Good morning everyone. Welcome to Grand Rounds. I'm just waiting for the thumbs up that our Zoom is. I got it. I got a thumbs up that our Zoom is on and ago. So as everybody's mingling in, I'll get going. And so thank you all for coming here. Have a great turnout in the auditorium and I'm sure there's many more at home on Zoom. It just makes me realize that everybody's very interested in blood and transfusion medicine and doing the best for our patients. So thank you all for coming here today. We're going to leave some time at the end for questions. So get your questions ready as you're listening to this talk. So the title of this joint anesthesia and surgery and perioperative grand rounds is pediatric patient blood management at Boston Children's Hospital. Current perspectives from transfusion medicine, blood bank and perioperative medicine. And first what I'd like to do is introduce the panel. So if I could ask Dr. Kelly and Dr. Mannis to come up, I will do the honors of introducing our three speakers today. So first I'd like to introduce Dan Kelly. So Dan is a graduate of Brown University and Brown University School of Medicine. He completed his pediatric residency training and service chief resident at Wild Cornel Medical Center in New York. And then he transitioned to Boston Children's Hospital where he completed his pediatric critical care fellowship followed then by a fellowship in transfusion medicine in Harvard at the joint transfusion medicine fellowship. In addition to fellowship training here into masters in healthcare quality and safety from Harvard Medical School. He's an assistant professor of pediatrics at Harvard Medical School. Kelly serves as a pediatric intensiveist in the division of medical critical care worries the director of patient safety and quality. And he's also associate medical director for the quality and outcomes for the Department of Pediatrics providing physician insight to the clinical pathways program. His interests are focused on improving patient safety and quality, especially in the safety and efficacy of pediatric transfusion and critical illness. He's co-chair of the DOD sponsored Titer Transusion and ECMO trial site PI PI for the NIH sponsored tropic study and co-chair of the hospital's transfusion committee and cheers of the PPSQ's Venus thromboembolism reduction transfer task force. So Dan Kelly will be speaking second. And then Dr. John Manis will be speaking after Dr. Kelly. John Manis is director of transfusion medicine at Boston Children's Hospital. He's an associate physician at Brigham & Women's Hospital in the Dean of Farber Cancer Institute. He trained in internal medicine and completed fellowships in hematology, oncology, and transfusion medicine. He joined the Department of Laboratory Medicine at Boston Children's Hospital and runs a basic research lab investigating the links between DNA repair and immunodeficiency as well as stem stem development and mobilization in sickle cell disease. He participates in over a dozen cellular therapy trials, including trials to improve mobilization and collection of stem cells for sickle cell disease. He's part of the Cure Sickle Cell Initiative Laws by the NIH where he chairs the committee for Aferesis Research and oversees clinical trial to collect stem cells for national repository. And he's also co-investigator, Gator, in multiple clinical trials, testing gene therapy for sickle cell anemia, and as well he is head of the blood bag and co-chair of the Trans-Usiung Committee with Dan Kelly. And then I asked John Manis to give an introduction for me. Thank you. It's a great pleasure to be asked and introduce Dr. Gooby. I mean, there's just need introduction to many of you, but it sometimes helps to put somebody's scholarship really in perspective. She's an associate professor of anesthesiology at Harvard Medical School and a senior associate in the Department of Anesthesiology, critical care and pain medicine here at Boston Children's. She's co-chair of the Parioperative Research Committee, and also for Parioperative Research, rather, and liaison for the Jehovah's Witness and Bloodless Surgery Patients. She developed, and this is incredibly important, the Boston Children's Hospital, massive hemorrhage guidelines, and this has really been a very impactful amount of work she organized and ran the first International Pediatric Patient Blood Management Masterclass in 2023. She's a member of the WHO Task Force for PVM and is vice chair of the American Society of Anesthesiology PVM Committee. She's on top of that, and her spare time, she's executive editor, for pediatric anesthesia, associate editor for the British Journal of Anesthesia, and associate editor-in-chief for the BJA Open Access Journal. She's chair of the Canadian Pediatric Anesthesia Society for Research Committee, and founder and chair for the Society of Pediatric Anesthesia, PVM Committee. These are all enormous accomplishments for the field, so it's a great honor to even be in this company. I'll ask you to sit down and I'll get started. So that's us, and here are the objectives today. We're going to define patient blood management and talk a little bit about Parioperative Patient Blood Management Guidelines. Dr. Kelly will discuss optimal blood use, risks of blood transfusion and safety considerations for children having elective surgery. Dr. Manna will highlight some of the blood bank challenges, and then we'll introduce the data from our Department Parioperative Blood Management Dashboard. I'll particularly talk about anemian over transfusion, and then briefly introduce the new Boston Children's Hospital, Massive Hemorrhage, Massive Transusion Clinical Pathway that's in a draft form at the moment. I don't have any conflicts of interest, and these are the disclosures. So why are we all here today? We're all here to talk about blood health. You've heard about heart health and probably liver and kidney health and gut health, but have you heard about blood health? Many of more of our patients and families are aware of this concept. Think about it. Blood carries oxygen from the lungs to all the vital organs of your body. It carries metabolic wastes for elimination through the kidneys, carbon dioxide for removal for the lungs. It's an important part of our immune system, helps protecting your body from disease and infection, and also it contains an elaborate system to stop bleeding and avoid clotting. Blood is really the river of life. It's an indispensable part of the infrastructure of your body and our patient's bodies and for life processes, and really that's what patient blood management is all about. It's all about all aspects of optimizing our patient's blood health. So an organ, what is an organ? An organ is a group of tissues that perform a special function. The circulatory system and all the blood it contains is the largest organ system of the body. Therefore blood is the body's liquid organ. Like many other organs or systems in the body, the balance and health of the blood must be maintained. We all know that blood has many functions. We've talked about the