Activity Transcript

Daniel T. Engelman, MD: Hello. I'm Daniel Engelman, medical director of the Cardiac Surgical Critical Care Unit and Inpatient Surgical Services at Baystate Medical Center in Springfield, Massachusetts. I'm also a professor of surgery at the UMass Chan Medical School. Welcome to this program titled, Prevention and Treatment of Bleeding Associated with Cardiac Surgery: Expert Perspectives. Joining me today is my friend and colleague Dr. Seenu Reddy, who is chief of the Division of Cardiothoracic Surgery at TriStar Centennial Medical Center in Nashville, Tennessee. Welcome Seenu.

V. Seenu Reddy, MD, MBA, FACS, FACC:Thank you, Dan. Good to be with you here today.

Dr Engelman: So today, we're going to delve deep into bleeding surrounding cardiac surgery, which is never really a problem. I haven't seen any bleeding after cardiac surgery. I'm sure you haven't either. But those surgeons that actually have to face this problem and those perioperative specialists, clearly, we need to have standardized evidence-based best practice. And we're going to try to delve a little deeper into what's out there in the literature and what people are doing and what we should do to, A, prevent it and, B, treat it once we see it.

Seenu, cardiac surgery is associated with a tremendous amount of blood utilization in this country and around the world. Obviously, cardiopulmonary bypass causes alterations in the blood hemostatic system, and we have a lot of tissues we're operating on and reasons why there's all this bleeding. But why has the use of blood increased so much over the last decade?

Dr Reddy: I think that's a great point, Dan, and I think it really comes down to this. We're operating on sicker, more complex patients. At the end of the day, the type of operations we're doing, the length of the operations, and also the preoperative status of our patients is probably contributing to this. We know, as you point out, that about 15% of all the blood products in the United States, the use of those blood products is associated with cardiac surgery. And really about 20% of the patients that we operate on are probably going to have some kind of hemostatic derangement that's going to require treatment. And then up to 2% to 6% of the patients after heart surgery may have to even return to the operating room to control that bleeding.

Dr Engelman: So let's assume you have a patient that's a little wet and you sit on it for a while and you drag your feet because you don't really want to open the chest again and increase his risk of subsequent infection. And that requires a couple units of blood just to get over that hump. What's the risk to benefit to that in your mind?

Dr Reddy: Well, I think the risk is substantial. Obviously, the benefit is you're trying to avoid a return to the operating room and exposure to the reopening or your sternotomy incision. On the detrimental side, we know that each unit of blood transfused is like a liquid transplant, and that we want to be very circumspect about when, how and how much we transfuse.

Dr Engelman: So, you say a liquid transplant. Can you describe a little bit more of what you mean by that?

Dr Reddy:I think what's now come to be recognized and fairly well demonstrated in the literature is that blood utilization, actually transfusion of packed cells, acts as an immunosuppressant for patients, has effects on their acute hospitalization as well as even longer term, in terms of increased infection risk, possibly increasing arrhythmia risk, and pulmonary complications.

Dr Engelman: So how much of the bleeding that we see after cardiac surgery do you think is what I would call "surgical bleeding" -- a lack of proline?

Dr Reddy: I think you talked about earlier, maybe just how do we frame this? I think there's pre-op factors, intra-op factors and then post-op factors. And certainly, one of those intra-op factors, proline deficiency's one of them. The number one thing we should always look to is ourselves. Have we checked every suture line? Have we checked the mammary takedown bed? Have we checked the sternotomy sites? All of this comes down to areas that we can potentially affect the amount of blood loss and periprocedural hemostasis.

And then of course, we know that there's some predisposing factors to what may lead to a higher risk patient, whether they're advanced age, preexisting anemia, maybe some kidney disease that causes platelet dysfunction, emergency surgery certainly, and then as we've talked about some of those sicker more complex patients that require mechanical circulatory support.

Dr Engelman: Because the longer you're on this bypass pump, the greater the risk of postoperative bleeding. Wouldn't you say that's true just due to the breakup and fibrinolysis of these cells and the consumptive coagulopathy and all of the activation of the cytokines that occurs on pump?

