SCCM Pod-531: CRRT Fluid Strategies: What Clinicians Need to Know

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Host Ludwig Lin, MD, welcomes Raghavan Murugan, MD, MS, FRCP, FCCM, a professor and leading expert in critical care nephrology. They discuss the latest insights on fluid management strategies during continuous renal replacement therapy (CRRT), drawing from recent research and white papers. Dr. Murugan emphasizes the importance of updated education on CRRT fluid removal practices to enhance clinical outcomes and patient care in critical settings. This podcast is sponsored by Baxter Health.

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Transcript:

Announcer: This podcast is sponsored by Baxter Healthcare Corporation. Baxter supports true patient-focused treatments with industry-leading CRRT technology and is a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury. Our commitment to you starts with education and provides complete support every step of the way.

Dr. Lin: Hello and welcome to the Society of Critical Care Medicine Podcast. I’m your host, Dr. Ludwig Lin. Today, I will be speaking with Dr. Ragi Murugan, MD, MS, FRCP, FCCM, about fluid management strategies during CRRT. New research and white papers have been published regarding fluid removal during CRRT, and education in these updated publications is very much needed to enhance clinical practices and improve patient outcomes.

Dr. Murugan is a professor of critical care medicine and clinical and translational science at the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania. He is also the director of the program for critical care nephrology, ICU medical director, and chief of critical care medicine at UPMC McGee Women’s Hospital in Pittsburgh, Pennsylvania. Dr. Murugan is an NIH-funded researcher with specific interest in acute kidney injury, fluid management, and CRRT. Dr. Murugan, welcome. Before we start, do you have any disclosures to report?

Dr. Murugan: Thank you, Dr. Lin, for having me today. It’s my pleasure and privilege to be in this SCCM Podcast, and I thank SCCM for this opportunity. In terms of disclosure, I am a consultant for Baxter Incorporated. I’ve received grants from Baxter. I have also received grants from NIDDK and other industry sources as well, none of which would conflict with my talk today.

Dr. Lin: Thank you for that. It’s a very technology-intensive therapeutic technology, so that part makes a lot of sense. And you are going to be so helpful in demystifying CRRT for all of us as critical care medicine practitioners. How do you see CRRT as a part of an AKI patient’s ICU care?

Dr. Murugan: CRRT is a vital component of ICU care for patients with severe acute kidney injury, just like ventilator is an important part of the care for patients with severe acute respiratory failure. CRRT provides a gentle and continuous method of kidney replacement therapy and allows for more precise fluid and electrolyte control compared to other modalities of kidney replacement therapy.

Dr. Lin: Can you describe archetypal clinical scenarios where you definitely feel like a patient should be having it in the ICU setting?

Dr. Murugan: Right. CRRT is useful under a variety of circumstances. Essentially, solute control and fluid management are the two principal reasons why CRRT is used. It is helpful for managing patients with severe hyperkalemia, severe uremia, and also severe fluid overload. CRRT can be used for both fluid regulation as well as for fluid removal.

So if you have a patient in whom there is a lot of fluid that’s being infused for various reasons, then CRRT could be used to control the fluid that’s going in, in terms of keeping the patient in a net even balance when it’s required. And CRRT can also be used for removing fluid when you want to get the patient into a negative fluid balance. Since CRRT therapy is provided for a 24-hour period, it provides a much better control over regulating volume in that patient.

Dr. Lin: I definitely came through critical care medicine with the view that it’s a more physiologically gentle way of doing electrolyte adjustment and fluid management compared to something like intermittent hemodialysis. What are your thoughts about that?

Dr. Murugan: Yes, that’s exactly right. CRRT is more like our regular kidneys, which work 24/7 to provide fluid as well as electrolyte control. Similarly, CRRT, since it runs continuously, provides continuous therapy for both fluid management and for regulating electrolytes, just like the regular kidney does.

It also offers a lot more flexibility in terms of managing the solutes as well as the fluid. If we need to increase, we can increase. If we need to decrease the rate of fluid removal, for example, we can do that. We can independently regulate the solute control, which is managing the electrolytes and the rate of solute removal from that of the fluid management. So they could be completely dissociated in terms of therapy. I think that that’s one of the greatest advantages of CRRT.

Dr. Lin: Right. That sounds huge. Before we delve into further details about CRRT, let me just ask you about scenarios where IHD is actually indicated where CRRT is not. Is there ever a clinical scenario where that’s going to happen?

Dr. Murugan: There may be situations where IHD is indicated. I think that if it is just for managing solutes, especially for patients who are hemodynamically stable, then certainly IHD could be used. The KDIGO guidelines, the Kidney Disease: Improving Global Outcomes 2012 guidelines, certainly state that both CRRT and intermittent hemodialysis must be used as complementary therapies in the management of a critically ill patient with AKI.