delicate balance between hemostasis and thrombosis, and suboptimal blood health can manifest as anemia, quagulopathy, bleeding, and thrombosis. And it's this suboptimal blood health that can compromise outcomes for our patients in our hospitals, especially those undergoing surgery. The default treatment for anemia and blood loss is commonly a blood transfusion, which is essentially a liquid organ transplant. So what is patient blood management? Patient blood management is a new standard of cure to optimize blood health. It's one of the few areas of medicine where all three can be achieved at the same time. There's much evidence to show it reduces risk, improve outcomes, and saves cost. And essentially, at the heart of patient blood management is improving patient outcomes. It's defined as timely, multidisciplinary application of evidence-based medical concepts to screen and diagnose anemia, to minimize surgical procedure on eye-atrogenic blood loss, to maintain coagulopathy, bleeding, and improve health of our patients through and multimodal strategies. And the World Health Organization recognizes this. There's an urgent need to implement patient blood management, given the global crisis of anemia, bleeding, a high morbidity, and mortality associated with blood transfusions, and the critical shortage of blood that ebbs and flows. The evidence is increasing, and you can see on the slide that there's evidence that patient blood management initiatives reduce mortality, reduce major morbidity, for example, myocardial infarct stroke, thromboembolic disease, reduce the acid of complications such as infection, decrease overall length of stay in the hospital and in the ICU, and decrease costs. There's no doubt a blood transfusion can save life in limb. And if we consider why blood transfusions are given in our hospital, it's the following list. For acute blood loss, anemia, to restore oxygen to delivery to vital organs and tissues, to treat low volume, hypolimia, hypotension, or hemostatic arrangement. So on one hand, a blood transfusion may be clinically necessary for life and maintaining vital organ perfusion. However, alternatives to blood product transfusion, or at least optimizing blood product transfusion may be the safest choice for our patients. So I'll next introduce Dr. Dan Kelly, who will talk about optimum use of blood, risks of transfusion, and safety considerations in children having elective surgery. Good morning, everyone. Thank you for the opportunity to present. What I was hoping to touch on was kind of thinking about this notion of the optimal use of blood, not fully defined, but there is emerging evidence. Highlight some of the risk of transfusion, especially the notion of transfusion-related immune modulation or trim, but as Susan mentioned, a transfusion has transplanted. And then highlight some of the hazards in and turn some of the safety considerations that we should all share. So as far as optimal use of blood, it really hasn't been defined, but the notion is thinking about the right product for the right patient for the right indication. Traditionally, it used to be, we transfused whole blood. That's not widely available anymore. We've really moved to component transfusions. However, when we do have whole blood, really it's reconstituted whole blood and that we take red cells in plasma and mix them to a specific matricrate. Really, you only use for very specific considerations such as exchange transfusion, some ECMO centers, and potentially cardiac bypass. But probably the least likely product that we use. As far as red cells, this is our most common product, but really the products are changing over time due to innovation, such that we're having constant improvement in some of the additive solutions that allow for improved storage, particularly in red cells, now we're able to store up to 42 days. And with some of the additive solutions, we're now able to change some of the viscosity of the product, which is important for some of the physiologic considerations when it comes to transfusion. However, despite all these innovations, we really, as a field, have not yet fully defined the transfusion thresholds for all scenarios. We'll get there in a moment, but we're kind of moving away from the notion of if we're going to expose a patient, let's tank them up and give them more and shifting to a less is more strategy. As far as platelets, in the past, these were really collected from whole blood units that we would remove platelets and make individual platelet components. Now, most of our transfusions, especially here at children, are collected through aferesis collection. And so we're able to collect a larger volume of platelets from a single donor and in turn decrease the donor exposure risk. One thing with platelets to always consider is that they are biologically active and cannot be stored at cold temperatures or frozen like plasma. And so in turn, it's very difficult to maintain a platelet supply. Typically, our shelf life is five days. And they're at higher risk of bacterial contamination because they're not chilled. And so with pathogen and activation technology, we are starting to improve the safety, but certainly platelets are one of our higher risk components. Plasma, we've really moved away from a lot of plasma transfusion in some of the bleeding diatheses. Now that we have factor specific components, but certainly plasma is still utilized. Most of the plasma that we actually transfuse here is what we call FP24. To meet true definition of fresh frozen plasma or FFP, that has to be processed and frozen within eight hours, which is technically very difficult to achieve. So most plasma that we transuse is what's referred to as FP24. So frozen plasma collected within 24 hours. And we see slight decreases in some of the factor levels there, but clinically, it really doesn't make much of a difference unless there are specific factor deficiencies. But an important consideration with plasma is that with all the processing, ultimately, the product ends up having an innate INR of somewhere between like 1.1 to 1.3. And so if you have a patient with mild coagulopathy, adding more plasma to the mix really won't help that INR if anything will kind of stabilize it. And then there's cryo, which certainly is available and then specific factor considerations. So this one to highlight some of those notions, but really to focus on when do we use products. And so there's been emerging evidence, but much of it is looking at very specific patient populations. And so now, currently, people are starting to put all these different studies together and try to start to generate guidelines. And so most recently, the American Association of Bloodbanks or the AABB came out with Red Cell Transusion Guidelines back in November. And they looked at studies including over 2700 patients and really took the angle of that restrictive versus liberal transfusion strategy. And so the pediatric specific ones, unfortunately, there's only two of them. Note that for critically ill children or hospitalized children who are at risk of critical