This is a case I saw earlier this year, a 66-year-old woman with a fall, has a fall coming off the commuter train. She has a minimal bump to the head, the details are not entirely clear. She's on a PIXA band for history of atrial fibrillation with no previous complications, no other significant history. On initial labs, unremarkable. She shows, the CT shows a left parietal subdural hematoma. Can people see it right there? On the neurocritical care boards, oh, plug, there is now an ACGME-approved neurocritical care board. On the SCCM boards, they'll usually say there's a left parietal subdural hematoma. On the neurocritical care boards, they'll just show you the image and you'll have to see it. Her anti-10A level for a PIXA band is 496. The usual range is 41 to 230, so she has a fairly intense anticoagulation response to a PIXA band. How many people use Teg? Is anybody using Rotem, the next iteration of Teg? So Intem, Extem, or Rotem, which is what our hospital and many hospitals went to after Teg, she has reduced clot formation, prolonged clotting time, and a reduced alpha angle, all going along with less intense blood clotting response. Due to concerns about thrombosis in the setting of AFib, no acute treatment was given. She has repeat CT about six hours later. You can now see the change in the subdural hematoma, showing clear interval increase in the volume of the subdural. This patient is then treated with a four-factor prothrombin complex concentrate and a repeat anti-10A level is 245, significantly lower than the previous level in the mid-400s. Sometimes these subdurals are easier to see in the coronal plane, and this is her CT after another six hours or so. See, this subdural looks about the same, and you can easily see it in the coronal section as well. Everyone see this? For the record, patients with anticoagulation and blood in the head, watch for waiting, is generally not the correct answer. So there aren't guidelines for reverse of anticoagulation trauma patients. There are well-established guidelines for reverse of anticoagulation in patients with spontaneous intramural hemorrhage. These are the guidelines that were published earlier this year as an update from the American Heart Association. They really, really, really want you to know how to reverse anticoagulations in patients with blood in their head. Because if you do nothing, the bleeding gets worse, and if the bleeding gets worse, the patients are much more likely to be dead or neurologically disabled. For patients who present with intramural hemorrhage while in anticoagulation, you should reverse them as soon as possible. For patients with vitamin K antagonists, for example, warfarin, patients should generally receive prothrombin complex concentrates as the first choice, not fresh frozen plasma, not cryo. Patients in prospective randomized clinical trials, patients with warfarin-related ICH who got prothrombin complex concentrate had faster normalization of the INR, less hematoma expansion, and there was a trend to reduce mortality. Trial was stopped early. So patients with warfarin-associated ICH should get prothrombin complex concentrates. These generally come in three- or four-factor, activated or inactivated. Your hospital has or should have some protocol of what dose to give and what agent you have this month. For patients who are taking dabigatran, it depends a little bit on when the last dose was taken. The specific agent depends upon the agent. So if the patient is taking dabigatran, there is a monoclonal antibody specific to dabigatran called adaricizumab or digibind. It's called adaricizumab. Digibind is for digoxin. I'm sorry. There's another cutely named reversal agent for dabigatran. Its generic name is adaricizumab. If you have adaricizumab, the antibody against dabigatran, you should give that. If you don't have it, and we oftentimes don't have it, apparently there have been some supply chain disruptions in the past couple of years, then prothrombin complex concentrate is your next best option. For patients who are taking factor Xa inhibitors, like rivaroxaban and apixaban, those are factor X inhibitors, as opposed to dabigatran, which is a factor II inhibitor. If a patient's been taking a factor X inhibitor, like apixaban and rivaroxaban, the next best thing would be to give factor X, which is andexanet alpha. So for those, if andexanet alpha is available, you want to give andexanet alpha to patients taking apixaban and rivaroxaban. If for whatever reason you don't have it, lots of places don't have it, apparently there's a supply chain crisis, then prothrombin complex concentrates are the next best choice. You don't have to copy this. This is available free online from the American Heart Association. So if you simply type in guidelines, you can pull up the guidelines, and it comes with lots of, with about 40 slides on this. Quick