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Pam Peeke, MD (Host):  Hello and welcome to The Society of Critical Care Medicine’s iCriticalCare Podcast. I’m your host Dr. Pam Peeke. Today, we’re going to be talking about COVID-19 and continuous renal replacement therapy. I’m joined by Dr. Michael Connor, Senior Physician and Associate Professor of Critical Care Medicine and Nephrology at Emory University School of Medicine in Atlanta, Georgia.

Michael Connor, MD (Guest):  Thank you. I look forward to this conversation.

Host:  All right. So, when people think about COVID-19, they think respiratory. But today, we’re going to be talking about something a lot of people were surprised with, maybe you were too; and that is acute kidney injury that’s a serious complication in critically ill patients with COVID-19. My goodness. There’s a reported incidence ranging from five to 25% or greater. So, why is this happening?

Dr. Connor:  Excellent question. As you know, the kidneys are rather sensitive organs and when patients become critically ill for whatever reason, whether it’s COVID-19 or other related or other respiratory illnesses or any other critical illness related issue; kidneys can oftentimes become dysfunctional and enter into a period of dysfunction that we call acute kidney injury. And this happens in a rather high frequency amongst patients in the intensive care unit in general even prior to COVID-19. We have on average, around 50 to 60% of patients in the ICU who experience challenges with acute kidney injury during their time in the ICU. And this continues in COVID-19. The challenge that we’ve noticed with COVID-19 is that the severity of acute kidney injury has been greater than what we typically see in general.

Host:  And we’re looking at why this happens. Factors like viral invasion, microvascular thrombosis, altered regulation of the renin angiotensin aldosterone system. I mean the list goes on. There’s hypovolemia, hemodynamic disturbances, inflammation. It sounds like an absolute mess. I almost feel like we’re talking about the lungs all over again. Don’t you?

Dr. Connor:  Yeah. And there’s actually quite a lot of what we call organ cross talk between the lungs and the kidneys. So, things that affect the kidneys oftentimes impact lung function and vice versa. But you’re absolutely correct, that all of those mechanisms can play a role in the development of kidney dysfunction and acute kidney injury in the COVID-19 patients. The challenge is trying to understand in a given patient, which of those issues is predominating whether it’s inflammation, volume depletion, or actually volume overload, and high PEEP can also cause acute kidney injury. And trying to understand whether any of those are modifiable to potentially mitigate or ameliorate the acute kidney injury before it becomes too severe or too established in a given patient.

Host:  When someone presents with acute kidney injury, what does that do to the mortality rate?

Dr. Connor:  Well the presence of acute kidney injury is certainly associated with an increased risk of death for whatever brings you into the intensive care unit. And that continues as well in COVID-19. It’s not clear that the acute kidney injury itself is increasing or causing a higher rate of death but it’s likely associated or it’s a marker of how sick the patient is. So, it gives you a window into the fact that this patient is sicker and therefore at an increased risk of death. But the presence of AKI is certainly associated with a higher rate of death of all things in the Intensive Care Unit.

Host:  Oh, okay. Now, let’s talk about some ways of treating this. Renal replacement therapy, why? Why do you go to this and when do you pull the trigger and say, this is absolutely the way to go?

Dr. Connor:  That’s the 64,000 dollar question that we continue to have difficulty answering within the nephrology literature and community. Let me take the first question first. So, renal replacement therapy or dialysis is a way to filter the blood of waste products, acids and fluid that may not be getting eliminated when the kidneys are not working properly. Certainly we do not rush or want to use dialysis in patients with acute kidney injury. It would certainly be preferrable to ameliorate or help mitigate acute kidney injury or prevent it all together so we can avoid having to initiate dialysis in patients. But we have no magic bullets and no medicines that can definitively treat acute kidney injury despite many decades worth of research in this area.

So, aside from understanding why they are developing acute kidney injury and addressing those issues; we have no real direct treatments for the renal dysfunction itself. So, unfortunately, it means that some patients progress to a point where they are making inadequate amounts of urine, they’re acid levels are accumulating, other electrolytes and waste products are accumulating and therefore, they need to get started on dialysis.

