This is the fourth of six in a series of COVID-19 question and answer calls offered by SCCM. My name is Lillian Emlett, and I am a clinical associate professor at the University of Pittsburgh in Pittsburgh, Pennsylvania, and this webcast is being recorded. The recording will be available to registrants within 24 to 48 hours. To access after the webinar, please go to covid19.sccm.org forward slash webcast forward slash. So really glad that everyone's able to join us this Friday again, we have a few housekeeping items before we get started. The primary primary point of this webcast is to answer your questions. So you will see to submit questions through the presentation, go ahead and type into the question box that is located on your control panel on the right hand side. Please note the disclaimer stating that the content is to follow is for information or educational purposes only. The data has not been peer reviewed and is based upon a small sample size with key aspects of information that may be missing or potentially single center experience. Advice is based on expert opinion during this webcast. And now I want to introduce your speakers for today. Dr. Marilyn Bullock is an associate clinical professor of pharmacy and director of strategic operations at Auburn University Harrison School of Pharmacy, an adjunct associate professor at the University of Alabama, Birmingham School of Medicine, and the University of Alabama College of Community Health Sciences in Tuscaloosa, Alabama. Dr. Robert Stevens is an associate professor in Johns Hopkins University with appointments in anesthesiology, critical care, neurology, neurosurgery, and radiology, and serves as an intensivist and neurointensivist at Johns Hopkins Medicine in Baltimore, Maryland. And now we'll get right to it with questions for our two panelists. So today, I guess I first just wanted to start with Dr. Stevens. I know we've been hearing a lot throughout the United States and through ELSO in terms of ECMO. So I'm just curious in terms of with the literature and sort of what's coming out with case reports and what is the role of ECMO in regards to COVID-19? Yeah, thank you very much for organizing this webcast and for inviting me. Regarding ECMO, I think I can speak from our experience here at Johns Hopkins, but also from discussions that I've had with colleagues in other centers in this country and also in Europe, and also from some of the published literature, although there's not a great deal. The approach that we've implemented here has been to select patients for ECMO using very similar criteria that we would use for other patients with severe refractory respiratory failure. These are generally patients who, in whom all of the other conventional interventions have failed. So maximized on the ventilator, maximized in terms of sedation paralysis, maximized in terms of proning, nitric oxide, and all these other interventions have been implemented and have not successfully corrected the underlying hypoxemia. So in those cases, if we believe that the patient has an underlying process that can be recovered, if we believe that the patient has a reasonable constitution in terms of age and comorbidities, then we will implement ECMO. And I can say that our local experience has been, I should say, reasonably good. We have put a total of 10 patients on ECMO. To my knowledge, the survival has been good and it gets better as we gain more experience. So I think that this is, again, very anecdotal. This is our local experience. But in summary, we select patients using the same criteria as we would in non-COVID respiratory failure, and we've had reasonably good experience. I know that reports coming from elsewhere have suggested that the mortality is extremely high for COVID-19 ECMO patients, but that has not been our experience here. I think the key in my mind is appropriate selection. Yes, that makes sense. You spoke a little bit about ventilation before ECMO and really optimizing and maximizing all potential use of tricks and strategies for advanced mechanical ventilation. I'm curious whether you have some tips and tricks up your sleeve at your shop that you'd be willing to share with our audience that are key points to remember to individualize the care of the ventilator management for each individual patient. Yeah, so Lillian, I think the key word is the one you just employed, which is individualize. If we've learned anything, it's that COVID is a complex disease and it's extremely heterogeneous in terms of its clinical presentation and also in terms of its underlying biology and pathophysiology. And so the reason I bring this up is because if we just focus on the lungs and on lung physiology, I think what we've seen and what many of our colleagues have seen is that there are almost no two COVID patients that are alike. There are some that are presenting with classic features of ARDS with low compliance, increased shunt, increased dead space. And in those cases, you know, we will obviously implement a strategy of maximizing de-recruitment or preventing de-recruitment and of course, lung protective ventilatory settings to minimize plateau pressures and driving pressures. But then there's another subset of COVID patients who are severely hypoxemic, but actually their compliance is normal. And on chest imaging, the degree of consolidation may be less severe. And we think that this represents a pathophysiologically distinct entity which may not be so responsive to high levels of PEEP and may actually respond better to interventions that could potentially increase VQ mismatching. And so in those cases, you know, when our workup has often shown that there's an underlying problem like multiple pulmonary microemboli or in other cases, not. But this is a different subset of patients where these sort of maximal ventilator settings in terms of high PEEP and lung protective settings may not be the best approach and where approaches that are targeting the vasculature may be more important. And I bring this up because there's increasing evidence that COVID is a disease that affects many different organ systems, but may have a particular affinity for the endothelium and for the vasculature. And we think that, you know, a significant proportion of the hypoxemia observed in COVID may be secondary to endothelial dysfunction in the lung vasculature. This is a hypothesis, of course, but I think there's good evidence to back it up. That's a great summary of all the different ways that pulmonary manifestations occur. In turning towards treatments and modalities, I think there's tons of questions that everyone always asks in terms of what types of treatments might we be able to offer. I think everyone's been desperately searching for this for the last two