COVID-19 question and answer call. This is the third of six in a series of COVID-19 question and answer calls. My name is Marilyn Bullock and I'm an associate clinical professor of pharmacy practice and the director of strategic operations at Auburn University Harrison School of Pharmacy and an adjunct associate professor at the University of Alabama School of Medicine and the University of Alabama College of Community Health Sciences in Tuscaloosa, Alabama. This webcast is being recorded. The recording will be available to registrants within 24 to 48 hours. To access, please go to covid19.sccm.org slash webcast. A few housekeeping items before we get started. To submit questions throughout the presentation, type into the question box located on your control panel. Please note the disclaimer stating that content to follow is for information or educational purposes only. The data has not been peer reviewed. It is based upon small sample size with key aspects of information missing and a single center experience. Advice is based on expert opinion. And now I'd like to introduce your speakers for today. Dr. Ashish Khanna is a staff intensivist and anesthesiologist and associate professor of anesthesiology and associate section head for research within the department of anesthesiology, the section of critical care medicine at the Wake Forest University School of Medicine in Winston-Salem, North Carolina. We also have Dr. Robert David Stevens, who is an associate professor in Johns Hopkins University with appointments in anesthesia and critical care medicine, neurology, neurosurgery, and radiology. He also serves as an intensivist and a neurointensivist at Johns Hopkins Medicine in Baltimore, Maryland. And finally, Dr. Pedro Salinas is an intensivist at St. Luke's Aurora Medical Center in critical care services and is a clinical adjunct professor at the University of Wisconsin School of Medicine in Milwaukee, Wisconsin. And now we'll get right into it with questions from our attendees. So we have several questions today. The first one is for Dr. Khanna. So Dr. Khanna, there's been a lot of discussion about proning in these patients. And is there any information that you can talk to us about proning in patients who aren't intubated or people doing this? Are they seeing any benefits? Yeah, Marilyn, that is a great question. Like you said, there's been a lot of discussion as regards proning and awake proning, as we call it, or self-proning, asking these patients to literally sleep on their belly for three to four hours and sort of give them a break after that has been seen to improve oxygenation. And that comes out of experiences across the country where we've, and I have done the same in my practice. And you can actually see patients go from borderline oxygenation, O2 sats in the high 80s, low 90s to all the way up to 96, 97 on the same amount of oxygen, nothing else changes. So physiologically, it makes a lot of sense. As we all know, it improves the VQ mismatch. It also allows oxygenation of areas of the lung that were previously not getting as well oxygenated when patients are laying supine. So lots of sense physiologically. And certainly it buys us time. I've seen a lot of patients who I would have otherwise gone ahead and placed them on mechanical ventilation, especially knowing that there is no bridge to non-invasive ventilation in these patients. So really, they reach a point on their oxygenation journey and they're not getting better. You're forced to intubate them. Self-proning has allowed us to buy time and hopefully for some sort of recovery period for them so they don't end up getting intubated. Now, the second part is slightly controversial because we don't know whether self-proning really is just delaying the inevitable, which means that, well, they'll continue to improve oxygenation to a certain point, but ultimately, they'll still end up getting intubated, in which case, should you just go ahead and intubate them early versus do the self-proning? And I'd love to answer that question in a more scientifically rigorous manner, but for now, I believe we're in self-proning and I think it makes a lot of sense, even if you can probably avoid intubation in one out of several patients. That's very interesting and definitely a different approach than we're, I think, used to using. Now, since we're on the topic of ventilation, Dr. Stephens, what are some general recommendations in non-invasive ventilation in patients who have moderate respiratory distress, so people who don't have ARDS? Hi, yeah, so that's an excellent question because you're referring to potentially a very large subset of patients who are hospitalized with COVID-19, the ones who have moderate, moderately severe disease who are not clearly requiring invasive mechanical ventilation. Can we support them with other means? And I would say most definitively, yes. So obviously, this would start with just supplemental oxygen either through nasal cannula or using a face mask. And this is actually sufficient in a significant proportion of patients. And those who appear to be failing, I think at this point, you reach a sort of decision fork in the road where you have to decide, are we going to proceed with invasive mechanical ventilation or should we try a more aggressive form of non-invasive respiratory support? And so the options for the latter would be high flow nasal cannula, which can deliver up to 30, 40, 50, 60 liters per minute of warmed, humidified air or non-invasive ventilation using, for example, a BiPAP machine. So I can only speak to our experience here at Johns Hopkins. We have made significant use of the high flow nasal cannula and we have found that that in combination with self-proning is an extremely effective intervention, which in our experience, again, this is largely anecdotal, has allowed us to, we think, to avoid going to invasive ventilation in a subset of patients. As far as the non-invasive ventilation, for example, using BiPAP, we've decided as a group of intensivists here to not use this strategy because of concerns about dissemination and aerosolization from these infected individuals. And so I don't have a lot of experience with BiPAP in this population. I do know, and I can report this having spoken at length with several of my colleagues in Italy, where they use these so-called helmets. And you perhaps have seen these photographs where they look sort of like astronauts. So it's essentially a device that delivers positive pressure ventilation non-invasively, but it essentially encases the entire head and part of the sort