question for you. Yes. So this is as of this year? Correct. Most of our questions that we'll see are going to be like two years ago. So most of our questions are going to probably just be asking us to choose prothrombin factor IV? So I can't say which question is going to be in the exam. These are updated guideline recommendations that reflect what the standard of care has been for a couple of years in the field. None of these are particularly new recommendations to the field. They're only now being codified by American Heart Association guidelines. So the papers on adiracizumab for dabigatran reversal and prothrombin complex concentrates, those references are now four or five years old. So those references are fair game. Thank you. In case you didn't hear about it before, if you don't know, now you know. We really want you to know this. For patients taking heparins, they may still ask you about this. For patients who have ICN triple hemorrhage while on a heparin drip, the correct answer reversal is protamine. For unfractionated heparin, this is a higher level of evidence because protamine clearly works for unfractionated heparin infusion. It is less effective for low-molecule heparins, but it's probably still worth doing. It is better than nothing. This is a really high-value slide. If you don't do this very much, look at this before you take your boards. They're likely to want you to know this, and it comes up a lot for patients who have intracranial hemorrhage with anticoagulation, especially as the novel or direct oral anticoagulants become more and more popular. Any questions about this? I have a quick question. Yes. Obviously, if someone's heparin, or heparin stop, and protamine, what are the last steps to counter that dose of protamine? If someone in a low-molecular weight heparin, do you have any good reversal agent for that? So if I understand the question, the question is, how do you reverse low-molecule heparin? The answer is, it depends upon the time from the last dose. The long after 6 to 12 hours, protamine has no benefit. If it's within 6 to 12 hours, your pharmacy probably has a protocol that goes to the dose and how much they should give. In general, for DVT chemoprophylaxis doses of 40 once a day, you typically don't reverse them because within a few hours, the dose is gone. For therapeutic anticoagulation of MIG, Brachig, low-molecular weight heparin, you typically will give protamine for those patients. Its effectiveness is not well-established. It is not completely effective, but is probably better than nothing. Make sense? The best test question, I'm not giving anything away, would be if a patient has intracranial has a severe bleeding complication while on an unfractionated heparin drip, protamine would clearly be the best reversal agent there. Does that make sense? Any questions about this case? So these do not have the audience response system, but we'll go through them. So a patient presents with sudden left-sided weakness for 90 minutes. There's a history of atrial fibrillation treated with a PIXABAND. The CT of the head reveals a small hemorrhage in the right frontal lobe. Which of the following is the most appropriate intervention? So ICH on a PIXABAND, the answer is ICH on a PIXABAND. So the best answer would be D. If you don't have D, A isn't terrible. If you don't have a PIXABAND and you can't get it, a prothrombin complex concentrate isn't the best answer, but that would be a reasonable thing to do. Fresh rose and plasma is not worthless, but is not the correct answer. It is clearly not as good as prothrombin complex concentrates or indexin alpha. Patients are more likely to have more bleeding, longer time to normalization of the INR, and the outcome will be worse. Alteplase is a distractor. If you just looked at this and said something neurologic, give TPA, that would be the exact worst thing to do. Don't do that. And cryoprecipitate has a lot of fibrinogen, factor VIII. That would be the answer if someone had bleeding from TPA. Cryoprecipitate would be an appropriate treatment there, but is not the appropriate treatment for a PIXABAND-related ICH, which impacts factor X, not cryo and factor VIII, not fibrinogen and factor VIII. A 55-year-old patient presents with three hours of left-sided weakness. His systolic blood pressure is 190. CT of the brain reveals an acute right frontal hemorrhage. Which of the following is the most appropriate systolic blood pressure goal for treatment? Any guesses? Any other guesses? 