Transcript
Speaker: Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound Critical Care provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now your host, Dr. Sergio Zanotti.
Speaker: Transfusion of red blood cells or another blood product is common in the intensive care unit.
Speaker: Some estimates indicate that almost half of patients admitted to the ICU will receive some kind of blood product transfusion.
Speaker: Blood product transfusions can be associated with complications and are often given in situations without a clear-cut indication.
Speaker: In today's episode, we will discuss current evidence and proper use of blood products in the ICU.
Speaker: Our guest is Dr. Janice Zimmerman.
Speaker: Dr. Sermermann is an adjunct professor of medicine at Baylor College of Medicine.
Speaker: She is currently president of the World Federation of Societies of Intensive and Critical Care Medicine.
Speaker: Dr. Sermermann is a master of the American College of Critical Care Medicine and the American College of Physicians.
Speaker: She's extremely active in multiple medical societies and was elected council member of the SCCM from 2001 to 2013.
Speaker: Dr. Sermermann has received multiple recognitions and awards
Speaker: including the Distinguished Service Award from SCCM in 2001 and 2013, and the SAFAR Global Partner Award in 2017.
Speaker: She has been involved in the development, revision, and promotion of the Fundamental Critical Care Support Course since 1995 and now given all over the world.
Speaker: Dr. Zimmerman is a world-recognized clinical educator.
Speaker: Her areas of expertise and interest include sepsis, overdoses, coagulation, transfusion, and parity in the ICU.
Speaker: It is a true pleasure and honor to have her on the podcast as our guest.
Speaker: Welcome to Critical Matters, Janice.
Speaker: Thank you, Sergio.
Speaker: So I think a great place to start would be from your perspective as an educator to share with us why you think it's so important for us to keep talking about the use of blood products in critically ill patients.
Speaker: Well, I think there's two main reasons.
Speaker: First of all, blood products may not always be available.
Speaker: I think we have
Speaker: often been complacent in thinking that we can always get the platelets or the blood that we need for our patients, but that is not necessarily true.
Speaker: The other factor I think we have to take into account is that these blood products are therapeutic agents, and as such, they have adverse effects that we need to factor in when we're weighing risk and benefits of transfusing any product.
Speaker: So we have to recognize that they may cause harm potentially in our patients.
Speaker: And I think that one of the interesting shifts and paradigms that we've seen over the years, maybe over the last 10 or more years, has been really from a very liberal approach to trying to push a more restrictive approach.
Speaker: Can you talk a little bit about how things have evolved in the last 15 years?
Speaker: Yes.
Speaker: I think this all started quite some time ago, if you go back to the original TRIX trial.
Speaker: which really started this whole questioning of our transfusion practice back in 1999.
Speaker: And that study was in critically ill ICU patients and showed that a threshold for transfusion of seven grams per deciliter was equivalent to using our, what used to be a traditional threshold of 10 grams per deciliter.
Speaker: So that started off the trend, but we now have even more randomized trials.
Speaker: I think many clinicians always said, well, that's,
Speaker: study is great, but that doesn't apply to my patient because they're old, they are on a ventilator, they have cardiac disease, they have renal failure, they have a GI bleed.
Speaker: So there was excuses that we used, but now we have more and more randomized trials to guide us in figuring out which patients are candidates for a restrictive strategy.
Speaker: So what I would like to do, Janice, is maybe next is to talk about the
Speaker: the three major categories of blood components, red blood cells, platelets, and plasma-derived components individually, and maybe dive a little bit deeper into what are the type of blood products that fall in that category and how we should think about them, and then talk more about what are the indications based on current evidence or current guidelines for each one of those.
Speaker: And maybe, as you said, we can dissect in some of these situations some specific patient populations
Speaker: So why don't we start with red blood cells, which is probably the most commonly transfused blood product?
Speaker: That would be correct.
Speaker: So, of course, the whole blood is a blood product, but we very rarely see the use of whole blood in the United States, at least, because we tend to separate the blood into three or four components so that we have more targeted use of the component.
Speaker: The most commonly transfused component is what we would call packed red blood cells, where the majority of the plasma has been removed.
Speaker: Now, there are other variations.
Speaker: There's leukocyte-reduced red blood cells, which those are, it's not a mandatory leukocyte reduction in the United States, but about 85% of our blood supply in the U.S. is leukocyte-reduced.
Speaker: We also have washed red cells, which are very uncommon.
Speaker: and used only in various selected circumstances, usually in patients who have multiple antibodies and are difficult to cross-match.
Speaker: And we also have irradiated red cells, which are used to knock out the lymphocytes, basically, and to avoid graft-versus-host disease in our patients who are severely immunocompromised and in the transplant populations.
Speaker: So basically, packed red cells are the go-to staple for blood, at least in the patients that we care for.
Speaker: Now, you asked about the indication.
Speaker: So interestingly, a decade ago, the recommendations for transfusions really didn't specifically comment on critically ill patients, but the more current guidelines actually
Speaker: do make more comments.
Speaker: There are several guidelines out there from the United States, American Association of Blood Banks, the National Blood Authority, and other countries such as Australia and also in Britain.
Speaker: And all have really proposed that a hemoglobin threshold for transfusion of 7 to 8 grams per deciliter is adequate for the majority of critically ill patients.
Speaker: There are still a few subsets of patients where we don't have sufficient evidence to make a restrictive strategy as our number one recommendation.
Speaker: And those would be patients who have active ischemia, such as an ongoing myocardial infarct, patients with intracranial events such as stroke, and also patients who have cancer.
