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Pam Peeke, MD (Host): 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 the 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 (Guest): Well, thank you very much for the invitation and happy to be here.

Host: Wonderful before we start, do you have any disclosures to report?

Dr. Neyra: Yes, I have provided consultation to Baxter. That is the company that provides these type of membrane, oXiris. And this will be the center topic of this discussion about blood purification.

Host: Wonderful. And 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 extra corporeal blood purification in COVID-19 patients. We'll also understand where oXiris can be used and discuss clinical cases of oXiris. Now, 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 the second, well, examples of how and when to use oXiris blood purification.

So, first let's just 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: Yeah. So, I think these are very challenging times. And we have learned during this pandemic that COVID-19 disease will create 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 endotoxins and cytokines, which are in some patients, if applied at the right time window, can be beneficial for their clinical course.

Host: Excellent. So, talk to us about the current use of extra corporeal blood purification in COVID-19 patients.

Dr. Neyra: So, we know that there is a group of patients that develop severe COVID-19 that will require ICU care, high requirements of oxygen, and sometimes mechanical ventilation. These patients that are considered severe COVID, typically will have also multiorgan failure and systemic inflammation. Among these patients, close to 50% will develop acute kidney injury. So, nephrologists are always involved in the care in these patients to evaluate needs of dialysis. In the ICU, we typically perform dialysis in critically ill patients with CRRT, what is a continuous renal replacement therapy. In this setting, we can provide different methods of dialysis including, recently expanded hemo absorption with some specify or newly developed filters. This has broadened the term of blood purification because we can combine different techniques on CRRT, which include effusion, typically is the same technique commonly done in any patient on hemodialysis, convection, which is exclusive to patients that are receiving CRRT. And, in addition to these, the hemo absorption properties of certain filters like oXiris. Farther, there, there are other filters as well that can have some removal 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 with the hypothesis that you can improve the clinical course, particularly hemodynamic status, and also function of organs like the lungs and the kidneys, if applied on the ideal time window that is early on in the course of acute illness.

Host: Excellent. So we're really addressing cytokine absorbing hemofilters aren't we?

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

Host: So when you're really talking about this, I think our listeners would really need to understand where oXiris can be used, when, so perhaps even an example or two of how you have utilized, this particular, hemofilter.

Dr. Neyra: So 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, 72 hours of a patient requiring CRRT support, due to a COVID-19 disease and multiorgan failure.

So in these patients, we typically will use it for up to three days. Typically one or two filters because these filters, will last on average, around 36 hours. So, we typically will use a couple of these filters in the first three days and early on in the course. So, for example, we have a patient with COVID-19 that has been in a different hospital and transfer, already for an ICU to ICU after more than a week of advanced organ support. Those 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 that is recently admitted, with decompensation from COVID-19 requiring ICU care and multiorgan failure, and the patient is being evaluated for CRRT; we will prefer to use the oXiris filter for at least the first three days to provide these enhanced hemoabsorption and therefore try to farther support these, significant inflammation that these patients develop.

Host: Excellent. Fantastic. you provided me with an excellent reference from a blood purification journal. And this is just in June of 2021. It was called Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients, a Prospective Cohort Study. And here we are really looking at hyper inflammation and coagulopathy, and in this case, the oXiris cytokine adsorbing hemofilter was used for extra corporeal blood purification. Tell us a little bit about the study.

Dr. Neyra: Yeah. So this is a study from Italy that very nicely described experience with patients that require CRRT and use oXiris. These patients had COVID-19 and they described the clinical course of these patients which was significantly improved if you assess markers of organ failure and for example, scores of critical illness, like the SOFA scores, which improve significantly when the patients received the treatment. They used a control group that was a historical control group.

And that's why we need to, of course evaluate this data with caution because these were not, this is observational data, not a randomized controlled trial. So, the control group was a historical, similarly sick group, in which the, the trajectory of the clinical course, was significantly different. So it was worse when the patients did not receive this enhanced chemoabsorption. So these suggest so far, that perhaps these enhanced hemoabsorption, these filters can provide some benefit in these patients. The authors mentioned it very clearly that when it's applied early on in the course of acute illness, multiorgan failure.

Now do we have data to support that these patients have better survival? Still, we 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 suggests that these patients have a better clinical course when they receive this treatment early on. And the data is evolving. I'm aware of some clinical trials are ongoing despite we're focusing on COVID-19 support right now, because that is in the US the emergency use authorization that we have for these filters. There are studies in Europe that started before COVID and in the sepsis population.

So, this concept of hemoabsorption is not new, is just, we have been pushed during this pandemic, to their rapid use because there may be a phenotype of patients that can benefit from it. Our challenge of course, is to identify who are these patients, confirm this with clinical data and also show that when we provide this enhanced treatment to these particular subphenotype type of patients, we can improve clinical outcomes.

As of now, data is evolving, but still, as I mentioned, the controls are typically historical controls and there are no randomized clinical trials to support it's standardized use.

Host: Fantastic. This is really, really helpful. And in this one particular study, there was a significant decrease in C-reactive protein, and control of IL6 and procalcitonin. I assume all of that was clinically relevant. I know the numbers decreased, but apparently overall, the patient outcome was excellent as well. Is that correct?