This is particularly important because neither of those modalities have shown to improve outcomes independently on its own. What I do in my practice is that, when a patient is hemodynamically unstable, which the majority of critically ill patients are, we use CRRT for both solute management as well as volume management earlier on during their critical illness. As they tend to improve and hemodynamic stability is achieved, then we transition them over to intermittent hemodialysis for both volume and solute management. So it really depends on the patient.

One advantage where CRRT is certainly more preferable than IHD is for volume management because we remove volume on a 24-hour basis, you know, continuously. It is better tolerated when we use CRRT to remove volume as opposed to IHD. Moreover, since we are doing volume removal for 24 hours, cumulatively, you can remove more volume with CRRT than with IHD alone, which typically runs only for several hours and then we have to stop. So in that way, CRRT is more advantageous. And observational studies clearly show where CRRT, when compared with IHD, is associated with certainly better volume control than IHD alone.

Dr. Lin: What are some common fluid challenges associated with patients undergoing CRRT?

Dr. Murugan: That’s a great question. The biggest problem with fluid management in CRRT is how do we remove the excess volume from the patient, right? This is really the holy grail of fluid management during CRRT. Even though most of the patients are severely fluid overloaded, most of that volume is actually in the extravascular space. They are not intravascular for a variety of reasons. They are hypovolemic, they are inflamed, they are hemodynamically unstable on vasopressor support and so on.

So removing that extravascular volume is a challenge. And often there is no one right way to manage volume during CRRT and a lot of time it’s based on a trial-and-error approach as well as the individual clinician’s experience in terms of fluid removal that sort of drives care for the patient. So when fluid is being removed using CRRT, there is a vascular refill that occurs from the extravascular compartment to the intravascular compartment that sort of balances off the rate at which the fluid is removed from the intravascular compartment.

As long as those are in equilibrium, then hemodynamic status is actually maintained. When the vascular refill rate is actually lower than the fluid removal rate, then that’s where the problem starts, where the patient then starts to become hemodynamically unstable and become tachycardic, hypotensive, and so on. Unfortunately, we don’t have a good way to tell us or measure the vascular refill in any given patient at the present time.

So we have to look at other surrogate measures of fluid removal, such as what is the heart rate, what is the blood pressure doing, what is the vasopressor dose, what is the lactate. You could use other metrics such as point-of-care ultrasound, etc., to sort of guide your fluid removal rate. But in fact, this is really the challenge that clinicians face when trying to manage volume at the bedside because we have no good way to assess the intravascular circulating volume.

Dr. Lin: This makes me want to ask you a little bit more about this in terms of the assessment and the resulting management strategy, because it sounds like you kind of have to carefully reassess these patients during their CRRT to see how much the intravascular volume is changing or changing at all. What clinical evidence is there and what kind of algorithm is there to be utilized as the optimal fluid management strategy for a patient undergoing CRRT?

Dr. Murugan: That’s a great question. As far as I’m aware, regrettably, there is no validated protocol for fluid removal during CRRT that’s been rigorously evaluated. There are no clinical guidelines about how to start or how to remove fluid and what should we be using to guide fluid removal and so on.

But having said that, research is slowly starting to provide evidence. There are newer studies coming up that include hemodynamic monitoring to guide fluid removal, unlike in previous studies in which hemodynamic monitoring has been, especially functional hemodynamic monitoring, has been used to assess fluid responsiveness in critically ill patients and then administer volume. Now the same functional hemodynamic monitoring has been used to guide fluid removal.

Those studies have just started to come up. Increasingly clinicians are looking into tools that they can use to titrate and then tailor fluid removal during CRRT. But unfortunately there is no one tool that has been validated. Of course, people can use point-of-care ultrasound and other measures. But one of the issues is that it’s not a continuous measure, right? You could assess it periodically. It requires somebody to use the ultrasound periodically to assess somebody’s volume status and so on.

That can be challenging. People use preload responsiveness, such as passive leg raising or pulse pressure variation. But none of these tools have been really well validated for fluid removal. And many of these tools are not continuous, they don’t provide a continuous measure of how to tailor fluid removal. That’s the real challenge.

Dr. Lin: It sounds like we are still awaiting the studies that can really guide us to do data-driven practice. What about the tools that are your go-to assessment tools for assessing volume status?

Dr. Murugan: Right. Typically in my clinical practice, I don’t look at any one single metric to titrate fluid removal. We have to take a holistic approach. I mean, I can give you general guidelines as opposed to what I use. First of all, I look at the patient and see what state, in terms of volume, is this patient in, meaning, is this patient still in the resuscitation phase or in the optimization or stabilization or de-escalation phase of fluid therapy?

