SCCM Pod-453 Extracorporeal Blood Purification

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Because COVID-19 can create a status of systemic inflammation, which can affect multiple organs, including the kidneys, the adjuvant therapy of blood purification has gained some recognition. Host Pamela Peeke is joined by Javier Neyra to discuss clinical cases and the use of extracorporeal blood purification in COVID-19 patients (Rosalia R, et al. Blood Purif 2021. doi: 10.1159/000515627). Dr. Javier Neyra is an Acute Care Nephrology and CRRT Program and Assistant Professor at the University of Kentucky Medical Center in Lexington, Kentucky. This podcast is sponsored by Baxter.

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Transcript:

This podcast is sponsored by Baxter Healthcare Corporation. When you choose Baxter for your CRRT program, you’re not only choosing true patient-focused treatment with industry-leading CRRT technology, you’re also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury. Our commitment to you starts with a program individualized to your facility’s needs and provides complete support every step of the way. For more information, visit us at www.renalacute.com. Baxter Healthcare corporation has provided funding for this podcast, but all content was developed independently by the presenter. Therefore, the views expressed on the podcast are those of the speaker and should not be attributed to Baxter Healthcare Corporation. For prescription use only. For the safe and proper use of this product, please refer to the operator’s manual. 

The Oxiris set device is authorized under EUA200164 emergency use authorization to treat patients 18 years of age or older with confirmed COVID-19 infection admitted to the ICU with confirmed or imminent respiratory failure in need of blood purification, including CRRT. This device has been neither cleared nor approved for the indication to treat patients with COVID-19 infection. The device is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the Oxiris set under Section 564B1 of the Act 21USC360BBB3B1 unless the authorization is terminated or evoked sooner. 

Pamela M. Peeke MD, MPH, FACP, FACSM: Hello and welcome to the Society of Critical Care Medicine’s iCritical care podcast. I’m your host, Dr. Pam Peeke. Today, we’ll be talking about Oxiris and blood purification. I’m joined by Dr. Javier Neyra, who is director of the Acute Care Nephrology and CRRT Program and associate professor at the University of Kentucky Medical Center in Lexington, Kentucky. Dr. Neyra, welcome.

Javier Neyra, MD, MSCS, FASN: Thank you very much for the invitation. I’m happy to be here. 

Dr. Peeke: Before we start, do you have any disclosures to report? 

Dr. Neyra: Yes, I have provided consultation to Baxter, the company that provides this type of membrane, Oxiris. This will be the central topic of this discussion about blood purification.

Dr. Peeke: Wonderful. For all of our listeners, we have learning objectives. First, we’re going to be looking at the pathophysiology of COVID-19, then the use of extracorporeal blood purification in COVID-19 patients. We’ll also understand where Oxiris can be used and discuss clinical cases of Oxiris. Why is this podcast needed? The bottom line is: It’s needed to bring awareness to blood purification strategies with COVID patients using Oxiris. What are the knowledge gaps that this podcast will address? The first is how blood purification can be used in COVID-19 patients and, second, how and when to use Oxiris blood purification. First let’s start with the pathophysiology of COVID-19 and why we’re having this conversation about blood purification in the first place, Dr. Neyra. 

Dr. Neyra: These are very challenging times. We have learned during this pandemic that COVID-19 disease creates a status of systemic inflammation, which can affect multiple organs, including the kidneys. For this reason, the adjuvant therapy of blood purification has gained some recognition, particularly because it can control dysregulation in the immune system and can address removal of cytokines, which in some patients, if applied at the right time window, can be beneficial for their clinical course.

Dr. Peeke: Excellent. Talk to us about the current use of extracorporeal blood purification in COVID-19 patients. 

