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Guidelines recommend against red blood cell (RBC) transfusion in hemodynamically stable children without cardiac disease who meet certain criteria. Maureen A. Madden, DNP, RN, CPNP-AC, CCRN, FCCM, is joined by Katherine Steffen, MD, MHS, to discuss the clinical and economic impacts of compliance with RBC transfusion guidelines, as discussed in “The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease: A Secondary Analysis of the Age of Blood in Children in the PICU Trial” published in the February issue of Pediatric Critical Care Medicine (Steffen K et al. Pediatr Crit Care Med. 2023;24:84-92). Dr. Steffen is a clinical associate professor of pediatrics at Stanford University School of Medicine in Palo Alto, California, USA.
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Category: PCCM Podcast
Dr. Madden: Hello and welcome to the Society of Critical Care Medicine Podcast. I’m your host, Maureen Madden. Today, I’ll be speaking with Dr. Kate Steffen, MD, MHS, and we’ll be talking about the article, “The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease: A Secondary Analysis of the Age of Blood in Children in the PICU Trial,” which was published this month, February 2023, in Pediatric Critical Care Medicine. To access the full article, visit pccmjournal.org. Dr. Steffen is a clinical associate professor of pediatrics at Stanford University School of Medicine in Palo Alto, California. Welcome, Dr. Steffen. Before we start, do you have any disclosures to report?
Dr. Steffen: I have no disclosures.
Dr. Madden: Excellent. I’m so happy to be here with you today and to talk about this wonderful article. Before we start to talk about the article, I’d love to know a little bit more about yourself and your research interests, if you’d be happy to share that with us.
Dr. Steffen: Sure. Thank you so much for the opportunity to speak today. In terms of this article, I will confess that I am not a hematologist nor a transfusion expert but came to the area of transfusion through an interest in implementation science. As some background, during my training, I became interested in improving the quality of care that we provide in the ICU, and I was given the opportunity early in my career to learn about implementation science and apply that within our pediatric critical care practice.
As I was starting getting interested in implementation science, the TAXI group was thinking about developing recommendations for blood transfusion, specifically red blood cell transfusion, for critically ill children, and I was asked to sit on that committee to help develop those guidelines as an implementation expert. So, with a couple of other implementation experts, we were at the table in developing those TAXI recommendations. Over time, I’ve stayed involved with the TAXI group and put a lot of thought and effort in terms of how to actually get the TAXI recommendations implemented in our practice, and I’m still working on that today.
Dr. Madden: Okay. So to have an understanding, you said you were given the opportunity to broaden your education in terms of implementation science, and now you’re considered an implementation expert. Can you tell me what that education is like and what is it that makes you understand the implementation component and how you can then create processes at the bedside to make this happen?
Dr. Steffen: Sure. When the TAXI guidelines were being developed, I was very early on in my understanding and expertise within implementation science. But with a couple other people who are more expert than me, we provided guidance to the TAXI group in terms of ensuring that the guidelines that were written were more implementable. Over time, I have gotten a bit more education within the area of implementation science and completed a training grant through the NHLBI within the area of implementation and looked at implementation of transfusion recommendations as part of that training. We did a qualitative study where we did interviews with providers within eight different pediatric ICUs, both CVICUs and PICUs and combined units, where we investigated people’s transfusion practices and their willingness to use the TAXI guidelines.
Dr. Madden: This is something that I’m so fascinated with, but we’re going to come back to it. A little bit more about some of the other research you’ve participated in. You’ve referenced TAXI and hopefully the individuals who are listening to the podcast already understand what TAXI is. But I’d like you to elaborate on that, because I know you’ve been on PALICC-2, you’ve also been on the ABC PICU trial, so if you can give some sense of how those all, other than pediatric critical care, what are the items that link these types of studies together?
Dr. Steffen: Sure. The thing that I think links these is that, in critical care medicine, and in pediatric critical care specifically, we don’t have tons of data, at least not the sort of degree of evidence that we have in adult critical care. But we do have the opportunity, I think, to refine and improve and optimize our practice through developing guidelines. The thing with developing guidelines, though, is that we want to make sure that the guidelines that are created are ones that people can actually use at the bedside. Creating guidelines that are difficult to implement really doesn’t do our practice any service and our field any service.