months. So, Dr. Bullock, I was wondering, what are some of the best ways to manage COVID-19 patients from your experience? And what are a few tips and pearls as a pharmacist and clinical pharmacist trying to guide our treatment teams, begging potentially for something, anything to try to offer to different types of patients with such heterogeneous microvascular or endothelial or pulmonary problems that they're exhibiting? I think that's the million dollar question. And to be quite honest, the answer I would have given you yesterday is probably not the one I would give you today. I think Dr. Stevens hit it on the head when he said that you have no two patients that are the same. And unfortunately, we're seeing that with clinical studies. We'll have one study that will come out and we'll say this drug works. It's wonderful. Everybody should use it. I think hydroxychloroquine is a prime example of that. You have half the studies that are coming out with it say it's helpful and it's useful, particularly in critical care patients. And then the other half that come out say, no, there's no difference between it and standard of care in terms of mortality or intubation. So some of the things we, you know, remdesivir, I believe since we spoke last, we had our last series, has gained EUA status from the FDA, which is very encouraging. They haven't published the data that that EUA was based off of, but it sort of tells you that at least it met the primary outcome, which was to be better than standard of care in terms of mortality. So we can, even though that data is not published, you can kind of assume that that standard was met. And it will be interesting to see what that data is made available. Unfortunately, it's really difficult. I think a lot of hospitals have been trying to get the EUA access to remdesivir and a lot of places are struggling. So we're left with what we were doing before, which many places are doing hydroxychloroquine. Some places are doing the IL-6 inhibitors with some success, particularly in your sicker patients. Convalescent plasma still seems to be probably one of the more encouraging therapeutics that are out there. And then a lot of people are, even though there's not a whole lot of data at this time, whether or not it works, they are using high dose vitamin C and zinc. And anecdotally with success there. So I think the biggest struggle that we have in this area, particularly maybe with hydroxychloroquine, is that we don't have a lot of standardization. One of the issues that I've noticed that's coming out, whether it's with studies or different protocols that universities have, is nobody can seem to agree on a dose. And so some of the things that we see in terms of arguments about efficacy and safety, a lot of that seems to be centered around the particular dose that's being used. So I will say in my practice, we have used hydroxychloroquine and vitamins. We have not been able to get remdesivir yet, though hospital down the street has and they've had success with it. We have not yet started using the IL-6 inhibitors, but we are working on protocols for them just because that does seem to be the direction that we're headed. And I don't know if Dr. Stevens wants to comment a little bit more about what they're doing at Johns Hopkins with things, because I know no two hospitals seem to be doing the same treatment approach either. Yeah, thanks a lot, Marilyn. I just wanted to add that and I think you'll agree with me that there is no current therapy that is really supported by a robust, adequately powered, randomized clinical trial. So a lot of the interventions that Marilyn mentioned are potentially useful and may turn out to be actually therapeutic, but we don't have good, robust evidence to support them. So if we wanted to look at things in a very sort of realistic fashion, we could say that there is no treatment currently that is known to be effective for COVID. There's a lot of hopefuls, some of the ones that Marilyn mentioned. In regards to the one that she mentioned in the last, which is the tocilizumab, which is the IL-6 receptor antagonist, we do actually use this drug. We reserve it for those patients who are rapidly deteriorating in the setting of a so-called cytokine storm. So we measure, we can measure the IL-6 levels in the bloodstream and those patients who have elevated IL-6 and in addition to other pro-inflammatory markers such as elevated CRP, elevated ferritin, we will implement the administration of this drug. We found it, again, anecdotally to be helpful and I think we have to await the results of trials to really make firm statements about any treatments. But I think we can, if we talk about treatment of COVID, we can break it down into sort of several different domains. The first domain, of course, is the supportive care that we provide in the intensive care unit in terms of supporting the respiratory, failing respiratory system, supporting the circulation, supporting the kidneys that are often failing as well. Then there's another domain which is, you know, trying to defeat the virus itself. So antivirals and Marilyn mentioned, you know, remdesivir, which is very interesting, developed for Ebola virus, but seems to have some efficacy against SARS-CoV-2. And then there's the anti-inflammatory therapies such as tocilizumab, which is really there to hopefully reduce the magnitude of the host response, because I think many believe, and myself included, that the, you know, part of the reason why these patients become so sick is not so much because of the pathogenicity of the virus itself, but because of an maladaptive host response with a very, very pro-inflammatory profile. So I think those are some of the things that we're looking at. And I think it's, again, the sad truth is we don't know yet. Hopefully we will know soon when the results of some large trials are published. But the reality is that right now there is no proven effective therapy for COVID. And if I may, I just want to add, Robert brought up a good point about supportive care. What we are starting to get more data on that I think we can maybe start to act on is the non-antiviral therapies. I think when this is all said and done, this is going to be a regimen, not just a drug. You know, these are going to be people who have a cocktail. It's going to be going kind of back to our critical care route. We're starting to see a lot more data about just how important it is to make sure that these patients have adequate, bare minimum, DBT prophylaxis, bare minimum. Some hospitals, including mine, just depending on the D-dimer level and the risk factor, they're moving more to full anticoagulation in these patients because of the thrombotic risk that these people were seeing more and more pose. We're also starting