of, and the neck. And so it's a way of delivering non-invasive positive pressure ventilation. And the Italians claim that this is highly effective in a subset of COVID patients. I personally don't have any experience. And I think this is a device that's not widely used in the United States. Interesting to see what kind of things are maybe coming down the pipeline there. Dr. Salinas, have you had any different experiences with non-invasive ventilation in your practice? So I think I'm gonna echo some of the comments by Dr. Stephens. And I think we initially, we thought that we had to do early intubations for those patients. And we're moving the patient from the floor to the ICU when they're on six liters. And then we learned that it was very difficult to extubate these patients. And many of them require re-intubation. And we were avoiding initially high-flow nasal cannula. As more data was available and we knew that the risk of aerosolization was not increased and then can also be mitigated with a surgical mask. We also have been having the same experience as others using the high-flow nasal cannula that in many patients can avoid being intubated. So it seems like everyone has had a fair amount of experience with nasal cannula and high flow. But Dr. Khanna, going back to proning, do you have any recommendations for how this might be able to be accomplished with BiPAP or CPAP if people do need to use those options? Well, honestly speaking, like the rest of the group here, I'm not practicing non-invasive ventilation on these patients just because the concerns with viral dissemination, the risk to the care providers is just difficult to justify using BiPAP and CPAP on these patients. So for me, just best practice right now is to go up to a high-flow or a non-rebreather and then that's not working, try self-proning. And if none of the above works, then yes, mechanical ventilation is the option, but I have essentially taken out the non-invasive ventilation from practice for these patients. Thank you. This is some very good information there. This next question is also directed for Dr. Khanna. There's been a lot of talk about permissible hypercapnia in these patients. Can you discuss the range or ceiling that you feel comfortable with in this population? Yeah, so Marilyn, I have kept these rules fairly simple for myself. You know, I would treat them based on the ARDSnet guidelines and stick to permissive hypercapnia as long as it's not affecting my pH and the pH doesn't drop really low. I allow CO2 to climb all the way up to 60, 70, even 80, depending on individual patient tolerance. And again, you know, interestingly though, I have not had, you know, probably the phenotype of ARDS that I've seen, I have not had a lot of lung compliance issues, although I have kept tidal volumes low and that has led to permissive hypercapnia, but on the other side, typically dealing with the stiff lung kind of ARDS. So yes, permissive hypercapnia, but mostly not very different from standard ARDS management. Very good, and so, you know, the best thing that we can hope for our patients is that they're gonna get better. So Dr. Salinas, when you have a patient who has had ARDS and they get better, how do you go about weaning them off the ventilator? I mean, it's normally a pretty labor intensive process and involves lots of different professions, the nurse, the respiratory therapy, physical and speech therapies. Do you bring all these people into the isolation room to work with the patient? What is your process? So let me just give you a little bit of background where I'm working. Right now we have a COVID dedicated unit of 24 beds. We have another extra unit. We have a total of six units ICU. Right now we're operating at around 70 to 90% capacity. And we have roughly between 40 to 60% of our patients who are mechanically ventilated. And I think we have been seeing the whole spectrum of lung injury from the preserved compliance, you know, hypoxemia to the typical ARDS that requires a strict tidal volume and the heavy sedation and neuromuscular blockers. And those patients stay with us for many weeks. And actually some of them, we have performed tracheostomies. We, currently we consider the patients to be contagious and we adhere to N95s and or PAPRs with eye protection and the gowns, you know, that we use the impermeable gowns when we do any irisolization. Once the patient is ifebrile for three days, we repeat the test and then we consider, you know, changing it to droplet. In terms of how many people are in the room, we need a team, but at the same time we try to minimize. So for example, for intubations, there's the person who's intubating the patient, the RT and the nurse, and there's two other people outside the room for backup. But it depends on the procedures we have. We have protocols for different procedures. Interesting. And you bring up a good point, Issa. Do you feel like that you consider these patients still contagious? Dr. Khanna, what about at your facility, if you have somebody who's been on the ventilator for two weeks or more, you know, beyond that magic 14 day window that we've all heard about, do you still consider those patients to be contagious when you use your ventilator weaning approach? Or do you feel like the virus has run its course and that they're no longer shedding the virus? And how does that impact how you'll extubate the patient? Yeah, Marilyn, you said the right word. So the magic two week window, right? So even though we feel it's that two week window, we know that there is no conclusive evidence one way or the other that viral shedding stops at two weeks or goes on three or four weeks. As we've heard from data coming out of other countries, it might go on for about three or four weeks. Now, typically, we do not retest our patients. Typically, we look at clinical features. So if they're otherwise better, which means in an intubated patient, you know, their pulmonary status is improving, their otherwise meeting weaning criteria, they've been afebrile for at least 72 hours. And their inflammatory markers are down. That sort of fits the big clinical picture that you could at best guesstimate say, hey, you know, likely this patient is not an active viral shedder. Having said that, at least in my institution, extubation is regarded as a high, high risk procedure in general. So whether someone's a week out or three weeks out, we are still presuming them to be positive and not just be positive, be active viral shedders. So we are assuming the same personal protective equipment policy, whether you're a week