Dr. Neyra: Absolutely. Yes, the markers of inflammation that you mentioned, clearly decrease, in the first day after the initiation of the treatment. So, I don't think there are doubts that these hemoabsorption can remove some of these cytokines and endotoxins. The question is, is this removal, which is non-selective, can be beneficial for the patients, in the sense that we can improve clinical outcomes.

So, the counter argument to this is yes, we are removing inflammatory markers that are not good for the patient, but at the same time, because it's, this is non-selective hemoabsorption, we are removing also anti-inflammatory cytokines that could be beneficial for the patient. So, that's why the key question is at what time, this non-selective enhanced hemoabsorption and removal of these cytokines and endotoxins is beneficial. So, the clinical trial that, its planned or it's ongoing, certainly, it's going to be very careful to design the timing of the intervention and therefore hopefully the best chances for success.

Host: Excellent. Now in your program at the University of Kentucky, have you noticed any difference between, what we call sort of the Alpha COVID and now the Delta, which of course now is the 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: Yeah, that's a very good question. And, we are in a small surge here in Lexington, Kentucky, so we are seeing more cases with the Delta variant very likely. The patients are different, I would say. In the past, we used to see patients that were typically in the ICU, the patients that were older with comorbidities, that were very susceptible to having these viral infection and multiorgan failure. These days, we're seeing a significant number of patients that are younger, without major co-morbidities, even a pregnant woman that most of them, I would say more than 95% of them were not vaccinated. And, it's a little bit a different phenotype.

Now when these patients that are younger, and with less comorbidity develop multiorgan failure, they are extremely sick. That's why at this stage of severity of illness, the mortality is, of course it's still being evaluated, but seems to be higher than what we saw in the past, that was already high.

So, that's why, these therapies have a hemoprofusion, sometimes, become even more relevant, because these are patients that if we really can support them during this acute process, they have some chance to survive and to recover organ function. We have been a little bit busier, I would say from the nephrology perspective with CRRT and blood purification in the past week, when we had patients that their frailty scores were high, there were more involvement of early conservative management, palliative care. But here, because we have patients that are younger, they have young patients, 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.

Host: 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 and that 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. They are immunocompromised, or they have really some comorbidity that put them at higher risk. Most of the patients I have seen in the last week, they were, all of them were not vaccinated and did not have any immunocompromised disease, or they did not have major comorbidity.

So, I think that it's clear. And I reviewed some data from Israel the other day that very unlikely somebody that had been vaccinated reach the ICU level. Even when they are hospitalized, most of them are not requiring ICU care. It's reflective of what I saw at least last week in, in our institution when I was on service in the ICU.

So, again, I mean, 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.

So, I think, we should try to use all platforms to encourage the population to be confident with science, 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.

Host: That is absolutely one of the best ways to end this podcast. I mean, such words of wisdom, especially, from you, Dr. Neyra, as you're surrounded by this on a daily basis. And it's just 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 just as it were blood purification and COVID-19 patients, just last word of wisdom.

Dr. Neyra: Well, I need to say that blood purification is an old concept. These techniques have been, developed and evaluated before in sepsis. They are more relevant these days because of the current pandemic and the necessity of trying everything we have to really support these patients that are critically ill.

Now, 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. This could enhance the way we not only support COVID patients right now, but in the future, we support patients that are in septic shock for different reasons.

So, we should be optimistic, to see these therapies of potential benefit. We should not be nearly stick to say like, there is no robust evidence because I always tell people, we are developing the evidence. So, our observations, developing our experience with these techniques are going to help, to really find that group of patients that could benefit from it. I just want to emphasize these therapies may not help every patient that is critically ill with multiorgan failure in the ICU. But it could help, in my view, some patients, we need more robust data to provide our colleagues at any hospital in the world, like better standardization of this type of care.

What I can say as of now we have heavily used it for the last year and a half. And this filter is safe for your patients. We have not encountered adverse events. It requires a little bit of preparation, different to the standard filters. That is the priming with heparin, saline with heparin. But other than that, the performance of the machine is very comparable.

Despite enhanced hemeabsorption, you will expect maybe more clotting. So, from that perspective, you should be comfortable if you have a program that can implement a new filter to use it. Now, my recommendation, as of now with my assessment of the data, is to use it early on in the course of acute illness and multi-organ failure, and carefully evaluate the patients and see what type of patients in your experience you are seeing that could benefit the most.

The other recommendation I have is that perhaps is not needed to be used beyond three days because the major advantage is early on in this removal of endotoxins and cytokines. So, 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 of the Society of Critical Care Medicine.

So I'm always happy to interact with colleagues and let's keep in touch. Let's keep learning together and let's keep beating this virus. And finally, I will re-emphasize, please get the vaccine and wear a mask. Show your care for humanity. Yes, taking care of the person next to you. And the how you do that with the vaccine and a mask.

Host: Fantastic. Boy, what an ending. I'm convinced, to say the least. Thank you so much. Everyone, we have been speaking with Dr. Javier Neyra and he is the Director of Acute Care Nephrology and CRRT Program and Associate Professor at the University of Kentucky Medical Center in Lexington, Kentucky.

And with this, we conclude another edition of the iCritical Care podcast. For the iCritical Care podcast, I'm Dr. Pam Peeke.