As a person who is interested in implementation, we have used specific implementation tools as the guidelines are being developed and written to ensure that we maximize implementability within the evidence that does exist. My involvement in both TAXI and PALICC has been to sit at the table and help the experts who are reviewing the evidence develop guidelines that people can actually bring to the bedside and apply. Sometimes we’re limited in the degree of specificity in how the guidelines are worded to make them maximally implementable, but we try our best.
Dr. Madden: Okay. We are going to spend a little bit of time talking about the actual article that you have just published, “The Impact of Restrictive Transfusion Practices on Hemodynamically Stable Critically Ill Children Without Heart Disease,” so your secondary analysis of the ABC PICU trial. If you could start to give us a little bit of background about this study and what your findings are?
Dr. Steffen: Sure. We wanted to look at how people were actually utilizing the recommendations from the TAXI guidelines. The guideline that has the most evidence is the one that recommends, in children who do not have heart disease and who are hemodynamically stable, to withhold transfusion in that clinical situation until the hemoglobin is less than 7. We wanted to see, in patients where that recommendation was followed, what was the outcome in terms of whether or not patients developed new or progressive multiorgan system dysfunction.
We looked at a variety of other secondary outcomes. But the population we looked at, because we had, I think, a convenience sample, was the population that were enrolled in the ABC PICU trial, which was a trial designed to look at the impact of the age of red blood cells. But again, we had a very large study with many centers participating and patients where we had specific transfusion data. That made it an attractive study to do a secondary analysis in.
Dr. Madden: And also relatively easy to access too, I would assume.
Dr. Steffen: Correct. Yeah, the data were recently collected and had many of the variables we were interested in looking at and the outcomes we were interested in investigating.
Dr. Madden: Looking at the article, you put research in context and what the study adds to the research also. TAXI, just to put it out there, is the Transfusion and Anemia Expertise Initiative that was published after the performance, correct?
Dr. Steffen: TAXI guidelines were published in 2018 and the ABC PICU study was completed before that. With that being said, the specific recommendation that we were looking at was encapsulated within the TRIPICU study, and those data were available long before the ABC PICU study was performed. So we can assume that the evidence was available to providers to follow the specific recommendation and that theoretically they should have been using it.
Dr. Madden: Right. When you look at TRIPICU, which is Transfusion Requirements in the PICU, that was published in 2007, it compared the restrictive hemoglobin transfusion thresholds of less than 7 grams versus a liberal hemoglobin transfusion threshold of greater than 9.5, as you said, in hemodynamically stable children. So we have this body of evidence, and I’ll also go out, as you and I are both pediatric critical care people, our focus clearly is on children, but we know oftentimes that the evidence from the adult population is very compelling, but when we try and translate it or implement it, it doesn’t always become something that is as useful in the pediatric population. That’s the incentive always for us to specifically study and find data that are specific to our pediatric population. Also, knowing that we have a much smaller population and we don’t have as many people to enroll or it takes a much longer time to do that.
Where I’m going with this, there’s a huge body of evidence that’s both adults, trauma patients, but now pediatric patients. Even Choosing Wisely has the component in there in terms of looking at how you assess your patient and their hemoglobin and to try and only provide a single unit at a time or a single packed RBC transfusion that’s appropriate for the individual receiving it. What are we doing here? Why can’t we take really good data that support the practice and implement it?
Dr. Steffen: I think that’s an excellent question and really the question that motivates all of my interest and research. We know that just placing a guideline in the literature doesn’t really impact people’s practice, unfortunately. It would be nice to be able to publish something and know that people were going to take it to the bedside and translate it. But we really need additional efforts to make that happen. That’s been shown, not just within critical care, but within all of clinical medicine, that we need additional effort to understand the context in which guidelines are being implemented, and then additional effort to make sure that they are being implemented in the way that they were intended. So again, the basis for the research that I am currently doing is to figure out what we can do to ensure that guidelines are followed, so we ensure that our patients are getting optimal care.
Dr. Madden: I had a question then in regard to the implementation science and where you are currently focusing on your research. Are you able to share some of the potential strategies that you’re looking at?
Dr. Steffen: Sure. I think we’re in the early stages of understanding what strategies may actually be effective in terms of implementing these specific transfusion guidelines. Like I said, we’ve done the qualitative work to investigate what might possibly be useful, but we have yet to test those strategies. I will say that the strategies include things like education, ensuring that we have buy-in from our hospital leaders, ensuring that we have all the providers who are both writing orders for blood transfusions but also administering blood transfusions involved in the implementation of the guidelines. Then finally, looking at our practice over time, are we actually achieving the outcomes and following the guidelines as we intend?
