The general philosophy that's embraced for a transfusion in critically ill pediatric patients is generally a restrictive one for transfusion, usually around seven grams per deciliter of haemoglobin across all pediatric age groups and disease processes. The risks that have been cited in the past for aggressive transfusion practices include a 50% risk of transfusion reaction in mostly transfused pediatric patients and then the neonatal sub population increased transfusion has been associated with an increased risk of neurocognitive abnormalities, the development of necrotizing enterocolitis and severe intraventricular hemorrhage.
But embedded in this cautionary tale is emerging evidence that there are pediatric patients that require not only large amounts of blood but massive amount of blood and that the approach to this group must be not just aggressive, but thoughtful and planned. The critically injured pediatric patient can no longer be an unplanned emergency, but instead a planned one.
The vast majority of pediatric literature regarding pediatric trauma indicated massive transfusions from combat situations where children are regrettably the innocent victims of war. This robust data set of blast injuries sprinkled with standard blunt and penetrating trauma is clear, children aren't little adults.
And despite the physiologic reserve that children have with significant blood loss and critical injury, combat literature demonstrates a higher mortality when injured than adults and higher mortality, the younger the patient. This erogenous population is difficult to address when medical interventions and outcomes.
Children have major differences in anatomy, physiology and response to injury based on the age and stage of development and robust studies with large numbers are needed to demonstrate effectiveness across the vast changes between the new born, the toddler, school aged child and the adolescent.
Additionally with only 7-16% of pediatric trauma patients requiring transfusion at all during resuscitation, and only 11% of those small sub set requiring massive transfusion, assessment of interventions is very difficult. However there are multiple compelling reasons to continue investigations into pediatric applications of massive transfusion .
First, trauma remains the leading cause of death in children with hemorrhage accounting for 20 to 40% of early trauma mortality and the number one preventable cause of morbidity and mortality following traumatic injury, second without a standardized approach to this severely injured children the likelihood of introducing harm increases and specifically there exists concerns that overly aggressive strategies increase harm to include transfusion associated with lung injury and hemo dilution associated depletion of factor 13 that contributes to clot dissolution.
And acidosis. [BLANK_AUDIO] What we are going to do today is we're going to describe the pathophysiology that changes during the acute traumatic hemorrhage in the kid we're gonna discuss the current literature in pediatric traumatic hemorrhage and protocols surrounding massive transfusion and then we're going to develop a practical approach to the manager of the pediatric patient with traumatic hemorrhage shock.This is a big task in the next 20 minutes but I think we can do it so hold on for the ride.
Again trauma remain the leading cause of death. Hemorrhage is preventable for trauma mortality if we're are treated aggressively and we're not sure in the literature what to do because our numbers are incredibly small. Let's talk about some definitions of massive transfusion. It is defined in adult as greater than ten units in 24 hours.
In children 40 to 70 ml's per kilo of replacement in 24 hours. In infants 80 ml's per kilo in 24 hours, and in neonates 90 ml's per kilo Per 24 Hours. A suggested practical definition is one amount of total blood volume in 24 hours, 50% of total blood volume in three hours, or 10% of total blood volume every ten minutes and as these vary by age.
So let's start with a case. This was my first month of my intern year a long, long time ago. And we were in the emergency department in our Adult Level One Trauma Center, and a multi-trauma came in at the same time. My patient was a six-week-old female who has been swaddled in a blanket, and not only was not in the car seat but was not in anything at all.
And was in a convertible. So she was swaddled in the front seat of the car, the car convertible is hit by a truck. She was thrown from the car and then also hit by an on coming car, as she lay in the middle of the road. She had a traumatic right leg amputation, and had massive hemorrhage at the scene.
Was intubated When I arrived to our emergency department with a dismal vitals signs and active bleeding. So what we did then back in the day, was we held pressure, put on a toner kit, gave a lot of blood, waited, held pressure, tightened the toner kit, gave a lot of blood and then she went to the operating room.
So this was our massive transfusion protocol back when I started residency and the outcome as you can imagine for this particular child was not good. There are a few things to know when we think about massive transfusion, here are the different types of blood products that are available to us in the emergency department to give, packed cells, platelets Plasma, FFP and FFP when thawed and precipitated becomes cryoprecipitate and activated factor seven or recumbent factor seven as we use it today.
