Hello, and welcome to today's webcast, post-acute sequelae of COVID-19. What can be done in and after the ICU to lower the risk of long COVID? My name is Rich Branson. I'll be moderating today's webcast. I'm a respiratory therapist, and I'm a professor in the Department of Surgery in the Division of Trauma and Critical Care at the University of Cincinnati and the editor-in-chief of the journal Respiratory Care. I do have disclosures. People that, companies that I do research with are consulting for Mallinckrodt, Pfizer, Ventec, Pfizer, and Zoll. None of these things we're going to be discussing today. Before we get started, a few housekeeping items. This webcast is being recorded, and the recording will be available in 24 to 48 hours at the website covid19.sccm.org backslash webcast or the AARC webpage listed. Please note that the disclaimer stating that the content to follow for information is for educational purposes only. The educational activity was funded in part by a cooperative agreement with the Centers for Disease Control and Prevention. The grant number is displayed here on the slide. The Centers for Disease Control and Prevention is an agency within the Department of Health and Human Services. Its contents do not necessarily represent the policy of CDC or HHS and should not be considered as an endorsement by the federal government. The Society of Critical Care Medicine and the American Association for Respiratory Care have partnered to produce this webinar on COVID-19. For respiratory therapists, the webcast has been approved for one CRCE by the AARC. Please note that you can only claim credit for attending the live webcast. From a standpoint of participation, in order to submit questions, you can submit questions throughout the presentation for our panelists. You can type the questions into the question box that's located on your control panel. If it has a triangle or arrow on it and it's facing right, click on it and have it face down and you'll see where you can type it in. There are also handouts that are available in the control panel for download as Adobe pages of the handouts and each of the slides that we're going to show today. So now I'd like to introduce our speakers. First we have Dr. Jennifer Posick, Dr. Posick is Medical Director of the Winchester Center for Lung Disease and leads both the Comprehensive Pulmonary Medicine Program, which forms the foundation of Winchester's consultation practice, and the Post-COVID Recovery Program, which provides evaluation and support for survivors of SARS-CoV-2 infection with persistent respiratory symptoms or complications. She also practices in Thoracic Oncology Program at the Smillow Cancer Hospital, focusing on treatment-related complications and pulmonary comorbidities in patients with lung cancer. Dr. Posick has nothing to disclose. Next is Joanna Stallings, Dr. Stallings is Medical Intensive Care Unit Clinical Pharmacy Specialist at the Vanderbilt University Medical Center in Nashville, Tennessee. Dr. Stallings is the Pharmacist for the Post-ICU Recovery Center at Vanderbilt, Vanderbilt Center for Critical Illness, Brain Dysfunction and Survivorship, and Pragmatic Critical Care Research Group. She is also Affiliate Pharmacy Faculty at Belmont University College of Pharmacy, Lipscomb University College of Pharmacy, and the University of Tennessee College of Pharmacy. Dr. Stallings also has nothing to disclose. Last but not least is Reema Mohammed, Dr. Mohammed is a Clinical Associate Professor of Clinical Pharmacy at the University of Michigan College of Pharmacy and Post-ICU Clinical Pharmacist Specialist at Michigan Medicine. She received her Doctor of Pharmacy from the James Winkle College of Pharmacy at the University of Cincinnati. She completed her Pharmacy Practice and Critical Care Specialty at Michigan Medicine. She is Board Certified Specialist in Pharmacotherapy and a Fellow of the American College of Clinical Pharmacy and an Innovative Clinical Model at the University of Michigan Post-ICU Longitudinal Survival Experience, the Pulse Clinic, in caring for ICU survivors and caregivers, including post-COVID-19 patients. Dr. Mohammed has nothing to disclose as well. So in order to get started, I'm going to turn this over to the speakers who are the experts. I'm just here to send your questions in the right direction. So I'm going to ask Dr. Pasek, when we have our first polling question, which is, which of the following is true of post-acute COVID-19 symptoms and the sequelae? Dr. Pasek? So, again, our first question is, which of the following is true of post-acute COVID-19 symptoms and sequelae? Is it that they are mainly attributable to deconditioning, that they are frequently associated with abnormalities in pulmonary function tests, that they may occur following any disease of any severity, or that they are associated with underlying pulmonary comorbidities? And so, yes, that is correct. We have observed that post-acute COVID-19 symptoms and complications have been identified in all patient populations following any acuity of initial COVID-19 disease. Next slide. So how common are symptoms in the post-COVID-19 population? Well, we don't know yet. And so it depends a bit on the time point following disease and which population you're talking about, whether it's all patients with COVID-19, hospitalized patients, or most specifically, the post-ICU population. And this information is evolving rapidly. Next slide. But if we start with the short-term view, the short answer is that symptoms are frequent. They are usually multiple in nature, but they're highly variable from patient to patient. This study from a group in Italy looked at symptoms 30 days post-discharge and found that 87% of patients surveyed still had symptoms, and that more than half of them were experiencing three symptoms or more, though there is some overlap with symptoms that were present during acute disease. The picture in the post-acute phase tends to shift a little bit, with some symptoms becoming more prominent than others. Next slide. And when you look a little bit further out, so at more like the one- to two-month time point, and you compare the patients who required ICU admission and those that required hospitalization but not ICU-level care, you start to see some important differences. One is that, as expected, symptoms are more prevalent amongst the post-ICU population, but that they align across both groups. I think, though, in particular, what I point out here is that, in addition to issues like fatigue and breathlessness, which are very common across different disease severity, the critical care group, in particular, had higher rates of neuropsychiatric complications relative to the hospitalized but not ICU-hospitalized group. Next slide. So when we talk about symptoms, what kinds of symptoms are being reported? Next. As we've already seen, it's highly variable, but it's important to recognize that there really are all kinds of symptoms being observed, and though we tend to think about COVID-19 as a respiratory illness, it's certainly not confined to the pulmonary system. There's a tremendous overlap with post-ICU syndrome, as you would expect, but really, symptoms can emerge in any organ system, in any combination. There are probably different phenotypes that are going to emerge with time, but we need more data, and hopefully, the meta-cohorts that will be developed as a result of NIH-funded research will help to clarify that somewhat. But I'd particularly highlight here that dyspnea, fatigue, exertional limitations, and then sleep disturbances, anxiety, depression, and PTSD are extremely common across all groups. So thank you, Dr. Posick, for providing a review of symptoms. So I wanted to talk about what is the impact of post-COVID-19 infection, and some of this data will include some non-ICU patients, but at least it gives