to see, I saw a study that was just published today and it was on a repository, so it hasn't undergone the full peer review yet. But it was interesting. It looked at patients who were on famotidine and looked at it and it showed that it was protective. Those patients were less likely to die. They were less likely to need to be intubated. But the people who were on PPIs, it wasn't protective for them. In fact, they had a higher risk of the primary outcome. So it may be that, you know, with our stress ulcer prophylaxis, we end up switching back to the HTRAs, which I feel like in the past decade we've gone to the PPIs. So we've also seen a lot of literature come out. Again, it's all retrospective, but it looks to be encouraging in terms of the protective effects of some of our antihypertensives. Now, that's not to say we should put normotensive patients on antihypertensives, but long term, it may impact how we're selecting these therapies for primary care. So there's been a lot of research done with regards to ACE inhibitors and ARBs. There's at least two studies, prospective studies going on right now where they're actually looking at putting people on Losartan with COVID-19 and seeing if that's helpful in both the people who were sick enough to be hospitalized and even those who have COVID-19 but are outpatients. So we're seeing some interesting data come across with these supportive therapies that I think that we also have to remember we need to watch for because, and Robert, I hope you'll agree, this is going to end up being a protocol approach more than it's going to be just, oh, this is the antiviral we need to use. Yeah, I couldn't agree more. It's a very complex disease and I don't think there's going to be a single silver bullet that cures this thing. I think it's going to require a sort of bundle of interventions that together will have a very significant impact. But I think alone, probably not. Yeah, I agree completely with that approach. Great. We did have some questions come in regarding therapies. So there was a question posed with one of our audience members on what are the suggested criterion for tocilizumab and is respiratory failure and are there particular ventilator settings that might be part of that criteria to be able to receive that particular drug? And if there is anything related to tocilizumab, what would you use as a second dose? I don't know if Dr. Bullock, if you want to take a stab at that one first. Most, all of the criteria that I've seen are sort of like what Robert said they're doing at his institution. These are going to be your sicker patients. So generally people that you've tried other options and they don't seem to be working. And on average, when you look at the few studies that we have available, they do seem to be started no earlier than, you know, three days out from the cytokine storm. So I don't, and these drugs are not, I mean, these are monoclonal antibodies. They're not entirely easy to use. They're not cheap either. But I mean, so most places are restricting them to infectious disease approval. You mentioned, you know, do you need a second dose? And that's been a big discussion. There's been a lot of protocols that were put out early that said, no, you don't need a second dose. However, I'm starting to see a lot of studies that are, I see a lot, a handful of studies that are coming out now that have looked at, at least retrospectively, the efficacy of teslosumab and they've used at least two doses. A few times I've seen three doses within 36 to 48 hours. And they've been encouraging results to study those studies that I'm talking about. So I almost think that we may end up using at least two doses of this drug. But again, those are retrospective studies. We really need a good perspective, randomized, controlled trial to answer that question. Yeah, I could just add that most of our experience with teslosumab is being with a single administration. The criteria that we use are quite specific. It has to be evidence of rapid and significant clinical deterioration. So worsening hypoxemia or, you know, circulatory shock often together and in conjunction with a pro-inflammatory signature in the bloodstream. So elevation in CRP, ideally evidence of elevated IL-6 and, you know, elevated white cell count or very low white cell count. These are the criteria that we use. And in fact, in our institution, the release of this drug has to be approved as a specific committee that has to review and approve it. So it's not given out easily. Yes, that makes sense. That's how it is here for us as well. We also had another question that was posed regarding anticoagulation. I think now it's pretty evident that the literature caught up to all of the case reports initially of the microthrombi and the widely wide d-dimer elevations and the questionable clinical correlations with all of that and there is wide differences between what people use for their anticoagulation regimen. A question was posed in terms of what is your criterion for recommendations for full anticoagulation specifically and if you have drugs of choice. I don't know if Dr. Wilk you want to take a stab first. Yes so you'll have to forgive me I can't remember our exact d-dimer cutoff that we have but it's fairly elevated elevated beyond anything that you would think even of just getting a vq scan or an ultrasound sound and someone who comes to the ER with a routine d-dimer screen so it's pretty well obvious that it's it's elevated it's not even just on the the cusp. I don't know that there's been a lot of distinction in the literature between low molecular weight and unfractionated heparins but most of the protocols that I've seen are pretty much using your those options. I haven't seen a lot of places that are utilizing your oral doacs for example particularly the ones that are available for dvt prophylaxis. I think just because these patients also have at least that we've seen some incidents of anemia and even thrombocytopenia I think that there's a maybe a just a comfort level of going with unfractionated heparin by some clinicians. I'm not going to say all just because you can turn it off and there's a little bit more safety control with it but I don't know that that's everywhere around the country Dr. Stevens. Yeah so it's an interesting question. The approach that we've taken here at Johns Hopkins has been to only treat if there's documentation of a dvt or a pulmonary embolism so that's for treatment dose anticoagulation. For the others we implement prophylaxis in general unless there's a contraindication we'll use a low molecular weight you know like enoxaparin and we've had some with you know our pharmacy and clinicians have also made some dose adjustments because of the hypercoagulable state of these