Narrator - Dr. Abel 00:00 Welcome to HelixTalk, an educational podcast for healthcare students and providers, covering real life clinical pearls, professional pharmacy topics and drug therapy discussions. Narrator - ? 00:11 This podcast is provided by pharmacists and faculty members at Rosalind Franklin University, College of Pharmacy. Narrator - Dr. Abel 00:17 This podcast contains general information for educational purposes only. This is not professional advice, and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - ? 00:27 And now on to the show. Dr. Sean Kane 00:31 Welcome to HelixTalk episode 134 I'm your co host, Dr. Kane, and I'm Dr. Patel, and the title of today's episode is hypertensive emergencies, demystified a brief clinical review. So today we're talking about the diagnostic criteria definitions and general treatment approach for patients with hypertensive emergencies. Dr. Khyati Patel 00:51 So Dr. Kane, for a topic like this, I know you spice up things by giving us a case, so let's hear it. Sure. Dr. Sean Kane 00:59 So this is kind of a typical patient that I would see in the ICU setting with hypertensive emergency. So this is a 55 year old male who came in with stroke symptoms. So he has right sided facial droop, right sided arm and leg weakness, sort of speech, and they say, Yep, he has an acute ischemic stroke. Unfortunately, his last known normal time was 12 hours ago. So he's outside of our typical TPA window, or alteplase window of three to four and a half hours today. His blood pressure is 260 over 150 millimeters of mercury, and his heart rate is tachycardic at 110 beats per minute. So given that sky high blood pressure, clearly the next question is going to be, what is the most appropriate approach to treat that patient's hypertension? Dr. Khyati Patel 01:45 And Dr. Kane, this is definitely your alley, because my eye just went a little bit wide. We're looking at that blood pressure number, but I'm sure it's very common for a patient to present with something like this when they have true hypertensive emergency, absolutely. Dr. Sean Kane 01:58 And you know, I think probably the best way to get started is definitions, because this is one of those areas where people get confused about what constitutes a hypertensive emergency versus urgency or crisis and things like that. So why don't we go through that just so we're all on the same page in terms of what exactly hypertensive emergency is, which is the focus of today's episode. Dr. Khyati Patel 02:20 We drive this differences. You know during the lectures too, that there are differences between emergency and urgency. However, there is this other term called hypertensive crisis, which is kind of like that umbrella term that puts both the emergency and urgency together. So again, that's defined as having blood pressure about 180 or 120 again, this is either diastolic or systolic or both being above the threshold. So not just exclusive. Dr. Sean Kane 02:49 Yeah, and you'll see a couple different definitions. 180 over 120 or above that is the 2017 hypertension guidelines threshold. So generally speaking, you'll see something around that and other guidelines or other documents as well. So anyone with a blood pressure above that, we call that a hypertensive crisis, and then we distinguish it between emergency and urgency. So hypertensive emergency, which is the focus of today's episode, is where you have that really high blood pressure, plus what they call target organ damage, which is objective damage to one or more organs caused by that really high blood pressure. So for example, it could be that you have a stroke, either ischemic or hemorrhagic stroke, that you have altered mental status, and we call that hypertensive encephalopathy. You have an acute MI or unstable angina because of the supply and demand mismatch in your heart could be that you have acute heart failure because your blood pressure is so high that your pulmonary pressures go up and you get pulmonary edema. Could be that you have a tear in your aorta, and we call that aortic dissection, acute kidney injury, is something that is potential, but kind of harder to distinguish if that's truly a result of hypertension or not. And then in pregnant women, eclampsia or preeclampsia, we worry about the brain in terms of seizures, but we also worry about the baby as well. So there's kind of two things at play that they're in addition to other target organs that can be affected in eclampsia or preeclampsia. Dr. Khyati Patel 04:15 So Dr. Kane, this is all pretty serious. You're talking about some of these vital organs being damaged because of this long standing very high blood pressure. And that's that's what it is. It's emergency. Gotta be treating as an emergency. But the other term we talked about, which is a hypertensive urgency. And the difference really here is that blood pressure is equally high, but there is no seeming objective organ damage that has appeared. That means the patients are relatively stable, organ wise, but the blood pressure is still high, so you still have that scary anxiety forming high blood pressure may have some