[BLANK_AUDIO] So the physiology of transfusion is very interesting. So note when you giving blood, you are not only giving blood, you're giving all of the things that are kept in blood products to help them stay on stay on the shelf and those include anticoagulants, preservatives and other additives to preserve shelf life, and these really are not of much interest to us until we reach that massive level, and so massive transfusion or ECMO will get you to these toxic levels and we you really have to start thinking about them in a massively or multiply injured trauma patient, the lethal triad that is held when this massive levels are reached or acidosis, hypothermia and coagulopathy and it's a viscous cycle, so hypothermia in the pediatric trauma patient is the result of shock and exposure and also large volume resuscitation using room temperature fluids.
Those decrease platelet activation and platelet dilution . Hemodilution then dilutes further clotting factors and also worsen hypothermia and then acidosis resulting from shock clouding. So each member of the triad makes the other member of the triadworse and then you spiral out of control.
There are many complications of massive transfusion, coagulopathy which we'll talk about in detail in a moment, electrolyte abnormalities which we'll discuss as well, acid base disturbances, volume overload, hypothermia, sepsis, multi organ failure and death, in the massive transfused pediatric patient independent in hospital and our mortality is about 25%.
These are the additives that are in your standard blood products and if you look over here in the ECMO column which is what we are thinking about in massive transfusion, you'll see that we've exceeded the toxic dose for most of these elements in almost every category. So let's think about this in part one.
So let's think about the acute coagulopathy of trauma and hyperkalemic cardiac arrest. This is really the reasoning behind why we think of massive transfusion protocols or damage control resuscitation. So damage control resuscitation with massive transfusion protocols is based on this philosophy.
Number one, allow more permissive hypotension to avoid disruption of the thrombi. Number two, spare large volumes of Crystal Colloidal therapy and Number three, transfuse with blood products preemptively using a balanced ratio. These approaches are really thought to mitigate the initial state of acute coagulopathy of trauma, which we will refer to as ACOT from here on, and the lethal triad of acidosis, hypothermia and coagulopathy more effectively than fluid therapy later on.
The predictors of mortality in ACOT are an INR greater than 1.5, and shock with a base deficit of greater that six. And this type of coagulopathy is likely much more common than we've ever suspected in the past, specifically in patients requiring transfusion support. And this association is independent of mechanisms and is also independent of whether you have head injury or not.
So pediatric acute coagulopathy of trauma is not a delusional effect as was previously believed but instead an inflammatory response to trauma. The effect is a combination hemorrhage tissue damage and hypo-profusion more than half of adult patients have evidence of ACOT by 25 minutes after their injury and about three quarters of pediatric patients upon arrival to the hospital.
Primary tissue damage exposes blood to collagen and stimulates the intrinsic and extrinsic clotting pathways, the subsequent depletion of clotting factors. Tissue hyper-profusion that results from hemorrhage subsequently stimulates the endothelium to produce that cascade that we all know about and hate and fibrinolysis and the clot destabilization and all of the rest and the final outcome of ACOT is then major platelet dysfunction which is independent predictor of mortality despite normal lab values.
ACOT has worsened unfortunately by standards with resuscitation strategies that use large volumes of crystalloid and these strategies have been standard and careful pediatric patients for many, many years and likely worsen their outcomes. hyperkalemic cardiac arrest is of particular interest in the multi transfused patient with severe trauma, and damage control resuscitation strategies that we need to look for in the future and massive transfusion have to take into account this increased susceptibility of children to hyperkalemia and subsequent cardiac arrest. The risk of transfusion associated hyperkalemic arrest is increased with the age of blood, the rate of transfusion, blood irradiation the cardiac output of your pediatric patient and the type of additive used.
So the prevention of hyperkalemic cardiac arrest has several strategies. Number one, the blood that's used for MTP protocols should be fresh, you should use a large bore peripheral IV for transfusion rather than central access and this is a big change as we often put in trauma introducers and this really great sick kids, but their transfusions should go in preferably, they should have a slower rate of transfusion to a goal of about five and 0.5 mls per kilo per minute and then blood should should be washed in anticipation of massive transfusion.
Let's briefly go through the massive transfusion protocol evidence, this will not take very long because there is not very much. There are models for massive transfusion that have existed over the past decades, the first is to have a transfusion specialists at the bedside guiding your transfusion oh wouldn't that be lovely.
Hello blood bank I know you are right around the hall and waiting for me to call you, so please come over and help me. I don't know a utopia in which this exists, it certainly does not It's not even in our Ivory tower academic centers so, I would be surprised if it happens anywhere else.
The second is lab testing driven transfusion and again if you can all get an INR back and before two hours then maybe this will work for you as well. And the third is the component driven or the balance transfusion approach and this is what we're gonna talk about today. This really has come out of the combat literature and has become standard of care in adults but cannot be translated to our pediatric patients.