patients so we use a sort of a dosing scheme which is a little bit hybrid in between the prophylactic and the therapeutic range but essentially we've you know I know that some centers have decided to go towards you know treatment dose anticoagulation even in the absence of documentation of a venous thromboembolic event but we have not we've decided not to do that. I guess I have a follow-up question based on what you said. It's challenging a lot of times these folks are hypoxic and respond well to proning or oxygen therapies initial ventilator management but about 10 days to 14 days they get worse again and we wonder whether the microthrombite or pulmonary embolism is a factor but by then they're a little bit too unstable on the ventilator to potentially make that road trip. I'm just curious in terms of any tips for how to make the diagnosis so that anticoagulant therapy can be started. Yeah so that's a great question I mean we you know we've relied a lot on ultrasound so obviously dopplers of the extremities to look for DVTs and then you know if there's evidence of you know significant right ventricular strain that is new in onset and it does not coincide with worsening necessarily of hypoxemia then that can be used as presumptive evidence in support of a pulmonary embolism and we sometimes will use that to implement treatment dose hyperin even in the absence of a CT scan let's say. So yes I think the the key is the echo and you know to look for RV strain and then dopplers of the extremities would be what I would propose in these very unstable patients. That totally makes sense. Changing gears just slightly the question was posed from one of our attendees was regarding whether anyone has seen anything regarding ABO blood type and also the thrombi formation whether there's a tendency for certain blood types or other blood factors that might predispose people to the embolic events. I don't know if Dr. Wilk wants to take a stab first. We routinely don't I mean unless you need blood we don't routinely type and crawl so we haven't looked into this I've only seen I think what most people have seen in the literature where there was that you know correlation early on that patients with O positive may be more protective than patients with A. I think it was A so but I clinically I haven't we haven't looked into this I haven't seen anything come out more recently to sort of support or you know go against those early findings. Great. Dr. Stephens. Yeah I'm not aware of that I think I indirectly heard about this but I'm I don't think I'm knowledgeable to comment on the specific relationship between the blood type and risk of DVTs or PEs. Right same here. So just changing gears slightly in terms of but continuing on the treatment there's been some reconsideration of steroid use there's a lot of controversy in steroids and critical care in general but I'm just wondering Dr. Bullock in terms of steroid use for COVID-19 treatment have you started to see sort of a pendulum switch back and forth now after about two months of our experience? Well I think the big concern early on was the data that we had from SARS and MERS where the patients who got steroids in those cases did worse overall and they had a more difficult time with viral clearance. The problem with COVID-19 is just the amount of ARDS that we're seeing in these patients and our steroids as everybody knows is remains a drug of choice in that kind of situation so I think what we're you know what we're honestly doing and what's recommended by pretty much every guideline that we've seen is that when you have your patients that are developing ARDS we're using steroids. There's not a lot of data in this group yet but that's not to say that those studies aren't going on. There's several big studies that are actually looking at steroid use in COVID-19. There's some small studies that have come out more so from you know early on in China where they would just sort of you know describe this is what we did this is what happened to the patients and even patients who got steroids it didn't seem to hurt them as much as it did in you know previous coronavirus situations so it seems encouraging. I will say that primarily this steroid that seems to be that seems to be being studied that's been reported in case reports and even anecdotal reports is methylprednisolone. I would think that if you're going to use a steroid at this time outside of sepsis and septic shock that's probably the one I would recommend just because that's where the data is we don't know necessarily some of the other pharmacokinetic and pharmacodynamic things with the other steroids would they be helpful or would they be hurtful but I think we're still at a we don't know overall. Some of those studies are set to conclude early fall so hopefully we'll have a lot more definitive answers about you know do they really hurt like we thought that they might. I don't know that we need to use these steroids up front in everybody you know and seems like when people come in with COPD exacerbations we've always been so quick to just throw steroids onto them. I don't know that just because you come in with COVID-19 you automatically need to get steroids. I think the pendulum has really swung and maybe not being as hesitant to use them once they do get intubated and to develop ADRS but beyond that I don't think that we're really have changed much in our approach than we were even a month ago. Yeah this is a Robert Stevens. I agree with Marilyn. I think that the key here is you know until we get more definitive evidence I think the key is appropriate selection of patients and maybe also timing. I think what we're likely to find when the trials come out is that steroids are helpful in a subset of patients with respiratory failure and COVID-19 disease. I think we may find as well that timing is key and that maybe early use of steroids when the virus is actively replicating may not be helpful it may actually exacerbate the disease but potentially use of steroids at a later phase when the virus is no longer so active and the primary process is this inappropriate or maladaptive host response with both systemic inflammation and inflammation in the lungs we may find out that the steroids are actually helpful at that stage. So I think those are the two things in my mind is selecting patients appropriately and then thinking about the timing. That totally makes sense. Which I guess brings me to my next question was do you guys know anything about or are either of your institutions enrolled in the REMAP COVID network of clinical trials? As most people probably know the REMAP is the randomized embedded multifactorial adaptive platform of COVID treatment therapies so that we can use artificial intelligence and electronic