you an idea. Next slide. So Moreno and Perez et al. looked at the impact of post-COVID-19 infection, and they evaluated the incidence of post-acute COVID-19 syndrome, or PCS, and they also looked at its components, and they also evaluated acute infection phase-associated risk factors. They defined PCS as persistence of at least one clinically relevant symptom, spirometry disturbances, and significant radiologic alterations. This was a prospective cohort study. It looked at about 422 patients who recovered from COVID-19, and most of them were about 66% had the severe form, which were of deinfection, and they were hospitalized. Only 9% were in the ICU. Unfortunately, about 14% of these patients died, and the investigators were able to follow up with about 277 patients, so 76% of the survivors, and they found that 59.9% of these patients presented with this post-acute COVID-19 syndrome, which is pretty significant. There was also a higher incidence of PCS, especially in patients who had severe pneumonia. It occurred about 60% of these patients. The most frequent symptom that was described in the study was dyspnea and fatigue, which is described in the previous studies. Dyspneic symptoms occurred about 12% of these patients, and that included headache, memory disorders, 9% still had abnormalities in their spirometry, and they also looked at factors that could be associated or predictors of PCS, and they didn't really see any baseline characteristics that would predict PCS from occurring. Next slide. And I'm sorry for this, very, very, there's a lot of details in this study, so I apologize for the small print in this table, but it's a very important study to look at. Chopra et al. looked at the impact of post-COVID-19 infection, and they described, so they described 60-day post-discharge clinical, financial, and mental health outcomes in these patients. It was an observational cohort study that included 1,648 hospitalized patients in 38 hospitals, and unfortunately of those patients, 24% did die during hospitalization, which is pretty significant, and 78% of those patients that survived went home, and about 13% were discharged to a skilled nursing facility or rehab facility, which I've seen as a trend, especially through our clinic, and 15% were rehospitalized within 60 days. The investigators followed up with these patients and completed, about 488 patients completed a 60-day post-discharge telephone survey, and as you see in this table, there were, you know, they looked at symptoms, so about 32% had cardiopulmonary symptoms, most common was cough and dyspnea, 12% had new or worsening difficulty completing their ADLs, almost half had emotional, had an emotional impact by their health, and about 12% of those patients sought care for mental health, so that's pretty important to highlight, and 40% of these patients who were employed could not return back to work, so that was because of ongoing health issues and job loss or job loss, so that's very important to note because of the financial impact that it does occur in these patients, and about 30% of these patients reported at least a mild financial impact from their hospitalization, so very important points to, in regards to the impact of COVID-19 on these patients, so next slide. So what can be done to prevent post-acute sequela of COVID-19 or PASC in the ICU? Next slide. So we think about the ICU liberation or ABCDF bundle, where A stands for assessing, preventing, and managing pain, B is both spontaneous awakening trials and breathing trials, C is choice of sedation or analgesia, D is assessing, preventing, and treating delirium, E is early mobility and exercise, and F is family engagement and empowerment. Next slide, please. So the Society of Critical Care Medicine coordinated this very large quality improvement project in over 15,000 adults a few years ago, specifically helping to implement the ABCDF bundle, and then looked at total and partial bundle compliance and associated outcomes. Next slide, please. And as you can see here, utilization of the ABCDF bundle resulted in a lower likelihood of seven important outcomes, so hospital death, next day mechanical ventilation, coma, delirium, use of physical restraints, ICU readmission, and discharge to a facility. And importantly, this was consistently a dose response. So in other words, the more you did of this, the better the outcomes you saw. Next slide, please. So I want to share with you the story of a patient of mine highlighting the multiple things. So first, the multi-dimensional and multi-system impacts that COVID-19 can have. Next, the complexity of post-discharge care and the importance of rehab. And finally, the potential neurocognitive and neuropsychological impacts of COVID-19 that may be overshadowed in the acute phase by cardiopulmonary issues. So this is a 55-year-old previously healthy gentleman who was hospitalized with SARS-CoV-2 infection after presenting with hypoxemia and pulmonary infiltrates. He required high-flow nasal cannula and ICU admission, but thankfully escaped intubation. He received antiviral therapy and corticosteroids, and clinical status improved. He did require two liters of oxygen at discharge. And by the time he presented to post-COVID-19 clinic, he had improving but persistent dyspnea, as well as daily palpitations. His PFTs and his room air oximetry, both at rest and with exercise, by that point were normal. But his subsequent CT scan showed some minimal residual fibrosis. And though not included here, he had a cardiac MRI that also showed evidence of prior myocarditis. EKG was unremarkable. Holter monitor demonstrated that his palpitations were only sinus tachycardia. He enrolled in a structured rehab program and made slow, steady progress after six months, and felt that he had largely returned to his functional baseline by that point. However, at a follow-up visit at our clinic, he reported significantly impaired memory and inability to multitask. He's a small business owner, and reported that he could no longer recall the names of his longstanding clientele, and was unable to balance his books. He reported increased depression and anxiety related both to his hospital stay and ongoing symptoms, as well as financial pressures. Neurologic imaging was unrevealing, and some of his symptoms improved with initiation of antidepressants, as well as cognitive behavioral therapy, but he's still not back to his baseline. Next slide. So, you know, before moving on to the next question, I think there's a couple of things I want to highlight. Looking back at his hospital stay, you know, where might have been the opportunities in light of what we've talked about? One was that, though he wasn't intubated, while he was on high flow, he was mostly in bed, because he would desaturate with any movement. So he really hadn't worked with physical therapy much. He was also very isolated from his family for the duration of his stay, and the focus really was on his oxygenation status, and not on other symptoms that he might have been experiencing, and that was true even of the initial post-COVID visit with us. He left the hospital on many new medications that he had not been on previously, and though we didn't recognize this initially at his first visit, it became clear that his sleep and circadian rhythms were a complete mess after discharge. So, sorry, next slide again. So, for patients with persistent dyspnea, how common are persistent radiographic findings or PFT abnormalities on follow-up? Again, this depends on the time point, the population you're looking at, and underlying disease. Generally, in COVID-19, those with radiographic pneumonia, the infiltrates are slow to resolve, slower than we might expect, so we shouldn't make assumptions about persistent interstitial disease too early. But like with SARS and MERS, we have seen a small percentage of patients