headache and accompanying symptoms, but a. And there is lack of that objective organ damage due to the high blood pressure. Dr. Sean Kane 05:05 And one of the challenges here is the term hypertensive urgency makes it sound like there's something wrong here. It's a hypertensive crisis. And really, these are misnomers. Patients don't have to be immediately treated if they have hypertensive urgency. And actually, if you go back to the older JNC hypertension guidelines, JNC seven, I'm going to quote from them, they say the term urgency has led to overly aggressive management of patients with severe, uncomplicated hypertension, which is not without risk, indicating that treating these patients with hypertensive urgency can lead to over treatment, which means that you give them drugs to drop their blood pressure, then they have side effects of the drugs, and those side effects are worse than had you just left their blood pressure alone and that aggressively treated it. Dr. Khyati Patel 05:51 So obviously, Dr. Kane that that makes a good argument here. But if you tell this to your patient, well, don't be rushing to the ER when you have a blood pressure, you know, beeping at you for 200 or above, then what do they do? How do we treat somebody who has blood pressure of, let's say, 220 over 120 but there is no parent target organ damage. Dr. Sean Kane 06:16 So there's actually guidelines specifically addressing this by the American College of Emergency Physicians, and they the guideline is called asymptomatic hypertension guidelines, and they are very clear that you don't need to give these patients aggressive therapy, no immediate medical treatment is required. Definitely don't give them IV anti hypertensives if you wanted to start some oral stuff because you feel that they have poor follow up or that there's some compelling reason to initiate therapy today versus at a follow up visit, you could potentially do that, but again, there's no compelling need to treat these patients immediately. Now, Dr. Patel, the conundrum here is in your outpatient clinic, for example, if someone walks in with a blood pressure of 220, over 120, the knee jerk is to send them to the ER, right? Because it's a scary number. And you know what kind of goes through your mind in terms of to send them or not to send them. Or what advice would you give that patient? Why might they go even if they have few symptoms? Dr. Khyati Patel 07:16 This is where the clinical judgment really plays a role. You know you're you have a history of the patient on your hand, because you're in the primary or, you know, outpatient clinic, so you know if the patient has had these issues before or not. If this is a first time, if, if really this is happening, because there is a precipitating factor, and we need to probably treat that. Maybe there's some sort of stress or an event that has happened in the patient's life. So you have to kind of pay attention to all of these surrounding factors as to what is causing the blood pressure to be high. Obviously, a keen look to make sure you discern that patient doesn't have that target organ damage. That's important we rule that out. Most physicians should not refer patients to the ER outpatient treatment, maybe intensifying the regimen, maybe making sure that they are adherent to the therapy. Maybe, you know, having patient follow up a little bit more closely to monitor the blood pressure, equipping them at home to monitor their blood pressure and giving them the tools to control that at home might be better. However, you know, if I was a patient, and if I had such non specific symptoms and I noticed my blood pressure to be high, my first inkling is I need to talk to my doctor, or, if my doctor is not available, go to the ER, especially in some cases, just, you know, men and women, the symptoms are not clear cut, as in men, right? And so we might be a little bit more cautious and have that get checked out. Perhaps it's an in office EKG that can be done rather than sending the patient to the ER, yeah. Dr. Sean Kane 09:01 I think the distinguishing factor here is that if you send someone to the ER, you're kind of doing it because you think that they need more diagnostic workup to potentially make sure that they don't have that hypertensive emergency. But if they go to the ER and they don't have that target organ damage, just because they went to the ER doesn't mean that you have to fix that number today. It means that they have asymptomatic hypertension that can be managed with chronic oral medications on an outpatient basis. And I think that distinction is Dr. Khyati Patel 09:32 really important. So having said that, going back to hypertensive emergency, I think it's really important that we set some groundwork for what are the treatment goals, right? So let's say you do find a patient who is in true emergency, and that patient goes to the ER, how would be an ER clinician perceive this patient's treatment goal? Yeah. Dr. Sean Kane 09:53 So one thing to appreciate is that we don't drop these patients to 120 over 80 immediately. And the reason. Deals with something called Auto