140, 140 going once, 140 going twice. In multiple prospective randomized clinical trials, 140 is the best answer. For patients who present with systolic greater than 180 or 180 to 220, rapidly lowering the blood pressure to systolic 140 leads to better outcomes. Some patients have less hematoma expansion. That is inconsistent in clinical trials. You see it more in patients who present earlier and patients who have more rapid titration blood pressure to goal. There was a prospective randomized trial of 140 versus 120. Patients who were randomized to 120 had no benefit and higher incidence of side effects, particularly acute kidney injury. So 140 is the best answer. Patient noticed this patient has a blood pressure of 190. When patients have a blood pressure of greater than 220, they were typically excluded from the trials of rapid blood pressure reduction. No one is quite sure what to do with those patients. This is one of these things where you ask four neurologists, you'll get five opinions. Most people will lower their blood pressure by 25% or so, not evidence-based, no prospective randomized trial to support that, highly unlikely to show up on a standardized test. But this sort of question for patients presenting systolic between 180 and 220 is a very fair game. And all these references are at least five years old by now. In general, they might ask, you could be, but probably won't be asked what the optimal blood pressure titration agent will be. Most of these trials have used nicartapine as the first-line agent. But in many trials, especially those worldwide, a wide variety of agents have been used and is often left up to the local investigator. And so you see everything from vasodilators to diuretics to beta blockers. Mostly in the United States, we use nicartapine. It's widely available, easy to titrate, and has a half-life that's compatible with an ICU nurse workflow, meaning that its half-life is something like, it takes about 40 minutes to reach its new steady state, which works well if you're going every hour or so vital signs. Something like clovetapine, which has a half-life in minutes, you need someone to sit there and titrate it, which doesn't work as well in the ICU and probably doesn't benefit a disease like ICH, but might be really helpful, say, in the operating room. In general, for patients who have anticoagulation who present with anything vaguely sounding neurologic, they should get a CT. CTs are most likely to show new hemorrhage in patients who have new focal findings, a new headache, altered consciousness. So people who are on a Pixaban and bump their head getting off the train have a low threshold for getting a screening CT in those patients. If the patient is non-communicative, you often can't tell if the patient's taking a direct oral anticoagulant with the INR. Dabigatran and Pixaban and Rivaroxaban often do nothing to the INR, and so you need other ancillary tests to see if the patient is taking another anticoagulant. Your hospital may have a protocol for this. Various hospitals will use Thrombin, Thyme, Tag, or Rotem to find patients that have severe deficiencies in coagulation. Those are harder to interpret, more complicated, or less likely to show up on a standardized test in your uncomfortably near future, but you should be aware of them that there are other ways to find patients on direct oral anticoagulants. Rivaroxaban and Pixaban, remember, are factor X antagonists, and factor Xa levels are generally now widely available. So you might get that as a hint. There are some risks to reversal of anticoagulation. Neurothrombin complex concentrates are potentially thrombogenic. In general, for patients who have blood and head anticoagulation, benefits strongly outweigh the risks. There are a couple of times when the risk-benefit ratio is less certain. So patients on a left ventricular assist device, patients who are on ECMO, patients with a mechanical valve, patients with a known left atrial thrombus are at higher risk for thrombosis and severe ischemic stroke as a consequence of getting a prothrombin complex concentrate or some other procoagulant drug. Those are more challenging cases. They tend not to make great test questions because there's lots of ways to argue them one way or the other. But something might show up along the lines of, which of these patients would be at, say, the highest risk for an ischemic complication of reversing anticoagulation? Something like a mechanical valve with a visible thrombus would be a hint. We talked about the choice of agents for reversal. I showed you that summary slide before from American Heart. Again, that's for spontaneous ICH. I'm not aware of guidelines on that for trauma. They'll probably be similar. Notice none of these included recombinant activated factor VII, which is not indicated for any of these. There is a clinical trial of factor VII for acute spontaneous ICH within two hours through the NIH Stroke Trials Network called FASTEST. Full disclosure, I'm the protocol PI for that trial. That trial is ongoing. No one is using factor VII outside of that trial, to my knowledge, for brain hemorrhage. If you don't know who your ICU pharmacist is and you really want to meet that person, start ordering factor VII. They'll