out or three weeks out, just because extubation in and of itself is just such a high risk procedure. And you bring up such a good point about how we don't yet have a definitive answer on how long the virus does shed. I wanna shift gears just a little bit and ask you, Dr. Khanna, what are your ventilator strategies when you have a patient who's on ECMO and also has COVID-19? So your typical ventilator strategies, again, are not very different from ARDS or respiratory failure management. We typically put them on the so-called rest settings, where we essentially allow the lungs to rest using either five and five or 10 and 10 of CPAP, just running some CPAP through the ventilator and allowing the lungs to rest as much. There is some thought that modes such as APRV might be beneficial in these patients. Again, there is no conclusive data to suggest that ventilating them on APRV leads to improved outcomes. So I assume them to, like, again, as I'm managing ARDS, I'll keep them on rest settings. I'll allow there at least 24 to 48 hour periods of my VV ECMO circuit to take care of the oxygenation part first. And once I'm going down on my sweep and things are looking okay, and otherwise there is an improvement in their overall status, then I'll start being more aggressive with trying to see what I can do with the ventilator and allow them to breathe on the ventilator a little bit, inch forward in that veening process. Dr. Stephens, do you have a similar approach at your facility, or do you look at it a little bit differently? Yeah, so I think one thing that emerges from this discussion and also discussions with intensivists across the world is that COVID-19 is an extremely heterogeneous disease. And even if we focus exclusively on those patients with acute respiratory failure that are the ones that we see in the intensive care unit, I don't know that we can apply general principles and standardized care in a way that would be satisfactory to some of us. And I'm speaking particularly about the physiology of COVID-19 pneumonia. I think what has been quite clear in our experience and in the experience of others is that some of these patients do indeed develop a physiology and a clinical and radiographic appearance that is highly consistent with ARDS, with poor compliance and severe hypoxemia and evidence of alveolar involvement. But I think we're also seeing that there's a subset of patients who really don't fit into that category. They have normal compliance. If you look at their imaging, the amount of parenchymal involvement doesn't match the severity of the hypoxemia. And so the question is what's going on in these other patients, who I think are quite a significant number of the ones that we see. Our impression, and I think that of others, is that there could be a very significant vascular contribution to the respiratory failure that is occurring in these patients. And this vascular contribution could occur by means of pulmonary microemboli, which have been described in several reports, or abnormal endothelial activation in the lung, and potentially also abnormal vasoconstriction or vasoregulation of the lung vasculature. And I think quite a few people now are realizing that there is a significant subset of patients with COVID-19 pneumonia and respiratory failure who do not have ARDS and who actually have probably a more vascular-mediated type of respiratory failure. And in those cases, I would think that the strategy of ARDSnet-type ventilation with very small tidal volumes and high PEEP may or may not be effective. I think this really needs to be resolved through clinical trials or potentially through bigger, you know, larger-scale observational studies. But I'm not convinced that all patients with COVID-19 pneumonia and hypoxemic respiratory failure necessarily need to be on the strict ARDS-type protocol. So I wanna bring in Dr. Salinas on this discussion about ECMO and the ventilator. Have you seen that ECMO's been shown to assist with COVID-19 patients when proning's not possible? So it's an interesting question. Actually, we reserved six beds for ECMO purposes in the cardiovascular unit, one of our ICU units, but we haven't done a single case yet. Even though we have more than 60 patients coming to our ICUs, we haven't had an ECMO case yet, so I cannot comment about it. Can any of our other panelists comment? Yeah, so at Johns Hopkins, we currently have five patients, COVID-19 patients who are on ECMO. We've applied, in general, the same principles in terms of patient selection as with non-COVID patients. These are all patients who are on VV-ECMO. All of them had severe refractory hypoxemic respiratory failure, refractory to maximal, conventional mechanical ventilation, maximum sedation, proning, neuromuscular blockade, you name it. All those things were applied and were ineffective. And then also the consensus had to be that these were patients who were salvageable, and that depends to a large degree on the existence of comorbidities and the age of the patient to some degree. So right now we have five. I think in total we've done, I think, seven patients, ECMO patients with COVID at Johns Hopkins. That's- Yeah, and I'll- Mostly, sorry, I didn't mean to jump in there. No, go ahead, doctor. Yeah, so I mostly share a similar experience as Dr. Stevens, even though we haven't had as many patients, but we've kept almost exactly the same criteria for patient selection as we would keep otherwise for our VV ECMOs. Now we've been, we've obviously tried to be very stringent about ruling out cardiogenic shock in these patients. You know that the viral syndrome is notorious for like a late onset cardiogenic shock, and we've been very particular about that. I mean, we do, the only patient we have right now in VV ECMO is a pretty interesting case in and of itself. And without revealing too many details, I would say that it's, you know, if someone is super morbidly obese, but is otherwise healthy and is fairly young, then that becomes a huge decision-making challenge. And that is the patient I have on VV ECMO right now. But, you know, these are some of the challenges. For example, I have other colleagues who've had to, for example, you know, think about tracheostomies in these patients. I've had other colleagues who had to think about obstetric patients needing advanced respiratory management, and how do you deal with that? So I guess the whole picture, as Robert appropriately put, is not as simple as ARDS. Truly, there's other factors, and we do know that there is a high compliance phenotype as well, which makes things slightly