we also added other prognostic factors, which were primarily the youth-themed factors, sorry, standard youth-themed variables that included age, sex, witness status, location, bystander, and bystander CPR. This is the Table 1, so patient characteristics based on outcomes in the treatment arms. As you can see, the proportion between the three groups as well as their values are fairly similar between the three groups with no significant differences between the three arms. What we're seeing here is looking at the time from 911 call to first dose of the ALPS drug, which could be amiodarone, lidocaine, or placebo, against the probability of survival to hospital discharge. The red line of placebo, as you can see in the graph, amiodarone, the black line, is consistently having a higher probability to survival to hospital discharge compared to placebo. When we looked at lidocaine, you can see that the line of lidocaine actually crosses both the placebo and amiodarone arm. If we were to break this down and separate them, this is the adjusted odds ratio for survival to hospital discharge between each of these comparisons. For amiodarone versus placebo, we can see that the adjusted odds ratio was consistently higher than placebo at all time points. When we looked at lidocaine versus placebo, lidocaine had a higher odds ratio of survival only at later time points compared to placebo. And when we compared lidocaine to amiodarone, again, we see that lidocaine showed improved survival only at later time points, while amiodarone had better survival at earlier time points. A similar analysis was done looking at good neurological outcomes at hospital discharge. And as you can see, similar to our survival to hospital discharge figures, the lines look quite similar, where amiodarone had consistently higher probability to survival compared to placebo, while lidocaine had lower survival and then crossed and had higher survival at later time points. When we break this down, looking at the adjusted odds ratio again separately, we can see a similar pattern, where amiodarone was better than placebo at all time points, lidocaine was better than placebo and amiodarone at later time points. So, showing that there's decreased survival for longer periods of longer times to drug administration really represents what we term as resuscitation time bias. So, it's not necessarily that the time to drug administration caused, sorry, led to what we're observing, but rather time to drug administration is also time to actual treatment. So, earlier interventions may actually represent earlier treatment, which is why we see differences between when we look at all three groups, amiodarone, lidocaine, and placebo, where earlier time points have better survival compared to later time points overall. So, when we look at shorter times to drug administration, survival was not different for, sorry, lidocaine versus placebo, where survival was higher with lidocaine than placebo after drug administration at later time points. Now, when we try to think of possibilities of why this is, is that patients with myocardial infarction or myocardial ischemia more likely had symptoms prior to cardiac arrest, where they might have called 911 at an earlier time point. Therefore, they might have had a shorter time to treatment if they ever went into cardiac arrest. And understanding that lidocaine may also increase the risk of asystole in myocardial ischemia patients. Also, from a pharmacological perspective, later in BF, conduction is already slow in the myocardium, and so the myocardium may be more responsive to further sodium channel blockade, which may be shown, which may represent that lidocaine may be more affected during this period of time. Of course, there are several limitations to the actual study itself. Being a secondary analysis, it's actually quite thought-provoking, a hypothesis generating in terms of why we're seeing what we observed. Again, the definition of shocker factor cardiac arrest that we use, what the ALPS trial used is, it's not consistent, it's not, it's not consistent with other published studies. And so we have to take that with a grain of salt. And for the ALPS trial, being a protocol analysis, they were underpowered in their, to determine their outcomes. So this also needs to be thought about as you interpret our results. So, in conclusion, what we saw was that amyloid improved survival over placebo at all time points. Lidocaine improved outcomes over amyloid and placebo only at later time points. And we think that prospective studies would be needed to better define the optimal time of drug administration in out-of-hospital cardiac arrest patients. And thank you. I believe that we'll move on to a Q&A session. Well, thank you very much to both Ravi and Steve. Those were a very great presentation. For the audience, if there's any questions you would like to ask, please type them in the questions box located on your keypad, and I will start with the first question. This one goes to Ravi. Why do you think COVID ARDS had lower survival? And do you think that that presents a different phenotype of ARDS? That's a very interesting and a very relevant question for this talk. Tony, thanks for asking that. There are several reasons for that. And I guess some of them we really would not know. But what we know is that COVID ARDS, especially when this device was used in the United States largely, was pretty early in the process of that pandemic. And at that time, there were no COVID-specific therapies. That would be the first thing. The second thing was the healthcare system was overburdened when there were too many patients admitted to the intensive care units with acute respiratory failure. And an overburdened system may not have performed as well as perhaps an optimally or usually burdened healthcare system. The third thing is also that COVID-19 strain, at least the earlier parts of the strains, were much more virulent. And that may have increased the mortality too. And also at that point in time, there weren't any vaccinations as well to prevent the infection or reduce the mortality and morbidity. So a combination of all these things could have accounted for such an increased risk of mortality. And from my observation, although I'm not an expert in COVID-19 ARDS, these patients were much more hypoxemic too. And such a hypoxemic patient is better managed on extracorporeal carbon and extracorporeal membrane oxygenation, which is full-form echo as compared to a low-form echo. Well, thank you. I think you bring up some very good, interesting points, especially with COVID and how it totally taxed our healthcare systems around the world, for sure. And I was just wondering, as a follow-up question, did you see any survival trends based on the year enrolled? And if so, what do you think these trends were attributed to? Potentially using it earlier on in the ARDS disease state or anything such as that? We did think about analyzing the data on a yearly basis to see whether there are any significant trends that we could notice or learn from. One of the problems that we had with this data was that the data was not a fairly large data. We only