Dr. Madden: Excellent. I really look forward to seeing those implementation strategies and the following research that comes behind it to see how successful we could be because, being a clinician, I really am invested in how we can translate the data and the guidelines into actual practice. In your newest publication, you talked about how the objective was to assess the clinical and economic impact of compliance with RBC transfusion guidelines, and you were very clear in your results and in your conclusions about the influence or the impact of compliance that it had on both the clinical setting and the economic components. I’d love it if you would discuss that a little bit.
Dr. Steffen: Sure. Like I said before, our primary outcome was looking at the incidence of new or progressive multiorgan system dysfunction. We found that there was no difference between development of that specific outcome, whether or not you were compliant or noncompliant with the transfusion guideline, meaning that patients didn’t do worse when you followed the guideline. We also didn’t see any impact in terms of the number of transfusions patients received, whether or not they developed sepsis, ARDS, if they developed nosocomial infections. We didn’t see any difference in terms of the worst patient’s PELOD score, their organ dysfunction score, between the compliant and noncompliant groups, and we saw no differences in mortality whether or not people followed the recommendations or not.
What we did see was an improvement in ICU-free days and ventilator-free days in patients who were transfused in a compliant manner. That was a sign potentially that we didn’t see differences in NPMODS. We did see this signal in terms of ICU-free days and ventilator-free days, which was, I think, good. The other thing that we found was that, based on the reduction in ICU length of stay, the estimated cost of PICU care and our physician fees were also lower; we had a reduction of about nearly $39,000 per patient when the guidelines were followed.
Dr. Madden: I think that’s a key element in this because we talked about guidelines. We keep going back to the guidelines and how they can actually be implemented. We know that we need to attract our clinicians to this evidence and have them believe that this is something that is safe and important and it’s going to improve our patient outcomes because we’re always also about our patient outcomes, but we have to have buy-in of everybody because ICU beds right now are just in such high demand. We need to have that decreased length of stay. We need to have decreased ventilator days because all of those impact outcomes in the short term as well as potentially in the long term in terms of quality of life. Lots of people are now studying post-PICU issues in that regard, but our administrators, our hospital people who are looking at this, if we can have significant reduction in costs where that money can be utilized somewhere else, I think that’s going to catch their attention.
Dr. Steffen: Yeah. I will say that this analysis also doesn’t consider the cost of the transfusion itself and the potential impact on ventilator-free days. So the potential cost savings is even higher outside of the analysis that we completed in the study.
Dr. Madden: And I know that you said the primary outcome was new or progressive MODS, but some of the things that people are very familiar with when we do utilize transfusions is having TACO, or transfusion-associated circulatory overload; people are really keen right now looking at fluid overload in our critically ill patients, but also TRALI, transfusion-related acute lung injury. Those are significant. I mean, we’ve talked about, over time, that we know transfusions are much safer because they’re being tested for the potential for infectious diseases and transmissions, but these other items that we can’t necessarily have control over 100% of the time are still significant impacts. Did you have that considered when you were talking about new or progressive MODS?
Dr. Steffen: We use a definition that’s established for new or progressive MODS, which doesn’t incorporate things like TRALI and TACO and, I think, importantly, the elements we don’t understand related to immunomodulation and transfusion. But obviously those are also the factors that would steer you away from transfusing unnecessarily because your patient could have one of those complications.
Dr. Madden: Exactly. Something that I want to try and understand a little bit more is, as we look at these studies that are coming out, we’re talking about being noninferior, so the concept that this new treatment is not unacceptably worse than a standard treatment. Very simply, it’s no worse, but it doesn’t mean it’s any better. What are your thoughts about the types of studies that we’re doing and how can we look at things that may show us something that’s superior?
Dr. Steffen: Yeah. I want to say that the initial TRIPICU study was done with noninferiority in mind, and many of these studies have followed that paradigm, partially because it’s easier to establish noninferiority than it is superiority and, in pediatric populations, it does seem like an attractive way to design a trial. This particular analysis, the secondary analysis, was looking at noninferiority for that reason because TRIPICU and ABC PICU had both used that standard to complete trials where we looked at superiority. They actually have to be designed differently. But I do think that it’s important to do so to encourage people to feel confident that they’re doing something that’s going to help their patient rather than something that’s not going to harm their patient.