Dr Reddy: Yes, I think for sure that's one of many risk factors is length of time, duration of cardiopulmonary bypass. But going back to what we said in terms of preoperative preparation for these patients, I think we also have to be understanding of the type of patient we're taking into the operating room. There are patient characteristics that could be very important in determining how they're going to behave, both intra-op and post-op. We know a nutritionally depleted patient, one with protein malnutrition, one that's already anemic, one that's debilitated, is going to probably bleed more. And remember, they're not going to just be deficient of packed cells or red blood cells; they're probably going to need factor repletion as well.

Dr Engelman:I like that you're talking about pre-op risk for bleeding. So, let's back all the way up to the pre-op visit with the patient. So, you see a patient, and they're anemic. They have a hemoglobin, let's say, is less than 12 or 13 g/dL. Do you think there's a role for treating these patients a little bit different, maybe postponing their elective surgery a little more until we can get their hematocrit up with either iron or erythropoietin? What are your thoughts?

Dr Reddy: Yeah, I think that's a great point. In the perfect world where we have time and they are truly an elective patient, that's absolutely something that needs to be done. And it's been shown that if you can even avoid, let's say you get your friendly cardiologist calling you and they've just done the cath that morning and they're like, "Hey, can I admit this guy, and you do him tomorrow morning?" -- Just that alone, if you can get him back to an outpatient ambulatory status, have a chance to evaluate just as you said what their blood count is, getting that blood count up if possible. And then looking through their medications, making sure they're not on antiplatelet agents. If they're on antiplatelet agents, other than maybe a baby aspirin, stopping those, particularly these P2Y12 inhibitors. Looking also to make sure they're not on herbal therapies. There are a substantial number of patients out there who take supplements, which we know the Gs, the famous Gs all can affect bleeding as well (eg, gingko biloba, garlic, ginseng).

Dr Engelman: Yes. The recent guidelines from the combined societies, the STS/SCA/AmSECT/SABM group, they talked about the amount of time you should be off these platelet-inhibiting agents. And in this particular manuscript, they said it was 3, 5, and 7 days before elective surgery for ticagrelor, clopidogrel, and prasugrel, which I think is a nice round number. I always remember it as 5 to 7 days is how long it takes a platelet to be manufactured and healthy. And so, hence you really want to have an entire half-life of new platelets that are not exposed to these antiplatelet agents before you go into elective surgery, if you're trying to decrease your risk of bleeding, if at all possible. Would you agree with that?

Dr Reddy: 100%. And I would also agree that the drugs dosed BID (twice a day) probably have a quicker washout, and that's why I heard you say the 3-day. There are also some adjunctive measures one can take. There are some assays out there that are commercially available now that can actually look at platelet inhibition, particularly salient to the P2Y12 category of drugs.

Dr Engelman: Yes. They talk a little bit about the role of those, but I don't think there have been a lot of studies looking at whether we can look at platelet inhibition. Because it turns out, a significant portion of patients actually have no inhibition whatsoever, despite being on some of these agents. And hence delaying their surgery provides no benefit. Zero. So it'd be nice to figure out who you can safely operate on without any weight because they're not inhibited.

Dr Reddy: Well, that's precisely at our center how we use those assays.

Dr Engelman: Excellent. Well, you're cutting edge. You're ahead of us.

Dr Reddy: I don't know about that!

Dr Engelman: So, moving out of the pre-op settings, so we looked at risk and we thought about getting patients off these agents that may increase bleeding. Oh, we should also talk about the DOACs of course, a lot of patients are on those. We need to consider stopping those obviously, if possible, because they really will cause bleeding.

Dr Reddy: Absolutely. I think we're seeing the prevalence of those go up. Number 1, because they work; number 2, because a lot of studies have shown they may be superior to warfarin. But having said that, you're right, we get a lot of patients coming in on those and they may not all have atrial fibrillation. They may be on it for other indications too, because we know prior pulmonary embolism and deep vein thrombosis are indications for those agents. But we really like to stop those at minimum of 48 hours, if not, 72 hours before major surgery.

Dr Reddy: What about a reversal agent?

Dr Engelman: It should be used in emergency cases and they're very specific to only certain DOAC. They only recently came out, but there is a role, yeah. The chance of having an emergency patient on one of those, that has a reversal, is so rare.

Can you remember using it, Seenu?

Dr Reddy: We've not used a reversal agent here.

Dr Engelman: So we've worked the patient up, we've gotten them ready for surgery. We either put them through an anemia clinic and built up their hemoglobin stores or gotten them off some of these poisons. We take them to the operating room. We do our best to do a timely operation, clearly there's some benefit to that as we've discussed. But you see a lot of friable tissues and bleeding and it's a reoperation and the mammary beds constantly oozing. What other things would you do operatively to try to decrease that bleeding before you leave the operating room?