Speaker: We still have more studies that are actually in progress for some of these patients that will help guide us hopefully in the near future.
Speaker: Now, in terms of other populations that I think are frequently recipients of blood transfusion to PACT-RBCs, could you tell us a little bit more about what we know today in regard of sepsis and GI bleeds specifically?
Speaker: Certainly.
Speaker: So in sepsis, the
Speaker: Surviving Sepsis Campaign Guidelines recommend a transfusion threshold of seven.
Speaker: And the major evidence for that actually comes from what's called a TRIS trial to transfusion in septic shock, which was from Scandinavia.
Speaker: And they compared a restrictive threshold of seven grams per deciliter with nine grams per deciliter for the indication for transfusion.
Speaker: And basically, they found that the major outcome, which was 90-day mortality,
Speaker: was the same in both groups, but you could actually avoid transfusion in almost 70% of the patients.
Speaker: The other interesting finding that has come out of some registry data in sepsis is that they showed there was an increase in infection and also hypoxemia with transfusion and septic shock.
Speaker: So there are potential downsides, at least from some retrospective studies.
Speaker: Now in the setting of GI bleed, this has been an interesting evolution.
Speaker: So the first study, it was often called the Barcelona study, came out in 2013, and it was a single-center study, but they basically took all GI bleeders.
Speaker: They took variceal bleeds, non-variceal bleeds.
Speaker: The only exclusion they had were those that were basically exsanguinating, and they applied a restrictive
Speaker: strategy of 7 gram per deciliter for the threshold with the liberal of 9 grams per deciliter.
Speaker: Now, all of their patients did undergo endoscopy within six hours, but what they found is that the overall survival was better in those who had a restrictive transfusion practice.
Speaker: And again, they were able to avoid transfusion in almost 50% of their patients.
Speaker: Now, it was, you know, people have said, and that was almost 1,000 patients.
Speaker: It was 900 and something patients, but people said it's a single center study.
Speaker: Well, that's actually been replicated to some degree by a trial.
Speaker: It was called a feasibility trial in the United Kingdom in upper GI bleed, but it was over 900 patients.
Speaker: And interestingly, they randomized hospitals, not individual patients.
Speaker: So one hospital had a restrictive strategy, and they used 8 grams per deciliter.
Speaker: and their liberal was 10 grams per deciliter.
Speaker: But what they found is, again, they used 28-day mortality for their outcome with no difference, and they could avoid transfusion.
Speaker: The other interesting thing is that they had more difficulty with adherence to the assigned strategy in the liberal groups.
Speaker: So the hospitals that were randomized to liberal strategies
Speaker: There was less compliance.
Speaker: I think it's because the practices were already changing during that time.
Speaker: So we have two good studies suggesting even in active upper GI bleed that a restricted policy will actually potentially benefit the patient.
Speaker: And I think that an important point that maybe you can comment on is that the numbers in terms of restrictive, the recommendation of seven for most critical care patients or seven to eight,
Speaker: for these categories that we're talking now, like GI bleed, really just refer to a when to transfuse just based on numbers.
Speaker: But there might be situations in which you might have a 7.5 or an 8.5 with other findings that might justify a transfusion.
Speaker: Can you talk about the idea of transfusion based on symptoms or findings that are objective?
Speaker: Well, I think that's extremely important, Sergio, because
Speaker: As clinicians, we focus on that hemoglobin number, which isn't really the most appropriate.
Speaker: We should be looking at what are the oxygen-carrying capacity needs of our patients.
Speaker: So clinical factors have to be a part of anybody's evaluation of the patient.
Speaker: So if someone is having symptoms of ischemia, that's going to be important, and you may change your threshold.
Speaker: Their hemodynamic status, how rapidly they might be bleeding, all of these would be taken into account
Speaker: when making that decision.
Speaker: So I think it's important to realize that recommendations are really that, recommendations.
Speaker: And we have to take those recommendations and then try our best with additional clinical information to determine what will work and will meet our patients' needs.
Speaker: Excellent.
Speaker: And you talked a little bit, Janice, about the cardiovascular patient, specifically those with MI or active ischemia.
Speaker: Any comments on CT surgery patients or cardiac surgery patients since these are populations that seem to also get a lot of blood transfusions and there seems to be a lot of quality controls in terms of their STS databases in terms of monitoring this?
Speaker: Exactly.
Speaker: So there have been several large studies now in cardiac surgery patients.
Speaker: So the initial one came from Brazil.
Speaker: It's called the TRACS study.
Speaker: And again, they used hemoglobin of around 10 is their liberal hemoglobin of 8.
Speaker: You'll notice in most cardiac, any type of cardiac population, lower restrictive is going to be around 8.
Speaker: And so they looked at these patients and found no difference in outcome.
Speaker: There was a second study of over 2,000 patients in the United Kingdom multi-center,
Speaker: again, that did not find any difference in infection or ischemic events.
Speaker: And that particular study was a little bit concerning because when they looked just at deaths, they found a slight increase in deaths in the restrictive group.
Speaker: But subsequent to that, there was an international randomized trial called the TRIX-3 study in cardiac surgery patients that found no difference in their endpoint, which was a composite of death
Speaker: MI and stroke, but they also looked at deaths separately, and there was no increase in deaths.
Speaker: So that was over 5,000 patients.
Speaker: So I think we can feel very comfortable saying that anywhere from 7.5 to 8 gram per decimeter threshold in cardiac patients, particularly those going for surgery, is sufficient for the majority of the patients.