So I look at that. If they just came in with septic shock and they got like five liters of fluid six hours ago, I’m not going to start immediate fluid removal because they’re still in this sort of resuscitation stabilization phase. When I am convinced that this patient is more sort of beyond the optimization and more in the stabilization or on the de-escalation phase, then I start to think about fluid removal.

Now, that assumes that the patient is relatively stable and responding to therapy. Let’s say, for example, you have a patient with severe acute kidney injury who’s coming in with pulmonary edema and who’s breathing 40 times a minute and the patient is on the verge of getting intubated and now we’re managing the patient with BiPAP. Certainly, and that patient is refractory to diuretic therapy, I am going to start CRRT and initiate rapid fluid removal on that patient. That’s a very unique situation where you would have to remove fluid very rapidly and quickly in order to rescue the patient from being intubated and so on. But not many of the patients would fit into that category.

Under those circumstances, I look at them very carefully and then I evaluate which phase of resuscitation they are in. Then, when I think that this patient clearly needs volume removed, then I typically start slow fluid removal based on the patient’s body weight. I don’t arbitrarily set fluid removal rate as 100, 200, and so on. I dose them just like how I dose a drug, so 1 mL/kg. I typically use predicted body weight because it is more accurate and it’s not confounded by other metrics that would affect patient’s actual body weight such as catabolic state.

If you are in the ICU for long periods of time, you lose muscle mass and you lose body weight. Plus, you know, a lot of the weight that you lose is sort of massed by the fluid overload that occurs. Moreover, there are measurement errors that occur in the ICU. So for many of those reasons, I use predicted body weight to dose the CRRT fluid removal rate.

Then I dose based on the net fluid removal rate. Let’s say for example, if the patient weighs 100 kilograms, and I want to dose the patient with 1 mL/kg/hr of fluid removal rate, then I start the patient on 100 mL/hr, which is 1 mg/kg/hr of fluid removal rate, assuming that the patient is not getting any intravenous fluids in that particular hour. If the patient is getting 200 mL, let’s say for example, or 100 mL in IV fluids in that same hour, in order to deliver a fluid removal rate of 1 mL/kg/hr, I need to remove fluid at a rate of 200 mL/hr because this patient is already getting 100 mL going into them in terms of all the IV fluids and other medications and so on.

So in that way, I have a better control of net fluid removal on an hourly basis that I then continue as tolerated by the patient. I typically do not go beyond 1.75 to 2 mL/kg/hr primarily because observational studies show that when you use a higher fluid removal rate, there is a higher risk for hemodynamic instability and there’s a higher risk of morbidity and mortality associated with it. So my approach has always been slow and steady wins the race as opposed to a sprint-and-pause strategy where you start really fast and then you have to stop because the patient is hypotensive and then you have to give a lot of volume back.

Dr. Lin: Right, that makes a lot of sense. And thank you so much for really emphasizing the importance of thinking about the net ultrafiltration rate rather than what the machine is taking out per hour, because depending on whether they’re on vasopressors or antibiotics, the actual rate could be totally different, right? That’s something really important for us to keep in mind.

Dr. Murugan: Yeah, that’s exactly right. The net ultrafiltration rate is really important because, if you think about it, any fluid removal is a form of controlled hypovolemia. And whenever we do any form of controlled hypovolemia, it is associated with cardiovascular stress. The body compensates for the hypovolemia by vascular refill, as we discussed. When the rate of vascular refill is not adequate to the rate of hypovolemia, then that’s where there is more stress on the cardiovascular system. Patients get tachycardic, hypotensive, that then causes ischemic organ injury to all the organs in our body.

That is why this fluid removal net ultrafiltration rate is really, really critical because it is a surrogate. Since we can measure cardiovascular stress directly on the patient, we can use the dosing to indirectly gauge what is the cardiovascular stress that I’m applying to the patient. This is really important because the fluid removal rate as well as the patient body weight actually drive it.

Let’s say, for example, a patient’s predicted body weight is 100 kilograms and you remove fluid at a rate of 100 mL/hr, that is 1 mL/kg/hr. If you have another patient with exactly the same characteristics, except that their body weight is only 50 kilograms, predicted body weight is 50 kilograms, now for that 100-mL fluid removal rate, the total net ultrafiltration rate for that patient is now 2 mL/kg/hr. So the cardiovascular stress that you’re applying to the patient is different based on your predicted body weight.

The easiest way to think about it is like how you set tidal volumes on the ventilator based on the predicted body weight. We don’t set a tidal volume of 700 mL/kg on every single patient, right? We measure it based on the predicted body weight and then set it at 6 mL/kg/hr and so on. That is because the amount of volume that we set or the fluid that we remove incurs a cardiovascular stress that is proportional to their body weight. That is why we use predicted body weight and we set according to the weight.