regulation, and this is a term dealing with different tissues in your body, mostly your brain, but kidneys, other tissues as well, they regulate through vasodilation or vasoconstriction, of the arterials that go to and leave the organ. So for example, if your current blood pressure is 90, your brain can make it so that the pressure to the brain is right at 120 whatever pressure it really likes. If your blood pressure goes up to 170 your brain can then vasodilate different arterials so that it still maintains that same blood pressure of 120 so auto regulation is a term dealing with these organs that can modify organ specific pressures so that the organs can maintain a given pressure that they like. Now what happens is that if you drop a patient's pressure too quickly, the auto regulation takes time to both kick in and to kind of resolve itself. So if you take a patient at a blood pressure of 220 and drop them to 120 they 20, there's not enough time for the brain to cause vasodilation or vasoconstriction in different arterials to accommodate for that blood pressure change, and then the pressure to the brain can become dangerously low, and patients can be harmed by that. So because auto regulation can take some period of time, we also tend to drop these patients' blood pressures a little bit slowly, so that there's enough time for auto regulation to accommodate their change in blood pressure. Dr. Khyati Patel 11:28 And really, the auto regulation is taking place to make sure that there is adequate perfusion pressure, that there is adequate blood flow in that organ. And if you don't make that a priority, then there is a chance of ischemic injury in that organ itself, whether it be, you know, heart, whether it be kidneys, or whether it be the brain, exactly. And so generally speaking, Dr. Kane, the blood pressure reduction is usually 25% over the first hour. And I believe you'd like to keep it matte simple. So shooting for 20% is the goal, yeah. Dr. Sean Kane 12:04 And if you look at the guidelines, they say no more than 25% historically, guidelines said 15 to 25% so I like 20% because I can do 10% off two times, which would be 20% and that makes the math easier. Dr. Khyati Patel 12:18 And so as we define the number about 180 over 120 was defined as the hypertensive emergency, plus the organ damage here, decreasing it to about 160 over 100 over the first two to six hours. If you're talking about numbers and not percentages, this is how it would look like. Dr. Sean Kane 12:37 And you know, Dr. Patel, typically, what's going to happen is these patients come in with really high blood pressures as they kind of get their hospital bed. They are lying down. Therapy is initiated. Their anxiety levels are going down. Many of these patients will drop their pressures on their own, in addition to the antihypertensives that we give them. And unless they come in with a crazy high blood pressure, if you drop their initial blood pressure by 20% most patients end up at that 160 over 100 mark, which is our goal, at that two to six hour time period. And then after that, over roughly about one to two days, that's when we want to continue to slowly drop their blood pressure to a more normal pressure. You know, something around 140 would be reasonable in that one to two day mark, but it does depend on the patient, what their normal blood pressure is, why they had hypertensive emergency, things like that, but generally speaking, our goal is that they have a fairly normal blood pressure by two days of hospital admission. Dr. Khyati Patel 13:35 So sounds like it's a 48 hour marathon that starts with about an hour or a few hours of a sprint, Dr. Sean Kane 13:41 Exactly, yep, yep, yep. And with that in mind, you know that is kind of the rule of thumb for most patients with hypertensive emergency, but there are some patient populations where we do intentionally rapidly drop their blood pressure, because the risks of doing that are small compared to the potential benefits of dropping their pressure quickly, because that high pressure is going to cause some damage. The classic example here Dr. Patel, is aortic dissection. If someone comes in with aortic dissection, and we'll talk about this later, their mortality rates are extremely high, and the higher their heart rate is, and the higher their blood pressure is, the more likely they are to die by that dissection getting worse and eventually rupturing. So in those patients, we don't care about auto regulation. We drop their heart rate to less than 60, which is our primary goal. We drop their systolic blood pressure to less than 120 within the first hour. So we don't do this 20% off thing. We don't do the 160 200 over two to six hours, we as quickly as possible drop their systolic blood pressure to less than 120 in that first hour. Dr. Khyati Patel 14:45 And another patient population would be your pregnant patient who have preeclampsia or eclampsia. However, this condition is rare, or somebody with pheochromocytoma. Crisis, again, this is a super rare condition. Generation, where we drop the systolic blood pressure to less than 140 in the first hour