Dr Reddy: I think it all begins with meticulous tissue handling and appropriate hemostasis at the outset. A lot of surgeons, I notice, sometimes try to save bleeding management until the end, but it's like bleeding begets bleeding. I think you have to be meticulous from the outset just like, I think, when you and I were talking one time, you said, "why don't we just treat all patients like Jehovah's Witness patients?" And I think that's right when you make your sternotomy, really get good hemostasis with the sternum right away. Don't move on with your operation with an oozing sternum. Number 2, if it's a coronary revascularization procedure and you've mobilized the mammary, make sure you have a very dry mammary bed.

Number 3, as you dissect your planes, particularly in redo, try to do a more atraumatic dissection. We know that the hand sweep that just pulls the heart away from the pericardium leaves a very raw surface, and those raw surfaces can ooze for quite some time. Obviously, the electrocautery should be used judiciously because even though it can help with hemostasis, it can be in injurious to tissues. And then finally, have a sense in your mind of all your suture lines: aortic suture line, atrial suture line, etc. and recheck those in a systematic fashion. We call it a quadrant check. We move through the mediastinum in a quadrant-type approach and making sure we look at all of those during the end of the operation as well, to make sure you have a dry mammary pedicle, you have a dry suture line, you have dry cannulation sites, dry atrial incision sites.

Dr Engelman: So it also goes without saying that pretty much every guideline that's been written has said that the standard of care now is to use some, either tranexamic acid or aminocaproic acid, in these patients to decrease those inflammatory cytokine-related bleeding episodes. And I don't think they've really been shown to be associated with any increased thrombosis.

Dr Reddy: That's right. I think those agents for sure have been shown to have a benefit. I think there's some other agents, when we can talk about in the postoperative management, if it gets more significant. But in addition to that, what about some topical hemostatic agents? Are you a believer in those, Dan?

Dr Engelman: I am in certain instances. There's a lot of them out there. I think that they overwhelm the market with all different types. And I think that it's hard to know exactly which one to use when, but there definitely is a role. I would say it's not nearly as standard of care as tranexamic acid and aminocaproic acid is.

Dr Reddy: Right. And proline, of course. I think the way I would think about them broadly would be, those that come out, sealants, so those are particularly useful maybe when you have a porous-type suture line or a suture line that's combining native tissue to maybe a graft. There are numerous sealant type products that you can apply to those. I think then there's some that are just called topical agents that are particularly useful for areas that are just generally oozy. A lot of the cellulose-based products that can help dry up that bleeding. There are some spray type products you can use to cover, again, these oozing beds. And then finally, there are a few products I think out there that can be used where there's even more active bleeding around on the myocardium itself, or suture sites that need a little bit of pressure in time that you apply them. So I think they're all out there. I think they should be used, as you said, with caution and maybe not first line. But I think they're good adjuncts, certainly in complex cases, particularly.

Dr Engelman: I'm struck by human nature in that if you, Dr Reddy, are operating on someone who's a Jehovah's Witness, and you're getting ready to leave the operating room and you're just about to close the sternum. Something tells me we just do 1 or 2 more quick looks and are a little slower with that closure and spend a little bit more time, because you know you don't really have that safety net. Would you tend to agree with that? And it's hard to admit, but I think we just treat them a little bit differently and I might add, it's how we should treat everybody.

Dr Reddy: Yeah, no doubt. I think that should be standard of care. But that standard of care should probably extend to the postoperative period, in terms of blood draws and what we're doing in terms of phlebotomy.

Dr Engelman: I totally agree with you. So let's talk about that. So the patient hits the intensive care unit and immediately we just draw a bunch of tubes of blood and send every lab under the sun. Even though that may have been done 30 minutes earlier in the operating room -- redundant, unnecessary, not really adding to it. And then we continue that throughout the entire intensive care stay. I think we really need to pay way more attention to the amount of blood we take off these patients because it's enormous post-op, and it's contributing to post-op anemia, which also contributes then I think to unnecessary transfusions. Plus, the use of pediatric tubes, I think that needs to be more widespread.

Dr Reddy: I agree.

Dr Engelman: What about at the time of surgery or immediately post-op?