health records across the United States to hopefully allow all the data that we are pragmatically beginning treatment with different patients to all be collated together so that we can merge both clinical equipoise and along with the research arms. I don't know if either of you guys have experience or know of colleagues who are participating in the REMAP COVID network. Yeah so I've heard about this trial I don't think we are a site but I've certainly discussed it at length with you know with actually the Dr. Angus who's the I think the one who invented this concept so the idea is I think really really interesting and it has to do with developing a clinical trial design that can adapt to the changing circumstances of the underlying population that is being studied and so it's a version of what you would call an adaptive clinical trial design where you know you classically think of a randomized trial as something where the rules are set at the beginning and you can't change them until everything is said and done but there's increasing evidence that you can you can actually change the rules you can have specific rules that are established at the beginning that help you to make changes in the protocol based on for example responses of specific patients based on levels of specific biomarkers and the whole the whole goal of all this is to optimize or to maximize the likelihood of demonstrating benefit so I think REMAP is a really really valuable trial I think we are not selected or we did not yet decide to participate but I think it's a potentially going to be the way to go for both identifying promising therapies for COVID but also for other conditions that we deal with in the ICU. We're also not a site in fact I don't think that there's any sites sites right now in the United States that I'm aware of I may have that wrong but I don't think that there are although I wish there would be but it the REMAP trial is I really like it because of you know we talked earlier about how this is not going to be a single drug solution this is going to be a regimen or protocolized solution and they are looking at essentially all of the therapeutic questions that we've talked about already today you know antivirals, steroids, anticoagulation, IL-6 inhibitors, even antibiotics so I mean they are in the ability to adapt because we're still fairly new in this virus's lifespan where think about it this virus is only about six months old six seven months old and think about how much has changed compared to where we usually would be at this point and we do need that ability to adapt because if you think about it what we were doing even just a month and a half ago in our ICU to treat these patients is most likely not what you're doing now and so being able to adjust for that or when you find that something does work and be able to make that as your control from an ethical standpoint I think is very strong so the nice thing about this trial that I like is the fact that it's not just going to give us one answer it you know like we've seen a lot in cardiology trials over the years I think this is going to be one where we're going to be able to pull answers for a lot of different questions that we have. I do wish we had more sites than we had any site in the United States but you know it does look to be like they are coming from well resource places in Europe and Australia and things like that though. Great thanks. I'm moving on to protocols guidelines and operations you know I think all of us have sort of had the lived experience now in each of our clinical groups where different folk need to spearhead the research arms different people need to figure out the protocols and guidelines some of us need to work on operations and some of us need to work on education and assimilation. I'm curious in terms of as you guys have begun to increase and flux the different volumes of COVID patients at your different institutions how has communication changed with the consulting teams daily normal care operations with the interdisciplinary care team that has to work in the ICU whether it be PT, OT, speech and also how that has been an effect on the patients and their families. I think all of us have seen the different stories about using FaceTime and video and Zoom to also communicate with our families. I'm curious to hear tips and tricks for improving that process for us in general. I think you're touching upon a really important aspect of this crisis. So I think by virtue of the fact that this is a very contagious infectious disease and the need for personal protective equipment this poses a huge challenge in terms of communication, communication within the teams taking care of these patients, communication between teams, communication with families, communication even with the patients. And the question is can we overcome those barriers and establish good communication so that care is delivered as a high quality and is effective. I don't know that we found the solution. We decided very early on to implement all the technology that we could. So we for example in many of our ICUs we round of the ICU to we round virtually meaning that a single member of the team will examine the patients with a head mounted camera. Usually it's just an iPhone. And the remainder of the team will be in another location and essentially will be able to communicate with both the team member who's examining the patients as well as the patient him or herself if they're able to using this setup. We've also made use of earbuds. So many of our nurses for example even when they're wearing these elaborate spacesuits are able to effectively communicate via the use of these Bluetooth earbuds. I think the issue you raised another communication I guess dimension which is communicating with families. And I don't know if this is the case in all over but I certainly here at Hopkins we've implemented very early on a policy of not allowing any visitors to the hospital. So and this is particularly difficult with critically ill patients some of whom are an extremist some of them who are even dying. How do we establish good communications with the family in order to make sure that they understand that they're making the right choices and that sometimes grim news can be effectively relayed. And I don't know that we found the solution. We've decided and I think this is done in many places to make sure that a member of the ICU team is on the phone with a family member at least once a day and sometimes several times a day to provide them with detailed updates. But certainly it's not it's not not ideal and there are many challenges especially when the complexity of the patients increases and when they're an extremist. So I don't know if Marilyn if you have any other insights. Yeah