more complicated and obviously we start thinking about things like hypoxic pulmonary vasoconstriction and so on and so forth. Interesting. Dr. Salinas, did you have something else you wanted to contribute? Yeah, no, I think that probably we share similar, you know, protocols for ECMO. We just haven't had those cases of refractory hypoxemia that usually will respond to different strategies on the ventilator or nitric oxide or proning. And the few deaths that we had, they have been late in their hospital stay. Now, one of the discussions that seems to have really dominated the news and discussion boards was the lack of ventilators. And I know many places were discussing putting multiple patients on a single ventilator. Dr. Khanna, is this something that you've done in your practice, and how do you handle having multiple patients on a single ventilator? This is probably the most controversial question of the entire webinar, right? I will say that when all this discussion initially started, you know, you and all the audience probably knows that the societies come out with a joint that, you know, we don't endorse practices like these. There's huge safety issues with trying to ventilate multiple patients on a single ventilator. Again, you know, I'm not sitting in a hot spot, so we've not had to go to that option and not even be close to going to that option. It was certainly not one of those things that we would have done. However, you know, my colleagues in New York City probably have some different stories to tell us. I have heard of and seen multiple such devices and innovative mechanisms of trying to ventilate two or more patients using a single ventilator, but I will say that it is, you know, again, you know, it's a risk-benefit situation. If I were in a situation that I absolutely ran out of every single mechanical ventilator in the hospital, including operating room ventilators, which we know can be used as ICU ventilators, then it would be a choice between hand-ventilating someone versus putting two patients on a single ventilator. I am probably more conservative. I would still probably use the option of hand-ventilating someone for a little bit of time until I could re-triage my resources. Other people might choose the two patients on one ventilator, but, you know, as we can all imagine, there is huge issues. We were just talking about how different one COVID-19 pneumonia is from the other, so you can well imagine trying to ventilate two or three sets of lungs with one basic setting on a ventilator, or even if you had the option of regulating airway pressure and PEEP and so on and so forth, I don't know how well you could do that by splitting circuits. And then, most importantly, what sort of resource drain would it place on your ICU nurses and respiratory therapists? I mean, that part people don't often think about. It's not just about putting multiple patients on one ventilator. It's about who's going to take care of them, and are they going to be confident enough to do it without causing more problems or inadvertent accidents? So, and then the whole weaning piece is a whole different story when you're trying to, hopefully not trying to wean multiple patients out of a single ventilator. So, I think it's complicated to different layers of imagination. Again, I would probably choose to stay away from it, but I think it's, in the end, it's also a little bit a matter of personal choice and how deep you want to go into the risk versus benefit discussion. Thank you. If I might, this is Robert Stevens. If I could just add, I agree with what Ashish is saying. I think the use of a single ventilator for two or more patients refers to a truly dire scenario of resource depletion. And quite honestly, despite many concerns and missteps, I think we haven't reached that scenario in most places in the United States. And so, I think it's kind of a theoretical question. I know that it was raised by some of our colleagues in New York City, but I would say that outside of that context, I can tell you, for example, in the state of Maryland, we currently are at 33% of ventilator capacity. So, that means, and most of the projections indicate that the peak of cases is behind us. So, we don't expect ever to have to go there. I also should just add, and perhaps you could comment on this too, Marilyn. It seems, I think, that the STCM issued a pretty clear sort of recommendation about 10 days ago, strongly against, recommending against the use of a single ventilator for multiple patients. I think there was a statement that was released by the STCM. Is that correct? I haven't seen that, but I think I've seen several statements in their guidelines. So, I'm gonna trust that what you said is correct. I'm pretty certain that they made a statement, unless they contradicted it since, but I think about 10 days ago or maybe two weeks ago, the STCM issued a statement about use of single ventilators for multiple patients, and they were quite firmly against it. Well, let's shift gears a little bit to maybe a different topic other than ventilators, because a lot of discussion has revolved on how we treat these patients, what kind of medicines and therapies do we use? And one of the ones that seems to have garnered a lot of attention, especially in the past couple of weeks, has been convalescent plasma. So, Dr. Stephens, can you talk to us about what the latest research is on plasma therapy? Yeah, it's an excellent question. Just for context, this notion of taking the serum of a patient who's recovered from an infectious disease and extracting the antibodies that are directed towards the pathogen, this is something that goes way back, more than 100 years. It's sort of intuitively quite simple, and it has been used in the past to treat other infectious diseases during the sort of period of time when more specific therapies have been developed. As far as the use of convalescent serum for patients with SARS-CoV-2, I'm aware of a single case report that was published in the New England Journal of Medicine, I think, maybe 10 days ago or two weeks ago, in a series of patients in China. And the results indicated that, I think, out of these five patients, I think four had quite a rapid and full recovery. So the early data was very, very promising. And as a result, there are many, many randomized trials that are currently ongoing to evaluate convalescent serum as a therapeutic intervention for COVID, for severe COVID-19. I am not aware of any of those randomized trials being published yet, but I expect that over the next few months, we will see these