find you and come talk to you about it. It's $10,000 or $20,000 a pop. In general, patients with intracranial hemorrhage should be monitored in an ICU setting for repeated neuro exams, repeated scanning, because the risk of hematoma expansion is high. In general, it makes more sense to move patients from an ICU setting when you know that hematoma expansion is not occurring, typically with two stable CT scans, four to six hours apart. Any questions about that? Make sense? Okay. Is there any indication for nimodipine in traumatic subarachnoid hemorrhage? I'm sorry. I couldn't see who was talking. I couldn't quite hear. Yes, sir. Is there any indication for nimodipine in traumatic subarachnoid hemorrhage? The question is, do we use nimodipine for traumatic subarachnoid hemorrhage? Long story short, the answer is no. It doesn't work for that. There's no good prospective randomized clinical trials to show that it works. It's not FDA approved for that. It's really expensive. Don't do that. That being said, there are some clinicians who will do that. In general, with traumatic subarachnoid hemorrhage, the blood is on the surface of the brain, as opposed to when you get vasospasm, you have to have blood near in the sylveon fissure, where the blood vessel is, and you have this large amount of blood right next to the blood vessel that triggers an inflammatory cascade, which then leads to proliferation of the media of the vessel, and ends up leading to constriction of the lumen, which is not really spasm, but that's what we called it, because that's what it looked like in angiography 40 years ago. You actually can prevent vasospasm with types of monoclonal anti-inflammatories that prevent white blood cell chemotaxis. Javier Provencio at UVA has a lab where he's done exactly that. You have a model of subarachnoid hemorrhage, you give an antibody that prevents white cells from going there, and vasospasm is effectively prevented. In general, the literature shows that nimodipine for traumatic subarachnoid hemorrhage is of no benefit. In general, that is not evidence-based. You may see someone do it. Can you comment about the seizure prophylaxis in ICH? So the question is, what do you do with seizure prophylaxis in ICH? Full disclosure, we published a bunch of this and we had funding to do this. In general, so about 15 years ago, the guideline recommendation was that in view that seizures are bad and potentially preventable with seizure medication, every patient with spontaneous ventrible hemorrhage should get a month's worth of phenytoin starting intravenously. The start to the story is actually Nancy Temkin's study in the New England Journal in the 90s where they gave prophylactic phenytoin or not to patients with severe traumatic brain injury, which was a Glasgow Coma Scale of 10 or less depressed skull fracture or contusion. In those patients, patients who got prophylactic phenytoin were less likely to have a seizure in the first week, but not later seizures. Nothing in the paper about outcomes or complications. And from there, it spread to everybody with blood in the head should get prophylactic seizure medications. Full disclosure, I did a lot of this. When I was a fellow at Columbia, we looked at the subarachnoid hemorrhage outcomes database. We found that the more phenytoin patients got, the more fever they had, the more complications they had, and the worse their cognitive function. In ICH, we found the same thing about five years later. More phenytoin led to more fever, led to worse functional outcomes in multivariate models, and this led to a change in guidelines for both ICH and SH saying, don't get prophylactic phenytoin. The world, of course, switched to levotiracetam about 10 years ago. Levotiracetam is associated with worse cognitive function, even though it is safer than phenytoin. It doesn't seem to make patients febrile. It doesn't have the same complications, but the side effects of levotiracetam are, as you might expect in the package insert, mostly neurocognitive. And if you measure cognitive function quality of life at follow-up, you'll find that patients who get levotiracetam prophylactically independently have about a half a standard deviation worse cognitive function. Full disclosure, our group got a grant for this in the papers in critical care medicine. Full disclosure, reviewer two is convinced that levotiracetam is neuroprotective in animal models of TBI. I'm not sure who reviewer two was, although I have my ideas. I'm pretty sure it's somebody at Pittsburgh. There are other clinical studies ongoing as to whether or not seizure medications might be neuroprotective in patients with severe TBI. My understanding is the jury is still out on that. The guidelines for ICH and SH say you should not give prophylactic seizure meds. You don't prevent that many seizures, and there are clear side effects. There was