Dr. Neyra: We know that there is a group of patients who develop severe COVID-19 that will require ICU care, high requirements of oxygen, and sometimes mechanical ventilation. These patients, who are considered to have severe COVID, typically also have multiorgan failure and systemic inflammation. Among these patients, close to 50% will develop acute kidney injury. Nephrologists are always involved in the care of these patients to evaluate needs of dialysis. In the ICU, we typically perform dialysis in critically ill patients with CRRT, which is continuous renal replacement therapy. In this setting, we can provide different methods of dialysis, including recently expanded hemoabsorption with some newly developed filters. This has broadened the term of blood purification because we can combine different techniques on CRRT, which include effusion, typically the same technique commonly done in any patient on hemodialysis; convection, which is exclusive to patients receiving CRRT; and in addition to these, the hemoabsorption properties of certain filters like Oxiris. There are other filters as well that can remove some of the pathogens. The field has really exploded in the sense that there are multiple available methods now to provide timely blood purification support to these patients if applied in the ideal time window, that is, early on in the course of acute illness. 

Dr. Peeke: Excellent. We’re really addressing cytokine-absorbing hemofilters, aren’t we? 

Dr. Neyra: Absolutely. These filters will absorb cytokines. Most of their success in what has been reported thus far has been evident when this treatment is instituted in the first 24 or 48 hours of a patient developing multiorgan failure and ICU care.

Dr. Peeke: When you’re talking about this, I think our listeners would need to understand where Oxiris can be used and when, so perhaps an example or two of how you have utilized this particular hemofilter. 

Dr. Neyra: Oxiris provides an enhanced hemoabsorption property. At the same time, you can continue to provide diffusion and convection, according to your prescription. In our institution, we created a protocol in which we use Oxiris in the first 48 to 72 hours of a patient requiring CRRT support due to COVID-19 disease and multiorgan failure. In these patients, we typically will use it for up to three days, typically one or two filters because these filters last on average around 36 hours. We typically use a couple of these filters in the first three days and early on in the course. 

For example, we have a patient with COVID-19 who was in a different hospital and transferred already from ICU to ICU after more than a week of advanced organ support. These patients probably have very little benefit of hemoabsorption at that time, so we are not necessarily using Oxiris in these patients. But in a patient who is recently admitted with decompensation from COVID-19 requiring ICU care and multiorgan failure, who is being evaluated for CRRT, we prefer to use the Oxiris filter for at least the first three days to provide this enhanced hemoabsorption and therefore try to further support the significant inflammation that these patients develop.

Dr. Peeke: Excellent. Fantastic. You provided me with an excellent reference from the journal Blood Purification from June 2021. It was called “Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study.” Here we are looking at hyperinflammation and coagulopathy. In this case, the Oxiris cytokine-absorbing hemofilter was used for extracorporeal blood purification. Tell us a little bit about this study. 

Dr. Neyra: This is a study from Italy that very nicely described experience with patients who require CRRT and used Oxiris. These patients had COVID-19. They describe the clinical course of these patients, which was significantly improved if you assess markers of organ failure. For example, scores of critical illness, such as SOFA, improve significantly when the patients received the treatment. They used a historical control group. That’s why we need to, of course, evaluate this data with caution because these were observational data, not a randomized controlled trial. The control group was a historical similarly sick group in which the trajectory of the clinical course was significantly different. It was worse when patients did not receive this enhanced hemoabsorption. This suggests so far that perhaps these enhanced hemoabsorption filters can provide some benefit in these patients. The authors mentioned that very clearly when it’s applied early on in the course of acute illness or multiorgan failure. 

Do we have data to support that these patients have better survival? We still do not have this type of data of hard outcomes to suggest that the use of these filters should be standardized. But the preliminary observational data suggest that these patients have a better clinical course when they receive this treatment early on. And the data are evolving. I’m aware of some clinical trials that are ongoing, despite the focus on COVID-19 support right now, because that is, in the U.S., the emergency use authorization that we have for these filters.

This concept of hemoabsorption is not new. It’s just that we have been pushed during this pandemic to their rapid use because there may be a phenotype of patients who can benefit from it. Our challenge of course is to identify who these patients are, confirm this with clinical data, and show that when we provide this enhanced treatment to patients of this particular phenotype, we can improve clinical outcomes. As of now, data are evolving, but still, as I mentioned, the controls are typically historical controls and there are no randomized clinical trials to support its standardized use. 