who've developed fibrosis, and many providers will tell you that, anecdotally, they've encountered patients with organizing pneumonia that have had some response to steroids, and there is limited data in the literature that supports this in certain individuals. What we see here is a really helpful study published in Lancet that looked at persistent symptoms, radiographic changes, and PFT abnormalities, specifically diffusion capacity reduction in patients who required no oxygen support at all during acute disease, those who were hospitalized and required nasal cannula, or those that required higher level support. And as you'd expect, all of these abnormalities are more likely if you were critically ill and had severe disease, but it's important to recognize that the differences in symptoms and radiographic changes are not so striking between the different groups, the different severity groups, until you come to diffusion abnormalities and PFT abnormalities. And I'd also point out that across all of these groups, the subjective impairments really don't match well consistently with the objective findings, probably suggesting that we need to look at other pathophysiologic mechanisms. Next slide. So, besides cardiopulmonary complication, what are other areas of concern in the post-COVID population? So, beyond the discrete end-organ complications, particularly cardiopulmonary complications, we really need to look carefully at the functional impacts, and we're familiar with this from thinking about post-ICU syndrome, of course. This study compared the ICU-admitted group versus the non-ICU-admitted group, and they share a lot of similarities, but I'd particularly point out that for both groups, but particularly for the ICU group, anxiety, depression, pain, and inability to resume usual mobility and activities are significant. And this highlights, again, the importance of paying attention to the psychological sequelae. I think it's also important to highlight that we should have awareness of healthcare disparities and anticipate barriers to home services and care post-discharge because of the areas in which these patients struggle, and highlights probably opportunities while they're still in the hospital and even in the ICU for involvement of social work, family engagement, and early assessment of post-discharge rehabilitation needs. Next slide. So how is assessment and treatment of pain different in patients with COVID-19? So we talked about utilization of the ABCDF bundle and how that may be preventative with regards to PACS, but some of these different assessments may be complicated in patients that have COVID-19, so thinking about pain. So some strategies that we would recommend would include nurses should coordinate with other bedside clinicians, such as maybe respiratory therapists who are providing a bedside care to obtain nonverbal pain assessment. So maybe, and this was really very, very important early on during the pandemic when we were really worried about shortages of PPE. So maybe the respiratory therapist needs to go in and adjust a patient's backpack or do something with a ventilator so they're already in full PPE. So maybe they could learn to do a pain assessment on a patient nonverbal pain assessment, such as maybe the behavioral pain scale or the critical care pain observational tool to help assess the patient's level of pain. In the absence of pain assessments, pain should be assumed to be present. These patients have a lot of pain, in particular, neuropathic pain secondary to the virus. So if we're unable to assess these patients to see if they have pain, we need to assume that it is there. And some of the different domains of the critical care pain observational tool, so the CPOT, may even be accessible from outside the patient's door. So thinking about if you're looking at the patient's facial expressions, you may be able to even determine that from outside the door, so not having to fully put on PPE and go inside to see the patient. Next slide, please. So risk factors for pain may also be different in patients with COVID-19. So we all know that bedside procedures are painful and require additional analgesia. If you're going to do dressing changes on a patient, if you're going to insert a chest tube, et cetera, and these procedures can be painful and the PAD guidelines and PADIS guidelines would recommend to pre-medicate beforehand. So in particular, these patients are honestly gonna probably have more procedures, so we're going to be more cognizant of this as we're doing these different procedures. And opioid tachyphylaxis occurs as soon as two days after opioid infusions initiate. So as I'm sure many of you all know that have taken care of many of these patients as I have, many of these patients end up on opioid infusions for a number of days. So it's important for us to think about this and realize that as we're doing pain assessments, such as the CPOT or the BPS, that we need to adjust patients' pain meds accordingly. And then as we talked about before, these patients have a lot of neuropathic pain secondary to the virus, so that's where pain medications such as brucavalin or gabapentin may be helpful in this patient population. Next slide, please. Also, high-dose, long-term opioid infusions are common in people that have COVID-19. So we really need to disregard concerns about post-hospital opioid use. I work in Tennessee. We are one of the worst states in the nation with regards to opioid epidemics, and this is something we're constantly thinking about, but we have to treat the patient's acute pain. We've got to not think about that acutely, and we can think about that more long-term as people are getting ready to transfer to the ward or transfer out of the hospital. So using high initial opioid dosing in pain, or pain meds in these patients, if they're on chronic opiates. So if you have a patient that, for example, maybe has cancer and is on outpatient opiates, we need to take that into account when we're determining what initial dose of maybe a fentanyl infusion or a hydromorphone infusion that we would put these patients on and realize that they're going to need a higher dose at baseline. All these patients, if you came to the COVID ICU with me every day, even this morning, bowel movements is a daily discussion. It may be awkward and not fun to talk about, but we've got to make sure it can become a big issue and that these patients are on an aggressive, very aggressive bowel regimen to make sure that all the opiates that they are receiving is not going to lead to terrible constipation. And also remembering to reduce or discontinue opioid infusion rates before performing SBTs. So remember, an SAT, the spontaneous awakening trial, is not only turning off the sedation, but is also turning off the analgesia in these patients as well. Next slide, please. So how can we optimize spontaneous awakening trials, or SATs, and spontaneous breathing trials, or SBTs, in patients with COVID-19? Next slide, please. So once again, with COVID-19, and when the pandemic first started, we were all nervous, and rightfully so, in what was going to happen with regards to performing daily SATs and SBTs. Not only were we concerned about running out of PPE, but we were concerned that these patients were going to be on such high doses of sedation, analgesia, and such aggressive ventilator settings that we weren't going to be able to do these every day. So once again, thinking about sedation assessments may be compromised in patients with COVID-19. So it's important, just like we talked about coordinating bedside activities with pain assessments, you can also coordinate those with sedation assessments. So when you're in the room for something else, maybe turning the patient, or drawing lives, giving medications, et cetera, that's when you could determine their level of arousal. So