papers appearing. And I think we will be able to make a more informed opinion about whether this is an effective therapy. I would say that the preliminary data is quite promising. Just at Johns Hopkins, we have, right at this current time, I think we have four separate clinical trials that are ongoing evaluating different modalities of convalescent serum. So there is a great deal of interest, there's enthusiasm. It may turn out to be an important therapeutic intervention, at least in the short term, until we discover more specific therapies. And you bring up a good point. I'm only familiar with that New England paper as well. But one of the things I've noticed is that a lot of the studies that are coming out are now being made available to the public, not in our traditional published peer-reviewed format, but on these medical repositories that don't have the same scientific depth. So Dr. Salinas, let's say some of this data did become available in these repositories just to get it out there. What level of evidence do you feel is comfortable to say that it's advisable to use plasma from COVID-19 patients to treat newly infected patients? Oh, this is an interesting question. I think, I mean, as Dr. Stevens stated, I mean, there are no, currently there are no recommendations, and the NIH also has no position that the new guidelines that were released recently, and everything is limited to reports and case series. Actually, the criteria that we are using, most of our patients meet those criteria. They basically have it to be a respiratory failure with an SpO2 that's the 93% and a PF ratio of less than 300 with bilateral lung infiltrates. So we are actually, right now, we apply, most of our patients, we apply for that convalescent plasma, but again, I really don't know the answer. I think, I'm hoping that we'll have that evidence pretty soon, but we are still, we are using it whenever we are able to get that convalescent plasma. So Marilyn, this is Marilyn Stevens, if I could just make a little comment as well. I think, you know, the patients with severe COVID-19 disease who are admitted to the intensive care unit tend to be so sick, many of them develop, you know, multi-system organ failure, that I think in, almost in desperation, a lot of clinicians are inclined to give a treatment, even if there's no, you know, there's no evidence of efficacy. And I think this is a temptation that needs to be resisted. So I could just tell you that our group here at Hopkins, again, has, you know, decided that we will, you know, strongly recommend against the use of any off-label unproven therapies that are being administered outside of a clinical trial. So that's our position. I know that that's not something that's being implemented in many other places. And I can understand that people would want to, for example, give convalescent serum just because the patient is an extremist, but our feeling is that it doesn't, you know, it's not justifiable. And that even on ethical grounds, it's much better to implement these therapies in the setting of a scientific investigation. I can't agree anymore. I think that we're waiting for that evidence and we also moved really fast. I mean, I remember when we were using hydroxychloroquine and then we stopped using it. And there's also a push to use, you know, some of these medications like tocilizumab and bring up some criteria. But yeah, it's very tempting. And I think it's a, it's also very risky. Dr. Salinas, you bring up a good point about tocilizumab. You know, what's the role in place of tocilizumab in treatment? Well, again, there's no, there's insufficient data. We have, our organization has developed some criteria for the so-called cytokine storm that includes LDH and IL-6 and ferritin and D-dimer and CRP. And even within our own criteria, you can see that as clinicians, we are trying to push that and give that medications to many of our patients. So at least within our group, we're saying, okay, we're going to agree with, you know, about these criteria, that very high LDH, very high ferritin levels. And we were talking about ferritin levels more than 2,000 and CRP also highly elevated. And again, it's all anecdotal. We have a few cases where we have used that tocilizumab. I personally have used it in two cases. And I think it's out of, like Dr. Steven said, it's more of desperation when we, our patients are rapidly declining. I mean, those two cases that I use, it's clearly, they progress really fast in matters of hours. And it's very clear that they have extremely high inflammatory markers. And anecdotally, it has worked for those patients, but again, there's no proof. And I wouldn't recommend to generalize that, you know, that recommendation. Right now, we don't have a good fit, I think, on any, you know, drug treatment. And one of the ones that seems to be very debated, in fact, I think it was dominating the SCCM discussion forum was steroids. So, Dr. Stevens, when do you use steroids? And I think that there's a good consensus that if you have someone who's in septic shock to use them, but other than that, if you've got a patient with COVID-19, when do you reach for steroids? Yeah, I would say almost never. We have, you know, I think the big concern with steroids is that it's a kind of double edged sword. On the one hand, it might tamp down the inflammatory response, both in the lungs and systemically. It may also have some beneficial effects in terms of the circulatory system. There is evidence for non-COVID, you know, community acquired pneumonia that steroids are beneficial. There's evidence that steroids may be beneficial in subsets of patients with ARDS. But I think overall, the big concern in terms of administering steroids in patients with COVID and pneumonia is that the sort of very broad and nonspecific immune suppression that it induces could actually contribute to a worsening of the underlying infection and even greater proliferation of the virus. So, I think our approach has been to avoid steroids and only implement them in very specific circumstances. For example, in non-resolving ARDS, you know, sort of the late phase, maybe when you're two weeks in or two and a half weeks in and it looks like there's continuing, you know, sort of fibrous proliferation in the lungs, there may be some interest in using steroids, although we've done it very anecdotally. I think in patients with severe circulatory septic shock, that is refractory to, you know, conventional vasopressor therapy, you may consider the use of steroids, but that's sort of not for the pulmonary indication. So, overall, I