so I'm at a large community teaching hospital and we also made the decision pretty early on not to have visitors and then the state made the decision for us to continue that policy. So even legally right now we're not allowed to have visitors except in certain circumstances. And I'll tell you that that's made things very difficult particularly with our older patients who are not good historians or have underlying levels of dementia. So just getting their background and understanding basic things that we would traditionally get. And so sometimes getting people on the phone is it's been a challenge. So you know just particularly if you have family members that are not as close as you would normally have. So sometimes we have been treating these patients a little bit more in the blind than we would have before COVID-19. And so that's been very difficult. We've done a lot of not necessarily virtual rounding but our residents have divided up where we normally would have a large morning report in one area. You know groups of very small teams have gone to rooms that would allow them to socially distance and so they'll round there. We've done for our younger attendings are still seeing patients traditionally but we're just to protect PPE only the attending and the senior level resident will go in the room. For some of our attendings and even residents who can't go see the patients because of age or underlying disease states we've also done the virtual rounding. So where the resident will take the iPhone in there and they'll FaceTime and do the assessment that way. So we've come across some of those solutions as well. So it's been interesting. There's been I think from a communication standpoint and this is certainly maybe outside my domain as a as a pharmacist but one thing I've noticed is a lot of your non-primary services sometimes are now wanting to wait until the COVID test comes back one way or the other before you know if it's not something that's emergent that they have to see the patient. They're wanting to wait until they that test comes back before they see the patient. So in some cases that's been appropriate to protect PPE and other times it's, you know, held up transitions of care and discharge for patients. I don't know if that's happened at Dr. Stevenson's location or not, but you know, it's just been an interesting communication thing. I think it's getting better as we get more comfortable with the virus and we know what to do with it a little bit more, but certainly up front there were a lot of issues of just getting everybody on the same page and, you know, trying to make communication be a little bit more streamlined. Yeah, and I think, so we've been talking about communication primarily at this sort of frontline tactical level, but I think there's another level of communication where things actually have significantly improved and, you know, over the course of this crisis at our institution and this is the sort of more strategic planning communication and what I'm referring to in particular is people, you know, very willingly engaging across divisions, across departments, even across schools to work in a very collaborative fashion and so this has been, for example, part of our response in terms of scaling or ICU capacity has really required us to work, you know, between, you know, pulmonary critical care, anesthesia critical care, surgery, medicine, all these pediatrics even have all been working, you know, very, very collaboratively in a very intense way and in a way that is not at all reflective of our common practice to really ensure that the institution was ready and able to confront a surge. So I think from that standpoint the communication has really, you know, the internal communication in our institution has improved by leaps and bounds in ways that probably would never have happened if there hadn't been this crisis. Thanks. I think you guys both bring up two really important points. Leveraging the use, novel use of technology in places that would be previously forbidden and then also the fact that medicine as a whole has come together from specialties and disciplines in this time and hopefully that's something that doesn't go away even as our case volumes go down. So that's a great side effect. In terms of also communication, how do you help our families and our patients transition from the ICU to other parts of the hospital to home? You know, having been in our care for so long we've seen a lot of media for people who as they actually entered the hospital to be a sort of a media event which is challenging and interesting for us to deal with because for most of us that's not our normal day-to-day when we used to take care of other influenza patients or other types of critically ill patients. But also emotionally to help support the family and the patient for that journey now for the transitioning into rehab. I'm curious whether either of you have had experience for coaching families and patients for what the next steps are as they transition out of the ICU communication-wise. Yeah I think you're bringing up a huge topic which we could easily spend a lot of time discussing. I think it's quite clear at least for the very sick COVID patients that the road to recovery is a long one. This is in general it's a protracted disease that people are often in the ICU for two weeks or even longer and as a result of their critical illness they're deconditioned. They often will acquire acute brain dysfunction and delirium and by the time that their sort of critical nature of their disease is beginning to resolve they've lost a lot of their physiological reserve. It's very obvious that they require a lot of attention both in terms of physical and occupational therapy, cognitive therapy, speech therapy. But also in some cases they're just not ready to go back home and so we've been working very closely with our physical medicine rehab colleagues to identify appropriate venues for them to go to as a sort of bridge between the acute care setting and home. We've had some cases of less severe patients where the transition was a little bit smoother and where they were able to go directly from ICU to step down and then ultimately were discharged home. Those were generally younger patients. I think the big challenge has been in the older population, people in their 60s, 70s or even older who to begin with had reduced physiologic reserve or maybe frail even before they developed COVID and now are in a state where it's going to take a long time for them to recover. I think the approach that maybe is at this current time is probably the most important in our view is early implementation of physical and occupational therapy. So rehabilitative care starting already in the ICU and this is something that