look at either their SAS or their RAS, the Richmond Agitation Sedation Scale. Nurses should coordinate with other bedside clinicians providing bedside care to obtain sedation assessments. So this is just like pain assessments. So maybe if a physician this time is going into the patient's room to do something, then maybe they can determine the patient's RAS or their SAS so we can optimally determine what we need to do with regards to the sedation and the analgesia. And then lastly, the Biospectral Index Monitoring or ABIS Monitor may be helpful in patients on continuous neuromuscular blockers, because we're obviously using a lot more neuromuscular blockade in these patients to help them maintain vent synchrony. Next slide, please. So severe hypoxic respiratory failure may require deep sedation. I think that all of us that have spent a lot of time in a COVID ICU would say that a lot of these patients, unfortunately, do require deep sedation as the first means of rescue when they have severe acute respiratory distress syndrome. So it's very important. I can't emphasize this enough that we have to establish a new sedation goal every day. So every day on interprofessional rounds, we need to discuss the patient's actual RAS and their target RAS. So if, for example, the patient's target RAS is negative five because yesterday maybe they were paralyzed in the morning, but we were able to turn off the paralytic and we were able to lighten sedation throughout the day, then the next day, maybe that their target RAS can be lightened. Maybe today they only need to be a negative two or a negative three. I can't emphasize how important this is to discuss this every day, just so that we make sure that we are making some movement with regards to lightening the sedation up on these folks. So ultimately, we can try to get the sedation off and be able to do a spontaneous breathing trial and extubate them. Optimize ventilator settings before making medication changes. So we obviously want to make sure that we are doing ventilator changes, such as maybe optimizing PEEP, for example, before we are completely being very aggressive with regards to sedation and analgesia. So optimizing ventilator settings first before we completely snow the patient with more analgesia and sedation, which might not be needed. Not all patients with ARDS require deep sedation. Once again, this is hugely important that we remember this. And it's important that, once again, that's why we have to discuss their target and their actual RAS on rounds every single day to make sure that we are changing this when we need to, because we don't want to leave these patients deeply sedated any longer than we have to. It's very important that we think about performing spontaneous awakening trials, even if the patient's not gonna be able to pass the spontaneous breathing trial. We know that sedation is bad. Sometimes we have to do it in these folks, and we're having to do it in a lot of these folks, and it's happened to be deep sedation. But we also know, Yaya Shahibi's work has showed us that it leads to increased mortality, and it also leads to longer time on the vent. So we need to try to turn off the sedation every day and the analgesia if possible, even if we're not gonna be able, the patient won't be able to pass the spontaneous breathing trial. And non-nurses can help support SAT efforts. My role as a pharmacist, the people that work in the ICU can attest to this every single day on rounds. I'm asking about spontaneous awakening trials. So you can use different types of champions to make sure that those are happening every day. And this is especially important in the pandemic. If you came to Vanderbilt, we have, and this is not uncommon in many institutions, we have a ton of travelers right now. And earlier on in the pandemic, we had nurses, respiratory therapists, and physicians from every different unit in the hospital and physicians, every different type of discipline. So it's important to have someone that is constantly there and experienced with working with these types of patients to make sure that this is happening every single day. Use sedation protocols. This is something, once again, we know to be helpful and is recommended in the PAD and PADIS guidelines. And we can't let 20, throw 20 years of evidence out the window. It's important that we still use sedation protocols. Midazolam can definitely hang around for a long time, especially if a patient's been on a high dose infusion. I think a lot of us forget that because we typically have patients on propofol or dexmedetomidine infusions, because those are the drugs of choice with regards to sedation in the ICU. But unfortunately, as we'll talk about in a minute, due to certain side effects associated with propofol, quite a number of these patients do end up on midazolam infusions. And secondary to it, having the active renal metabolite and also undergoing oxidation by the liver. If patients have renal or liver dysfunction, or even if they're a larger patient, once you turn it off, it can hang around for a number of days. And then lastly, performing spontaneous breathing trial safety screen, regardless of the perceived SBT success. I'm sure Rich could attest to this, but sometimes patients surprise you. You think that, hey, there's no way on earth this patient's gonna pass the spontaneous breathing trial, but you still need to assess the safety screen every single day with hopes that eventually they will pass. Next slide, please. So how is the use of sedation different in patients who have COVID-19? Next slide. So analgesics and sedative drug interactions are quite prominent in patients that have COVID-19. So hypertriglyceridemia can occur secondary to the cytochrome storm mimicking HLH in these patients. So it's not uncommon to check baseline triglycerides in these patients, and they already have triglycerides of like 800 or 900, maybe secondary disease, or honestly, it might just be your patient population that has baseline high triglycerides. So we need to, as we have patients on prolonged infusions of propofol, we need to be very conscious about propofol infusion syndrome. So you think about patients that get the profound metabolic acidosis, they can get rhabdo, they can get renal failure secondary to the rhabdo, and they can also develop cardiac abnormalities such as arrhythmias that mimic Bergada syndrome. So with regards to this in our unit, we check creatinine kinase levels, and we also check triglycerides in these patients every three days. And our specific cutoffs are for the creatinine kinase, we have a cutoff of 5,000, and for triglycerides, we do not use propofol with a level higher than 1,000 would be our cutoff. Some institutions do use 1,200 as their cutoff, but it is important to set some form of threshold because unfortunately you are gonna see your patients reach this threshold once they've been on propofol for a number of days, and then they can be at risk for developing propofol infusion syndrome, and also drawing labs and things would be prohibitive if they had super high triglycerides as well. We also wanna think about monitoring the QTC in patients that are on methadone, which may be an option in a lot of different institutions, especially earlier on in the pandemic when we had a lot of drug shortages. So using drugs that we're not as familiar with, like methadone, it can really prolong your QT, so just remember to check that. And also, if you use antipsychotics, if your patients have severe agitation and you have considered those, then also remembering to check the QT in these patients as well. If your institution uses IV acetaminophen or paracetamol, the use of that can cause hypotension. I think that's something that if you're not familiar with that drug that a lot of people forget, so that's very important to remember as a lot of these patients are