think the evidence supporting the use of steroids is extremely inconclusive. There's mixed reports. I've heard, I've spoken with colleagues, both in China and in Italy, who have told me that they felt that it was beneficial, but we were not, I mean, our group has not been convinced by that data. And so, we're using it extremely, extremely sparingly at this time. That's interesting. And I think it's always important to see how it's, what experiences people in different parts of the country are having. Dr. Salinas, what's been your experience with steroids, and when do you choose to use them? So, yeah, it's certainly an unresolved question, and I don't think I pretend to have the answer. I mean, you can see the same different groups get to a very different conclusion. I mean, the SSCM recommends using steroids for patients on mechanical ventilations who have developed ARDS, and the IDSA recommends against it. The NIH guidelines are big, and they don't favor, or they're against steroids. One particular group of intensivists, which is a large group, initially, we said no steroids at all, and now we are considering adding some steroids. I mean, we certainly see a pattern where patients have seven, you know, the typical story, they have seven to eight days of symptoms. They come to the hospital, usually to the medical floor, and then three or four days later, they end up coming to the ICU. So, we have that question, is that, is there an intervention at that point when there's, you know, the, there's decreased viremia and inflammatory phase is more prominent, and is there a window to mitigate a lung injury? Again, I don't think that we all were practicing, and there's a consensus about that, but we're considering, you know, should we start some steroids on some of those patients at, you know, week two. Interesting. It'll be, I think, very nice when all, we get through the next few months, and we'll have a little bit more data to answer exactly what we need to do with these stories, because I feel like everyone has the same questions. Dr. Stephens, you know, we still have a lot of other options that are being thrown out. It seems like I turn on my computer every day, and there's 10 new random drugs that have been proposed for use in COVID-19. Can you update us on any drug treatments that are available for COVID-19? Yeah, so you alluded to hydroxychloroquine and chloroquine, a lot of discussion, debate about these agents. I am not aware of any conclusive clinical trial supporting the use of either hydroxychloroquine or chloroquine as an effective agent to treat patients with COVID-19 disease. The reports that came out of France and China, as best I can tell, were inconclusive. Another drug to consider, a sort of class of drugs, are the antivirals. So there's been a lot of discussion recently about remdesivir. This is a drug that was initially, I think, developed for the treatment of patients with Ebola virus infection. Again, there are other sort of case theories coming from China suggesting benefits. I think there was a lot of enthusiasm even until last week, but the most recent data, which is not yet published, I think, is suggesting that it may not be efficacious. It may not be the hope. It may not be bearing out the hopes that were initially inspired by this drug. There's also a couple of other drugs. There's lopinavir, ritonavir. These are, I believe, HIV, anti-HIV drugs, and they're also undergoing testing. So perhaps you're aware that there is a large multi-center trial organized by the World Health Organization. It's called Solidarity. There's four different arms of this trial. There's remdesivir, lopinavir, ritonavir, and then also lopinavir, ritonavir combined with interfering beta, and then there's chloroquine and hydroxychloroquine. I think the short answer to your question is that all of these drugs are under investigation, and I think we really need to wait for the results of these large-scale trials to be made public so that we can make strong conclusions about therapeutic efficacy and also about the balance between efficacy and toxicity. I think one of the concerns in particular about hydroxychloroquine, but may also be relevant to some of the other drugs, is the toxicity of these medications. And I think you bring up a good point. I guess the good part about that is there are at least now several large randomized controlled trials that are underway both in the United States and worldwide using these main candidates, and they should be concluding sometime around late fall. So that'll be really good. I want to switch gears just a little bit away from therapies to complications because, you know, as more and more patients develop COVID-19, we're becoming more aware of things we hadn't heard of before. And one of those is just how hypercoagulable some of these patients seem to be with reports of patients developing pulmonary embolus and even cardiac complications. So Dr. Salinas, what's the recommended role of getting serial labs in these patients? So getting serial troponins and CKEs and even D-dimer to help manage this hypercoagulable state. I think the short answer is that we don't know the implications of all those markers. I think we have created an order set so we can order those inflammatory markers and follow them. But I think it's very interesting, how do you interpret those? I mean, we certainly see those patients who have these very high inflammatory markers and rapidly progress, but we also have seen patients who have, you know, moderate elevations of those markers who also clinically deteriorate. So it's difficult to interpret the same thing for those hypercoagulable states. Some of them don't have, you know, markers of hypercoagulable state and they develop a lot of clotting when they are on CRRT. And those patients, sometimes we put them on higher dose of anticoagulation just because they are clotting the system, the circuit. I'm aware of all the complications that have been reported and also the cardiovascular, you know, complications. I'm particularly interested in the cardiovascular complications and I have done more than 20 echoes on these patients, try to understand what, you know, we see anything early. And right now we have received IRV approval so we can start looking for early signs of myocarditis and IRV dysfunction. I can tell you, I mean, but this is just personal, that I have seen IRV dysfunction without any evidence of pulmonary embolism. And we know that, we know that patients with ARDS develop IRV dysfunction with shock or without shock. So that's been my experience