we believe very strongly in at Johns Hopkins is that rehab care should not necessarily wait until people are out on the floor or even in a rehab center. It should start in the ICU. We're very fortunate to have a very engaged PM&R group and also very engaged therapists who are there from the get-go taking care of these very sick patients. Yeah, I would just echo that some of the patients who come in are not, some of our patients that we've come in that have transitioned out of the ICU, they had one or two underlying factors but they weren't altogether frail before they got the virus. So I think that they just maybe, so many of our patients who get critically ill are not, were not prepared for how deconditioned they would be and so setting expectations of you know, maybe you should consider rehab versus just going straight home depending on what is available has definitely been a challenge but also making sure that if it is somebody who does elect to go home ultimately knowing that at least you know, they're still viral positive and some of our patients have been healthy enough to be discharged but still we're testing positive for the virus, making sure that they did follow the quarantine rules and which has been interesting because you know we've had to make some, you know, making sure that we worked with family members and partners to get you know, their new medications to them but not necessarily interact with the patients has been, it's just taking a lot of strategic work up front to know that you're going to have to be a little bit creative and think outside the box but it has been, it has been manageable. Great, so I want to start taking some of the questions from the audience and just want to remind people if you jumped on late, if you have questions feel free to type them into the box and we'll ask them to our panelists. So one question actually returns back to tocilizumab. Do either of your institutions routinely place a PPD prior to tocilizumab treatment? That has not been our practice but I've heard of that being done, you know, I don't know, Marilyn? We have not yet, that's not to say at some point that we, that we wouldn't but you know we have not got to that point yet so and I think the theory is in the few patients that we have used the ILA-6 inhibitors is that if they're that sick at that point, you know, the risk outweighs the, I mean the benefit outweighs the risk. And same for my institution, I don't think we placed a PPD before we administered. The other question is, so given the fact we have some unknowns in terms of therapeutics, what treatments can you actually safely recommend for COVID-19 critically ill patients? I know Dr. Stephens wants to tackle that one first. Yeah, so I think it's interesting to observe the, there's a bit of a gap between what we're recommending sort of as an institution and what is actually happening in the clinical units, right? So, so for example, our, we have a interdisciplinary critical care committee we meet weekly to, you know, for strategic planning and we made a statement already several weeks ago where we recommended against the off-label use of unproven therapies, so that included things like hydroxychloroquine and antivirals and steroids and etc, azithromycin. So we recommended against using those and I think the statement was broadcast, you know, across the institution, but the fact is if you, you know, we're obviously not going to be policing individual providers and it's a fact that we have, you know, some very experienced clinicians who feel strongly that, that they want to use, you know, therapy X or Y and we're not going to stop them. So we have, you know, we have people here who are on hydroxychloroquine, we have people who are receiving steroids, we have people who are even receiving different, you know, antivirals. Now, I think the therapies that appear quite promising and where we have some experience and also we have ongoing protocols here are things like convalescent plasma, convalescent serum. This is something that, you know, we discussed at another webcast, but essentially it's a very old therapy that was instantiated already more than 100 years ago. The idea is to derive from patients who have, you know, recovered from COVID to derive their plasma and extract the antibodies from, from them and then re-infuse them into people who are becoming ill with COVID. And there is some preliminary evidence to support this. And so this is something that I think some of our, I think in fairness, some of my colleagues are quite interested in. There's also recently a report, I think it's not yet published, but it's, it's out there about the use of intravenous immune globulin. I think there is a study that is ongoing in Europe. And I've spoken to some of my colleagues who were quite enthusiastic about IVIG. Again, this is not published, so I'm not, I want to make sure that people don't think that I'm recommending it, but it's certainly something that is under investigation. So those are sort of immune modulating therapies that potentially could be of interest. Dr. Bullock? Um, so we, I guess, we did not take the stance that Hopkins did in terms of not recommending off-label therapies. We are, have just gotten into the process of sort of finalizing an optional order set, but it's again, nothing that's mandated that you have to follow. So most teams have sort of been prescribing what's out there. So the service that I work in, we have been using hydroxychloroquine. We've also been using zinc and vitamin C. We've not used some of the other options like lopinavir, ritonavir. And then of course, like most places, we can't get our hands on remdesivir or even convalescent plasma, this institution that I'm at. So I think it's, but then again, in some of our older patients, like very, very older, you know, old patients who are not, who are in the ICU, but are not necessarily intubated or in, you know, what could be dubbed as the cytokine storm, we've elected not to use potential antivirals with those patients, and have just used supportive care measures. And so, and I think this is probably the truth at most hospitals. There's just not a lot of consistency in terms of what most people are using. And even within, we had a discussion about this earlier this week, even when people are using the same drug, are they using the same dose? And is that impacting the results that we're getting? So I wish that we did have more consistent protocols, but we just, honestly, there hasn't been. And if you look at most of the guidelines that have been put out, most of them have, you know, have really taken very little stance on most things, you know, except to say maybe don't use this outside of a clinical trial. So everybody's kind of left to the Wild West, if