How we make that decision though remains a challenge. What’s clear from the literature in all patients in the ICU, and this likely is also true with COVID, although we have no defined studies yet in COVID with regards to dialysis. The decision to start dialysis should not be based on a BUN or a creatinine level or any other sort of single lab test but rather it really needs to be based on how the patient’s overall clinical trajectory is doing. We usually suggest that providers think about the demand on the kidney and the capacity of the kidney to be able to handle those demands. And if the demands on the kidney from fluid accumulation, acid accumulation and other things far outweighs the kidney’s ability to perform at the current moment; then we generally suggest initiation of dialysis to fill that gap and to help return the patient to a more steady state.

Host:  What about the issue of continuous renal replacement therapy? When do we look at that as a consideration?

Dr. Connor:  Sure, well in the United States, the overwhelming preponderance of ICU based dialysis has moved over time to a more prolonged therapies or gentle therapies such as continuous renal replacement therapy or a related mechanism called prolonged intermittent renal replacement therapy. The more gentle slow continuous approach to dialysis generally is better tolerated by the patients and allows for more accurate and steady return of the patient’s fluid balance back to their euvolemic or sort of normal fluid balance state. Conventional hemodialysis that’s performed over three or four hours that our patients with chronic kidney failure get dialysis in the outpatient setting in this fashion is generally not tolerated particularly well by ICU patients overall.

So, at least in the United States, we have moved and migrated over time to a more continuous basis of dialysis that we call CRT or continuous renal replacement therapy.

Host:  How long does that last, typically?

Dr. Connor:  Well it goes on continuously.

Host:  When do you pull that trigger?

Dr. Connor:  Once we decide to start dialysis, and a dialysis catheter is inserted; then the device will be running ideally 23+ hours a day until the patient’s kidney function has either recovered or the patient is otherwise proving to be more stable and potentially ready to leave the intensive care unit, at which point, we would transition to a more conventional means of dialysis on transfer.

Host:  Based upon your own experience, I’m just curious, at Emory; how many of these, just roughly, how many of these patients with COVID-19 related acute kidney injury are able to turn it around and don’t end up with what appears to be more of a permanent damage?

Dr. Connor:  That’s a great question. So, unfortunately, because this disease is still new, over the course of the last eight months; we have not a lot of publications so far that help us understand how the patients are recovering from acute kidney injury and whether they have developed any chronic scarring or what we call chronic kidney disease. Our experience here in Atlanta both at Emory and Regionally, has been that the overwhelming majority of patients who survive the COVID-19, do experience recovery of the kidney function and are no longer dialysis dependent either at hospital discharge or shortly thereafter. And this experience is generally mirrored with what I’ve heard anecdotally from my colleagues in the nephrology and critical care community around the world, in Western Europe and in Asia as well. So, the overwhelming majority of these folks with acute kidney injury do recover and no longer require dialysis should they survive their time in the hospital in general.

Host:  Interesting. Very interesting. And since you brought that up, the whole issue of what’s been going on around the world and I asked you anecdotally about Emory because there’s a paucity of data our there for the obvious reason. This is a very recent pandemic and we’re just – we’re learning as we go along. But do you think that there’s an issue with the preparedness of most hospitals to be able to handle something like acute kidney injury because this really requires the availability of machines, consumables, staff, clinical expertise, acceptable alternatives and a real close collaboration between critical care and renal services. You’re very fortunate because Emory is one of the top Universities in the world. I wonder however, what’s happening in the hinterland because if this is really turning out to be one of the most common as it were serious complications outside of respiratory; do you think most hospitals are ready?