So here is what we know, in adults, a plasma, to packed cell to platelet ratio of 1:1:1 improves survival and trauma, we know that. The studies have come out and this is what we do. In children, we know a little bit, what we do know is that vascular injuries as a subset of major trauma has approved survival when using adult transfusion guideline of balanced ratios of plasma to packed cells to platelets.
We know that kids have an increased susceptibility to hyperkalemia, and then we need to watch for that with those strategies that we have looked at on the last section. We know that children have a greater physiologic reserve for blood loss, and so we are a little bit hesitant to start these aggressive strategies in children.
And we see their abnormalities a little bit later than we do in adults. This is a difficult conundrum for us. We also know the use of FFP in pediatric trauma increases the risk of venous thrombosis and so as we add this things in , we wanna think about whether those balanced transfusions should include FFP or not.
What we don't know is about the true incidence of pediatric traumatic coagulopathy is. The main question that we have to answer today and in the future is, does this transfusion protocol such as this impact overall pediatric mortality? Does FFP impact mortality independently? And when in the world do you start a massive transfusion protocol in the first place? So number one in the literature, one of the first Pediatric MTP's and literature was a retrospective review of 105 massive transfusions, 6,675 total patients in seven years at a single institution.
It included all level one trauma patients less than 18 years of age and excluded mortality in the first 24 hours to eliminate a survival bias. The results were important for several reasons first only 7% of patients received transfusions at all, affirming the difficulties and demonstrating benefit in an oncoming condition.
And second, traumatic brain injury rather than hemorrhage was the cause of death in all of their fatalities, which limits the ability to analyse independent effect of an MTP on overall survival. The study found no increasing survival based on the use of higher plasma and PRVC and platelets PRVC ratios but did demonstrate that the presence of this protocol improved delivery and communication regarding the use of blood products.
Two additional pediatric MTPs instituted at single centers either 1:1:2 or 1:1:1:1 ratios. The second one included cryoprecipitate and both of these studies again unfortunately demonstrated no changes in survival when compared to a pre-MTP cohort but confirmed ability to obtain and administer blood products rapidly demonstrating that if you have a protocol it works.
So the process outcome were great but the clinical outcome were not. So let's talk about a couple of other things. How do we test? Can we do massive transfusion that is testing driven? Let's talk about a couple of upcoming novel treatments and then some prediction models for massive transfusion protocols.
So first of all if ACOT or coagulopathy of trauma is independently associated with pediatric morbidity and mortality then rapid identification and management should be a critical component of trauma resuscitation and currently there are limits to this process at the bedside using convectional testing.
Convectional coagulation test only address part of the coag cascade and are not reported in a clinically timely manner for the massive hemorrhage patients. And are also performed at 37 degrees which limits the ability in the hypothermic patient to really address their true status. Given the rare occurrence of the severely injured pediatric trauma patient requiring transfusion support increase frequency of coag testing is suggested for this subset of patients.
And there are some really interesting bedside testing that might help us do this in the future better than we do it now. So Thromboelastography, TEG and rotational thromboelastometry or ROTEM have been described as alternate and viable options for ACOT identification and therapeutic guidance.
These tests use rapid whole blood analysis of coagulation and demonstrate results in 30 minutes. A small volume sample is required and the testing temperature, here's the cool part, the testing temperature can be adjusted to that of the patient to more accurately reflect their coagulation status.
The development of rapid TEG demonstrated results within five minutes by adding tissue factor to accelerate activation of the clotting cascade and this maybe the answer for us in the future to guide bed side testing for rapid transfusion. So what about recombinant factor VIIa. It seems like the thing that we give just to stop bleeding in it's tracks, why would we not use it as an adjunct to massive transfusion protocols for pediatric patients.
Unfortunately, recombinant factor VIIa has been even though considered as an adjuvant therapy. Pediatric trauma is limited with only case reports for our evaluation. However their have been none of those studies that demonstrate change in mortality in adult patients much less pediatric patients and no recommendations exist for it's use outside of approved patients with bleeding disorders currently.
What about Trans-exemic Acid which is a antifibrinolytic. This has been recently studied as an adjuvant to blood products in pediatric trauma patients. In the PED-TRAX study , It was previously studied in elective and semi -elective Pediatric surgery with known significant reduction in blood loss and transfusion requirements in a cocken review For a scoliosis surgery and other big neuro surgeries and orthopedic surgeries.