illness that are hemodynamically stable and without a transfusion dependent hemoglobinopathy, a cyanotic cardiac condition or severe hypoxemia, they recommend a restrictive strategy. So waiting till the hemoglobin is less than seven to transuse as opposed to the traditional 9.5 threshold. They do note that for patients with cardiac lesions, there are different thresholds for a biventricular repair waiting for seven. If it's a single ventricle parliation raising that to 9. And then really kind of in between for uncorrected congenital heart disease, summer routine 7 and 9. I will say that these are generalized guidelines. They don't apply to all specific patient populations as with any guideline. Specifically, they don't mention pulmonary hypertension in here. They don't mention ECMO. But it does start to align with many recent guidelines. So you can see over the past couple of years, the UK recommended 7 without major hemorrhage, European side of anesthesiology between 7 and 9 effective leading. The taxi guidelines are probably the most robust that we've seen in pediatric critical care. In general, if hemodynamically stable, waiting till 7, although there's many caveats in this document and really points kind of a guidepost for further investigation. And then more recently, the Society of the RAS Exurgents, they recommend a restrictive strategy but don't offer a specific claim and globin threshold. And so it kind of begs the question as to why does all this matter? Why should we be thinking so critically about this? And what we're starting to see is that in certain patient populations, it could be that red cell transfusion itself is harmful. So looking at the pediatrics, severe sepsis or septic shock cohorts, a study of nationwide and we'll look at in a little more detail in the next slide, noted increased duration of organ dysfunction for critically ill children in general. And others, single center study, although with 800 patients, noted that those transfused had either increased risk of new or progressive organ dysfunction. This increased risk or decreased duration rather of mechanical ventilation and non-transused patients in pediatric ARDS. And in a large pediatric trauma study, a registry study, those who were transfused had increased risk of development of ARDS after adjusting for other markers of severity. And so to look a little more specifically at the nationwide study, they looked at 94 critically septic patients. So patients admitted with sepsis requiring basal active transfusions. And what they noted was that it wasn't really the same effect for all patients. So those who had a lower shock index, so lower severity of disease potentially, they actually seemed to have worsening predicted outcomes, such as worsening days of organ dysfunction for those that were transfused as compared to those who were not transfused. Potentially suggesting that transfusion alone was potentially altering their organ dysfunction. And when you look at this from the initial hemoglobin level prior to transfusion, in general, those who were transfused had more organ dysfunction than those who were not transfused. And so one of the theories behind this is that there's this notion of prim or transfusion related immune modulation. And so although we cross-match and the products are compatible, there are innate immunifex with exposure to transfusion. And what we're seeing is those patients who have lower TNF alpha production capability. So those who are ayurisk of immune suppression are more likely to see the untoward immune effects following transfusion. In this study, note it as days of organ dysfunction. And so to try to look at this a little more robustly, tropics is a multi-center observational study that we are participating here at children's. And what we're doing is enrolling patients who are admitted to the ICU with sepsis on basal active infusion and monitoring certain biomarkers in immune function for those that are either transfused or not transfused. And what we're aiming to do is determine what clinical, hemodynamic or blood product factors should drive transfusion decision making for these patients. And more importantly, to also look at some of the immune types to try to predict which patients may actually be harmed by a red cell transfusion when presenting with critical illness. As far as other patient populations, transfusion and ECMO is probably one of our largest utilization in the building, aside from the oncology patient population. And so as we all know, patients who are on ECMO require frequent red cell transfusion. The purpose being to address bleeding, but also to improve oxygen delivery. And that threshold for what is the optimal thresholds transfused optimized delivery has really not been established. But what we do know is even when controlling for other factors, transfusion alone is an increased risk of mortality. We transfused quite a bit in ECMO and often it's quite necessary so you'll see on cannulation day day one. Typically on average is between 100 to 125 ml per kilo of red cell exposure. And then that decreases on subsequent ECMO days. But what you'll see is that on this bottom line that's got the kind of dotted presentation here, many of these patients are transfused even when their hematocrit is already above 35 and they're not clinically bleeding. Which begs the question is to do they truly need that transfusion. And really what is driving this is that if you look at the effects of transfusion as far as improving oxygen delivery and in turn mixed venous saturation, what we see is that amongst both cardiac and respiratory indications for ECMO, only about 5% of the transfusions actually increase your mixed venous saturation. And so is there an opportunity there to try to think a little more carefully about doing each of transfused as much as we do in ECMO. And these are just two studies highlighting that concept that even when you control for other illness severity and reasons for cannulation, transfusion alone in ECMO is associated with increased mortality. And if you look at the volumes, it's actually quite impressive. In the Mizinsky study, there's about 30 CCs for Kilo per day of ECMO. And O'Hallarin is actually a local study here from children's and it was about 40 per Kilo per day. But if you think about a small three kilo neonate on five days of ECMO, that will ultimately get you about a half a liter of blood, which is a significant exposure for the patient. And so fortunately the Department of Defense has provided us with funding to launch TIDER, which is a multi-center, I think we're at 18 centers now. Trial, looking at this question of do we use a chemo-goblin threshold or do we look at clinical markers for when we should transuse? And so we're actively enrolling patients who are less than six years of age, who are on VA ECMO. And the schema is that we randomized to either an indication-based arm, which I'll mention, or use whatever the local center specific threshold may be. And our primary clinical endpoint is the change in the pediatric sequential organ function assessment score. So