obviously on vasopressors. And non-steroidal agents in general should be, initially it was recommended that they should be avoided. However, you just really have to consider your specific patient population. Is your patient already in renal failure? Obviously, you're going to want to avoid these. They can be beneficial in certain patients if they don't have renal dysfunction, if they don't have a high GI bleed risk, et cetera, they can be helpful to decrease utilization of opiates. Next slide, please. So there is an increased risk for opiate and sedative withdrawal in patients that have COVID-19. So this is where you're going to want to think about enteral administration to help decrease withdrawal from these agents. This is something, once again, some of our ECMO patients in particular who have been on high doses of sedatives and analgesics for a number of days, one strategy that you could consider to help wean them off that we've definitely had to implement is giving enteral maybe methadone, or it could be oxycodone, something you can crush and give per tube, or benzodiazepines potentially as well, such as diazepam or lorazepam to help decrease withdrawal in these agents. And you do have to make sure enteral absorption is reliable because obviously if a patient is in shock and on high-dose vasopressors, then enteral absorption may not be reliable. Next slide, please. We also, as I alluded to earlier, I think all of us can attest to that, unfortunately, we're using a lot more neuromuscular blockade in patients with COVID-19 as rescue therapy for ARDS. So with regards to recommendations for that, you would want to consider using intermittent boluses first. So what we typically do is try to give patients intermittent doses of Vecuronium first. And if they are responding to that, but they can't tolerate the hypoxia in between doses, that's when we would consider putting them on a continuous infusion. We would do a susatocurium infusion typically just because we wouldn't have to worry about any hepatic or renal metabolism issues since it undergoes Hoffman degradation. And also something very important, we're all familiar with spontaneous awakening trials and spontaneous breathing trials, but something that doesn't really have a name that we need to think about is a paralytic holiday. Absolutely. Every day, we need to be discussing whether or not we can turn off a patient's paralytic. And this needs to occur daily. At the most, you would wait two days until the patient becomes dyssynchronous on the ventilator or patient movement has occurred. Next slide, please. So how do you recommend preventing and treating delirium to prevent PASC in patients with COVID-19? So delirium screening will be reduced in patients with COVID-19. Once again, this was particularly problematic early on in patients due to their concerns about running out of PPE. So delirium should be assumed to be present in the absence of assessment results. So we know that COVID-19 involves the brain. And so it essentially itself, the virus can cause delirium. We need to prioritize delirium screening in periods of greatest wakefulness. So in other words, one of the best times that we can do this is when we have whitened the patient's sedation or turned off their sedation and analgesia to really determine if the patient is CAM positive or if their ICD-SC would indicate that they have delirium. Other bedside clinicians can be trained to perform either the CAM ICU or the ICD-SC if the nurse cannot. So once again, I know how to perform these tests as a pharmacist, physicians know how to perform this, nurse practitioners, PAs, respiratory therapists. I don't think there's ever been a time in critical care that we all needed to work together as a team than COVID-19. So once again, everybody can learn to do these assessments. And when you're the one in the room, then you can be the one that's doing this assessment. And then also just talking to patients and ask them if they are scared and if they are fearful and what we can do from a non-pharmacologic standpoint to help the patient feel more comfortable. Next slide, please. It can also be challenging to recognize and reduce potential modifiable risk factors for delirium. So new delirium can be a red flag for worsening sepsis, a new acute neurologic injury, or the need for fluids or electrolytes. Maybe your patient's hypoglycemic or hyponatremic or hypocalcemic, these all might end, or delirium may be the red flag for any of these different abnormalities. Just like we would talk about in non-COVID positive patients, we need to think about a non-pharmacologic strategies to prevent and treat delirium. So trying to normalize their sleep-wake cycle and to try to make it as quiet as possible, to make it dark at night, to help these patients sleep better, to decrease the risk of delirium. And then also drug-associated delirium is often dose-related. We obviously know that steroids decrease mortality in COVID-19 patients, and we're using a lot of these, which is further exacerbated delirium in these patients. And then we've talked about why sometimes we might have to use benzodiazepines in these patients. So we want to think about using as small a doses of these agents as possible, but sometimes it is what it is, and you have to think about it is what it is, and you have to use these agents in these patients. Next slide, please. So which medications have been associated with increased risk of ICU delirium? So for the medications, as Joanna has already mentioned a lot of them, you've probably already seen this or are familiar with this mnemonic, Dr. Dre. The biggest thing that I wanted to highlight is looking at the risk of delirium and being associated with appropriate pain management, sedation. So as Joanna mentioned, the use of benzodiazepines, especially high-dose benzodiazepines, have been utilized a lot more with the COVID-19 ICU patients. And then looking at the ABCDEF bundle, so very important to implement it, use it, but those are potentially some of the medications, especially focused on appropriate pain management, managing the patient appropriately, and then the choice of sedation. And the management of COVID-19 patients, ICU patients, can be extremely difficult, very, very different. As Joanna mentioned, the use of benzodiazepines usually is not recommended as first line, but sometimes we have to use it, especially if a patient has high triglycerides with propofol use. The use of neuromuscular blockers, again, it is more likely, especially in the COVID-19 ICU survivors or ICU patients. So it's very important to think about this tool, especially for the management of delirium. And again, highlighting here more medication-related factors such as the use of benzodiazepine. So next slide. So can patients with COVID-19 achieve early mobility? I love this answer. 