Dr. Peeke: Fantastic. This is really, really helpful. In this one particular study, there was a decrease in C-reactive protein and control of IL-6 and procalcitonin. I assume all of that was clinically relevant. Is that correct? 

Dr. Neyra: Absolutely, yes. The markers of inflammation that you mentioned clearly decreased in the first day after the initiation of treatment. I don’t think there are doubts that this hemoabsorption can remove some of these cytokines. The question is, Can this removal, which is nonselective, be beneficial for patients in the sense that we can improve clinical outcomes? The counterargument to this is, yes, we are removing inflammatory markers that are not good for the patient, but at the same time, because this is nonselective hemoabsorption, we are also removing antiinflammatory cytokines that could be beneficial for the patient. This is why the key question is, At what time is this nonselective enhanced hemoabsorption and removal of these cytokines beneficial? The clinical trial that is planned or ongoing certainly will be very careful to design the timing of the intervention and therefore hopefully the best chances for success.

Dr. Peeke: Excellent. In your program at the University of Kentucky, have you noticed any difference between what we call the alpha COVID and now the delta, which of course now is a predominant variant in the United States? We already know that delta is far more contagious, but is it also associated with some nuances here, as we speak about blood purification in severe COVID-19 patients? 

Dr. Neyra: That’s a very good question. We are in a small surge here in Lexington, Kentucky. We are seeing more cases, likely with the delta variant. The patients are different, I would say. In the past, we used to see patients in the ICU who were typically older, with comorbidities that were very susceptible to having this viral infection and multiorgan failure. These days, we’re seeing a significant number of patients who are younger, without major comorbidities, even pregnant women, of which most of them—I would say more than 95% of them—are not vaccinated. It’s a little bit of a different phenotype. When these patients who are younger and with less comorbidities develop multiorgan failure, they are extremely sick. That’s why at this stage of severity of illness, mortality of course is still being evaluated but seems to be higher than what we saw in the past, which was already high.

That’s why these therapies of hemoperfusion sometimes become even more relevant because these are patients who, if we really can support them during this acute process, have some chance to survive and recover organ function. We have been a little bit busier, from the nephrology perspective with CRRT and blood purification. In the past when we had patients whose frailty scores were high, there was more involvement of early conservative management and palliative care. But here, because we have patients who are younger, they have young families, there is a lot of effort to try to provide them all the support we can. It’s definitely a different phenotype of patients and probably challenging for the system again. 

Dr. Peeke: This, needless to say, is greatly worrisome, especially since it’s a different demographic and a surprise, I think, to many, certainly to our wonderful colleagues in critical care to see such young people. I have another question for you that’s related to this, which is: We’re starting to see breakthrough cases of people who have been fully vaccinated, and yet they have contracted COVID-19, one would assume the delta variant. Are these people as sick? Are they also coming to the ICU?

Dr. Neyra: We don’t see these patients that much in the ICU, unless they are susceptible, immunocompromised, or have some comorbidity that puts them at higher risk. Most of the patients I have seen in the last week, all of them were not vaccinated and did not have any immunocompromised disease or a major comorbidity. I think that it’s clear. I reviewed some data from Israel the other day that it’s very unlikely that somebody who had been vaccinated would reach the ICU level; even when they are hospitalized, most of them do not require ICU care. It’s reflective of what I saw, at least last week, in our institution when I was on service in the ICU. I use this platform and this conversation to encourage the population to get the vaccines and certainly to wear a mask because you don’t want to be exposed to what we are discussing right now, blood purification. When you get to this level, your mortality rates or your chances of dying are really high. I think we should try to use all platforms to encourage the population to be confident with science and to get the vaccine. And hopefully soon we’re going to have some schemes of boosters for the more susceptible patients and also for the more exposed population, like healthcare workers. 

Dr. Peeke: That is absolutely one of the best ways to end this podcast. Such words of wisdom, especially from you, Dr. Neyra, as you’re surrounded by this on a daily basis. It’s so terribly important to follow science and certainly the words of experts like yourself. Do you have any final comment to your peers out there who are listening in and learning all about Oxiris and blood purification and, as it were, blood purification and COVID-19 patients? Any last words of wisdom?