more or less the change in organ function scoring. And then there's also interestingly, the thing we're particularly excited about is looking at the longer term neurodevelopmental outcomes for these patients, both at 18, 24, and hopefully with funding, we'll get to 36 months. And so the two arms are the standardized, whatever the local transfusion threshold may be at each center. And then the intervention arm is kind of a waterfall approach in that if the patient's leading a recommendation to transuse, if not, we then look at certain lactate levels or lactate trends and then transfuse. But if neither of those are met, we recommend waiting for him at a crative 25. And why does all of this matter- we talked about the immune function, we talked about, you know, do we really need to transfuse as much? All transfusions be it red cells or other components, do have hazards associated with them. The UK has a really impressive blood management approach as to the Canadian centers. And a little more robust than the CDC, which is on some angles of voluntary participation. But the UK data is more robust and more timely. And so this is the serious hazard of transfusion report for 2022. And as you can see, certainly not without risk. Most of the errors are what we consider to be near missed and not harm the patient, but certainly potential opportunities. And then as you go down the list, it's some of the clerical errors that occur with blood banking. We know transfusion reactions, but it's really stuff in red that we should be concerned about. These are errors that are potentially avoidable. And so it does highlight the fact that we certainly, as careful as we may be, there is still unintended harm to the patient. And the harm varies by the unit. So platelets are much more likely to result in either febrile or allergic type reactions. And so that's why you'll see more transfusion reactions associated with platelets. And then all products still have concerns. But looking at the data from the US, most recently, we've, the most recent cohort reported that was from 2013 to 2018. So in the US blood system, rates of serious reactions. So this is 16 for 100,000 transfused units as an aggregate number. You can see that there was 23 deaths associated with transfusion, most of which were associated with transfusion associated circulatory overload. So a large, oncotic load to the patient that resulted in often symptoms of congestive heart failure. And again, these are pediatric and adult cohort data or trolley. But as we see here locally as well, allergic and febrile non-hemolytic reactions of the two most common febrile non-hemolytic, meaning patient developed to fever during transfusion, not due to homolysis. And they're after delayed serologic transfusion reactions. So development of red cell antibodies following transfusion. And so as you can see, there's certainly not without risk. These are all reported locally to our blood bank. And actually, it's coming up in just a second. We track these and report them nationally. So we participate in this data surveillance. As far as how does this compare to each unit, it depends on what you're transfusing. In platelets and plasma, we see more allergic type reactions in red cells. We see more febrile reactions and transfusions associated circulatory overload. So certainly not without risk. We have seen great strides in decreasing the risk of viral transmission over time with transfusions. So you can see HIV is down to 1 in 1.6 million. And then this question also comes up with trim and transfusion immunodulation. Does that clinically translate to risk of infection? And it really depends on what patient-specific cohort you're looking at and what study, how the study was structured and kind of what they defined to be infection. But a recent cock and review kind of has this hovering slightly below one. It's like 0.97. So certainly a risk something to think about. But we really don't know for sure as far as the true risk of infection. But as you can see, if not infection, there may be immune consequences to this. And then just looking closely at children's, we do monitor this. We participate in the CDC Hemovigilance Program. And on average, for all the units that we do transuse, we're right around 1% or slightly below 1% month to month. And this includes all types of reactions. And so recognizing that this isn't what is not without risk. If we're going to move towards safe transfusion, which obviously we're actively doing, there's always room for improvement. It's really not test having the right components. But it's on all of us to think about having the right decision making, the right decision support behind that, the processes, and making sure that we're thinking critically about when we transuse. Is it really worth the risk of transfusion? Are we transusing the right product in our root transuse and the right volume of product? Now I'll turn it over to Dr. Manus. Thank you. Thank you. I wanted to give a quick overview and really succinct. There's a lot of activities in the blood bank and we support a lot of the hospital. But I want to point out today is some of the challenges we have and that you also see that we could help improve from the blood bank side, but also change your expectations of what. And that's really the largest thing we could really change now is what should you expect when you water blood, if you water blood, when you're giving blood? I'm not here to tell you when to use blood. We have experts that just were up here to tell you when to use blood. I'm here to tell you when you want blood, what should we be thinking about? So there's specific challenges in pediatric blood banking. You know, I'm going to go over the landscape. What do we do here at Children's Hospital? The special blood needs for children and component modifications. What are we doing to the different components? What should the blood bank know? What should you be telling us about your patients? There are many different things about the patient that would help improve the speed with which we get blood back to you, but also in the type of blood product. Emergency release, massive transfusion, that's all about language and understanding what language needs to be used and communicated, because it's all about communication and understanding the efficacy of transfusion. And I'm just going to touch on COVID because that's it's COVID. It affects everything we do even today. So a whole blood collection, what would you last year here at Children's Hospital? This is just for children's. We have 8,100 donors. The vast majority of red cells collected on a bloodmobile going around. Platelet collections, 3,000 platelet donors. We generated 11,500 red cell units. That's just here in our own blood bank. Platelets, plasma, cryo, 20,000 blood components were made and moreover what you really need to know is that we transfuse a lot of blood. Lots of blood. I'll show that in the next slides. We have specialized components, wash products, different types of washing, reconstituted red cells, custom aliquots will give you what you want