Okay, so we're going to move into the late-breaking abstract presentations. The first one is on tranexamic acid use in craniosynostosis surgery. Dr. Mark Proctor. Okay, thanks. Mark Krueger just told me I pulled strings to get this talk, but I don't think so. I think it was on the science itself. So I'm going to talk about a recent randomized blinded study we just completed looking at two different dosing regimens for TXA in craniofacial surgery. I especially want to thank my co-authors. Dr. Susan Gooby is really the principal investigator on this. She's one of our excellent craniofacial anesthesiologists. And the other docs are assistants, our plastic surgeon. And Nicola Disma was the anesthesiologist that was working both in Italy and at Great Ormond Street in London. We have no conflicts of interest. So as we all know, significant blood loss is fairly common in complex craniofacial surgery. And multiple techniques have been described to decrease allogenic blood transfusion. So some of the blood conservation strategies have included autodonation and blood salvage, boosting the preoperative blood count, probably not a conservation strategy but a way to avoid transfusion using erythropoietin and iron, and decreasing overall blood loss. And I think we've also seen this in our institutions with improved surgical techniques, improved anesthetic techniques, and the use of pharmacologic agents. I'm going to focus today on the antifibrinolytics. So antifibrinolytics have a very well established role in surgery for both decreasing the blood loss and decreasing blood transfusion. And there have been traditionally three major agents, a protanin, TXA, and Amicar. A protanin is actually off the market. So the first nice study about a protanin came out of Michigan, but because of complications, that one's off the market. So you're really down to TXA and Amicar. There was a very nice Cochran study in 2011 that summarized 252 randomized trials in this regard, over 25,000 patients, and really found that these were very effective for minimizing blood transfusion. So just to review, how do these drugs even work? So in the normal course of clotting, fibrinogen in the presence of trauma is exposed to thrombin and forms fibrin, which is essentially a clot. At the same time, plasminogen will break down into plasmin, and plasmin breaks down the clot. So you have a constant process of forming clot breaking down the clot. So anti-fibrinolytics work at preventing the conversion of plasminogen to plasmin, and as such, you don't break down the clot. So essentially, anti-fibrinolytics are clot stabilizers. So TXA, it's a synthetic drug. It's actually very low cost. It was used quite extensively in a study called the CRASH-2 study, which had a 40% reduction in mortality when this was administered to trauma patients in the field. And this was mostly done in places with limited resources. So it's an extremely effective drug. In 2011, we did a randomized blinded study looking at either TXA or placebo and found a very significant reduction in blood loss. So if we look here, the blood loss, focusing here on blood loss, was cut in roughly half, 65 mLs per kilo versus 118 in the group that got placebo, and transfusion was 32 versus nearly 60 in the group that got transfusion. So we saw nearly a 50% reduction in blood requirements. And in the same issue, so the journal anesthesiology published our study and another study from France that came out at the same time, and it's essentially become standard of care now to use TXA in these cases at many institutions. These are four other articles that have come out since those original articles. The top two are from the group in Phoenix with Ruth Bristol. The third one is from Nate Seldon's group, and the bottom one is from Dan Couture's group in North Carolina, and essentially all showing the same thing, a substantial reduction in bleeding in the craniofacial cases. So again, sort of standard of care, but there are the potential for side effects, and they all appear to be dose-related. So awake patients getting TXA, and you see this in the cardiac world, the adult cardiac world, they can have nausea, diarrhea, and orthostatic events. Thrombotic events is sort of the big concern that people have about the use of TXA, and although we haven't seen that in the pediatric population, there's at least one surgeon I know that says he's heard of it happening, and seizures also appear to be a dose-related effect. So in 2013, our group did a pharmacologic study and showed that the dose you really need to achieve in the blood is 16 micrograms per ml. So if that's the case, how are we doing at the higher dose, and it seemed like we were way overshooting that. So our hypothesis was that a lower TXA dosage will be as effective as the current higher dosage in decreasing the blood loss and transfusion in craniofacial surgery. So we did another randomized blinded study this time. It was a multi-center study, so it was Boston Children's, it was the group in Genoa and a group in England, and we had a high dose group, so this was our original regimen, 50 milligrams per kilogram loading dose, and then 5 milligrams per kilogram per hour, that's what we used in the 2011 study, and the low dose was one-fifth of the dosage regimen for the loading dose, and it was the usual IRB approved, and we also used standardized anesthetic and transfusion management, which I'll go over. So it was a very simple study, there was two outcomes, blood loss and volume of PAC cells transfused, and again, standardized transfusion protocol, so instead of being subjective, our anesthesiologists would give the blood based on preset criteria and in preset ways, so if the CRIT got below 25 in the OR or 21 in the ICU, they would give blood. And we also did a standardized blood loss assessment, so that it wasn't based on what the surgeon calculated, but it was calculated, so you didn't actually know the blood loss until the next day, because it was based on how much fluid, et cetera, the patient got, and just of note that the calculated blood loss was usually about three times what the surgeon estimated. So results, we had 68 patients enrolled in the study, and this was powered to achieve significance, if there was any, mean age was eight months, and there was no significant differences between the groups at baseline, as you can see here, they were very well matched for age, weight, gender, ASA classification, whether or not they were syndromic, pre-op hematocrit, and pre-op platelet levels. Did we achieve the necessary dose of 16 micrograms per mL? Yeah, we exceeded it in both groups, so in the high dose group, they were achieving on average 50 micrograms per mL blood levels, and the low dose, they were still achieving 25 micrograms per mL. So both groups achieved a therapeutic range, and what we found was that there was no significant difference in blood loss in the two groups, it was essentially identical, no significant difference in transfusion rates in the two groups, just a few millimeters per kilogram, there were no complications noted in either group. So in conclusion, our prior study showed that TXA significantly reduces blood loss and transfusion rates in craniofacial surgery, and really has become standard of care in a lot of institutions. This study has confirmed that a lower dose of TXA is equally effective as a higher dose, so in light of this data and the potential for dose-dependent complications, the higher dose regimen should probably be abandoned in favor of the lower dose. Thank you.

tranexamic acid

craniosynostosis surgery

blood loss

transfusion needs

antifibrinolytics