Speaker: Excellent.
Speaker: And in terms of just the more practical aspects of a transfusing
Speaker: PACT RVCs, what is your usual practice or current recommendations in terms of how to transfuse?
Speaker: I mean, do we do it one at a time, depending on the situation?
Speaker: What is the expected response that we should be looking for?
Speaker: And how do you usually do this at the bedside?
Speaker: Well, I think, again, one of my personal
Speaker: strong recommendations is really to transfuse one unit at a time in almost all of your patients and reassess.
Speaker: Why do I say that?
Speaker: Well, we used to have this kind of dogma that you had to, if you're going to transfuse, you have to transfuse two units.
Speaker: Well, that was often way more than most patients need.
Speaker: And if you actually look at these randomized trials that have been performed, all of them transfuse single units.
Speaker: When they get a value, if they meet a threshold, they got one unit and then they rechecked.
Speaker: And you'll actually save a lot of blood and be surprised at how well your patients will do.
Speaker: So when it comes to predicting the rise in hemoglobin, that's a little iffy.
Speaker: So we always say that one unit of blood will raise the hemoglobin by one gram per deciliter in the average patients.
Speaker: but one unit in a small elderly patient may raise the hemoglobin by two.
Speaker: So you have to take into account the size of your patient, also the fluid status, because if you're giving them lots of fluids, you're actually hemodiluting.
Speaker: You're not changing the red cell mass or the oxygen carrying capacity, you're just diluting a measurement of that hemoglobin.
Speaker: So I think the most important thing at the bedside, unless someone's actively bleeding,
Speaker: a significant amount is to transfuse one unit at a time and then reassess.
Speaker: So the final question before we move on to another blood component would be related to the age of the blood that we're transfusing.
Speaker: I think historically people in critical care have thought that the older the blood, the least ability it had to carry oxygen and maybe other issues related to that.
Speaker: Could you just comment from your perspective, where do we stand there and is there anything really
Speaker: practical that we should be worried about?
Speaker: No, we don't have to worry.
Speaker: That's the bottom line.
Speaker: And I think that question has come up over and over, but we now have randomized trials in critically ill patients, cardiac surgery patients, and even all hospitalized patients.
Speaker: And even in pediatrics, it shows that fresher blood has no benefit on mortality.
Speaker: And I think
Speaker: That's good news so that we don't have to try to figure out how old the blood is that we're going to give to our patients.
Speaker: So it doesn't seem to matter, despite the fact that we know there is what's called an aging lesion in units of red cells.
Speaker: It doesn't seem to be the criteria that impacts the outcome for our patients.
Speaker: Excellent.
Speaker: So let's talk about platelets.
Speaker: And I think that this is often a source of confusion for people ordering the platelets because of the different types of platelets and what they really mean.
Speaker: Can we start maybe, Janice, by talking about the different types of platelets that we have available in most of our ICUs?
Speaker: Okay, so this is important to get right.
Speaker: So there's two types of platelet products.
Speaker: One is called random donor.
Speaker: And this is where the platelets are separated from a donor's unit
Speaker: of blood.
Speaker: But there's also what we call pharesis platelets, and this is where we gather the platelets from a single donor specifically.
Speaker: So pharesis units have the equivalent of about five to six units of random donor platelets.
Speaker: And each institution probably has, you should probably know what your usual is.
Speaker: So in many institutions, the majority of the platelets may be pharesis units.
Speaker: And others that depend more on blood bank or central or district blood bank, they may be getting more of the random donor.
Speaker: Now, the yield of random donor platelets has increased so that where we used to have a 10-pack and then a six-pack, the usual pack now of random donors is about five units.
Speaker: So most blood banks, if you order one thinking you're doing a pharesis unit, will know that you're looking for those five units.
Speaker: it is important to kind of know what you're getting in your institution because it, again, this is the blood product where we have the scarcest supply.
Speaker: Platelets are only viable for five days.
Speaker: They're kept at room temperature and then they're gone.
Speaker: They're not usable after that time.
Speaker: So it is our most precious commodity on the blood product side.
Speaker: And from a patient perspective,
Speaker: Does it make a difference where it's single donor or multiple random donors?
Speaker: There's less risk of alloimmunization with the single donor.
Speaker: But if you're getting platelets transfused quite a bit, then you're going to be exposed to multiple donors anyway.
Speaker: But in theory, you have less exposure with the phoresis unit since they're coming from single donors.
Speaker: So in terms of practical aspect, really the idea for the clinician at the bedside is to understand what they're getting so they know the quantity and understanding that five to six of the donor units is going to be equivalent to the amount of platelets for transfusion with a thoresis single donor unit.
Speaker: That's correct.
Speaker: When you talk about indications for platelets, and I think that as you highlighted, Janice, being this such a scarce
Speaker: commodity or scarce a blood product I think it's even more important that we be very conscientious in terms of using it when it's indicated and what are the current indications and I know that we don't have as many studies as we have in RBCs but why don't you just walk us through where do we stand in 2020 for this well there's usually two indications for platelets one is to treat thrombocytopenia with bleeding or thrombocytopenia
Speaker: with a prophylactic approach.
Speaker: Now there's also potentially platelet dysfunction, which is probably the least common but becoming an issue with our use of antiplatelet drugs.
Speaker: But thrombocytopenia is the most common indication.
Speaker: All of our evidence comes from hematologic and oncologic patients.
Speaker: We have no evidence from randomized trials in the critically ill patient population.