with those markers. Great. Thank you very much. It's very interesting. I think as time goes on, we'll start to get a little bit more of a comfort in what we need to do with these patients in terms of, you know, will our daily labs stay the same or will they sort of develop a new look and feel to them? One of the things that has come out over the past four months is a lot of different places have developed protocols to handle the unknown. And Dr. Stephens, I know you said that you haven't experienced, you know, a flood of critical care resources like maybe you planned for, but, you know, what do you think for those places that are having, are in a hot spot, or even if in your facility you were to have a resurgent of cases, what would be the best way to handle bed expansion for critical care and for developing shuttered facilities? Yeah, so this is a really important question. And really what you're talking about is the adaptability or the resilience of health systems and also of healthcare staff in terms of rising to the challenge of a major surge in patients with, you know, in the setting of a pandemic. So I think we've learned a lot from the experience of our colleagues in other countries. I'd like to reference what happened, for example, in Northern Italy, and also in Spain. And what you see over there is that they were met with quite a sudden surge in a very large number of patients who are, many of whom were needed hospitalization and intensive care, and they were not prepared. And the result was that their systems were quite rapidly overwhelmed. And I think the high mortality that was observed in those countries could at least in part be linked to the fact that the health systems were not in a position to accommodate so many critically ill patients. So lack of intensive care, beds, lack of intensive care staff, lack of ventilators. I think in the United States, we have had the sort of advantage, so to speak, in many places to observe and what was done elsewhere and also to prepare. And this is certainly the case, I can tell you, in the state of Maryland. So we've, you know, in addition to all the sort of measures taken at the state and municipal level within the health system, for example, in Johns Hopkins, we adopted a very deliberate approach to scale up our intensive care capacity. So we've, I think, more than doubled the number of intensive care beds, and this has been accomplished by converting non-intensive care units into intensive care units. So for example, one of our post-operative recovery rooms is now a full-fledged intensive care unit. The pediatric intensive care unit is now being converted into an adult intensive care unit. The neurocritical care unit has now been converted into a COVID-19 ICU. And so there's been, really, it's been remarkable to see how flexible and how resilient the system is in terms of increasing capacity, but that's not the whole response. The response also needs to include assigning staff to all these newly converted intensive care units. And so for this, we've reached out into other departments and divisions of the hospital. And so we have, for example, non-intensivists, non-intensive care attending physicians, and also residents who are coming to help in the intensive care units under the supervision of the intensive care team to help out with care of patients. And also there's been a great deal of flexibility, adaptability on the part of our nursing colleagues. And many, many nurses, for example, who were not critical care trained have been assimilated to help out in the ICUs. In the department, for example, of anesthesia here at Johns Hopkins, we have a large number of CRNAs, and many of those have been assigned to work in the intensive care units as nurses to support the mission. So I think overall, it's been a really, really remarkable example of how you can flex up capacity in a very rapid fashion and do it effectively. So I think overall, we feel quite safe. We don't feel like we're going to be overwhelmed. And part of this is because we've been able to, I think, take the lessons from what was done elsewhere. And the last question I have from the pre-submitted questions is for Dr. Salinas. One of the concerns with any patient is, what if they develop a code? And certainly we don't want to have all of those people who were in the code and who are dealing with everything. Have you, at your facility, developed a specialized code cart? Well, we have developed also a PPE super box. So when we run to codes, we have that black box with more impermeable gowns and N95s and face shield mask. And we also have protocols. So we limit the personnel that goes inside the room. So it's only the respiratory therapy is a nurse and doctor or the physician who is going to be intubating the patient. So yes, we have developed protocols just to limit the exposure and some extra equipment readily available. We also have deployed some glide scopes or other medial laryngoscopes to medical units so we can have all the equipment available. Thank you very much. And we have a time for just a few questions from some of our attendees. The first question I think is very interesting and it's really directed to all of our panelists. Some initial retrospective studies out of China are showing that there's a strong relationship between the development of sepsis in COVID-19 patients and then subsequent mortality. Can our panelists comment on if we're seeing similar results here in the United States? We'll start with Dr. Khanna. Sure. Yeah. So again, no data that's published or we can use to substantiate this. I would say that yes, it's understandable that you have overlying sepsis on top of everything else that's going on and the mortality factor would increase. So yes, I would expect that to happen. But no data that I am specifically aware of and no personal experiences here. I wonder what the rest of the panelists think. So I'm sorry, is this question about bacterial superinfection in COVID-19 patients? Is that the question? No, it's just in general about patients who've gone on to develop sepsis, whether it's from a bacterial infection or from the COVID-19 specifically in mortality. What kind of connections with the rate of sepsis development and mortality are you seeing? Yeah, I think it's a bit early. I mean, we haven't really comprehensively compiled our COVID-19 critical care data, but a subset of these patients, especially the ones with a more severe respiratory failure who require high doses of sedation to optimize synchrony with the ventilator and optimize gas exchange. Those patients, a