With that being said, this is the level of evidence we have, and it doesn’t mean that, just because we haven’t established superiority, we shouldn’t be attentive to the guidelines and trying to follow them. So we would encourage people to look at the TAXI guidelines and to integrate them into their practice, particularly those that have a reasonable level of evidence behind them. There are a fair number of elements within the TAXI guidelines that are expert-informed, but we’d encourage people to think about those elements of their practice and integrating the expert-informed guidelines to the degree that they felt comfortable because I think, in reviewing them and having had experience using them as a clinician, they can be quite helpful in terms of thinking about a patient and doing our due diligence in terms of limiting the adverse outcomes of transfusion as well.
Dr. Madden: That’s the point that’s so hard to implement; it’s back to that word of implementation and implementation science. As I said, I’m really involved in guidelines and trying to see how we can get people to adopt them and comply with them, and that’s a significant challenge. I mean, even standing at the bedside, I’m going to put you on the spot though, are you compliant with your data?
Dr. Steffen: I think it’s hard for us all to follow guidelines. We tend to have this idea that our patients are special or different, but I think that it’s important to think about how your patient fits within the guidelines. I think that, many times, the way at least these guidelines are written, the TAXI guidelines, in the cases where our patients are not hemodynamically stable, we’re not obligated to necessarily follow that as, you know, specific threshold of 7. It really comes down to clinical judgment.
I think that where we need to go, going forward, is to really start to think about how our patients are clinically, how tolerant are they of their anemia, what’s their trajectory in terms of, are they improving, are they getting worse in the ICU? In cases where their trajectory is reassuring and they’re tolerating the anemia physiologically, they’re not having significant physiologic sequelae that show that they’re not able to manage this particular hemoglobin, it’s reasonable to monitor those patients until the time where they do really start to manifest symptoms of being intolerant of their anemia because we have evidence that transfusion may not be as safe as we once thought, and that really puts the onus on us to monitor our patients carefully until that time where they seem to be not tolerating but also has the benefit of not transfusing unnecessarily.
Dr. Madden: Right. I think that’s the hardest part, as you said, at the bedside. You’re evaluating your patients and if you’ve known them, you understand where their trajectory is and you want to follow these guidelines and you do so. Then, there’s the Monday morning quarterback coming in, that fine line about when is the right time and you shouldn’t wait or you waited too long. Always really challenging questions that I think every clinician starts to have some thoughts and discussions in their own head about. I think I’m going to wait to see the future with all of your implementation work and see what you can come up with. Hopefully, that will help all of us really put these guidelines into practice and be much more compliant with them. I think the statistic in there was the compliance was 44% of the time.
Dr. Steffen: 49% of the time. I guess people were noncompliant 49% of the time.
Dr. Madden: It still isn’t a great number of compliance either though.
Dr. Steffen: Right. No, I mean we have roughly half of patients are being transfused in a manner that wasn’t in line with the guidelines. There’s lots of room and I think that’s the important takeaway from this paper, that that there is a lot of opportunity. Even, I guess, in centers that are participating in these research studies, they’re still not following the guidelines when they look back at their practice. We all have the opportunity to do better.
Dr. Madden: True. I think we could continue to go on for a while, but our time is coming to a close. I just wanted to see if you had any other thoughts that you’d like to convey before we say goodbye.
Dr. Steffen: No, I think that pretty much covers it. I think that, again, we did demonstrate that our patients, when we transfused in a compliant manner, had more ICU-free days and more ventilator-free days, and we were able to reduce costs. But notice that we did have, like we’ve just discussed, suboptimal compliance with the guidelines, which points to the need for structured formal ways to address implementation, much like we’ve also been talking about. Looking forward to potentially coming back with more data about how specifically to make that work for people in the future.
Dr. Madden: Excellent. Dr. Steffen, I want to say thank you and I appreciate your time to discuss this new publication that I think is going to have influence in pediatric critical care. At this time, it concludes another edition of the Society of Critical Care Medicine Podcast. For the Society of Critical Care Medicine, I’m Maureen Madden. Thank you all for joining us and remember to rate, review, and subscribe.
Maureen A. Madden, DNP, RN, CPNP-AC, CCRN, FCCM is a professor of pediatrics at Rutgers Robert Wood Johnson Medical School, and a pediatric critical care nurse practitioner in the pediatric intensive care unit at Bristol Myers Squibb Children’s Hospital in New Brunswick, New Jersey.
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