First Critical Care Congress. I'm Neha Dangaich, I'm a Neurointensivist, the Systems Director for Neuroemergencies Management and Transfers, Research Director for Neurocritical Care and Recovery at the Icahn School of Medicine at Mount Sinai. I have no relevant disclosures. We're gonna talk about time is brain, the need for parallel processing and staying up to date with evidence in stroke care, and specifically stop that bleeding brain. For hemorrhagic stroke, subarachnoid hemorrhage and intracerebral hemorrhage account for about 15% of all strokes. In both of these stroke subtypes, rapid recognition of the underlying primary neurological injury, both recognition and prevention and treatment of secondary neurological injury can lead to improvement in outcomes. ABC, like all emergencies, is always going to come first. We'll talk more about blood pressure control, reversal of underlying coagulopathies, diagnostic imaging, and some neurosurgical considerations. Just a few key things to keep in mind, distinguishing between SAH and ICH. SAH tends to occur in younger patients, ICH varies depending upon the underlying etiology. And blood pressure goals before an aneurysm is secured, perhaps an SVP goal of less than 140 would be appropriate. In ICH patients, we'll talk more about this, SVP goal of about 140 to 160 should be appropriate. ICP management in both of these stroke subtypes is going to be similar, and neurosurgical consultations right from EVD for CSF diversion, as well as monitoring, craniotomy, and we'll talk about some minimally invasive evacuation techniques for ICH. Good critical care practices, multidisciplinary team management, on a case-by-case basis, deciding about whether you really need to use seizure prophylaxis, or when somebody's seizing clinically, treating their underlying seizures, and appropriate glycemic control. For spontaneous ICH, the most common cause is hypertension, about 80% of these bleeds will be deep, about 20% of these bleeds will be low-bar. Thalamus, cerebellum, pons, and basal ganglia tend to be the most common locations. For low-bar ICH, the context really matters. It matters who the patient is. For example, you could see a low-bar ICH in a peripartum patient, and that should raise your suspicion for sinus venous thrombosis. If you see a low-bar ICH in a patient who's had cognitive decline over the past few weeks to months, then you should think about cerebral amyloidosis. If there's a history of underlying malignancy, you should think about the possibility of a hemorrhagic metastatic lesion. So all of those things, depending upon the context, will help you decide what the underlying etiology may be. In a younger patient who has a low-bar ICH, there are scores, for example, the secondary ICH score that may help us identify which patients are going to need a cerebral angiography, and whether there is a risk of having an underlying vascular malformation or not, such as an ABM or a dural AV fistula. Just a quick recap of how do you calculate the volume of an ICH. So this has both implications for overall prognostication, as well as guiding management in the acute phase. So thinking of the ICH volume of a spontaneous ICH is similar to the volume of an ellipsoid. Here's a formula, ABC upon two. About a third of ICH patients will experience hematoma expansion within the first three hours. So it's very important to prevent early deterioration and hematoma expansion. And almost 20% of these patients are going to deteriorate within the first few hours after hospital arrival. So what can we do to prevent hematoma expansion? So first, let's take a look at blood pressure targets. So quick look at ATAC and INTERACT, two large multicenter randomized controlled clinical trials ATAC conducted in North America and INTERACT, predominantly European. Trials, neither of them showed differences in death or disability. However, the risk of developing AKI was higher in patients who were enrolled in the intensive SPP arm of ATAC2. What medications are you going to use? These are some possible drips that you can consider, nicardipine, clevidipine, labetalol. But my suggestion would be to avoid sodium nitroprusside or nitroglycerine. And oral agents, as you're titrating these drips off, could be ACE inhibitors, beta blockers, or calcium channel blockers. For patients who have hemorrhagic stroke with underlying coagulopathy, let's spend a little bit of time thinking about what's going to happen to these patients. So with this patient who has an underlying coagulopathy, where is this coagulopathy coming from? So the incidence of ICH ranges from about 0.3 to about 0.6% in patients who are taking oral anticoagulation. And in patients who are taking direct oral anticoagulation agents, the risk may be between 0.1 to 0.2%. Overall, we know that the incidence of ICH has remained stable in the United States, but with the increasing incidence of AFib, with the increasing proportion of our older patient