99% of you all said yes, which is definitely the appropriate answer. Next slide, please. So, we'll look at this case study. A 65-year-old man is admitted to the COVID-19 ICU with a previous medical history of hypertension, diabetes, and obesity, and he is currently receiving BiPAP. So, what are some ways that he or to involve the family? So, things that we could think about with regards to the family. If you're like my institution, we didn't have family visitation early on. I think most institutions were like that. So, we had to get pretty creative. We had to use things like iPads or maybe even an iPhone, and the nurse or restorative therapist or pharmacist, physician would use that to help the family be able to interact with the patient. So, that was one idea. Now, at Vanderbilt, we do have family visitation between 1 and 3 p.m. every day where the family can come in and sit outside the patient's room and interact with the patient. And I think that's really been beneficial for not only the patient, also the family members, but also the staff as well. If the patient was sedated, what could have been done to involve the family? So, once again, like we talked about using tablets or using phones, even the patient sedated, we were still doing this to let the family members see the patient, and even that provides some peace of mind to the family. And what are some other non-pharmacologic interventions that could be incorporated into care to help him think of the family? So, typically, we would think about doing things like putting pictures in the room. Once again, depending on your institution's rules, you might not be able to bring in like pictures and frames, but you can print off pictures and maybe put them on like a bulletin board on the wall, different things, like anything to really help the patient feel at home and more normal. It's going to make them feel better and more comfortable and help potentially decrease their anxiety. So, those are just a few examples of what you can do to make the patient be connected with their family, even if their family can't be physically present. Next slide, please. So, this is a polling question. So, which of the following medications may be inappropriately continued in a post-COVID-19 patient after hospital discharge? So, that's good. So, definitely, all of these are potentially inappropriately continued medications in the post-COVID-19 patients and even in just post-ICU patients after hospital discharge. And so, as far as...there was one study by Tully et al. that reported that 28% of patients had medications continued with ICU-only indications, and that includes things such as PPI for stress-related or stress ulcer prophylaxis, the use of antipsychotics for severe delirium. So, that's pretty significant, and it's very important that, especially when patients are transitioned from the ICU to the floor, that these...that we do intervene and make sure that these medications are not continued on the floor and then post-hospital discharge. So, it's important, again, to evaluate that the medications all have an appropriate indication. And then, as far as opioid use...so, it can be appropriate in certain patients, but it's important to evaluate the PAN management plan, especially when we're sending these patients home. Opioids, especially if they were priorly or on opioids before, is the dose even appropriate? Do we need to think about renal considerations, liver considerations? And then also evaluating, are there other mechanisms? Can physical therapy help? Do they need to be on a medication to help with neuropathic pain? So, opioids may be appropriate, but, again, looking at the overall pain management plan. Next slide. And so, what are the points that should be covered before discharging a patient, especially a post-COVID-19 patient? And this is a very, very helpful infographic, a great tool to use, and remember, prior to discharging a post-COVID-19 patient. And some questions to ask. So, I call this the the dirty dozen. So, there are 12 points to cover before you do discharge the patient home. And some questions to ask are, are their home medications mostly restarted? So, some examples are, you know, during their ICU stay, especially if they had changes, they had acute renal failure, changes to the renal function, that can prevent us from restarting their ACE inhibitor, for example. So, we really need to think, before we send these patients home, is there a plan? When is it safe to restart these medications? And then also thinking about maximizing these medications. So, inhalers, so, or if they're a patient who has diabetes and they were not managed, or not, their diabetes is not under control, we need to make sure that when we do restart these home medications, that they are being also maximized to its full potential. Also, another question is, do they really need to be on the antipsychotic, PPI, H2 blocker, sleep aids, or opioids? And we've already talked a little bit about this previously, but these are potentially inappropriate medications that would, that I have seen continued post-hospital discharge. And then, what's the plan for anticoagulation? And a lot of these patients are started on anticoagulation and are discharged on therapy with no clear plan. So, it's important for us to set a plan and say, okay, this is the duration of anticoagulation prior to sending these patients home. Another question is, what is the plan for who the patient should call in the event of a new issue that arises prior to their first primary care provider visit? So, who should they contact? Should there be an outreach to these patients when they do go home? And then, encourage patients to gently push themselves to move and exercise. Of course, we know that deconditioning and fatigue are major problems in these patients, so it's important for us to provide a plan that's realistic, but we do know that immobility is bad for recovery for these patients. We should ask ourselves, are there lines or temporary devices and are they out? And if not, do they have a written list of all these lines, tubes, strains that they may have been discharged on, you know, or they had during the hospitalization? And then, I wanted to highlight that these patients can be completely overwhelmed with their post-discharge recovery and they have a million things that they need to do after they're being discharged from the hospital. So, it is crucial before they go home to give these patients and their caregivers a few things to follow up on, especially what are the absolutely key things that they need to follow up on immediately post-discharge. It is always better for the patients to have absolute key things then to follow up on than being overwhelmed and confused and do none of it. So, very, very important to highlight what are the key main things for them to follow up on. And then, we do know that the top five reasons that patients get readmitted after severe infection, especially looking at the post-sepsis literature, we do need to educate these patients and their family members or caregivers on how to respond to early signs of repeat infection. If they have congestive heart failure or risk, looking at those because those are potential risks for readmission. Aspiration, acute kidney injury, and COPD, especially if they've had a underlying COPD condition. Is occupational physical therapy. Have they seen the patient and did they come up with a plan for the patient? And then, very important that I see a lot of is that can they really pay for the follow-up and medication therapy that they need? And as you remember, as I discussed earlier, is that a lot of these patients can't go back to work or have lost their jobs and that and then sometimes not just family members, but our family members, not just patients, but it can impact their family members and their caregivers as well. So, can they really afford all these follow-up appointments as well as medication therapy? And then, most importantly, we really need to ask, have we given information about PICS or post-intensive care syndrome? And there's a lot of references that are out there, especially for providing education. And then, definitely a great avenue for these patients, if there is a post ICU clinic or post COVID clinic out there for follow-up, that's another resource to utilize. Next slide. So, I wanted to kind of finalize, you know, really looking at the patient, kind of what happens through the patient's recovery and what happens in their ICU stay. So, this is a case that I've actually seen in the clinic more recently, but this is a 47-year-old woman who had a history of morbid obesity, came in with ARDS from COVID-19 and was complicated by several things. The patient did receive ECMO. The ICU stay was complicated by septic shock, AKI, delirium, post-ICU anxiety, probable was PTSD. The other complications included worsening depression. The