Disclaimer2: 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 are 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 needs and provides complete support every step of the way. For more information, visit us at www.renalacute.com.

Pam Peeke, MD (Host): Hello and welcome to the Society of Critical Care Medicine Podcast. I'm your host, Dr. Pam Peeke. Today, we will be talking about continuous renal replacement therapy and anticoagulation. I'm joined by Dr. Rajesh Speer, who is research specialist at the University of Alabama at Birmingham School of Medicine Nephrology Department. Welcome, Dr. Speer. Before we start, do you have any disclosures to report?

Rajesh Speer, PharmD: Yes. I have a patent for citrate 0.5% solution.

Host: Excellent. Thank you very much. I want to review the learning objectives. Understanding the use of anticoagulation in CRRT is essential. We're going to be discussing different options in citrate. We'll be discussing the benefits of low-concentrate citrate versus high-concentrate citrate. We'll also be discussing differences between compounding versus commercially available products.

Why is this podcast needed? To educate clinicians about utilizing anticoagulation in CRRT, as we see more clinicians exposed to the utilization of CRRT. This podcast will give a pharmacy point of view. Knowledge gaps that this podcast will address: number one, what anticoagulation is ideal for in CRRT; number two, other considerations to keep in mind during CRRT; and number three, what type of citrate is ideal for use in CRRT? Dr. Speer, why is anticoagulation so important and what are some considerations with CRRT?

Rajesh Speer, PharmD: Well, thank you for letting me have an opportunity to speak on this topic. It is one of the topics that I'm very passionate about. I started working with Dr. Ashita Tolwani back in 1999 on this citrate protocol for the CRRT at University of Alabama at Birmingham. The CRRT belongs to a family called renal replacement therapy, which is an umbrella of all types of renal clearance, which includes the intermittent, the continuous or a hybrid type.

CRRT stands for continuous renal replacement therapy, which means that's a 24-hour therapy. What we would want to do is to make sure that 24-hour therapy runs for 24 hours in order for the patient to get the most benefit. However, the studies have shown that our delivery dose for the CRRT dose is actually about 20-30% lower than the prescribed dose. And so, that causes a concern because if you're not actually clearing what you're supposed to clear, the patient is not benefiting fully. So then, you start looking at what is causing this decrease in dose.

There are many, many factors that can lead to decrease in dose. But one of the biggest challenges, there's a circuit life of a CRRT machine that is affected. While there are parameters such as the vascular access and other things such as the patient's own condition, a hypercoagulable situation, those things we may not be able to control. But one aspect that has been known to cause a problem is insufficient or inadequate anticoagulation in the circuit. So, that is one of the reasons why anticoagulation is so important in keeping the CRRT's circuit running, so we can decrease the chances of having inadequate dosings. So whatever we prescribe, we want to be able to give to the patient. So, that is why it's important.

And so, the special consideration in regards to CRRT, as I said, C stands for continuous, so therefore a continuous anticoagulation is needed. So, we have patients in the ICU setting who are unstable, very ill patients that are using this therapy, and they are already prone to bleeding and other complications. We really need to look for an anticoagulant, which is effective in providing us an appropriate dose, but not anticoagulate the patient, and that we need the circuit to be anticoagulated, but not the patient. So, we want to not minimize any kind of bleeding complications to the patient. So, the gold standard, heparin anticoagulant, it's very easy to use, it's easily available everywhere. But it does have a lot of problems with bleeding. So, the challenge with CRRT is trying to avoid anticoagulation, which causes increase in bleeding and other complications with the patients.

Host: Thank you so much, Dr. Speer. So, you mentioned heparin. What are the key differences and benefits of using citrate versus heparin?

Rajesh Speer, PharmD: Heparin, generally, systemic bleeding is just one of the biggest problem. It is cheap. It's available everywhere. It is used commonly in the outpatient dialysis and the intermittent hemodialysis. However, when you're using a 24-hour continuous renal replacement therapy, then it becomes a challenge because that heparin actually causes some systemic bleeding and may lead to some systemic bleeding. That is where it becomes challenging.

And then, we've also looked at the difference between the actual filter life with the filter of the circuit. Despite heparin being an anticoagulant that can lead to some anticoagulation in the circuit, it does not still leave the filter life as long as the citrate. Citrate is much better in prolonging the filter life than heparin. So, the filter life is prolonged with citrate. The benefits of the citrate is the way it works, it anticoagulates the circuit only, but does not anticoagulate the patient, and it does not have the bleeding side effects, which is the biggest difference in there besides increasing the filter life.

Host: Fantastic. All right, Dr. Speer, what are the best practices for using anticoagulation and citrate with CRRT?