The mechanism by which this works is through inhibition of plasminogen activation and the activity of plasmin thereby decreasing fibrinolisis. It can be administered side by side with the balanced transfusion protocols that we talked about before. So an interesting In study a PED-TRAX was a cohort of 766 pediatric patients in Afghanistan who were less than 18.
10% received TXA which was predicted by the presence of greater injury severity, hypotension, acidosis and coagulopathy. A single adult-fixed bolus was given with no subsequent re-dosing within three hours of The hours of injury. The addition of TXA was independently associated with a decreased mortality odds ratio with similar trends in severely injured patients.
Additionally, there was suggested of improved neurologic outcomes at discharge and no association with increased thrombotic complications. This is really exciting for massive transfusion protocols and is being undertaken by PECAN as a multi-site trial here in the next few months.
So wait for those results that should be coming at the conclusion of that study, so pretty exciting stuff here. So what about prediction models? We're talking about High risk for morbidity and mortality here, is there any thing that we can do at the bed side to predict who needs this and who's gonna get sick and who doesn't need it?That we can be a little bit more cautious about rapid transfusion.
The big score has been suggested as a good predictor of in-hospital and early mortality and morbidity in Pediatric Trauma patients. The big score is base deficit, INR and GCS and it's been evaluated for Pediatric Trauma patients in military and civilian settings, given the observation that acidosis, ACOT and brain injury are common and predictive of poor outcomes in children.
So this is one of the first prediction model that actually include GCS because of the high incidence of pediatric head trauma as a cause of morbidity. So this scoring system uses important factors that are missing from other injury severity scores and they can be calculated right at the bed side rather than retrospectively like the injury severity score.
So the big scores calculated as a base deficit plus 2.5 times the INR plus 15 minus the GCS and a score of greater than 16 is associated with a 50% mortality. This score emphasizes that obtaining early labs in pediatric trauma patience which may uncover unrecognized injury severity are very, very important for prediction and this should be a good indicator for thinking about that multi-injured patient who needs transfusion.
You might wanna kick in to your massive transfusion protocol. So, let's go back to our case that we started with. What we did then and what we do now. In 2012 we instituted at our institution, a massive transfusion protocol, it can be activated immediately by any member of the trauma team.
So RT, nurse, physician any body can activate this and everything is pre-prepped and right around the corner. We use a 1:2:1:1 ratio of FFP, packed cells platelets and cryo. Plasma always remain thawed and we've cleaned it out usually every two days on average at four to acknowledge the risk of hyperkalemia and cardiac arrest, it is CMV safe and irradiated and washed and is shipped all together in a cooler kit.
Unfortunately, when I first started working on this, we used it very, very infrequently, we didn't need MTPs at all and I thought well we did all this work for not a lot. But over the last 3 months we've used it 12 times, unfortunately in Indianapolis. And that is for reasons that with my other hat on as deputy health commissioner of our State Department of Health, I'm sad about.
So we've had multiple pediatric fatalities from multi-trauma, car accidents and also drive-by shootings in Indianapolis over the last several months. So how are we gonna find some consensus around MTPs? What we know is that MTP protocols improve communication around trauma and they improve rapid delivery of blood products to the emergency department.
However what we don't know right now is what the survival impact is around MTPs in the pediatric patient. It'll be interesting to see what the addition of TXA to MTP protocols does for that overall survival rate. The next steps of course are we need some help from the researchers in the audience to figure this out In the long term.
And multi-center trials in the pediatric population are on going, our hospital is one of those sites and we'll be interested to see what this looks like in the long term. Thank you very much for your attention and have a great rest of the week. I'll answer any questions that you might have. Yes sir? >> Hi, I'm glad you include TXA I was actually wondering about that My question is has anyone talked about using combination of platelet TXA, plus TXA, soaked dressings and you have a large internal bleeding what would you guys recommend? >> So we certainly have not ventured even remotely that close in our particular center into TXA added to our MTP or any of that.
However obviously in combat sites those things have been added on. It'll be interesting to see how these larger studies in pediatric patients with TXA at all pan out. I think very hopeful on the landscape. Yes sir? [INAUDIBLE_AUDIO] >> They are grouped in our institution, there are multiple different versions of MTP protocols across the country some with single donor, some with grouped.
Yes sir. >> [INAUDIBLE_AUDIO]. >> So some of the earlier studies were 1:1:1 then added in cryo and our pediatric surgeons specifically so when you have an absence of literature you have an excess of opinion, that's my general take on life right? [LAUGH] . So they were very excited about having more platelets and so that was the reason for the increase in that volume.
[BLANK AUDIO] Okay. Well thank you everyone for your kind attention, have a great evening. >> [APPLAUSE]
