no disclosures. If your center is anything like mine, almost as soon as you put your patient on CRT, someone starts asking, when can they come off? And usually this is meant by sort of a blank stare by everyone, at least when they ask me. So we're going to go through today what is our current guidance on our CRT liberation practices. Does it really matter when you come off or if you fail? What are we currently doing? What evidence do we have for that? And then what should we do? So if you're familiar with the Kidney Diseases Improving Global Outcomes, AKI guidelines, you will see that they recommend that you stop RRT when you don't need it anymore. That's a good idea. But it doesn't really actually have much guidance, so that's how you do that. It should be, your renal function should be adequate to meet your patient's needs. Your renal replacement therapy should be no longer needed because you either met your goals or it's not consistent with your current goals. So that's a guideline, but not necessarily helpful on a patient-by-patient basis. I was lucky enough to be a part of a group that convened as the 26th Acute Disease Quality Initiative, or ADKI, that was focused on pediatric AKI and CRT. And we were assigned to a work group that was specifically devoted to thinking about issues related to CRT. And we had one specific area that we devoted to CRT liberation as kind of this big, like, gaping hole in our knowledge base. And we thought about how do we think about the approaches to de-escalating continuous renal replacement therapy, liberating from it, rehabbing your patients off of it, both from a global perspective and from a kidney perspective, and then what kind of kidney follow-up do they need. We're not going to talk a lot about follow-up today. I recommend that they have some, but we're going to focus on those first three. So our consensus statement was a little bit more precise, but maybe you might find this not quite that helpful on a patient-to-patient basis either. But we noted that what you're going to think about when you think about whether a patient is ready to come off of CRT is whether they, what your patient-centered goals of care are, how much kidney recovery you've had, what's the physiological stability of the patient that you're treating, what is their current fluid balance, what is their sort of global recovery and rehab priorities, and then you want to use those factors to inform your decisions about how you're going to move forward. So does it matter when you come off and if you fail? There may be some pediatric data coming out about this soon, but currently what we have is adult data. This was a single center retrospective study that spanned about an 11-year period and involved over a thousand adult patients after 72 hours after their first liberation attempt. So this was an intention to try to take someone off and keep them off. They looked at the outcomes for those patients and they noted that about 20% of them remained off, good for them, but about 40% needed to have their CRT reinstituted and another 40% died. More importantly perhaps, the days since your CRT liberation attempt and your cumulative probability of kidney recovery, you can see that there were differences in outcomes based on whether you successfully liberated or whether you actually had to be reinstituted on CRT. And so for that group that had to be reinstituted, their degree of renal recovery out at 90 days was significantly less than those who successfully liberated. So it may matter when you come off and it may matter to your patients overall outcomes and their renal outcomes. I don't need to tell this group about PICU liberation or ICU liberation, but we know that if you aren't able to get your patients up and moving and off those beds, that their outcomes are worse. That's a really challenging feature when you're trying to deal with somebody who's hooked up to a CRT machine. As a matter of safety, the machines are highly sensitive to movement and changes in pressure, both access pressure, filter pressure, all of those things. And so a pediatric patient who isn't able to be told to just sit still isn't necessarily going to be able to be free of their sedatives, their ventilator support, even maybe perhaps their vasopressor support if you're managing a blood pressure issue while they're on the machine. So liberating in a timely fashion from CRT impacts your ability to implement these other ICU liberation things that we know impact long-term patient outcomes. So what are we doing right now? Well, we were lucky that the European Society of Pediatric and Neonatal Intensive Care decided to try to find out what factors are influencing people's decisions to try to take someone off of CRT. And you can see that this was a study that incorporated the PICUs from all over Europe. And it was perhaps intuitive, but very interesting to see how people did this. I like that they did this in a ranked order system. So you can see that the majority of people are using native urine output at some specific threshold to determine whether they think their patient is ready. The next most popular thing was just clinical improvement in sort of a global sense. But the next most preferred method of deciding whether someone was ready for CRT liberation was actually just sort of resolution of their fluid overload, which makes sense. A lot of our patients get put on specifically because of their fluid overload. Not only did they have... oh, and the