and confirm. Okay, have a good day. There's in terms of you here at Children's, we're very self-sufficient. Needless to say we're almost fully self-sufficient, almost at 100%, greater than 90%. We have a fantastic blood donor center and we're able to supply blood for the whole hospital. We only are buying very boutique-like products to come in. This pie chart, lots of colors I apologize but try with me. What this is, each of these little high slices is a different part of the hospital and it helps put the blood usage in perspective because everybody assumes that there are areas using the most blood and I don't mean this in a bad way because it's your optic. What you could see is that the outpatient, the green biggest buy is the largest user of blood and actually that speaks to what kind of patient needs this blood while in the OR and in the units it's a bridging therapy and we express many of these patients to make their own blood get better and get by. You have surgery, you get better, you're in the unit, you'll get better. The outpatients, many of these patients have either hemoglobinopathy or malignancy and they're chronically transfused so that really also helps you think about why do you need blood and when to give blood so a lot of these triggers may be very, very different for your patient population. The information, what you need to know and think about at times when you're ordering blood is that the information system on the blood bank side is not native to whatever you're seeing. It never will, well I don't know if it'll ever be but it won't be for the next decade at least and that is because the FDA regulates the IT systems in the blood bank and no electronic medical records supplier. For example, Epic wants to deal with that. They just let boutique software companies make blood bank systems. You could just imagine the two different systems trying to talk to each other. That's enough said with all the challenges we have with Project Mosaic but it's always a challenge. So just what you see on your side is not necessarily what we see so that's why communication is very important. For example, while you may be thinking about things like yellow products being plasma platelets together, we don't think that way on the blood bank side and we also can't assume that location will dictate urgency. In other words, we get many calls like well I'm calling from 7th South, right South, of course I need blood, why would I call you? You just need to use specific language and I'll get into that in the next few slides. There's a combination of electronic verbal and paper. We'll do our best to get whatever you need. Again, communicate and moving forward we have a lot of opportunities for electronic ordering, scanning and whatever way we could be able to get blood to you. Pre-transfusion testing, it has its challenges of course, newborns and young infants less than four months of age. They're in a special category. You can't believe these patients very easily. They don't make antibodies. So for these patients, if we don't know their blood type, we'll just give own negative units and that is our policy. If we do have a blood type, we'll give blood specific but nevertheless for either one, either whether we know or not, we could get blood to you very, very quickly and it's not a problem for less than four months of age. After four months of age, we do have special considerations for getting testing. Now, the FDA mandates the blood bag, whatever we dispense that has to be tested and cross matched and that's an important term. That's we have that contract with the FDA otherwise, we have to report it. So if we tell you something is emergency release, it does not mean this is unsafe blood. It just means that you understand we have not finished our complete regulatory testing. It is probably the most safe blood we can get to you. It will probably be identical to whatever we would give even after testing, but we have not jumped through all the regulatory hoops to be able to do that and we don't of course we can't just change rules on the fly. If there's a patient who doesn't have a blood type here, it could take up to two hours and that's something that's very, very important because that could be done in pre-op testing. So day of testing, you'll have delays. It really does take that long. It's not something that it's not like a sodium where an instrument just does it. There's manual, there's review, it takes time. It's for us, what you need to tell the blood bank, let us know if somebody's been previously transfused or if they've been pregnant. In the new ethics system we're going to make this a lot easier for everyone to communicate through ethics, whatever you know about the patient, that you'll be able on your evaluation of the patient ahead of time. Tell us. Tech and screen many of you all know that it's good for three days and up to 30 days we do 28 days here. If drawn in special parameters is now patient. We usually need 1, 6, no, 2, the amounts change. We'll try to do our best with whatever we get, but understand that if there's anything that changes the results, there's a delay. We'll ask for more samples, but what I want, this is a very busy slide. The takeaway message here is, communicate with us if you need blood urgently, we'll get blood to you. That is the most important thing. We never want a patient not to get something. It may not be the most ideal unit, but it will be a safe unit, and it's really a medical decision, your decision on when and how to give it. We do need two separate specimens that standard of care in most pediatric and most hospitals, and if you use a PPI-D, positive patient ID, scanning, scanning, phlebotomy does in the future with the epic change, that'll be the standard something called BPM, that many of you may be involved with in the Mosaic project, and that will help speed up order delivery. Let us know if there are any chronic problems, sickle, self-alce, see me the most important. That's going to be rare and we'll know ahead of time, but I'm just letting you know. It's also especially important to identify direct transfers into the OR. So you know when a specimen is received, and this is the last of the didactic slides I would say, there's labeling requirements have they been met? Do we accept this specimen? You can see all this step-wise, all these steps required until we could release blood. There are many, many steps. Has it been labeled correctly because many errors, if not most errors, are the wrong labeling, either of the tube or a transfusion? So that is something that we don't take lightly. Has the order been put into the LIS, the information system correctly, the laboratory? Is there historic type? Can we do cross-match? Can we release the blood? So this can take time. In terms of cross-match to transfusion, what is a cross-match? What is a transfuse, a screen? When you have a screen and the screen is negative, meaning there are no antibodies present to red cell antigens. That's what we're testing for. In other words, if we give a random unit, can there be a homolysis? If the screen's