Rajesh Speer, PharmD: The best practices, in order to use CRRT, what I have found over the years is you need to really understand your system, what you actually have, what you are working with, your staff and what equipment you have, and really understand what limitations you have. If you are using heparin in there to make sure that the protocol is standardized and everybody's following it, everybody knows what needs to be done. Citrate, the same thing. I definitely would advise to make sure the citrate is something that, while it has a lot of benefits, you really need to understand the complications citrate can lead to if you don't understand how citrate works. I think the best practice is to know your entire team is available for doing the CRRT, your dialysis nurses or ICU nurses, staff in the pharmacy to make sure that you guys are all doing it in the same standard protocol in order to make sure that you run a smooth program.

Host: Excellent. Thank you. Dr. Speer, can you describe the differences between using low-concentrate versus high-concentrate citrate in CRRT?

Rajesh Speer, PharmD: Yes. Unfortunately, in the USA, when we started using the citrate in 1999, there's really nothing available that is a low concentration of citrate. What is available is solutions such as ACDA 2.2% or trisodium citrate 4%, which are actually approved for blood banking. By the fact that they're approved for blood banking and not for CRRT, their formulations are definitely high in sodium. For instance, ACDA has a sodium of 200 millimoles per liter, whereas the trisodium citrate has over 400. So, they're hypotonic solutions that, when you are using in patients other than to store blood, it can cause all kinds of metabolic problems. High concentration of trisodium citrate is also another problem.

So, the problem is everybody, when they were started using citrate, there is nothing available in the United States commercially that was less than 2.2% or maybe even 1.3%, but there was not an isotonic solution available in the United States. And that is what people are using because it is commercially available as an off-label. The physicians are using citrate as an off-label because it is not an FDA-approved solution right now. That causes metabolic problems. Whereas if citrate was available as a isotonic formulation, then some of the side effects and some of the things that citrate can lead to do not have those same types of consequences, or they do not occur that rapidly as they do with the concentrated solutions.

Host: Thank you. Dr. Speer, what are the challenges that exist in compounding low-concentrate citrate?

Rajesh Speer, PharmD: There are many challenges. When we finally decided what we were going to compound as a low concentration in our practice, it became evident that for our practice we needed a standardized solution. Reading many articles of seeing some of the errors in our institution and others, if commercial solutions are not available to your choice, then standardize a solution, so that every physician is using the same solution. And that will tend to decrease error.

However, compounding solution generally, they cost more because it's not available commercially. They have shorter expiration date. They can lead to error because each bag is made in the pharmacy one by one. It's not the same thing that you have as manufacturer standards to follow. Most pharmacies are not equipped to accommodate that. It depends on number of patients you have. Like during the COVID time, we had about 30 to 40 patients a day in there on CRRT, and that was difficult for a pharmacy to make that many bags per day per patient.

So, it is very labor-intensive, very costly, prone to errors. But I think most of those can be minimized as much as possible by standardizing it. Standardize your order sets, so that different physicians are not picking different solutions. That was one of our biggest challenge at the beginning as well, is that CRRT, the order sets were available for them, to just pick anything that they wanted. And so by minimizing the choices in ordering, putting the standard solutions in there. And usually, they're so good in selecting what's standard already because then they don't want to customize things in there. So offering those choices as only choices, that has helped us keep it as a standard solution for our institution.

Host: Excellent. What words of advice do you have for a critical care team at a hospital that is interested now in beginning to use citrate, and they have utilized heparin in the past?

Rajesh Speer, PharmD: My suggestion is form a team that has champions from pharmacy, nursing, physicians, that's what we had, in order for it to go forward; dialysis nursing, ICU nursing, et cetera. We wanted to make sure that all areas were heard and concerns were met from everyone. This started out with stocking the solution on the unit, compounding in the pharmacy, making sure that we can rotate stock, et cetera. So, develop a team, find out what you really have available at your institution regarding machines. Some machines cannot do all variations of CRRT. So, find out your capabilities, so you know what your limits are. And then, learn one technique and do it well. That would give you far better results than trying to go to saying, "I'm going to do CVVH, CVVHD." Select one, make your team comfortable with it, develop the protocol, standardize things. And if you do those things, I believe that you will be on your way to success. While citrate is a scary thing to many people who are not used to it, definitely, if you understand how to use it and understand how citrate works, you will be able to manage it much better than what you thought you could.

Host: Thank you very much, Dr. Rajesh Speer, for being on the podcast. This concludes this episode of the Society of Critical Care Medicine Podcast. Thank you.

Disclaimer2: 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 are 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 needs and provides complete support every step of the way. For more information, visit us at www.renalacute.com.

Disclaimer: Pamela M. Peeke, MD, MPH, FACP, 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, and Assistant Professor of Medicine at the University of Maryland. She holds dual master's degrees in Public Health and Policy, and is a fellow of both the American College of Physicians and 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 bestselling author and is a science and health advisor for Apple.

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