fair number of them in our experience go on to require vasopressor support to sustain appropriate tissue perfusion. And in those cases, it becomes a little bit sometimes difficult to say, is this truly septic shock or is it just a secondary effect of the massive amount of sedation that they're receiving, which can also have vasoplegic effects and also can diminish cardiac inotropy. So I don't know. I think there's clearly a subset of patients who do develop a viremic septic shock, but it doesn't seem to be the most common presentation in our experience. And I think we're seeing a lot of hemodynamic instability that is secondary to the therapies that we're implementing. Things like high PEEP and keeping the patients extremely dry to minimize volume overload and also the elevated doses of sedatives. Dr. Salinas, what have you seen? I think it's difficult to comment, but I totally agree. I think that's the trade-off. I mean, when we implement the heavy sedation and paralytics, and we certainly see that these patients require more vasopressors and it's difficult, but they also are at a higher risk for developing infections, especially when they remain, you know, intubated and heavily sedated for two or three weeks. So I don't have any conclusive data about it. And we are certainly, initially, we're very conservative with the fluid management, because again, I mean, there's the risk of this patient developing RV dysfunction. But what I have seen too is that some of these patients, because of their respiratory failure and the diarrhea, they also come severely hypovolemic initially. So it's a difficult balance. And I think it's case by case. Yeah. You know, one of the things that Dr. Stevens mentioned is we just haven't had a chance to look at our database yet. And so I think downstream, it'll be very interesting to see if, you know, that does become one of our big causes of sepsis, or if it is truly from all of our therapies. Our next question is for Dr. Khanna. Going back to proning, you know, one of our attendees wanted to know how you're securing airway ETTs to prevent movement and air leaks. You know, they're seeing some air leaks after proning. So what's your experience and advice? Sure. I guess the proning that we talked about earlier during the panel was awake proning, which really is awake, non-intubated patients self-proning themselves. Clearly no issues with securing any airway in that scenario. The proning experience as far as proning intubated patients is fairly similar to proning intubated patients with ARDS in general. I personally have not seen excessive air leaks. We do have specific nursing and respiratory therapy teams that are experienced with handling proning patients. So we just deploy those teams. Honestly speaking, you know, we've, the course of the disease is such that if you get mechanically ventilating them and proning them, then we would rather consider a VV ECMO if it comes to that path. The non-intubated proning, again, no problems at all. We'll do one last question, and this can go out to any of our panelists. One of the reports in New York is that a lot of patients who've become trach have a lot of difficulty being weaned from the vent. At a previous SCCM webinar, it was mentioned that ENT had recommended not traching the COVID patients. Has that changed? What's the recommendation now about patients receiving a tracheostomy? I can take that. Oh, sorry. Go ahead. I think inevitably there's going to be a subset of these patients who will require tracheostomy. These are the ones who have prolonged mechanical ventilation, who have maybe failed, you know, one or several attempts to extubate. We've set up a dedicated tracheostomy service interdisciplinary group composed of surgeons and anesthesiologists who are assuming these cases at Johns Hopkins. I think ruling out tracheostomy is not a feasible option because some of these patients do require prolonged ventilator liberation. Dr. Khanna, did you have something to add? Yeah, absolutely. I mean, I absolutely think that we should not rule out tracheostomy, specifically now that we are looking at a cohort of patients who are on VV ECMO, and they're going to be difficult to, you know, get off. Not only are they going to be difficult getting off ECMO, but they're going to be difficult in terms of pulmonary rehabilitation. I would rather do a early tracheostomy in these patients versus risk, you know, extubation and respiratory failure and reintubation. All that would be fairly risky in these patients. So, at our institution, there is no problems with doing a tracheostomy on these patients, with the understanding, again, that, you know, it's a high-risk procedure for viral dissemination. So, everyone in the, again, we don't do percutaneous tracheostomies on these patients. These patients would have to go to the operating room, being done by a surgical team and ENT team, and everyone would have adequate personal protective equipment. But again, no reason not to do a tracheostomy on them if it's so desired. And just to finish this out, Dr. Salinas, do you have any thoughts about this? Well, I can tell you our experience. I mean, the ENT are not performing those tracheostomies, and there was a, you know, discussion in our group if we were going to be doing those tracheostomies. We have done some of those tracheostomies. We have modified the protocols so we can minimize aerosolization, and certainly it's treated as a high-risk procedure. But we have certainly done some tracheostomies with good success. Again, it's unavoidable, and these patients stay on the ventilator for many days and sometimes weeks. Well, thank you all. And this is going to conclude our question and answer session. Thank you to Drs. Khanna, Stevens, and Salinas for participating today, and thank you to the audience for attending. Again, this webcast is being recorded. The recording will be available to registrants within 24 to 48 hours, and to access it, please go to covid19.sccm.org slash webcast. There are more question and answer calls scheduled on the dates listed here on the slide. All of them begin at 1 p.m. Central Daylight Time, and we hope that you'll be able to attend. If you have any questions regarding nutrition for COVID patients, please join us for our webcast next week on April 30th at 10 a.m. Central Daylight Time. And that will conclude our presentation today. Thank you. Thank you.

COVID-19 treatment

proning

non-invasive ventilation

steroids

convalescent plasma

critical care bed capacity

coagulability

tracheostomies

mechanical ventilation

research