Speaker: All the recommendations that you will see come from expert consensus and extrapolating the data from these heme-onc patients.
Speaker: The majority of patients, platelets in the ICU are transfused prophylactically, not for active bleeding.
Speaker: The other thing to keep in mind is that even when we transfuse platelets,
Speaker: platelet count may not go up in about 50% of our patients.
Speaker: So even though we think we're doing something, we may or may not be, which really means it's very important for you to reassess the impact of a platelet transfusion by getting a post-transfusion platelet count.
Speaker: And I think that another important aspect, which I think is something that sometimes we don't talk about as much, is there are situations in which the platelet count may be very low,
Speaker: but because of the clinical context, a transfusion should be considered very, very, very strongly in terms of its risk.
Speaker: And I'm talking about situations like autoimmune, thrombocytopenia, TTP, HIT.
Speaker: Could you comment on how you approach those cases?
Speaker: Well, Sergio, those are interesting cases because they're often what we would say at a stable state.
Speaker: That's not really the appropriate term.
Speaker: somewhat ironic, I guess, but their platelet count isn't changing.
Speaker: So it's low, but it's not changing.
Speaker: And that's a different patient than the one whose platelet count is dropping rapidly.
Speaker: So in idiopathic autoimmune thrombocytopenia, thrombotic thrombocytopenic purpura, we usually will settle, even if they're at 8,000, certainly we don't transfuse at all if they're above 10,000 and they're not bleeding.
Speaker: Now, there are a few circumstances where if they do have life-threatening or significant bleeding, you may be forced to get platelets, but you have to remember that you really have to think about doubling the amount of platelets that you give.
Speaker: The usual amount is not going to work because they're going to be subjected to that environment where there's going to be that increased destruction.
Speaker: And I think a practical question that I've seen a lot of our listeners face in daily practice is
Speaker: a patient with TTP low platelets and needs a dialysis line for pheresis.
Speaker: Some people always transfuse, some people don't transfuse.
Speaker: I know there's no randomized studies, but what's your recommendation, Janice?
Speaker: I personally would not transfuse, I think, in this day and age with the use of ultrasound guidance particularly.
Speaker: And in many of these patients, in most of what you've described, TTP and ITP, their coagulation cascade is working.
Speaker: It's normal.
Speaker: So in those circumstances, I would not transfuse platelets.
Speaker: I mean, I have put in central lines in patients who have platelet counts of 3 and 4,000.
Speaker: You also have to keep in mind when the platelet count gets that low,
Speaker: you don't know whether the platelet count is 1,000 or 10,000.
Speaker: There's so much variability when you don't have much to count there.
Speaker: But I would not recommend transfusing those populations just to put in a central line.
Speaker: So save the platelets, but make sure you only stick once, right?
Speaker: Well, you want your most experienced person, and you definitely want to use ultrasound guidance.
Speaker: Absolutely.
Speaker: What about situations where people talk about platelet inhibition, so normal numbers,
Speaker: active bleeding, but you're concerned about maybe platelet inhibition from medications.
Speaker: How do you handle those, and what is the current recommendation?
Speaker: Well, I will tell you what happens.
Speaker: In the majority of cases, somebody's going to give platelets, particularly a neurosurgeon, if it's somebody with an intracranial hemorrhage.
Speaker: And this is, I think, an area where it's an evolution as to what we do.
Speaker: So in vivo studies and in vitro studies have suggested, and volunteers have suggested that perhaps transfusion of platelets will reverse some of the platelet function defects.
Speaker: However, we don't have good evidence.
Speaker: There was a very interesting study that was called the PATCH trial, and that was looking at giving platelets to one group of patients who had intracranial hemorrhage, and the other group got
Speaker: standard care, which was not platelet transfusion.
Speaker: And they had to be randomized and given the appropriate treatment within six hours of arrival.
Speaker: And obviously, these are patients where bleeding has significant potential consequences.
Speaker: Now, of course, the investigators expected platelet transfusions to be of benefit, but what they actually found
Speaker: is that those who got platelet transfusions had an increased risk of death or dependence at three months.
Speaker: So there's some retrospective studies also suggesting in intracranial hemorrhage that giving platelets may be harmful.
Speaker: So what we think might have been logical, we have to reexamine, I think, and realize that giving platelets
Speaker: to someone on an antiplatelet drug is not likely going to stop the bleeding.
Speaker: I think that's an important point because, like you said, it's something that right now very frequently occurs in practice and just understanding what we know so far, I think, can maybe guide a therapy in a more evidence-based way.
Speaker: Right.
Speaker: And actually, even the association, oh, I'm sorry.
Speaker: Go ahead, go ahead, go ahead.
Speaker: The association, go ahead.
Speaker: The American Association of Blood Banks actually made no recommendation for intracranial hemorrhage patients that were on antiplatelet therapy.
Speaker: So it just says there's really no evidence at the current time to really say much at all.
Speaker: I think so something to follow, I mean, and see if we get any further evidence down the road.
Speaker: And I think the final group of blood components is plasma-derived components.
Speaker: And I think as we keep moving forward, the evidence seems to be becoming more scant.
Speaker: But what are the current types of plasma-derived products that we utilize in the ICU?
Speaker: And then maybe you can talk a little bit about what are their indications.
Speaker: Well, obviously, the most common one is fresh frozen plasma.
Speaker: There's also cryopour, which has the cryoprecipitate removed.