This is true even in obese individuals. The reason being, in obese individuals with a lot of adipose tissue, since much of the adipose tissue has very little vascularity due to endothelial dysfunction and so on, the cardiovascular stress applied to the patient is still about the same. Just because they are overweight doesn’t mean that they incur less cardiovascular stress. That is why this predicted body weight is useful even in obese individuals.

Now, obese individuals do hold more fluid in the fatty tissue, so they may require a longer fluid removal than a non-obese individual for the same degree of fluid overload. But you can manage that by running the CRRT for a longer period of time at a slower rate to get a volume control compared to a patient who is non-obese.

Dr. Lin: Sounds like the key takeaway is to think about fluid removal via CRRT in per-kilo thoughts rather than like a standard unit. You just pointed out that we need to be flexible in terms of our end point. Somebody with a higher BMI, for example, may need a longer time to clear a certain amount of fluid overload. What would be the key clinical questions that we should be asking in fluid management to know when to start, I guess, but when to stop CRRT fluid removal?

Dr. Murugan: Typically I think that those are clinical questions that need to be studied more rigorously in clinical trials. But I do think that, you know, the current KDIGO guidelines do suggest that you start fluid removal when there are life-threatening changes in fluid balance. Now what is a life-threatening fluid balance? It’s highly debatable. But I think in most patients, we would know the trajectory of where the patient is heading in terms of the fluid balance and what the hemodynamic status that gives you an idea about when to start fluid removal.

Now, when to stop fluid removal? This is also a great question. I think that it again depends on overall fluid balance of the patient. So if we do find that there’s a recovery of kidney function or if the patient clearly started to make urine and there is no pressing need to continue CRRT, it is safer to hold off at that point and wait and see, or maybe even if the patient is hemodynamically stable, stop CRRT and look at the patient and see whether the kidney function would recover.

There have even been studies actually showing that a higher rate of CRRT is inversely associated with the rate of urine output and so on, meaning that, when you use CRRT and remove fluid in an extracorporeal manner, it reduces the incentive for the kidneys to filter and remove volume. So for that reason, when we do have signs of kidney recovery, when the patient starts to make urine, for example, I would typically say 500 mL in 24 hours is the threshold that I use. At that point, it may be reasonable to hold off CRRT and then wait and watch and see what happens to the kidney function in the next 24 hours to 48 hours and then see whether you can totally stop CRRT in that patient.

Dr. Lin: You’ve discussed in detail a lot of individual care that really needs to be taken to make sure that the CRRT is optimized. That makes me want to ask you a question about how CRRT fits into this modern world with the ICU Liberation Bundle, where a lot of the best care is bundled and is predicated on doing things in a protocolized fashion to save time and to optimize outcomes. Where is the intersection between that type of an ICU Liberation Bundle and the personalized assessment and care that is necessary for CRRT?

Dr. Murugan: Thank you for asking that question. Currently, if you look at many of the ICU bundles, there’s a lot written about how much fluid we should give, for example, and so on, but very little is in these bundles about fluid balance and fluid regulation and targets for fluid removal. So I think that we need to incorporate fluid management using CRRT in some of the care bundles.

There have been studies published showing metrics for fluid removal. So 80% should be the prescribed versus what is delivered should be the target. Having dashboards and other metrics and periodic evaluation are really, really critical to frequently assess fluid balance in each and every patient. Every patient, just like everything else in medicine, there’s no one size fits all. We need to look at the clinical status of the patient and to titrate fluid removal and so on. But I do think that evidence has started to accumulate on how fluid management should be done in CRRT.

And there are more studies on what rate we should remove fluid, when we should start, what we should use to guide fluid removal, and so on. I think that these should be a part of the AKI bundle going forward. In general, fluid management per se, because as we all know, fluid overload is an important cause of morbidity and mortality in critically ill patients.

Dr. Lin: It sounds like this will be the next step in the development of the ICU Liberation Bundle. Ragi, thank you so much for joining us and giving us these pearls of wisdom. This is going to conclude yet another episode of the Society of Critical Care Medicine Podcast. If you’re listening on your favorite podcast app and you like what you hear, consider rating and leaving a review for us. For the Society of Critical Care Medicine Podcast, I am Dr. Ludwig Lin. Thank you so much for joining.

Announcer: This podcast is sponsored by Baxter Healthcare Corporation. Baxter supports true patient-focused treatments with industry-leading CRRT technology and is a partner dedicated to optimizing your clinical success in treating patients with acute kidney injury. Our commitment to you starts with education and provides complete support every step of the way.

Ludwig H. Lin, MD, is an intensivist and anesthesiologist at Sutter Hospitals in the Bay Area of Northern California and a consulting professor at Stanford University School of Medicine, where he teaches a seminar on the psychosocial and economic ramifications of critical illness.

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