population, with the increasing incidence of DVTs, PEs, the use of the vitamin K antagonists or DOACs is going to continue to increase. This predisposes to an increase in the incidence of anticoagulant-related bleeds. So how do we begin to think about the different reasons for antithrombotic-related bleeds? So the VKAs, vitamin K antagonists and DOACs, and then you have the COX-1 inhibitors, the P2Y12 or ADP receptor antagonists, maybe some antiplatelet activity with SSRIs and PDE inhibitors. So I won't focus a lot on antiplatelets. Let's talk more about how to reverse coagulopathy from vitamin K antagonists, as well as DOACs. So when we look at the major bleeding rates for vitamin K antagonists versus target-specific oral anticoagulant therapies, we know, here's a zoomed-in look from the systematic review. So we know that the risk of major bleeding is lower with target-specific oral anticoagulant therapy as compared to vitamin K antagonists. So first let's talk about how to approach vitamin K-related ICH. So stop the VKA, but you also need to know what is the underlying reason for which a patient was on a VKA-like warfarin. Vitamin K, preferably using intravenous dosing, 10 milligrams, followed by, depending upon what the INR is, using an additional one to two doses thereafter. Additional agents that must be considered should we reverse this patient with FFP or PCC, prothrombin complex concentrate. So in this study that included about 1,400 patients, they were found to have certain risk factors associated with the oral anticoagulant-related ICH. For example, having underlying seborrheic microbleeds or diabetes mellitus. We know that coagulopathy with an oral anticoagulant is an independent risk factor for mortality as well as poor functional outcome. And failure to reverse INR within the first two hours is an independent predictor of morbidity and mortality. Thus, reversing coagulopathy really helps us uphold timer's brain. So how do we choose the right VKA reversal agent? So just a quick recap. So here are our choices, FFP or PCC. Different types of PCC, three-factor PCCs, four-factor PCCs. How much of the two, seven, nine, 10, or the extrinsic pathway clotting factors are available in these helps distinguish between these different types of products. Specifically in K-centra as well as in Bebulen, which is a three-factor PCC, and K-centra, which is a four-factor PCC, we know that they're going to contain heparin as well as protein CNS and antithrombin. Other products such as NOVA7 is activated factor VII, FIBA is activated factor VII, and inactivated II, IX, and X. So PCC versus FFP, what should we choose? So in this study that included over 200 patients, so essentially looking at pre-infusion and then how rapidly, so within the first 30 minutes, how rapidly PCC was able to reverse INR. So although there was no difference in the excellent and good outcomes, INR reversal was much better with four-factor PCC. So superiority of four-factor PCC was confirmed and no difference in thrombosis. Specific differences between the use of four-factor PCC and FFP, rate of administration fast, FFP will take hours, large volume will need to be administered, for example, 15 to 20 cc per kg of FFP, time for preparation, minutes, FFP may take up to 40 minutes or so. And overall, the risk of volume overload, trolley, taco, et cetera, much more with FFP. Cost, FFP much cheaper as compared to K-Cetra. What about Innexa? So specifically thinking about medications that are factor Xa inhibitor reversal agents. So in Innexa 4, that specifically looked at anti-factor Xa activity. At the end of the infusion, we're still seeing no anti-factor Xa activity, but this activity begins to reappear at four hours, eight hours, 12 hours, both for patients who received it for reversing the effects of apixaban as well as rivaroxaban. And what is even more important is the cost associated with low dose and high dose. So is hemostatic efficacy equal to good clinical outcomes? The simple answer is perhaps not. So in Innexa 4, that included about 137 patients, the biomarker use was anti-DENI, and I just showed you how this biomarker was tracked in reverse AD that specifically looked at PraxBind or the reversal agent for dabigatran. Again, a really good biomarker reversal. This study that we just discussed comparing FFP versus four-factor PCC, again, we clearly see superiority of four-factor PCC for vitamin K antagonists. And in upright, looking at four-factor PCC for patients who are on DOACs, we are seeing some excellent to good outcomes, but in some ways comparable to what we see for four-factor PCC and Coumadin. Cost effectiveness, this is a challenge. When you look at these numbers, this do give us pause. For either RootCC-MAP, it's a little over 5,000, and Dexanet, like I showed you, very costly. And four-factor PCC, again, more costly as compared to using FFP. Then what about antiplatelet agents? So there are various proposed medical therapies