a paper in Lancet Neurology last month that suggested levotiracetam might be of benefit in patients at high risk for seizures. Small study, 50 patients, imbalanced at baseline. We'll see what people do. Full disclosure, I tried to get the NIH to fund a trial of this a couple years ago. We didn't get through the StrokeNet process, so it didn't get funded. The short, long story short, guidelines say don't do that this year. In high risk patients like with mechanical valve and LVAD, when do you start putting them back on anticoagulation? The question is in patients who have a risk, who have a hemorrhage, but are at high risk for recurrent ischemic events like an LVAD, when do they go back in anticoagulation? This is one of those questions where you ask three neurologists, you'll get five opinions. The American Heart Guidelines really hem and haw about this, and they leave you with the very reasonable but not particularly helpful advice of consider the individual as risks and benefits. Most people will give an answer of between one to four weeks, where one week is reserved for patients at high risk and a month or two for patients who are at somewhat lower risk. Not super evidence-based, doesn't make a great test question, not settled clinical medicine. Most people will disagree. It's a tough one. Dr. Pistoris? I know the guidelines were written for inter-brain, but do you follow the same general guidelines for stuff going on in the brain? So the question is, if we have well-established well-referenced guidelines for spontaneous ICH, can you also port those over to traumatic brain injury? That seems reasonable to me, but I've learned that the people who trauma are very, very different than the people who do spontaneous intracranial hemorrhage. They don't talk to each other very much, they tend not to have a very high opinion of each other's literature, and they don't want to adopt somebody else's guidelines. This goes along with some papers in Science and Nature recently that people who try to go from one field to another are typically punished for it, as you try to do more integrative team science. People tend to like their own thing, and we have found that when porting stuff. That seems to be the case in ICH and TBI as well. I think that's reasonable. In the case I showed you here, where this patient was taking a pixaban, had a small subdural, and the group decided to watchfully wait, that was a bad call, it's generally a bad call. I personally would have given this up. And then they gave the wrong reversal agent, it was also not a great call. If you asked me, the patient should have gotten index and alpha at the time this scan was done. That would have been the correct thing to do. Not class one evidence based, but that would have been the appropriate, that would have been the, if there were a test question like this, I didn't write one, but if there were one, and you saw a scan like this, and the patient on a pixaban, I would think the best answer would be to give this patient index and alpha. Other questions about this? Yes, sir. Can you talk about the use of anti-10A for the oral anticoagulants? Can you talk about that a little bit more? I'm sorry, can I what? Can you just talk about kind of how you would use anti-10A for the direct oral anticoagulants? The question is, do you use anti-10A levels the way you might use, say, INR for warfarin? The short answer is that part of the claim to fame of the direct oral anticoagulants is that you don't have to check labs. And so to my knowledge, it's not standard of care to check them for a therapeutic response. It's intuitive that more intense anticoagulation would lead to a higher rate of complications. I've not seen that published anywhere. You can use these. Anti-10A levels have become more commonly available in hospital labs in the way that we've all sort of gotten away from PTTs and moved to anti-10A levels. Does anyone's hospital still use PTTs for dosing heparin? A couple do. Who's using anti-10As for heparin dosing? A couple. So at my hospital, we can't get PTTs anymore. We haven't been able to for a couple years. We can only get heparin anti-10As. And so we ended up with this suite of anti-10A levels. And it's not our protocol to check them, but we just see them popping up in the labs. And they seem to correlate with the intensity. And I put it here as illustrative, but it's not standard of care. This is just illustrative. I simply meant it here to be illustrative of this is a biomarker of coagulation. And when you do something that should make the patient less anticoagulated, the labs seem to follow along. Full disclosure, we did a whole thing with platelet activity assays and spontaneous ICH. Of course, we have another award, but that's a whole other topic that I won't bore you with today. Other questions about this? Thank you all for your time and attention. So, we