patient did have baseline depression prior to being admitted, had an ILEUS, AKI was sent home on hemodialysis, did have some VTE, so was discharged on rivaroxaban, so anticoagulation, had hypertension, had hyperglycemia, so she had possibly underlying diabetes that wasn't diagnosed prior to her ICU stay and was discharged on insulin. She was eventually discharged on a long-term acute care facility and finally discharged home after three months and the only medication she was on was allergy medication. So, next slide. So, I wanted to share with you this. So, the patient was really on one medication, really using it as needed prior to hospitalization and now she is on many medications and this is very, very common and I'm seeing it a lot in our post-ICU, especially post-COVID ICU patients, but just some things to highlight. Now, she's, she was on dialysis. She was put on several medications for dialysis. As her renal function improved, some things that did continue were Lasix, for example, and the patient was confused. She was saying, well, I'm going to the bathroom very often. Why do I need to be on this medication? So, some things, again, if you're going to put a discharge a patient on a medication, we need to come up with a plan or follow-up as far as when these medications need to be stopped. Other things are like anticoagulation. The patient was put on insulin, but really could not afford the insulin therapy, which we know is very, very expensive. The patient had sleep issue, insomnia, depression, so I wanted to at least give you a visual of, you know, this is, this is very, very overwhelming for a lot of these patients, so we really need to try to keep things simple. Next slide. Okay, thank all three of you. We have about nine good questions I'd like to throw at you, so in order to get them done, we're going to have to be pretty brief, but one of, I'll combine two questions. One question was, has speech therapy been involved in outpatient clinics, and what about the use of cognitive screening for these patients before they get discharged? So, speech therapy has been very helpful, particularly for patients who have swallowed dysfunction or just phonation issues during their admission. This obviously often combined with other kinds of rehab. Cognitive screening is very important. You know, I would say even more so post-discharge than pre, but sometimes by identifying cognitive issues early when sedation and analgesia has been minimized as much as possible can be a helpful flag for setting up success for the outpatient provider. Thank you. So, there have been two questions about nutrition. A comment that these patients are very hypermetabolic. What about feeding? Limitations of feeding due to hyponasal cannula or the use of non-invasive ventilation, and is there a, you know, a chronic hypermetabolism associated with this disease post-acute care? I guess I can say that we are very I guess I can say that we have certainly seen a number of patients who have come out post-discharge with significant weight loss and more specifically significant sarcopenia. Not so much ongoing hypermetabolism post-discharge though. Thank you to other questions. Joanna was asking about a value, a laboratory value for deciding not to use propofol, and somebody wants you to clarify, was that for triglycerides? Yeah, I'm sorry if I was confusing. So, 5,000 we would think about for your cotinine kinase, and then we think about 1,000 is what we use. Some people use even 1,200 for a cutoff for triglycerides. Okay, thank you. Do any of you have experience with patients using, you know, because they've been isolated so much, the ICU diaries? I do. We had an ICU diary program, like pre-COVID, and that's something that honestly we didn't do a lot during COVID, but we are starting to re-implement that. But I think that it's been something that's been really, really helpful for patients to be able to, or physicians, nurses, pharmacists, respiratory therapists, etc., to be able to write in. We've had people come to our post-ICU clinic who really value that, that we're able to look and see, essentially, remember their story better, what they might not have remembered if it wasn't listed in a diary. So, I think they're very helpful. Joanna, why have you? Somebody wants to know, why would you turn off the opioid infusions when you do the SAT, SBTs? Wouldn't some of these patients need the continued pain control? Well, so the ABC study led by Tam Dorard-Wright that was published in Lancet actually turned off the analgesia and the sedation. So, I think that what you're asking is if a patient still was in pain. So, if their CPOT indicated they were in pain, absolutely, you would put it back on. You've just got to see what the patient is able to handle. So, we've got to try to turn these things off, but absolutely, you would never be cruel to a patient and always treat their pain appropriately. Yeah, thank you. Bruce Robinson did some work on that when we were doing SBTs in trauma patients. One of the questions is about anticoagulation guidelines post-discharge. Are there any guidelines yet about what anticoagulants patients ought to go on post-discharge? I think that's still an area of uncertainty, you know, except for patients who have had, you know, clear documented thromboembolic events during their illness. I don't know, Joanna and Reema, if you have more to add. My understanding is that also is an undocumented area that unless there's a reason, obviously, if that patient got a DVT or a PE and they have an indication for it, then we would continue it. But just because they have COVID, I think that most of us would be very hesitant to do that, especially with the data coming out in the ICU, or three studies stopped essentially to show us that it was harmful and that we wouldn't do that. Yeah, I agree. I think initially we were using anticoagulation early on for most of the COVID-19 ICU patients, but no, now it's documented or high risk of VTE. But as far as the plan, I think it's just what, you know, what was present. So if it's a PE, if they had underlying, you know, coagulopathies, things like that, that's usually what we set for duration. Okay, thank you. There's a question about intracranial, elevated intracranial pressure in COVID-19 patients and any effective opioids. I haven't seen this reported. Do you have any experiences? Has anybody monitored ICP in these patients? I have not seen that. I don't know if Reamer or Jennifer can attest to that, but I have not seen that. I haven't been aware of that, but someone with neurocritical care experience might have a different perspective. There's a question more about the post-COVID clinic. You know, how quickly can you get it set up? Do you normally do pulmonary function testing on these patients? Do they get a CT scan, a six-minute walk test? What's the timing for follow-up? Is it, you know, from discharge to the first time you see them? And how often are you using telemedicine to follow up on these patients? Lots of good questions in there. Go ahead, Joanna. I was just going to say, in our PICS clinic here at Vanderbilt, it's taken us about a month or so, even two months, to see the patients because a lot of patients go to a facility. It's not really beneficial to see the patients when they're still in a facility. You want them to actually be at home. And then the other part I'll answer is that we had actually started a telehealth program just prior to COVID, which has been really helpful. And our attendance rates have actually skyrocketed in COVID secondary to using a telehealth. So we have utilized that a lot. If Jennifer and Reema want to answer some of the other parts. Yeah, I think telehealth has tremendous potential across the board, both in early evaluation and in follow-up, because access to post-ICU care and post-COVID care is such an issue in terms of