had about 159 patients over an eight-year period. That leaves with us about 18 to 19 patients per year. And to complicate things further, COVID-19 was there in the last part of the study period. And that way, the data, whatever, even if we have analyzed that way, not have really reflected truly as to what is the time relationship to the survivor. So we did not really analyze the data, but obviously with a larger data set and perhaps a better understanding and better outcomes of COVID in at least the last year or so, we definitely would be interested in looking at such outcomes on a yearly basis. Well, thank you very much. Steve, I do have a question for you. It's not surprising that delayed treatment led to worse outcomes. And your data makes a case for early amiodarone use. But really, when do you think lidocaine shouldn't be administered? Yeah, that's a very good question and somewhat tough to answer. There are numerous studies that show that lidocaine does improve ROSC overall. But when you look at our study, looking at the timing of drug administration, it really does appear that lidocaine has better effects when it's given at a later stage. So not really early in the cardiac arrest, but at a later time point. And we're looking anywhere from our data shows that anywhere between 15 to 20 minutes, if you're comparing whether you would like to use lidocaine versus amiodarone. Well, thank you very much. I do have a question for you, Ravi, from the audience. Can you speak to the average time frame that these patients required E-Corps? And are there plans to study these patients who required it past the 36 hours in your study? Sorry, the first part is the average time that we used the E-Corps or the average time. I didn't get the first part of the question. Yeah, the first time was, can you speak to the average time these patients required E-Corps? They're required for about seven days or so. And this is slightly larger than what was used in this trial too, which means that, you know, perhaps patients who are unwell will need E-Corps for a longer period of time than the shorter period of time. Well, thank you very much. I think, Steve, this question is for you. The discussion on lidocaine helping preventing re-fibrillation is very interesting. Regardless of the cause of cardiac arrest, is ongoing myocardial ischemia with prolonged CPR something that we should be more concerning about to clinicians? Yeah, it's a good point. As you know, and everyone who does cardiac arrest or manages cardiac arrest, it's such a messy environment with lots of different causes. I think it makes sense right now that during resuscitation, during CPR, you have to choose an antibiotic that works. And as you get ROSC, although there are no clear clinical studies that show which antibiotic is better at preventing re-fibrillation, it may be that amiodarone might work a little bit better in preventing re-fibrillation, mainly because there may be prolonged ischemia and there's potential negative effects of lidocaine in patients that have myocardial ischemia. Well, thank you. And I'm also truthfully eagerly awaiting your epi study you're looking at. Because one of the last code situations, personally, I went to, I didn't realize until afterwards the patient had, he had bad cardiovascular disease. Cardiovascular disease. And I think with his PEA, we gave him way too much epinephrine. So I think these can actually help us care for our patients a little bit more in the hospital as well. And with that point, how do you think the results of these data should be extrapolated to in-hospital cardiac arrest? Yeah, so what was previously thought was that the in-hospital cardiac arrest world was very vastly different than the out-of-hospital cardiac arrest world, mainly because of comorbidities they've been admitted. They're admitted patients mainly because they're already sick. But as time has gone on and we're looking at prospective registries, the differences are less than what was previously thought. And so when you're thinking about myocardial ischemia leading to cardiac arrest, patients in the in-hospital world as well as the out-of-hospital can have myocardial ischemia leading to cardiac arrest and should be treated fairly similarly in terms of cardiac resuscitation drugs. So I think this can likely be extrapolated fairly well to what we're seeing from this study to the in-hospital world. Well, thank you very much. And Ravi, one last question for you. Why not surprising those with a PF ratio of less than 100 or more likely to survive to hospital discharge? How can the selection of E-corp be changed to really improve the outcome? So this study shows that PF ratios of less than 100 are not really suitable for instituting extracorporeal carbon dioxide removal therapy. And such patients should be managed on a full form of cardiorespiratory support with extracorporeal membrane oxygenation. Now, this is an important point because when we choose this device, we have to be mindful of what this device does and what exactly the patient will need. This study says that if patients have moderate to mild ARDS with PF ratios of more than 100 and realistically speaking more than 150 or 200, they will benefit more from such a device. So it helps in device selection significantly. And it's using this in patients who are extremely hypoxemic can be in a way harmful for the patients and perhaps should not be used based on this data until there is further data to clarify its role in such type of patients. So essentially it tells that, you know, people with severe respiratory failure should not be managed with this. And they should be perhaps treated with ECMO based on other published data as well. Well, thank you very much. And Steve, I got another audience question from you. The point was made that amiodarone may increase the QCC interval. So is this reason why amiodarone can increase the interval? Is that why it's best to use lidocaine later on in the course of ACL? I'm sorry, you cut out there, which interval was the question describing? Amiodarone potentially can increase the QCC interval. And the audience asked is that partially part of the reason why lidocaine might be better in prolonged ACL situation? Yeah, I think so. I think that's a good hypothesis when we're thinking about it. That with prolonged ischemia, there are many electrolyte abnormalities. The heart is going to different rhythms, particularly the potential of a long QT. That may be part of the reason as well where amiodarone does not appear to be as effective as lidocaine during that time period. Well, thank you both. And I would like to thank our audience and both Steve and Robbie for excellent presentations today. That concludes our question and answer session. And thank you for you guys for attending. Again, everyone who joined us today for the webcast will receive a follow-up email that will include an evaluation. Please take five minutes or so to complete the evaluation. Your feedback is greatly appreciated. And thanks again for joining us today.

webcast

Hemolung

respiratory failure

ventilatory support

ARDS

antiarrhythmic drug treatment

cardiac arrest

optimal timing