that do need to be studied in prospective evaluation in human studies. DDA-VP, while the 2016 guidelines from the Neurocritical Care Society recommended 0.3 micrograms per kg of DDA-VP in patients who are getting antiplatelets and need to undergo neurosurgical procedures, this is questionable, particularly with some recent studies. The utility has been brought into question. The PATCH trial only included patients who were on Cox inhibitors. And this study showed that the administration of platelets is not without risk in patients who have ICH. But this may not be generalizable to patients who are undertaking P2Y12 inhibitors. And overall, the odds of death and dependence was higher at three months in patients who received platelets. This is a summary for different agents from the 2016 Neurocritical Care Society guidelines, very comprehensive guidelines. And again, they do recommend DDA-VP, particularly for patients who will be undergoing neurosurgical procedures. So what about some neurosurgical options? Any patient who has a cerebellar ICH of more than or equal to three centimeters in any diameter, you should discuss, before presenting surgery as an option, discuss with your neurosurgical colleagues whether you are in agreement with offering surgery to this patient based on their baseline functional characteristics and timing of presentation. But this can be a truly life-saving and quality of life-adding surgery. EVD for CSF diversion, as well as for measuring ICP. For patients with lobar or deep ICH, there are a few different options, including should they undergo open craniotomy and evacuation? So stitch one and stitch two both evaluated this question. And in stitch one, perhaps superficial hemorrhages, those within one centimeter of the cortical surface, were thought to benefit from surgical intervention. In stitch two, favorable outcomes were seen in both groups. So in essence, no difference in outcomes in both the control and the surgical arm. And decompressive craniotomy, about a third of these patients, appropriately selected patients, will have favorable neurosurgical outcomes. So identifying who's at risk of developing hematoma expansion radiologically. CBA should be equal to CTA. So using that paradigm of early rapid neurological imaging, make sure that you also get a CTA of the head and neck, irrespective of whether you're suspecting an acute ischemic stroke or a hemorrhagic stroke. If you're able to get an MRI in the same time period, and as rapidly as you would be able to get a CT head and CTA, then you could, the American Heart Association recommends you could opt for an MRI. The question arises, when somebody has a spot sign or not, should you attempt to remove this blood? How should you remove blood? And when should you remove it? So there are some pharmacological catheter-based therapies. There are some mechanical therapies, lots of different types of minimally invasive evacuation therapies. I'll talk a little bit about SCUBA, which is a stereotactic ICH underwater blood aspiration technique, as well as MISTI, which is stereotactic aspiration with thrombolytic agents and clot lysis using TPA. So MISTI, which is a landmark randomized controlled clinical trial, looked at stereotactically guided thrombolysis, and up to nine doses of one milligram of TPA were given. And in patients who had less than 15 cc's of residual hematoma, they did have good outcomes, but specifically looking at MISTI versus standard medical care, there was no difference in functional outcomes. For SCUBA, in this technique, this procedure is performed in the cerebrovascular angiography suite. And here's a scope that's used for, a type of scope that's used for minimally invasive clot evacuation. From our single center experience, where we started cohorting and triaging the care of all of our ICH patients at a single center, we found that SCUBA, a centralization of the inter-hospital transfer process, can improve access to normal therapies, such as SCUBA. Time is brain, and what we found was the odds from time to evacuation suggest that for each additional hour, there was a 5% reduction in the odds of achieving a favorable outcome. So the faster this clot is evacuated, the better the outcomes. So in summary, time is brain for ICH. Using the principles of rapid diagnosis and treatment of the underlying primary neurological injury, prevention of secondary neurological injury, preventing early hematoma expansion by targeted blood pressure control, reversal of underlying coagulopathy, and appropriate diagnostic image. For example, CT head along with vascular imaging CT of the head and neck, and consulting with your neurosurgical colleagues can not only save lives, but also improve outcomes. So with that, I'd like to say thank you for your attention, and I look forward to taking your questions.

hemorrhagic stroke

subarachnoid hemorrhage

intracerebral hemorrhage

neurological injuries

multidisciplinary team management