were fairly worried that we weren't going to make it through all of the questions. And as you can see, we did. We set aside, we have a couple of bonus scenarios, which if it's okay with you, we'll go through the bonus scenarios and then we'll be done. So we will probably finish up a little bit early, but we did write a couple more questions just to, again, we thought that we weren't going to get through them. And so, we appreciate everybody's forbearance and we will see if we can set up the bonus questions. So, scenario has a 68-year-old with hypertension, presenting with fever, nausea, vomiting, and confusion. She's febrile, has a not elevated or low blood pressure, tachypneic, and has a SAT of 92 on room air. She's disoriented, has right CVA tenderness, and has a white count of 22 of creatinine, that's 2.3, and greater than 50 white cells per field on urine microscopy. And she has some right perinephric stranding, but no stones. She started on antibiotics and admitted to the ICU. And just to highlight a couple of things, even though she's not hypotensive, she's confused and has a creatinine of 2, so she's got organ failure and an infection or sepsis. So which of the following statements about this patient's acute kidney injury is most correct? It's due to ATN as a result of decreased blood flow. It's unlikely to be attributable to sepsis because she doesn't meet the current consensus definition of sepsis. Her AKI is unlikely to be attributable to sepsis due to a normal blood pressure. The patient's AKI puts her at an increased risk for secondary infections during her hospitalization. Given her stage 3 AKI in the setting of sepsis, she'd likely benefit from preemptive renal replacement therapy before the development of an urgent indication. So this is a scenario, so we don't have the audience response. What do people think? A couple. A couple more? Yeah. How about heat? And the rest? Yeah. So as I alluded to in the scenario, the patient does meet sepsis criteria, infection, organ failure, and while you can't quantify it, it's still a syndrome rather than a disease and there's no biomarker. For sepsis 3, if your SOFA score goes up by more than 2, that would be considered to be organ failure. And a creatinine of 2.3 gives you 2 SOFA points, and confusion probably gives you a couple more. A normal blood pressure doesn't rule out sepsis, and given that the blood pressure is normal, while flow and blood pressure probably don't mean the same thing, A is likely not correct. So one of the things about sepsis is that if you get it, you're likely to get it again. You're likely to be readmitted to the hospital, either for sepsis or cardiac issues. And the other thing about sepsis is that if you do develop acute kidney injury, you are more likely to get a run into another infection. So here's the rationale. Acute kidney injury is common. It's especially common if you develop a septic shock. And it is the most frequent cause of kidney injury in the ICU. If your kidneys fail, like any other organ, the more organs that go down, the more likely you are to die. And there is a prospective cohort study, the Picard study, that followed about 600 patients with sepsis and acute kidney injury, and they were likely to develop a reinfection. So just like sepsis is likely to put you at risk for developing another event of sepsis after you have it, sepsis and acute kidney injury probably puts you at higher risk. Whether that's due to problems with the host defense system or the fact that you've got an additional catheter in that puts you at risk for infections probably isn't clear. Jad, any, would you add anything to this? Okay. So in the same patient, her creatinine goes up to 4.5. Urine output remains adequate and matches her input. Her mean arterial pressure is 80. She's got a normal pH, and her K is okay. Which of the following statements is correct about potential treatment options? Firstly, renal replacement therapy has been shown to improve mortality in sepsis with acute kidney injury. The serum bicarbonate infusion has been shown in patients with acute kidney injury to shorten length of ICU stay. The use of diuretics in kidney injury has been shown to improve mortality. Low dose dopamine is useful here to prevent worsening kidney injury. And E, in the absence of an urgent indication for renal replacement therapy, careful monitoring is the best approach. We are selecting A, B, C, D, E, I see D, E, how many Es? Yeah. Okay. Everybody. And that is the correct answer. And now there are three large studies, one of them specifically in sepsis patients showing that early RRT, the only thing that it does successfully is make it more likely that the patient's going to be exposed to renal replacement therapy while they're in the hospital. If you start it early, again, you're going to need to put in a catheter and you're more likely to, you're