Speaker: Then, of course, cryoprecipitate is the other plasma-derived component, which we're actually seeing probably more use of cryoprecipitate today than we have in the past, particularly in the setting of trauma and massive transfusion.
Speaker: And I think that there's also a new prothrombine complex
Speaker: concentrated products now that are done, I guess, by engineered.
Speaker: Are those something that most ICUs you think are utilizing these days?
Speaker: Well, I think, again, it's prothrombin complex concentrates, which are really only indicated for the reversal of coagulopathy due to warfarin when there's active bleeding or invasive procedures are being planned.
Speaker: So it's not really...
Speaker: to be used, nor should it, for frozen plasma, be used to correct the number, the INR.
Speaker: These are products that should be considered when someone has active bleeding or a need for a procedure.
Speaker: So it's interesting that the prothriamin complex concentrates have not been utilized in a randomized trial with bleeding as an outcome.
Speaker: Basically, what these products do show is that they can reverse
Speaker: coagulopathy faster than fresh frozen plasma.
Speaker: And often, of course, that's a smaller volume and it doesn't need to be thawed out so it's available more rapidly.
Speaker: But as far as whether one is better in stopping bleeding, we don't know the answer to that question.
Speaker: Okay.
Speaker: And in terms of the use of fresh frozen plasma, I think that's another blood product that is often overutilized, I think, in my opinion.
Speaker: but can you talk a little bit about what are the actual or current indications and how we should think about thresholds and plasma?
Speaker: Well, the indications are pretty straightforward.
Speaker: You have a documented coagulopathy and either active bleeding or planned surgery or invasive procedure.
Speaker: So you'll notice that there's nothing in the recommendations about treating an INR, which I think what you're referencing in your statements is that
Speaker: people tend to treat a number rather than whether the patient has bleeding.
Speaker: And that's where a lot of the overuse and a lot of the variability that we see in practice comes in is when patients are getting treated because their INR is prolonged.
Speaker: And I think that a common indication clinically, or a common use, I should say, clinically is like you said, Janice, is a high INR in somebody who needs a procedure.
Speaker: And there seems to be some literature to suggest that that really
Speaker: It doesn't help, and it's just an overuse of fresh frozen plasma.
Speaker: Could you comment on that?
Speaker: Well, this is where we sometimes have disagreements with our consultants, particularly in interventional radiology is where I found it.
Speaker: So the evidence would suggest from studies, most of which are retrospective, that an INR that is less than two, you're not going to have any benefit by giving fresh frozen plasma, and you will likely not change the INR very much.
Speaker: And we also know that the INR and even a partial thromboplastin time do not predict bleeding.
Speaker: So many of us have had the frustration where you have a patient who needs, let's say, a catheter placed in the interventional radiologist wants the INR below 1.5.
Speaker: Well, that's, again, then you're pouring in a lot of volume, which is one of the major adverse effects of fresh frozen plasma is volume overload.
Speaker: The other interesting thing for clinicians to remember is that the actual INR of a unit of fresh frozen plasma is about 1.5 to 1.7.
Speaker: So that's why you're never usually going to correct to quote some of these normal values that some people are aiming for.
Speaker: Excellent.
Speaker: And you did mention cryoprecipitate.
Speaker: Can we maybe start by saying what's the main difference with fresh frozen plasma and cryo?
Speaker: and what would be the indication and appropriate use of cryoprecipitate?
Speaker: Well, cryoprecipitate really contains a subset of everything that's in fresh frozen plasma since it's precipitated from that.
Speaker: So I always think of cryoprecipitate as a source of fibrinogen.
Speaker: That's how we typically use it.
Speaker: It also contains factor VIII and factor XIII and von Willebrand factor.
Speaker: But if the patient, such as a hemophiliac, needs factor VIII, we have much safer, more specific products.
Speaker: So today, I would say look at cryoprecipitate as a source of fibrinogen.
Speaker: And the indications there are then for low fibrinogen.
Speaker: And often this is in the setting of massive bleeding, trauma, obstetrical catastrophes where fibrinogen is often needed.
Speaker: Okay.
Speaker: So you did mention as complications from thresholds and plasma or common complication, potential volume overload.
Speaker: So why don't we move into some of the complications and adverse effects of blood component transfusion?
Speaker: I think that as you mentioned earlier, we should think of all these products, not only as scarce goods, but also as therapeutics that can cause harm in patients, especially when not utilized in the right context.
Speaker: So how do you think about
Speaker: blood transfusion or transfusion-related complications in general?
Speaker: Well, yeah, I think every clinician should be knowledgeable about the adverse effects so that they truly can provide patients and families with the information that they need to make an informed decision.
Speaker: And again, it's a weight of the risk and the benefits.
Speaker: Someone who's bleeding massively, the risk
Speaker: are negligible, benefits are high.
Speaker: But in someone who's not bleeding, who really may or may not need a transfusion, then the risks kind of go up a lot and that ratio changes.
Speaker: So I think we're all familiar with some of the catastrophic effects of an acute transfusion, a hemolytic transfusion reaction.
Speaker: Those are fairly rare today.
Speaker: They can still occur.
Speaker: The most common adverse effect is going to be the non-hemolytic transfusion reaction.
Speaker: So this is the febrile reaction, just the fever, the chills.
Speaker: And this is most common with platelets, but it can be seen with red cells, particularly those that are not leukocyte reduced, and also with plasma.
Speaker: So those are minor, but they're
Speaker: often engender an investigation.
Speaker: Sometimes people are put on antibiotics because they have that fever when it's not necessary.