negative, we could practically just take any unit that's ABO compatible, pull it off a shelf, give it to you, and it's safe. And that's something that's what we usually do. If something has a positive antibody, we usually let you know. And also, that's what we care about. That is a small, small minority of patients. A cross-match is a reservation when you have a very high likelihood that you will need blood. And the ratio you could see here is below two, which is great. That means we're thinking about blood. Although it does change with each product and also by location, which I'll show you. You can see for red cells, for all other products, when we dispense it, you can see the return. That's the yellow or whatever color you want to call that, close to yellow. Bar, the third bar. You can see it's really red cells that get returned. And that's understandable. If you're in the OR, you want that insurance. But how much insurance do you really need? We all know we over buy insurance. And part of blood, patient blood management is to understand A, how much insurance you need and B, when to trigger that transfusion. And what you could see here when comparing blue dispensed to red by area is that really it's, who's returning the most blood? It's really a lot of the surgical uses of blood. Or a lot of areas, the OR, for example, it's a little bit off. You can see it on the third from the right column. A lot of blood nearly half is returned. It's about a third. Other areas use every drop they'll get. So there are a lot of areas where there's still room to improve. That's not our biggest motivation in the blood bank. We're not here to tell you, no, don't take blood. But we're here to tell you, think about what you're really going to use, what you're really going to need. And also remind you with metrics that you're actually not always using everything you order. So think about it because that takes it out of the inventory and actually causes delays on other ends. I talked about testing emergency release. I think I touched on that. But what's important here to take home is if you need blood, you have to use that term to the blood bank. You actually have to spit out emergency release. You can't say, I really need blood. I really need blood now. Please give me blood. You have to, we need that language. We need that handshake. Massive transfusion protocol. Again, it's different when we say massive transfusion protocol for that. That just means the blood bank running ahead and being prepared for you. X number of units of each of the blood products. Susan has Dr. Gooby is a champion, a leader in the field and has developed protocols with her colleagues to be able to tell you what to do once you get that blood and transfuse it into the patient. So the massive transfusion protocol, which you should call the blood bank to enact, when you think you'll have need a lot of blood, is simply to let us know for this patient, do whatever you can to speed it up and have everything available. How safe is that blood when we emergency release or when we have an MTP? You could see here the rate of homolysis or antibody formation is really quite low. There was a single institution study done out of brown and there were cases though of fatalities. This is in trauma patients, adult and pediatric, where there was unmatched blood being transfused and that was in patients with pre-existing antibodies. So I'm not saying there is no risk. It's low risk and it's something really to think about before you're asking. Just to touch on testing of blood, COVID vaccines, the blood supply, COVID gave us many challenges. However, we did quite well. We never had a delay in any surgery because we didn't have blood, unlike other hospitals, unlike the adult hospitals. The pediatric sections are very, very motivated. We test for many things, HIV and in fact the real rate of HIV is even of febrile non-humiletic reactions is much slower here at children's because we universally look or reduce our products and it's less than 1,000 will be a real febrile non-humiletic reaction and HIV transmission is probably closer to 1,000,000. We do all these screening tests. However, there's a large concern that's ever evolving for COVID and what do we do for COVID? Many, many patients do not want blood from COVID-vaccinated patients, donors. And for many reasons, the majority are political reasons or thought reasons. And I'll tell you, I've been surprised by some patients that are worried. In other words, there are parents that come in and say, my kids having heart surgery. I've heard that the vaccine affects the heart. Should I worry? And you know, there, it gives you a pause to think, but we have those data. We know that it does not affect that many, many patients have had it. But what's most important is to remember that you're not transmitting the vaccine, you're transmitting antibodies. And these antibodies are probably already present and even many of these donors. We do not test for COVID. The private companies that do, we do not. Most hospitals do not. And this was a huge issue because the FDA even came out. This was in October of this past year and drew caution to these asks for COVID negative blood and really came out with those scientific evidence for the adverse outcomes. Two, last topics I just want to touch on, a minute of peace. We're participating in many, many studies here. One of the studies is to try to understand when what is the variability amongst units of blood. When you get a blood product, remember, it's almost artisanal to use a term. It's from one donor. It's not the same product amongst it's been stored differently. It comes from different donors. It may, some donors are better than others. So we're trying to understand that we're participating in a NIH trial to try to understand that. And the best patients we could really study that in is the next slide, is an impact study, is those with hemoglobinopathy. But what I want to point out here and the reason I'm bringing this up is we're also part of a group that is interrogating every transfusion, hematic writ, every lab that every patient in the past five years at children's has in our electronic medical benefit. And I really want collaborators to come forward. We'll help analyze those data with you. If you have any questions about, for example, how much blood did patients after why procedure in our hospital use, return, what was the impact on them, hematic writ, hemoglobin, we could help with those studies. And those are very, very critical studies. Future directions, whole blood, I'm touching on, whole blood we don't have, it's investigational, we use reconstitutional. The studies using it in trauma will help to understand, Dan touched on the institution specific practices and the variability of practice. And the last slide is really what we're really trying to get here at Children's Hospital is a transfusion safety officer. And that will help understand and follow the metrics for hospital-wide blood utilization review, quality assurance, having somebody on the field to be able to understand blood usage. And