actually more likely in two of the three studies to be on dialysis a month out. So you're more likely to be exposed to it, you're not going to improve mortality, you're more likely to have complications, and so it's probably not a good idea. And this is, I guess, the challenge that we all face in taking care of critically ill patients. You think that something would make sense, that you'd remove bad humors, that you'd remove volume, you'd keep your, you know, you'd get the patient better. But when we test it formally, it turns out not to be the case. And again, the Akiki study looked at it and there was really no difference in the primary outcome measures, and most of the patients in the delayed group did not require dialysis. And the more recent trial, and this had about 3,000 patients in the New England Journal, and again, there's no difference in primary outcome measure at 90-day mortality, and those who were randomized to early dialysis were more likely to be on dialysis at 90 days. So it makes sense, but it doesn't work. Any role of high-dose lube diuretic and metolazone combination to try to improve that ATN? And did it show any improved recovery? Yeah, so that's a great question. There's an older study, it's probably 20 years old, that showed that if you give diuretics before you call a nephrologist, rather than calling the nephrologist up front, that the patients do worse. What that means probably is that patients who get diuretics and don't get better, because if you gave diuretics and they did get better, you wouldn't call a nephrologist. So this is probably a case of selection bias, and that's the only study that I'm aware of. This is like after we hydrate them and they have overcome the sepsis, and they're adequately hydrated, and now they are fluid overloaded, and they're developing crackles and all that. I mean, of course, you said there is adequate urine output, but I was just wondering if using the diuretics at that stage would expedite the recovery. So there are a number of observational studies that show that fluid balance while you're in the ICU is associated with outcome. So it makes perfect sense that patients, or it would make sense that if you gave diuretics to prevent fluid overload, that patients would do better. In the absence outside of the FACT fluid trial, which was done in patients with lung injury who were not in shock, which showed that if you diurese people aiming for a CVP less than four or a wedge pressure less than 12 or 11, forgive me, I don't remember the number because we don't put in many PA catheters anymore. But you get people off the vent two and a half days faster without changing mortality. So that's the only study that I'm aware of that shows that diuresing patients, and they didn't have kidney injury here, and giving the diuretics didn't make kidney injury worse. And it actually, it made it, there was a trend, if you believe trends, towards not requiring renal replacement therapy in those who were given diuretics. Would you add anything, Steve? I think the point that I know sometimes happens is during the de-escalation phase of the resuscitation, somebody that's remaining on the ventilator who may be in very positive fluid balance, there is a role for diuresing the patient to maybe expedite or get them off the ventilator sooner. And that's assuming they don't have, you know, moderate or severe kidney injury. But if they do, oftentimes the reverse also happens where the nephrology team may actually suggest try escalating doses of loop diuretics first. And if they don't respond, okay, we'll agree to dialyzing the patient. So that sometimes happens. I know it happens at my place. I feel sometimes that that's just a delaying strategy, but it's hard to argue when early or more urgent RRT also makes a difference. And so it's sort of like, okay, maybe we'll try the diuretics first at escalating doses, you know, 60, 120, 200, IV infusion, of course. But many times if the patient is just progressing with the acute kidney injury, it's inevitable that they're going to wind up requiring, you know, CBVH or CBVHD, depending on how bad the electrolytes are. But oftentimes these are decisions in the battlefield that you just have to navigate. So there is role for diuretics in the de-escalation phase of resuscitation and somebody without severe acute injury, if you're trying to get them off the ventilator, keeping the fluid balance on the conservative side and maybe even negative, you know, after a few days is always a good strategy. Of course, staying away from making them hypotensive to try to get them off the ventilator, but even that strategy has not been definitively shown to improve mortality, but it gets them off the ventilator quicker. And of course, that's always something that you would want to achieve anyway, since many patients with sepsis, septic shock, they die from other causes