Speaker: So there are some consequences of even these minor reactions.
Speaker: I think others are fairly rare.
Speaker: We talked about transfusion-related infections.
Speaker: And although the risks have really, really decreased significantly, there is still a small risk for transmitting hepatitis and even HIV.
Speaker: But I think one of the interesting things as we evolve, whether it's climate change or the global travel of everyone, we have now these emerging diseases that may be transmitted by flood.
Speaker: So things such as Zika virus, dengue fever,
Speaker: And even influenza theoretically could be transmitted from blood products, although it's not been described yet.
Speaker: We have these emerging diseases to worry about, which we are not able to test for in the blood banks at this time.
Speaker: So we have to realize that there's always something coming down the road that may infect our blood supply.
Speaker: I think one of the unknowns that we
Speaker: struggle with in the critically ill patients is the concept of immunomodulation.
Speaker: There's a lot of data out there showing that blood transfusion is associated with worse mortality, increased risk of infection, organ dysfunction.
Speaker: Now, that has been very difficult to prove in any prospective trials, but there's a consistent signal there that suggests
Speaker: that when we transfuse these foreign proteins into a recipient, there may be some alteration of their immune response and even the release of inflammatory mediators that can have consequences for our patients.
Speaker: The volume overload, which is the transfusion-associated circulatory overload, or TACO, is now actually becoming the number one cause of death from blood transfusions.
Speaker: And it typically is more common with blood, red blood cells, and plasma because they're obviously high volume.
Speaker: And that has actually displaced the acute lung injury.
Speaker: Transfusion-related acute lung injury is one of the number one causes of death associated with transfusion.
Speaker: And the reason for that is that transfusion-related acute lung injury can occur with any blood product but was more commonly seen with plasma.
Speaker: And so the blood banks have moved away from accepting all donors and moved to a male-only plasma supply.
Speaker: And they also will accept women who have never been pregnant, but it's predominantly a male plasma supply.
Speaker: And that has actually significantly reduced the risk and incidence of transfusion-related acute lung injuries.
Speaker: But it's still there and it can still occur, but volume overload is kind of now one of our major problems.
Speaker: And I think in terms of obviously volume overload, it's more from a clinician perspective is using practices like you mentioned of giving the unit, checking the response, making sure we don't overdo it if unnecessary, using blood and products.
Speaker: when indicated and then monitoring the patient as we would monitor any patient that we're getting, I mean, large amounts of fluids, but I think something just to keep in mind as the most common cause of death now, so something that we should be able to handle and recognize very early.
Speaker: Right, and distinguishing between acute lung injury and the volume overload can be a little bit difficult, but you're less likely to have fever with volume overload, less likely to have leukopenia with volume overload.
Speaker: So again, it's supportive care in both cases.
Speaker: But the interesting thing is that many people don't realize it can actually cause death in your patient.
Speaker: And I think from a blood-bound perspective, though, having the diagnosis right is important because a transfusion-related acute lung injury probably will prompt a different line of investigation on that blood product that volume would, right?
Speaker: That's true.
Speaker: Well, I think the blood banks will investigate both, and it's often very difficult to separate those.
Speaker: But either way, I think you just have to be able to recognize something could be related to a blood product transfusion and initiate that investigation.
Speaker: We talked about indications and some of the practical aspects of transfusion, individual units of blood or individual types of blood products.
Speaker: But there are situations, especially in trauma, but also I think occur in every ICU where there is truly active and life-threatening active bleeding that requires maybe the transfusion of large amounts of blood products in a short amount of time.
Speaker: And what now people have talked about as massive blood transfusions.
Speaker: Could you comment on where we stand there and what are some of the things that
Speaker: that maybe don't do this on a regular basis should be thinking about to make sure that when they need it, they do it the right way?
Speaker: Well, I think this is another area that is still undergoing an evolution.
Speaker: The blood product ratio approach has been promoted, particularly in the field of trauma, although the evidence for benefit has really not been
Speaker: come forward from the clinical trials.
Speaker: Even the proper trial, which was actually did not meet their end point, so it was a negative trial, and only a subset that showed they didn't die of exsanguination in the first 24 hours, but they still went on to die, leaves people with questions.
Speaker: And the trauma population is different than the ICU population, and there are some retrospective studies suggesting that
Speaker: these blood product ratio, applying that approach in different patients may not necessarily be of any advantage.
Speaker: I think every institution should probably have a massive transfusion protocol, particularly anyone dealing with obstetrics, and most do have an approach.
Speaker: And again, it's monitoring platelet counts, monitoring your coagulation.
Speaker: And I think
Speaker: when you can't get your laboratory back in a fast enough time, which is often the case if someone's bleeding, you probably are going to use some type of blood product ratio of red cells to plasma to platelets just based on the clinical status of the patient.
Speaker: And is there a ratio that you use?
Speaker: I mean, just out of curiosity, Janice, I know you mentioned that there's no good clinical study-driven data, but just in terms of what you have used in your practice?
Speaker: I really don't have any one thing I can point to.
Speaker: All I only thing I would say is that since I'm a medical intensivist, I think what I've learned over the years is to look at the fibrinogen a little bit more because you'll often find things that you didn't realize were going on.
Speaker: So in other words, their coagulation parameters may look pretty good, but their fibrinogen is now 100 and they're still bleeding.
Speaker: So I find that, um,
Speaker: Paying attention to fibrinogen is a little bit of a change, I think.
Speaker: Excellent.