Dr. Neyra: I need to say that blood purification is an old concept. These techniques have been developed and evaluated before. They are more relevant these days because of the current pandemic and the necessity of trying everything we have to support these patients who are critically ill. If we can see the light or the half-full glass of this pandemic, it has helped to put some support from the private sector, from the NIH, and from different sources into developing more knowledge about these blood purification techniques. These could enhance the way we not only support COVID patients right now, but in the future would support patients who are in septic shock for different reasons.

We should be optimistic to see these therapies of potential benefit. We should not stick to saying there is no robust evidence because I always tell people we are developing the evidence. Our observations, developing our experience with these techniques, are going to help find that group of patients who could benefit from it. I just want to emphasize that these therapies may not help every patient who is critically ill with multiorgan failure in the ICU. But in my view it could help some patients. We need more robust data to provide our colleagues at any hospital in the world better standardization of this type of care. What I can say now is that we have heavily used it for the last year and a half. We have not encountered adverse events. It requires a little bit of preparation, different from standard filters, that is, priming with heparin, saline with heparin. But other than that, the performance of the machine is very comparable. Despite enhanced hemoabsorption, you would maybe expect more clotting.

From that perspective, if you have a program that can implement a new filter, you should be comfortable to use it. My recommendation, as of now, with my assessment of the data, is to use it early on in the course of acute illness and multiorgan failure and carefully evaluate the patients and see what type of patients in your experience you are seeing who could benefit the most. The other recommendation I have is that perhaps it need not be used beyond three days because the major advantage is early on in the removal of cytokines. I think we should all work together. This is a great opportunity to have this conversation with a great host and, of course, a great platform—the Society of Critical Care Medicine. I’m always happy to interact with colleagues. Let’s keep in touch, let’s keep learning together, and let’s keep beating this virus. Finally, I will reemphasize—Please get the vaccine and wear a mask. Show your care for humanity, yes, taking care of the person next to you. How you do that? With the vaccine and a mask.

Dr. Peeke: Fantastic. What an ending, I’m convinced, to say the least. Thank you so much. Everyone, we have been speaking with Dr. Javier Neyra, who is the director of the Acute Care Nephrology and CRRT Program and associate professor at the University of Kentucky Medical Center in Lexington, Kentucky. With this, we conclude another edition of the iCritical care podcast. For the iCritical Care Podcast, I’m Dr. Pam Peeke. 

This podcast is sponsored by Baxter Healthcare Corporation. When you choose Baxter for your CRRT program, you’re not only choosing true patient-focused treatment with industry-leading CRRT technology, you’re also selecting a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury. Our commitment to you starts with a program individualized to your facility’s needs and provides complete support every step of the way. For more information, visit us at www.renalacute.com. Baxter Healthcare Corporation has provided funding for this podcast, but all content was developed independently by the presenter. Therefore, the views expressed on the podcast are those of the speaker and should not be attributed to Baxter Healthcare Corporation. For prescription use only. For the safe and proper use of this product, please refer to the operator’s manual. 

The Oxiris set device is authorized under EUA 200164 emergency use authorization to treat patients 18 years of age or older with confirmed  COVID-19 infection admitted to the ICU with confirmed or imminent respiratory failure in need of blood purification, including CRRT. This device has been neither cleared nor approved for the indication to treat patients with COVID-19 infection. The device is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the Oxiris set under Section 564B1 of the Act 21USC360BBB3B1, unless the authorization is terminated or revoked sooner. 

Pamela M. Peeke, MD, MPH, FSCP, FACSM is a nationally renowned physician, scientist, expert, and thought leader in the field of medicine. Dr. Peeke is a Pew Foundation Scholar in nutrition and metabolism, assistant professor of medicine at the University of Maryland, holds dual master’s degrees in public health and policy and is a fellow of both the American College of Physicians and the American College of Sports Medicine. Dr. Peeke has been named one of America’s top physicians by the Consumers Research Council of America. She is a regular in-studio medical commentator for the national networks and an acclaimed TEDx presenter and national keynote speaker. Dr. Peeke is a three-time New York Times best-selling author and is a science and health advisor for Apple.

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