eventually, but at least early on, your goal should be to try to get them ventilator free as quickly as possible. So in that setting, diuretics may also have a role. Thank you. This is an extraordinarily important clinical situation, when to give diuretics, but it's mostly a data-free zone in that there are not trials to inform the decision. So I doubt that you'll be asked something about this. Many people now are concentrating on giving less fluid during the initial resuscitation, and there was the English trial, which acronym I don't remember, that was published earlier this year, comparing less resuscitation with the usual 30 cc's per kilogram of fluids in sepsis, and there was no difference in outcomes. And then the Pedal Networks trial is close to being published, but is not, on the limited versus aggressive fluid resuscitation, and that I think will add some more information. But many people are not giving as much fluid as people did 20 or 30 years ago in the initial resuscitation, especially after day zero. The other relatively common scenario is this idea of giving metolazone, and the idea there is because it acts on the proximal tubules, okay, you're kind of promoting forward flow, and then the Lasix acts on the distal loop of Henle, and so you're kind of maybe having a dual effect. Another strategy might be swap out the Lasix to Bumex, so that's also done, maybe that's more potent. But a lot of these diuretic strategies really are very stylistic and have not been definitively or conclusively have indicated, at least in the limited trials to date, most of them are observational, small studies to suggest that strategy helps. But outside of the FACT trial that Dr. Sivransky mentioned, where conservative fluid strategy works in getting the patient off the ventilator, it gets them weaned faster. But I think in terms of mortality outcome, it doesn't seem to pan out. It's always something that I think, at least in practice, we try to adhere to, but I think for the board examination, they really only want something that's concrete, evidence-based, guideline-based, rather than more controversial or stylistic type questions. And I'll ask Dr. Patel to weigh in as well. So two things. One, there is, I think, going probably nearly two decades ago, there was a study that looked at using Lasix and changing patients from oligurek ATN to polyurek ATN. And that did not show any improvement in AKI. There is evidence that essentially shows that you can get these patients off the ventilator faster, but there is no evidence that there is an improvement in AKI recovery. Will make your urine output look better. So it's one of the ways to prevent these patients from going on dialysis. What we do know is, as we showed in the AKI study, or the AKIKI study, once they go on dialysis, their recovery is definite. They tend to stay on dialysis. So your goal is to not put these patients on dialysis. And the indication for going to dialysis is refractory hypervolemia and refractory hyperkalemia. So you use the Lasix, and you use progressively higher doses of Lasix to prevent them from going into AKI. The Lasix and metolazone combination is mostly used in cardio renal syndromes. So if you have an AKI because of increased preload or renal venous hypertension because of just backflow or RV failure, those patients you tend to use metolazone Lasix combination more. It's generally not something that is used in AKI because of septic shock or an ATN from an underlying sepsis or drug-associated ATN. So we have now successfully made it through the bonus questions. So you have successfully completed the interactive sessions. I'd like to thank everybody for their attention and their questions. So one of the things we know to do when we do this again is to have more bonus questions in case we finish early. But as we've mentioned before, this is the first time we've done it this way. So if you have ways to improve the interaction, to improve this, if there are things we should do differently, we would really welcome your opinion about how to make this better. So thank you. What else do we need to – you heard about how to get CMEs. Are there any other issues? No. We want to make sure you had a good time and that this was very educational. Good luck with your respective board examinations. I know some of you might be taking it in a few weeks, others probably taking it later this fall in November. So all the best. And we really would appreciate your feedback about this format as we move forward to try to do the same course at three other sites, Orlando, New Jersey, and Los Angeles in the coming weeks. So thank you so much for your attention and time, and safe travels back home. Take care.

66-year-old woman

parietal subdural hematoma

apixaban

anti-10A level

prothrombin complex concentrate

intracranial hemorrhage

direct oral anticoagulants

reversal agent