Speaker: Another situation that we talked, I mean, in a similar bit with the platelets, but I think that also would be useful to t alk a little bit more about detail is those patients who have an autohemolytic anemia.
Speaker: And those are usually young patients or can often be young patients with very, I mean, low hemoglobins.
Speaker: Is there anything in particular that's recommended today or that you would state for our clinicians?
Speaker: It's how they approach transfusing these patients.
Speaker: Oh, gosh, these are terrible circumstances.
Speaker: And I would say the most important thing is educating patients.
Speaker: If the patient's not able to participate, educating the family about the risk and what you may have to do.
Speaker: So this is where, you know, you're calling the blood bank.
Speaker: They're saying, I can't get you blood.
Speaker: It's going to take hours to try to elute the antibodies and identify them.
Speaker: And yet you have to give something to that patient.
Speaker: And I think here, many of us are called on to sign for least incompatible blood, which they will release with a physician or a clinician's signature.
Speaker: And we shake in our boots, and we're very cautious.
Speaker: And what we do is you just initiate the transfusion at a very slow rate, and you watch the patient.
Speaker: but I don't have a magic bullet for this type of patient.
Speaker: They create havoc in the ICU, and I think what you have to realize is that at some hemoglobin level, you're going to have to try to transfuse them, but that communication and education of families and patients is critical to making sure everyone understands what you're doing and why you have to do it.
Speaker: Absolutely, and I think that because we don't see these cases as frequently,
Speaker: we sometimes forget that in those patients who have refractory autoimmune hematemia, the mortality is very high because at one point they probably get into trouble when we transfuse with these blood products that are not compatible.
Speaker: Exactly.
Speaker: A situation that I think occurs in every ICU and I still think, I mean, raises obviously questions and concerns, and I would just want your opinion or what could be some of the pearls that you could share with us
Speaker: is patients who refuse blood products, especially, I mean, certain beliefs like Jehovah's Witnesses.
Speaker: And I think there's always a lot of confusion around this.
Speaker: But what is your general approach to these patients, Janice?
Speaker: Well, it's kind of a multimodal approach.
Speaker: I think the first thing is to minimize blood loss, which means you use pediatric tubes.
Speaker: And we have to stop
Speaker: needing information in other words we as clinicians we focus on those numbers we want that daily hemoglobin and this is where you have to say no so maybe checking a hemoglobin every other day not checking liver function tests whatever you can do to reduce the amount of blood that is removed from your patient you have to do that and
Speaker: deal with the uncertainty of not knowing those lab test results every day or every six hours.
Speaker: Other than that, there's really, there are no approved blood substitutes.
Speaker: Again, you explain the consequences to your patient.
Speaker: Most are very adamant in their refusal of the blood products, and we end up respecting that.
Speaker: And at some point in everybody's career, you're gonna have a patient
Speaker: such as that who will die because they would not receive blood substitutes or blood or any other type of blood product.
Speaker: And there's really, it's not satisfying, but it is respecting the patients and their wishes.
Speaker: And that's the best you can do at this point in time.
Speaker: Absolutely.
Speaker: So we talked to, and I think an important point also for our audience is that since it's a,
Speaker: valuable resource, and like you said, a scarce resource, I think it's important not only to think about the outcomes aspect of medicine, but also the other part of a value equation is cost and making sure that we are good stewards of resources.
Speaker: And it is interesting that of the five recommendations that the American Board of Internal Medicine and Critical Care have done on the Choose Wisely campaign many years ago, two of them fall exactly into what we're talking about, which is
Speaker: limiting, I mean, a more restrictive blood transfusion threshold and the limitation of daily blood work for many reasons.
Speaker: But I think that two of the five fall directly in this discussion that we're having today.
Speaker: Exactly.
Speaker: And actually, more societies and organizations have signed on to that recommendation.
Speaker: The Critical Care Society Collaborative, the American Association of Blood Banks, the American Society of Anesthesia,
Speaker: Society of Hospital Medicine, American Society of Hematology.
Speaker: So everybody is supporting that recommendation for that lower threshold for transfusion.
Speaker: And the last, Ed, I think part of the clinical discussion that I wanted to just touch on was what are some alternatives to transfusion of blood components?
Speaker: And I think that there are certain things that we use in some situations that might be helpful, and I just wanted to make sure that we touch on them for our audience.
Speaker: So maybe we can start by talking about blood substitutes, if there's anything right now that people are utilizing that you can mention.
Speaker: There really isn't.
Speaker: People have tried the perfluorocarbons, the hemoglobin-free solution, the free hemoglobin solution, and unfortunately, the adverse effects of these products has been pretty significant.
Speaker: So nothing is approved at this point in time.
Speaker: Other than that, we try a few little tricks here and there.
Speaker: I think the antifibrinolytic agents are very interesting.
Speaker: The tranexamic acid is being used in a lot of surgical areas and a lot of studies coming out where they will use that to prevent bleeding.
Speaker: It's been used in trauma with the CRASH-2 study, and it's been used in obstetric hemorrhage.
Speaker: So these are agents that are being used
Speaker: Explored I think in many different circumstances not really in the medical ICU type of patient or in ICU patients They still have that propensity to form clots, which is always a concern We have vitamin K for warfarin related bleeding.
Speaker: It takes time to kick in We know that erythropoietin is not of any benefit and actually can increase the risk of thrombosis so trying to jump start the red cell production isn't recommended and
Speaker: But I think one thing that is at the forefront right now of transfusion medicine is the concept of blood management.