with that, Dr. Goudloubler. Thank you, Dr. Manus and Dr. Kelly. I'm going to run through what I have to say quickly, because I want to leave some time for questions. But what I wanted to talk to you was our, to make you aware of our perioperative blood management dashboard that was an initiative with the Department of Anacesia Critical Care and Pain Medicine to track metrics on patients that are bleeding. And this is basically what the dashboard looks like. I'm not going to take time to go through it, but on the top, you can see we can track total blood given over time, red and yellow. We can track it in a number of different ways. And also we can attract what specific surgeries we're transusing. So there's no doubt that patients in our operating room are bleeding. And this is a snapshot from the dashboard of non-cardiac surgeries at Boston Children's Hospital. And you can see some of the highest transfusion are things we talked about already, ECMO, a lot of general surgery cases, multivisceral and intestinal surgery, some cranial and crater remodeling, a soft-achyletrija is certainly a big transfusion center. And you know, all of these, all this evidence that we're talking about really doesn't pertain to the dynamic flow of what happens in the operating room. And I just wanted to point that out, you know, we use blood and blood products in the operating room in a very, very dynamic setting. And it's very difficult to do studies on that. But having said that, you know, we definitely have exposure to blood products of our patients. Very, very frequently is well intended. But I wanted to show you the over-trans-usion data from our dashboard. And what this shows is in each cohort of patients, we looked at over 130,000 patients. And you can see on this figure neonatal up to infant up to adults. And what really I want to show you is if you look at the red and the orange, all of those patients are patients who buy the restrictive threshold, who were exposed to blood products, who got over-transfused by the definition from taxi, which says that a target red blood cell transfusion should be 9.5. So all of these patients in the red and yellow were well over 9.5. So there may be an opportunity to improve what we do so well as far as exposure, at least for volume of transfusion for our patients. The second thing I wanted to show you besides over-trans fusion is talk a little bit about anemia. Two slides on that. We have a worldwide crisis of iron deficiency anemia. And we see it here at Boston Children's Hospital in our pediatric patients. This shows pre-operative anemia by age category, over 50% of our patients who have a hemoglobin coming from surgery are anemic, mostly mild, but we do have an incidence of anemia that's high. Mostly it's iron deficiency, although it could be also chronic disease. And if we look at the distribution across different services, you can look at your own service and see what the incidence is. For example, transplant is 67%. And then when we look at our dashboard and we look at pre-operative anemia and interoperative transfusion, there seems to be an association at least those patients who are anemic and got a transfusion in the blue versus those who were not transfused and not anemic. There seems to be a higher risk, which makes sense, right? Those patients who are anemic at our higher risk of needing a blood product transfusion. And just to point out that our evidence-based guidelines is the non-treatment of pre-operative anemia. It's a substandard clinical practice for adults and children. We have good evidence-based guidelines to say that given that anemia is a strong predictor transfusion and is associated with averse events in children and adults, we really should be screening these patients pre-operative knee, not the day before the week before the pre-operative clinic. And to try to give an initiative to improve what we're doing in a craniacinastosis surgery, we started a chowee protocol where all patients, as soon as they're booked for craniacinastosis surgery, are given an option for iron or EPO. And then we follow those patients. We're having great success. It's an ongoing study now and that we're been treating patients who not only are anemic, but also just increasing their hemoglobin before surgery to optimize their own red blood cell mass before they lose blood interoperatively. So that's one initiative that we started here. Can we improve outcomes by optimizing that's to be determined? And then the third thing I wanted to talk to you about was pediatric mass of hemorrhage guidelines. And I'll only tell you that there is evidence-based recommendations that we should have, not only a mass of transfusion protocol, which I like to say is an idiot-proof way of getting the blood bank to give you blood fast, then you decide what to do with it and how to give it. But we really need to manage the child that's hemorrhaging as well as the transfusion to. And that's why it's recommended that we have massive hemorrhage guidelines. Many of you in the operating room I hope are aware or have seen this mass of hemorrhage guidelines. We can click a button on the aims in this whole pop-up if we have mass of hemorrhage. And basically the mass of transfusion protocol is in the red and all of the other things to manage the massively hemorrhaging child is in the blue. And this is something we've been using for the last four or five years, which I helped to design. But what I was also asked to do is to put this into a, what do you call this thing, a flow chart thing, clinical pathway. Thank you, Steve. A massive hemorrhage clinical pathway. If you want to scan this, you can use your phone to scan the QR code up there. It's just a draft. It's in progress. It's, you can't read it. I appreciate that. But I wanted to let people know that this is something that we've been coming and we've been designing so that if your patient presents actively bleeding, identify the cause, control bleeding, maintain the blood pressure and cardiac output, send a sample to the blood bank. Is it mass of hemorrhage or not? And then you follow the pathways of what to do. So that's for the clinician. But what about our nursing staff? How can we help you know, really ask for what we want and get it as quickly as we can. And together with Monica Climent and the, and the, the Center for Safety and, sorry, get, remember what that's called Monica. PPSQ and with innovation design, we've been trying to come up with an activation aid that's very practical to use in a clinical situation. So, you know, for your, for your nursing in the operating room, if the, if we want to activate the mass of transfusion protocol, protocol, call for emergency relief, release if we have a massive hemorrhaging patient. Here's what you need. You need to provide this information. Yes, you need an MR number, which is something that many of the nurses have brought up to me is that if a patient's directly admitted to the operating room, getting that, I patient identification is very important before blood can be released from the blood bag. But this really shows