supply demand. I'd point out that each post-COVID center is really different from one another, depending on the populations they're focusing on, the stakeholders involved, the resources that they have. And so they've really emerged organically at different centers, and each has something else to offer. We've found at our center, at least with time, that the six-minute walk testing is incredibly enlightening, as is outpatient physical therapy re-evaluation, to really hone in on functional limitations in multiple dimensions. Pulmonary function testing is helpful, but often normal in absence of persistent radiographic findings. And conversely, we very rarely find unexpected radiographic findings in people with normal PFTs. So I think the six-minute walk is a priority, as well as functional assessment, screening for psychiatric mood disorders, and screening for cognitive impairment. Yeah, and I agree with that. With the post, I mean, every clinic is very different, but I would say definitely, you know, the telehealth, I know initially when we were having the, you know, last year with the surges, telehealth is crucial because, you know, we would do outreaches to all the patients who were in, who were ICU, in the ICU, and you know, assess, should we see them in our clinic? We don't, we have very limited availability. So can we see them in the clinic? Can we provide the care through telehealth? But it's, it's, it's definitely very, very helpful initially. And there's a specific question about the patients who really have primary pulmonary manifestations long term, you know, I'm sure there are no guidelines by now, but what are the recommendations for treating people who have these persistent ground glass findings on CT, shortness of breath, exertion on dyspnea, persistent cough? I think indeed, there are no guidelines both for even meeting criteria for, for post-COVID conditions at this point, though, I think that is coming soon. And because the pathophysiology of these symptoms is, is not yet understood, there are no guidelines for treatment. But we do find that depending on the nature of the patient's symptoms, that different sorts of approaches, very patient-centered approaches to rehabilitation can be helpful. I think first and foremost, though, ensuring that you've excluded any other contributors to their symptoms is really important. And that's where that, you know, it really has value to get them in early, back to primary care, and back to a post-COVID experienced clinic to, to rule out those other issues. But addressing rehabilitation needs early is important in this population. So I have to say, one observation that I have after 30 years of ARDS research, all non-COVID, is that it was rare for somebody to develop de novo respiratory failure. So not COPD patients or, you know, chronic lung disease patients. Trauma, sepsis, pneumonia, develop ARDS, and then go home on oxygen. It seems like in COVID-19, the number of patients who go home on oxygen is markedly greater. Is that your perception, or does anybody have data? I don't have data, but certainly, you know, the duration of intubation is skews towards longer. There are patients who certainly go home and continue to require oxygen. The majority of people we've seen, even who leave the the hospital on oxygen, do wean off. Those people who don't, though, are the ones that really require additional attention and evaluation. And we have had findings on imaging that are suggestive of organizing pneumonia in a few, like vanishingly few. And, you know, based on the, the limited data that's published, we have tried steroids to success in some of those patients. But there are no formal guidelines yet. Okay. I did want to stress, too, is, like, coming up with a plan. So, some of these patients go home on oxygen, but is there a weaning plan, you know? And sometimes the patients, what I've noticed is, like, they are, it's anxiety-driven. So, even though they just feel like they want to continue on, on HOMO-2, but they're, they're just worried about weaning off, and, you know, it's, it's very anxiety-driven. There is this big group, though, that's normoxic, but dyspneic, and that's real, and it's not all anxiety-driven. So, it probably reflects that there are these other pathophysiologic mechanisms leading to ongoing dyspnea that routine evaluation doesn't really elucidate, and that's why we have to dig deeper and look at other causes. But that's, by far, the largest phenotype we see are people who are not on oxygen any longer. Their saturations are normal, but they're still profoundly dyspneic in addition to symptoms. So, two more questions. One question about any recommendations for the bowel regimen in these patients. Well, be as aggressive as you can possibly be would be my recommendation, and we usually start with, like, some senin, some docusate, some mirilax, and that doesn't usually work, and so we end up putting them on oral Narcan, honestly, and that usually does the trick, and then we end up, like, they'll be on four milligrams TID for a few days, and they end up on eight milligrams TID. If they have an ileus, then you, obviously, the oral Narcan is not going to get there, so you might try a methanolotrexone. We've tried Golightly drips, where you literally are, like, infusing that kind of, like, somebody's going to get a colonoscopy. That also does the trick. I mean, whatever you can do, obviously, an enema, you name it, we've tried it, especially, I should emphasize, in pregnant women, and with all that estrogen, they are particularly very, very, very constipated, so whatever works, please try it. And then one question about the recovery and active IV trials. Are these studies, aren't they studying anticoagulation in the outpatient setting? I'm not familiar with either trial. They are, but they're still not formal recommendations. Okay, right. Okay, so, hopefully, we'll have some data. All right, we went over a little over time, but I wanted to get in everybody's questions. Thank you for everybody who attended. Thank you to the speakers. I mean, you did a great job with a really emerging problem. I think it's pretty interesting for me, again, from a respiratory therapy ventilator standpoint, whenever we talk about a situation like this, where there's concerns over ventilator shortages, we always talk about polio and what happened during the initial polio epidemic, and one thing that people forget about is that polio was, you know, was the paralysis, but post-polio rehabilitation, you know, maybe that's post-polio ICU syndrome. Those patients went through horrible, painful rehabilitations, and then, as they get older and get better, then they get post-polio syndrome and end up going back on a ventilator with non-invasive ventilation, so maybe there's something we, more than we can learn about COVID-19 from polio than just ventilators and worrying about having enough of them. So, again, thank you guys very much. I learned quite a bit today. As a reminder, this webcast is being recorded. The recording will be available on 24 to 48 hours at covid19.sccm.org backslash webcast or at the AARC web page that's listed at the bottom of your slide. Please be sure to visit SCCM's COVID-19 Rapid Resource Center at the site listed below in blue for more resources. The webpages featured as additional resources are clickable in your handout that is downloadable in your control panel. For respiratory therapy members at the AARC, be sure to check out the website. For respiratory therapy members at the AARC, be sure to visit the AARC COVID-19 News and Resources at the site listed in blue. Again, thanks to everyone, and that will conclude our webcast for today. Appreciate your time.

long COVID

ICU patients

recovery period

fatigue

dyspnea

pain management

sedation optimization

delirium prevention

medication risks

post-ICU follow-up

research