Speaker: And this is a more comprehensive management of the patient by identifying anemia early, say before surgery, and trying to correct that if possible, if they need iron, and also minimizing blood loss during surgery using cell saver technologies.
Speaker: And then also applying that restrictive strategy post-surgery in many of these patients.
Speaker: So you'll see that term, more comprehensive blood management, which really means looking at the bigger picture.
Speaker: And reducing phlebotomy is part of that as well.
Speaker: What about the use of desmopressin and vitamin K to decrease, I mean, the incidence of cragulopathy or bleeding?
Speaker: Well, desmopressin is kind of an interesting drug.
Speaker: We use that really for more platelets defects, functional defects, particularly in the setting of uremia.
Speaker: And the data is not great on whether it changes outcomes.
Speaker: And unfortunately, with that particular product, you get tachyphylaxis.
Speaker: So it's not very useful after one or two doses.
Speaker: And often we don't
Speaker: see people that are that uremic anymore.
Speaker: If we do, we can get dialysis started, which might be a better way to improve platelet function.
Speaker: And vitamin K still has its place.
Speaker: I think it needs to be used judiciously.
Speaker: Again, you know, it shouldn't be used just to correct a mildly prolonged INR.
Speaker: But in someone who's not bleeding and is on warfarin and their INR is prolonged considerably, that's a very reasonable intervention rather than giving fresh frozen plasma.
Speaker: So you have time to correct that INR if they're not bleeding and otherwise stable.
Speaker: This has been an excellent discussion.
Speaker: I think a lot of very actionable and useful tips for the clinician at the bedside.
Speaker: I do want to be respectful of your time, Janice.
Speaker: And tradition at the podcast is to end the discussion with a couple of questions that are not related to the clinical topic.
Speaker: Would that be okay?
Speaker: Sure.
Speaker: So the first question relates to books, and it's what book or books have influenced you the most, or what books have you gifted most often to others?
Speaker: Oh, that's two different types of books.
Speaker: So let me tell you, the book I've gifted most often is because I've given to graduating seniors from high school, and it's a Dr. Seuss book called Oh, the Places You'll Go.
Speaker: And it has a humorous and interesting message for people going out into the world.
Speaker: Of course, what I do is I put money in between the pages.
Speaker: So they have to read the book to get the full benefit of their gift.
Speaker: So that's the one I gift most often.
Speaker: But I think the books that I've enjoyed, or at least I think have really influenced my love of reading, were historical fictions.
Speaker: So...
Speaker: Leon Uris, Exodus, Topaz, the Hajj, even James Michener, Hawaii.
Speaker: I even read the whole book about Texas, which is not his best work, but it is, I think what I've found through these books is that history can come alive and it makes it a lot more interesting.
Speaker: So I like a lot of different types of books, including science fiction, but I think historical fiction is one of the, those books have really
Speaker: kept me reading.
Speaker: Excellent.
Speaker: And we will definitely reference these in the show notes.
Speaker: And the second question relates to what do you believe to be true in medicine or in life that many other people don't believe?
Speaker: I think what most people don't believe is that they are not biased.
Speaker: They feel they are honest and
Speaker: don't have biases.
Speaker: And I think what I've learned is that we all have biases and we have to recognize them.
Speaker: And I think this impacts medicine and of course outside of medicine as well.
Speaker: So when we go to the bedside and we do things a certain way because we believe that is the way to do them, sometimes we close our minds to other options.
Speaker: And so I think
Speaker: one of the things as a clinician that we have to do is manage those unrecognized biases that affect not only our interaction outside of medicine, but also our patients.
Speaker: Absolutely.
Speaker: And I know that one of the areas of interest for you, I mean, both in terms of practice and in terms of your activism within the societies, but also from an educator is
Speaker: the inequality that we see in ICUs, and that can be at multiple levels, patients, colleagues, et cetera, et cetera, and finding parity there.
Speaker: And I think that implicit bias, I mean, are big drivers of that.
Speaker: And I think till we recognize, we can say whatever we want that we're not, but until we recognize the behaviors that are almost automatic in us, that's never going to change.
Speaker: I agree.
Speaker: I'd say we all think we don't have those biases, but we do, and we have to learn to recognize those.
Speaker: And the last question just relates to what would you want every intensivist or APP who's listening to us today to know?
Speaker: Maybe I could change that to what every clinician should do.
Speaker: And I've always, I've kind of lived my whole medical life through this, and that's always to put the patient first.
Speaker: Because I think more so today, we tend to get distracted by, we have coders who come and ask us to change this or that.
Speaker: We have quality measures that we're told we have to do that may or may not be right for our patients.
Speaker: or even guidelines where we say we've got to do this or that, and we're not putting it back into the perspective of the patient that's in front of us.
Speaker: So I think what I would like for everyone always to do is always put the patient first, always.
Speaker: And I think it's a great way to end, Janice.
Speaker: And I think what I find that fits into that recommendation is that too often I find people arguing about who is right,
Speaker: as opposed to focusing on what is right and what is right for the patient is what we really should be focusing on in the hospital.
Speaker: Exactly.
Speaker: Well, this was a great conversation.
Speaker: Thank you so much for your time and sharing your expertise with us.
Speaker: I definitely hope that I will have you back on the podcast soon.
Speaker: And again, thank you for your time.
Speaker: Thank you, Janice.
Speaker: All right.
Speaker: Thank you.
Speaker: Thank you for listening to Critical Matters, a Sound Critical Care podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound Critical Care is transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