Dr. Connor:  Yeah, it’s a great question. So, first of all, remember that in general, about 12 to 15% of all ICU patients do require dialysis during their journey through the intensive care unit even prior to COVID-19. And this varies a little bit from intensive care unit to intensive care unit depending on sort of the flavor of the type of patients that tend to come into that intensive care unit. But what we’ve noticed with COVID is that this percentage has been maybe a little bit higher, more on the order of 10 to 20% of the ICU patients have been requiring dialysis. I’m not generally concerned about most hospitals being able to provide a form of dialysis whether it’s continuous dialysis or any of the other modalities such as prolonged intermittent dialysis or conventional dialysis in the ICU. Most hospitals have experience and protocols in order to be able to do that.

But certainly, at Emory, and around the country, the influx in patients and the increase in total number of intensive care unit patients has certainly presented some challenges because if we have say 100 ICU patients with COVID, we’re going to very quickly potentially reach the limits of what type – of the numbers of machines and disposable supplies as well as nursing staff to be able to provide dialysis to such an increased influx of patients. So, this has certainly presented a challenge and admittedly, our institution as well as many others around the country have not really previously considered dialysis surge capacity. In other words, if you have a natural disaster of any sort, and you have a big influx in patients; dialysis availability has never really been generally very high on the planning priority for hospitals. Ventilators, you heard a lot of discussion about around the country with both the government and other physician and hospital leadership about the availability of ventilators in the pandemic. But there was very little if any discussion about the availability of dialysis machines.

And at all hospitals, they have far fewer dialysis machines than we have ventilators.

Host:  Oh how interesting. So, this is real wake up call.

Dr. Connor:  It certainly was for us. We recognized before we had an influx in patients based on reports from Western Europe that there likely was going to be an increased rate of dialysis and so we quickly developed a very robust surge plan. This has been mirrored by many other institutions and we’ve both adapted what they’ve done, and they’ve adapted what we’ve published in this regard. And we certainly have had to become creative with regards to how to ensure that we have appropriate supplies of disposable supplies and how we navigate and efficiently deploy dialysis machines. Fortunately, dialysis can be modified and doesn’t need to always be overtly continuous in all patients. Unlike a ventilator, where you can’t use a ventilator half the day on one patient and move it to another patient for the second half of the day. We can certainly modify how we provide dialysis and think about how we can increase the capacity by changing our approach to how we do dialysis. And so that was a very important part of our surge plan as we thought about this.

Host:  I love it. And that’s a word to the wise out there. We frankly don’t know where this journey is going. You know that and I know that with the pandemic. And right now, just to be as prepared as possible especially with regard to acute kidney injury is absolutely paramount. So, speaking of that, for one of our last thoughts about issues that can occur in the treatment of the COVID-19 patients who do have AKI. There’s an issue of increased filter clotting during continuous renal replacement therapy. A lot of this having to do with the anti-coagulability and the anticoagulation issues that can arise specific to COVID. Can you address that?

Dr. Connor:  Yeah, excellent question again Dr. Peeke. Anytime we’re providing dialysis, hemodialysis or blood based dialysis where the blood is circulating through a circuit, there is certainly risk that the blood can clot within that circuit thereby causing blood loss and circuit failures where the circuit would have to be disposed of and restarted. And the reason for that is that the blood is not used to being in contact with essentially plastic tubing and plastic membranes and so those can certainly activate the clotting cascade. And clotting of dialysis machines especially continuous dialysis machines that are running continuously is an ongoing vexing problem in the ICU.

What we have learned about COVID-19 fairly unequivocally and I think generally agreed upon around the entire world is that COVID-19, when patients are critically ill, clearly induces a hypercoagulability, in other words, it causes the blood to clot more frequently inside the patient. And this is certainly true as the blood is circulating through an external device like a dialysis machine. So, we noticed very early on that we were having significant troubles with functioning of our dialysis machines and clotting of the machines and this was seen all around the world. And we’ve had to become creative and much more aggressive with how we use blood thinners to try to keep our dialysis machines functioning properly so that the patients can receive the benefit of the treatment.