you pathways to go through. What do you say if you need emergency release? What do you say if you need to activate the mass of transfusion protocol or if you need specific problem products to mass, uh, manage massive hemorrhage? Um, so to finish that out, I just say that we have much, much evidence from many different, uh, societies and, uh, that leading transfusion of products independently increases morbidity, mortality, length of stay, hospital costs. As a matter of fact, it's said to be, uh, from the shots report that the adverse reactions are 2.5 times as high in children than they are at adults. Uh, so that's something to be thought about that this patient blood management is something that is now a new standard of care. And there's much information on, um, you know, reductions in, uh, red blood cell transfusion, really complications, infection rate, thrombone, bolic events, mortality, number of days in hospital by implementing all of these patient blood management strategies. So I'll conclude, uh, with some time left for questions that I hope our panel today is, uh, informed you a little bit about patient blood management, uh, helped you think about utilizing blood conservation techniques, think about optimal blood use, um, try to not ignore anemia, uh, avoid over transfusion when possible. There will be new guidelines for activating mass of hemorrhage protocols and massive transfusion protocols. And really, this is all to promote a collaboration between transfusion medicine, the blood bank, and what we do in the operating room. Uh, and I, I would like to promote considering a patient blood management program at Boston Children's Hospital, where we'd be the first children's hospital ever. There's many, many adult hospitals who this all comes together in a patient blood management program, uh, type scenario, which is not just bloodless medicine, but, but also optimal use of blood products. So I'd like to acknowledge and thank, uh, Joe, uh, Carvero and, uh, all the Department of Anesthesia for, uh, support for the, um, the dashboard and, uh, Monica and the patient safety and quality program and then some work that we've done with the, uh, immersive design system. And that's all I have. So we have, uh, five minutes left for questions. So I, Dan and John, to come up and join me up here. And if anybody has any questions, we'd love to take them, uh, and just to highlight to this, this is January is National Blood Donor, uh, month. So please give blood. Susan, um, thank you so much, um, for your leadership, uh, the thought process you've gone through for anemia over transfusion and just raising our awareness with the, um, dashboard et cetera. It's just been wonderful work. And thank you all for what I think was an incredibly useful grand rounds. So really appreciate it. I'm sure there are a lot of questions. I just have maybe one to start here, which is, um, maybe it's, uh, urban myth, but we think a lot about the age of blood that we're transfusing. Um, just wondering, should we be concerned about the age of blood, particularly when we're transfusing significant amounts of blood to say small patients in terms of acidosis, hypercalemia, et cetera, et cetera. I'll start with that because wake-up safe does, um, does, uh, mandate that if the patients less than 10 kilos, uh, that they will be get fresh blood because of the risk of hypercalemia. So that's one of the things that I think automatically the blood bank will send you if the patients less than 10 kilos or less than a year, is that correct? Yeah, depending, depending on the procedures and the need, um, the biggest risk is, potassium is, uh, was pointed out. And the biggest risk for high potassium is irradiation. So everything we do in the blood bank, we irradiate on demand. So it will be the least calcium, potassium, which product. So it's, we have an extra layer of protection built in, which isn't built in in other institutions. In terms of age and outcome, even those are mainly adult studies and nothing's ever been borne out that it significantly makes a difference. And the spoiler is that most of the blood that we dispense has not been stored for long at children's. So even if you activate the massive transfusion protocol, you get the, the blood that's available fast, um, that won't be that old. That's good to know. We actually try to enroll as an age of blood study and we just use the blood too quickly to have separation between the two arms. So two part question, one actual question and two thought process and advocacy. The question is, point of care testing for biomarkers in the OR, other than hemoglobin and lactate. Where are we? What things can we be looking for oxidative stress? The advocacy part is this doesn't stop here. Recovery models, you know, we'd see a lot of these kids come out from trauma with hemoglobin to seven and put in recovery models and they simply couldn't do it because they just two week, two fatigued. So there's still a lot of work to be done in terms of management of these patients once they leave the hospitals. And we're really falling short for these patients all across the board. Great point, Bill. The first point was physiological markers or biological markers. You know, that's where individualized patient medicine is. That's where we're going. That's why we have our mass, massomometers. So now we can monitor noninvasively hemoglobin levels, but also we can monitor end organ, oxygen perfusion, you know, which is what you think you're looking at with ECMO trial. We can monitor lactates in our blood gases. There was a clinical focus review that we wrote advocating for monitoring physiological markers to really try to know what the blood is delivering oxygen to the end organs. Well, what's going on with the end organ? I mean, that is really the basis sometimes for transfusion. And so that's I think where blood management is moving is to monitor this. And we have the capability in our operating rooms for some of those point of care testing. The second is, you know, you're absolutely right. You know, that long-term outcomes are what's most important or just as important as short-term outcomes. And it's really harnessing the power of the patient's own blood. So managing anemia not by transfusion, but managing this chronic anemia by, you know, iron transfusions, intravenous iron transfusions. Look, they do this a lot in adult hospitals for managing those patients, you know, postoperatively. So that's some ideas I have. I don't know Dan if you have anything else. I would agree and it's a great point. I think the other thing is the neurodevelopmental piece. And that's what we're excited about with that trial is we'll start to see that. Truly, yeah, the short term, but it's really the long term. But it's remains to be seen. I think that's why finally it's nice to see funding coming through for these kind of studies. I think it's a little after eight. So many of us need to get to the OR. Thank you all so much. These is incredibly helpful. Thank you, everyone. Thanks again. Thanks, Joe. you
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