last preferred was GFR improvement, which I don't think will surprise anyone, but it was interesting to note. The other interesting thing is thinking about people's strategies for liberation. So are they using diuretics? Are they not? What are they thinking they're going to do? And so you can see here that about an equal number of people were doing a diuretic bolus followed by an infusion, and some were just doing a diuretic bolus, or some had a variable approach based on patient condition. And a less common incidence was sort of a fluid bolus then followed by a diuretic that was the least common one, but something that some people were employing. So really a fairly wide variety of approaches to even how you attempt to get someone off, which I think is also, you know, consistent with our lived experience. So what should we do? Again, the data is not real strong. This one is from an adult study. This was from the Dunn RRT study. They tried to do a systematic review and meta-analysis of 16 variables that they identified from 23 adult studies. However, the heterogeneity of definitions and practices amongst those studies precluded a meta-analysis of most of the variables that they were looking at. But they were able to do a pooled analysis of urine output, which showed a pretty good sensitivity and specificity for suggesting someone was ready. But again, the heterogeneity among those studies precluded them from identifying how much urine output was enough. So more urine output is good. How much? Still an open question. There is a pediatric study on this particular topic, which again showed that your likelihood of successful CRT liberation was higher when you had a higher urine output in the hours prior to attempted liberation. And this was with or without diuretics. What about biomarkers? So there is some evidence of improved prediction of eventual renal recovery based on biomarker studies. That has ranged from urine HGF to IGF-BP7, TMP2, N-Gal, urine, but maybe also some plasma. And then some other sort of emerging biomarkers. But it's worth noting that these are mostly biomarkers that we've used to identify renal injury rather than renal recovery. So what people have tried to do is identify when the injury is lessening. What we don't know is when the injury lessens, does the recovery start to accelerate or increase? And so we don't have that information to try to help us identify when the kidneys are able to do the job on their own. So that role in determining liberation readiness is really still very unclear for all of us who are invested in this question. This was a nice algorithmic layout of sort of the decision-making process about CRT liberation. I think it sums up probably what you're already doing. You're identifying whether or not your patient is hemodynamically stable. You're identifying whether or not the objectives for which you put the patient on CRT were achieved. That might be fluid balance. It might be clearance of an intoxicant. It might be clearance of solute. And then this one tends to be the thorniest one I find in pediatric patients. You're assessing if the minimal daily obligate inputs are sufficiently low to allow either the native renal output to keep up, the urine output to keep up, or to be sort of compatible with an intermittent dialysis modality. And in adults they're saying that's less than two liters a day, but we know for pediatric patients that's often quite a bit less, and can be highly dependent on whether on the age of the patient. Are they an infant who takes an entirely liquid diet? Are they on TPN? Are they requiring a lot of medications? Like these things can really significantly impact whether or not you can meet that criteria. And then there's some options for how you might proceed. So you assess their urine output. Here they suggest more than 400 mils a day. There are other studies that suggest more than 500, but again those are adult patients, and that is usually described as being without the help of diuretics. So if you look back to an older study, again in adults, they looked at whether or not there was a threshold of urine output that was predictive, and they found that if you had over 400 mils of urine output without diuretics, you had about an 80% likelihood of coming off. But if you gave someone diuretics, that number came over to over two liters to have an 80% likelihood of coming off. So if you add diuretics, you're not really sure what information that's adding to your to your deliberation decision. So if you have your urine output, it's quite low, but the patient is otherwise pretty stable, you might consider transitioning them over to an intermittent hemodialysis mode. If however they have a nice brisk urine output and you feel like they're able to keep up, then maybe you're gonna say I'm gonna plus or minus diuretics, try to see what they can do with their fluid balance and their and their solute clearance over time. So in conclusion, I think we can agree that CRT liberation is a really vital component of high-quality CRT delivery, and I would argue high-quality critical care delivery. Current practices vary widely. I can only imagine if we extended that European study more broadly across the world. And our evidence for best practices and outcomes is lacking, especially in kids. We're hoping to correct that sometime in the near future. Thank you and we'll move on.

renal replacement therapy

CRT liberation

renal recovery

clinical guidelines

pediatric nephrology