Fortunately, this has been paralleled by general recognition in the ICU in general, that COVID-19 patients need enhanced preventative measures to prevent blood clotting while lying in bed all the time. Certainly as you know Dr. Peeke, patients that are in the ICU for a long time have a risk of blood clots and we have standard ways to try to prevent those blood clots in the ICU, but many centers now have enhanced those and become more aggressive with how they treat and what medicines they use to prevent blood clots. And so, we have been using more medicines to prevent blood clots in general, that has had a beneficial effect on helping our dialysis machines continue to run as well.

Host:  Excellent. This is wonderful. This whole episode, we’ve been talking about COVID-19 and continuous renal replacement therapy and really talking about the incidence of acute kidney injury which originates with the COVID-19 viral infection and solutions whether it’s just a straightforward renal replacement therapy or dialysis or continuous dialysis considerations looking also at problems that are unique to COVID-19 with regard to anti-coagulability and anticoagulation methods to address this. And one of the most important points you brought up so beautifully, is what do you do to prepare. What’s the surge plan and every single critical care unit needs to really be able to address this, be prepared, quite frankly we don’t know what’s going to be happening. We’re just trying to stay ahead of other problems. We’ve learned already as you said, in eight months a lot and we continue to do so. and needless to say, until we have a more permanent solution to this viral crisis; critical care units all across the country are going to have to be at the ready and having enough renal dialysis resources is absolutely critical.

Dr. Connor:  If I could add on to that. I completely agree, but I would also just endorse that this isn’t purely and shouldn’t be purely intensive care unit or given individual hospital or health system surge plan. The hospital and health systems need to have a surge plan, but we also need to look to our government leadership and industry to also prepare from a regional and national perspective as well. Dialysis supplies obviously need to be produced at a higher rate. We need to make sure that the disposable supplies and the various solutions that we use are strategically positioned and moved to new hot spot areas early because it can be difficult to move these type of supplies when the crisis has already hit. So, there needs to be not only a local response, but also a regional and national planning process as it pertains to dialysis. And having such a process in place, would not only benefit us during this pandemic, but it would also provide for much better preparations for future pandemics or other sorts of large natural disasters such as earthquakes or weapons of mass destruction or anything else that may affect the health and safety of the population at large.

Host:  I couldn’t have said it better. And I’m so glad you said that because what you did was you took it to the highest level which is let’s just look at this as an incredible phenomenon. It’s not a matter of if, it’s a matter of when. This is not going to be our last pandemic by any means. And more importantly, there are other disasters and you said it so articulately, this is a government policy area that has to be addressed. And I hope to heaven, that state by state, and also the federal level there’s an acute and urgent awareness of what needs to take place now for overall preparedness. So, I’m just so glad you said what you said Dr. Connor. Do you have any last thoughts for your peers out there who’ve been listening intently to your words of wisdom about all things COVID-19 and acute kidney injury?

Dr. Connor:  Just please don’t hesitate to reach out for further assistance. There’s resources at the SCCM. We also have lots of published resources. Our surge plan an dour dialysis protocols are all published if people search for Emory Healthcare and COVID-19 resources you’ll see those on the website. And I’m always happy to field emails and phone calls from colleagues concerning these issues. These are challenging times. We all have to work and learn together. And I look forward to learning from all of my colleagues as we move forward as well as you, Dr. Peeke, as we move forward. Hopefully, in a future podcast maybe you can share some information about COVID-19 related malnutrition and recovery strategies.

Host:  Oh my gosh. Absolutely, no question. I’m actually working on a clinical protocol with the dysautonomia syndrome that we see in the post-COVIDs now which can be up to 15% and it’s very striking. There’s so many things to learn here and my gosh, we just have to run with it. Everyone, we’ve been listening to Dr. Michael Connor, Senior Physician and Associate Professor of Critical Care Medicine and Nephrology at Emory University School of Medicine in Atlanta, Georgia. This concludes another edition of the iCriticalCare Podcast. For the iCriticalCare Podcast, I’m Dr. Pam Peeke.