Dr Reddy: I think there are a broad array of pharmaceutical compounds we can use including factor repletion, going from factor VII repletion, utilizing desmopressin to activate platelets. Obviously, the other blood products that may reverse vitamin K inhibition type scenarios. All of those are available and should be used judiciously, but appropriately. I think they all have a role. In your center, are you using the factor VII-type adjuncts or maybe something like-

Dr Engelman: So I actually originally started using a factor IX, years ago, and then we went to a factor VII, and then we have now, moved to a prothrombin complex concentrate (PCC), which has multiple factors in it. And in fact, just recently, there was a nice publication showing that it is relatively safe without any increase in hypercoagulable complications, in post-cardiac surgical patients who had an INR greater than 1.6, who required some factor correction because of persistent yet non-surgical bleeding. So what I like about that is it gives cardiac surgeons another tool in their tool chest to potentially use in patients that may have coagulopathies after surgery, but don't necessarily meet the standard of going back to the operating room. Though I certainly would not use this as a first-line and it may remain very expensive.

Dr Reddy: No, like your center, it sounds like we first correct the initial coagulation profile. If there's ACT prolongation or PTT prolongation, we give more protamine. If there's an INR elevation, we give the of course, plasma. And if we see a derangement in the fibrinogen values, we might use cryoprecipitate and certainly replete platelets if they're deficient as well. Having done all of those things, if we see ongoing bleeding, then the factor repletion compounds really then have a great role.

Dr Engelman: Right. But I might add also that the natural reaction to seeing abnormal coagulation profile or thrombocytopenia, is to replace those. But in a patient that's not actively bleeding, we have to hold back because you're not doing the patient any favors giving them factors, and the same with blood, if they don't actually need them. Would you tend to agree with that?

Dr Reddy: That's exactly right. And I think that's where maybe the role of thromboelastography may come into play, really trying to be more specific and purposeful, intentional, how we transfuse patients. Do you use that yourself?

Dr Engelman: We do. We've used it for many years. So we have some of the original machines that required interpretation of graphs that sometimes was above the abilities of the surgeon while he was operating, and someone showing him a picture of how the clot was forming behind him. It was not very intuitive, but the newer machines are much more intuitive and they actually tell you what to do and what to replace or not to replace. And I really think that will guide our treatment of postoperative bleeding much better and reduce the amount of unnecessary transfusions of both blood and factors.

Dr Reddy: Yeah. Viscoelastic testing has shown its role certainly in trauma populations and in mass transfusion situations like that. But I think the role in cardiac surgery continues to evolve. And as you point out, as the technology gets better and the interpretive abilities get better, we may be able to do a much better job.

Dr Engelman: What do you think about the role of temperature management to reduce bleeding after heart surgery?

Dr Reddy: You bring a great point. I think more and more recognition in the periprocedural space of hypothermia is really coming to the forefront. We all use hypothermia purposefully during cardiac surgery to protect organs, to allow us greater time to do intracardiac repairs, certainly for neuroprotection. However, once that component of the operation's over and you've come off bypass and you've reached normothermia, the maintenance of that normothermia, that becomes very important. And we know that if a patient again becomes hypothermic, that all sorts of bad things can happen. Higher infection rates, certainly more bleeding. And we know that factors have a harder time working in a cold patient than they do in a normothermic patient.

Dr Engelman: I completely agree with you. I couldn't have said it better myself.

Moving on from that, let's talk a little bit about appropriate transfusion triggers, the dangers of transfusion. And I like this wording "anemia tolerance," because that's really what it is. It makes you a little bit uncomfortable when the hemoglobin gets very, very low after heart surgery and you have some new grafts on there and the blood pressure's very labile ... and you're thinking, "Geez, is hemodilution involved? How much lower is this hemoglobin going to go?" But what does the data really tell you? What's your interpretation of it about when we should transfuse? What are the triggers?

Dr Reddy: I think that the term "trigger" may be misleading to people. But I think the broader way I try to think about it is, are you a restrictive or permissive transfusion center? And I think most of us have gravitated to try to be more restrictive, recognizing the deleterious effects of willy-nilly transfusion in our patients. Having said that, I think then the second component to the answer is, it depends, right? So, we don't want to withhold, as you and I have talked about in the past, lifesaving therapeutic transfusions. At the same time, we don't want to give excessive transfusions to treat a number. So what we try to do is combine the understanding of what is the patient's hemoglobin or hematocrit value, combined with what else is going on in terms of tissue oxygen delivery, and the ability to achieve that?