you will, and are they right or are they not? I think time will tell. But, you know, with, you know, sort of the size of the institution I am, that's the approach that we've used. Yeah, I mean, the good news is that there are multiple randomized trials that are ongoing. The results of many of these will be out over the next few months. So we will know a lot more about what is effective and what is not. I think in the meantime, you know, since, as Marilyn is saying, we don't have robust data, I think it's reasonable for individual physicians to utilize their pathophysiological reasoning and implement therapies that they believe will be effective in a specific patient. And then, of course, once the data comes out and we have robust evidence, then I think we can develop more firm guidelines. But I know this is a bit frustrating, Lillian, but there is no proven therapy. I mean, I think we have to be emphatic on that. There is no proven therapy. So at this time, it's really for individuals to individual providers and physicians to decide what they think is going to be effective based on their knowledge and pathophysiology. And that being said, I know that it is very frustrating, but we have to think we're used to waiting months to years for these studies to be conducted and then for the data to be analyzed and released. And we're talking about very large international clinical trials saying that they're going to be able to wrap up by September and maybe we'll have the data by October. I think that we have to respect that. And I think that we have to appreciate just how quickly the investigators went from conception to data analysis. I mean, that's almost unheard of in most cases. And so it's frustrating now because we're in it. But I think, you know, by the time we go through the second season, we're not going to be flying blind like we are now. We're going to have more concrete answers. I mean, I would add to that, that if you look at the pace of scientific progress that has occurred in response to this disease, it is it's dizzying how rapid it's been. I mean, you know, the disease was basically recognized in December. You know, a few weeks later, we had already sequenced the genome. You know, we'd already developed, you know, diagnostic tests with PCR. We now have antibody tests and we're actively exploring, you know, therapeutic regimens, the results of which will be available over the next few months. There's also a lot of progress with vaccines, which I expect will be, you know, by by the early next year, we'll be ready for for for campaigns. So the pace of progress has been stunning. I mean, it's absolutely astonishing how quickly things have gone. And I think this is really evidence of, you know, what what people can do when when they're confronted with a massive challenge like of this nature. I can I totally agree with both of you, I think what's interesting to me is the fact that good, individualized, excellent, critical care supporting the person through whatever pathophysiology is exhibited by the individual patient with their endothelial problems is what we need to do our best at. I don't know there's going to be any therapy. What we really need to reinforce is that people will get better. We've seen all of these cases. There are long, hard courses for both families, the patients and the staff. However, if you do meticulous, individualized, critical care, supporting all the different organs that may be affected to buy time. And I do think that's something we've covered already earlier in terms of the remap COVID and having other randomized trials will help with all of that. We did. We did already address earlier in the recording regarding the D-dimer and the anticoagulant question. And I guess the only other last question that I'll ask in terms of is the convalescent plasma in terms of there was a question that came in in terms of the widespread use and whether there's any recommendations for access to be able to to gain access to the convalescent plasma. So I can tell you that at Hopkins, we've we are only administering convalescent plasma in the setting of existing trials. We have actually three ongoing trials using different dosing regimens and different timing regimens. But that's how we do it here. The data on convalescent plasma is promising. There's some really, really promising data coming out of China. Some of it is published. It's really essentially case series and some of it is not published. I think we have to really wait for the trials to be published to to get a better sense of the efficacy. But it is promising. I think it's it could wind up being a sort of intermediate therapy that we could implement until we have a more definitive treatment. And I would I would just agree, I mean, it's not a new concept that convalescent plasma is about a hundred year old therapy that's that's been successful in lots of other situations. And so but, you know, it's only been in the past maybe months that we even knew what antibodies to target for neutralizing purposes. And even then, I think that we still don't have an exact answer. So I would just echo that a lot of the data we have that's published, some of those patients were very sick, but they were also healthier at baseline. And so I think that it would be good for us to have some data in patients who are what we've been told are the more traditional COVID-19 patients, older, comorbidities, overweight, things like that. I'm very encouraged by the data that I've seen in the reports that are coming out from trials that are ongoing in the United States, including places like New York. But, you know, it's not going to be something it's not, you know, get any time you give blood products to anyone, it's not entirely, you know, without risk option. And so we just have to wait and see and get a little bit of a sense of, you know, what patients are going to benefit the most from it, you know, how high do your titers have to be before you qualify for donating and things like that. Excellent. We thank everyone for attending our question and answer session. This concludes our question and answer session. Thank you, Dr. Bullock and Dr. Stevens. Again, thank you to all of our panelists for joining us today. Thank you, Dr. Bullock and Dr. Stevens. Again, this webcast is being recorded and this recording will be available to registrants within 24 to 48 hours. To access, please go to covid19.sccm.org forward slash webcast forward slash. There will be more Q&A calls scheduled on the dates listed here. All of them begin at one central time. And this concludes our presentation for today.

COVID-19 treatment

ECMO

ventilation strategies

proning

individualized care

Remdesivir

IL-6 inhibitors

convalescent plasma

steroids

communication in the ICU