What's going on in terms of their organ-end perfusion? And then how much pressors and support are they on? So if a patient is on high-dose pressors, we think is not having adequate oxygen delivery and may have a hemoglobin value in the 7.6 g/dL range, we may transfuse that patient to improve all of those things. And then we may have another patient with a hemoglobin value 6.9 g/dL but is off all pressors and seems to be making adequate urine, maybe they're just hemodiluted and just need more diuresis.

Dr Engelman: Yes. I agree with you. I've tried to look for evidence of end organ straining for better oxygen, organs that are starving for oxygen. And what manifestation are they showing me? Well, what can you see? You can see a rising lactate. That makes me feel as though those muscles need a little more oxygen. I use biomarkers for kidney stress, or even if I see the creatinine rising, which would be a little bit late, that would be acute kidney injury, or if the urine output's low and I'm thinking this oliguria is the early onset of acute kidney injury, so maybe the kidneys need a little bit more action. Or as you point out, patients who are stuck on multiple pressors and may be tachycardic and don't seem to have a lot of reserve and are getting dyspneic and hypoxic. Those are the patients that I will be more likely to transfuse in the 7.5 g/dL hemoglobin range. But other than that, I think most of the data now is pushing toward a restrictive philosophy down to about 7 g/dL.

Dr Reddy: I would agree with that. I think if our audience really needs to fixate or hang their hat on a number, I think 7 g/dL is a very reasonable number, with the caveats that you and I have discussed around those numbers. But at the end of the day, it's oxygen delivery... tissue delivery of oxygen, and as you point out, lactate clearance to be able to do all that. But let's not forget out there one of the things that can reduce oxygen consumption is also appropriate pain management, avoiding tachycardia, treatment of hypo- or hypertension. So, it's a lot of the great stuff, all of our critical care specialists and perioperative specialists do, which is that critical care.

Dr Engelman: I completely agree with you. It also brings to mind the transfusion threshold on pump in the operating room, when you have huge fluid shifts. Up until now, we've come up with some arbitrary numbers. There hadn't been too much data, but recent analyses have shown that on pump all the way down to a hemoglobin of 6 g/dL, every unit of blood that's transfused promotes an adverse effect to the patient. So really you can't use hemoglobin on pump as your trigger necessarily, but more likely more beneficial is the O2 delivery, where we're looking at a 270-280 mL/min measure for oxygen delivery on pump to determine whether or not the body is actually getting enough red cell carrying oxygen. So it's not just a blood count number. It's more sophisticated. Would you agree with that?

Dr Reddy: In fact, that's what our center uses here. It's a DO2 (arterial oxygen delivery) number that we use in every patient because at the end of the day, that's what matters. And what we're realizing now, it's not just flow rates. In the old model of perfusion, they always used to just calculate an index and say we're flowing a 2-0 index or a 2-1 index. Well, that may or may not be adequate for the patient. It really depends on the patient's size, if they're volume overloaded... There are many other factors, and we know there are a lot of tools available to them when you're on pump, by ultrafiltrating, retrograde autologous priming... There are many adjuncts of tools we can do to really get the hemoglobin level corrected to a point where you're delivering appropriate oxygen.

Dr Engelman: Those are all great points. Are there any other closing remarks you'd like to make to our audience about blood conservation, anemia management, how to control bleeding, be it minor or major after cardiac surgery?

Dr Reddy: The biggest point I think to be made is one that you and I have talked about during this discussion this afternoon is, which is, I think you have to be intentional. And I think the leadership often comes from the team that's at hand to take care of these patients: anesthesia, critical care, and obviously cardiac surgery. And I think you got to touch all phases like we've talked about, the preoperative area, making sure you've done everything you can to make that patient a person that's going to minimize the amount of blood they lose. Intraoperatively, being meticulous, using hemostatic agents appropriately, managing the pump appropriately, managing their temperature appropriately. And then finally postoperatively, making sure that all of the adjunctive care elements that we've talked about are put into place.

Dr Engelman: It's a great summary. Seenu, I want to thank you for this great discussion, and I'd like to thank our audience for participating in this activity. And if they would please continue on to answer the questions of follow and complete the evaluation, it would be appreciated. Have a great day.

Dr Reddy: Thank you. Thank you so much.

This transcript has not been copyedited.