again, because the benefits outweigh the risk. Dr. Sean Kane 15:09 So now Dr. Patel that we kind of understand what we want in terms of what blood pressure we want. The next logical question is, how do you want to get there? So what therapies do we give for these patients with hypertensive emergencies. Dr. Khyati Patel 15:22 Well, with the nature of how quickly you want to drop blood pressure in some of these patients, I'm going to guess that they're going to have to do IV therapy, quote, unquote, to get the party started. Exactly. Dr. Sean Kane 15:34 So, you know, we're going to exclusively use IV therapies and true hypertensive emergency because we want tight control of dropping their blood pressure. And you know, if you give a too large of an oral dose, that is a long acting oral therapy, you can't take it back, right? So we're going to favor parenteral therapies, especially in the first day or two, that have shorter half lives, that allow for titratability, so that we can have kind of the target blood pressure that we want. Now, interestingly, in terms of which IV therapies you give, there really are very few preferred therapies. We'll talk about a couple specific examples where there are preferred therapies, but 99% of the time, you can pick from a variety of different options. And in this episode, we're going to focus on the more common options that you're going to see in clinical practice. Dr. Khyati Patel 16:20 And so you're saying that there is a specific pattern that we or approach that we select here, like we mentioned, there is not a preferred anti hypertensive, but we want to make sure we are starting with IV agents, more so than the IV agent. We want to make sure that there is something quickly available and we are able to give to the patient right away, such as IV push over like an IV bag. Can imagine IV bag, you know, takes a little bit longer time to get the, you know, IV access started. Pharmacy, to compound it, you know, flush the line, prime the line, all that stuff. So IV push is a quick way to get things going exactly. Dr. Sean Kane 16:59 So if the patient truly has a hypertensive emergency, and your goal is to drop them 20% in the first hour. You could probably give them an IV push of labetalol or hydralazine within five minutes. Versus if you're going to go with an IV infusion without a bolus dose, it's going to take a lot longer for that infusion to really kick in and even be initiated in the patient. So typically, we're starting with an IV push until the drip is available, then we're going to transition those patients to continuous IV infusion. And again, the drug therapies that we're picking are going to be shorter acting and hypertensives that allow for that really tight blood pressure control. And it's really this Goldilocks approach where we want to steadily drop their pressure, but we don't want to overly do it because of the auto regulation issue. So short acting or short half life means that it's more titratable, which means that we get tighter blood pressure control, which is what we want in these patients, especially in the first couple hours of initiating therapy. There are a Dr. Khyati Patel 17:54 few therapies that fall under this category of either IV push or IV infusion. However, in order to keep it simple and to focus on this episode, we're going to take a shorter approach here and talk about some of these really good evidence based therapies, two IV push agents and three IV infusion agents. Dr. Sean Kane 18:16 And if you look in a textbook or look at the guidelines, they're going to list many more therapies, and pharmacists in particular, definitely need to know about these other drugs. But in clinical practice, we basically play with these five therapies, two IV push and three IV infusion. And it's pretty rare that we go outside of that scope in terms of these five drugs. So we're going to focus on that for the podcast. Dr. Khyati Patel 18:36 And so something that you're going to grab first like an IV push therapy, labetalol comes to mind. It's probably the most commonly selected agent. Dr. Sean Kane 18:46 Oh, for sure. So this is commonly selected because people are comfortable with beta blockers. It's an alpha one beta one beta two blocker. So it's a mixed blocker, and that alpha one blockade is going to give us that vasodilation that perhaps we wouldn't get as much of from a beta one–selective beta blocker like metoprolol as an example, Dr. Khyati Patel 19:04 we will have to be careful, however, to use labetalol in somebody who came in with acute heart failure, or, you know, pulmonary edema, or somebody who has airway diseases like COPD and asthma, so those things need Dr. Sean Kane 19:17 to be ruled out. And, you know, Dr. Patella, I feel like the heart failure thing is easy to forget. Beta blockers are negative inotropes, and in the long run, in chronic heart failure, they're helpful for systolic heart failure, but in the short term, they can worsen or exacerbate heart failure. So someone comes in with hypertensive emergency, manifested by heart failure with pulmonary edema. If you give them labetalol, you're going to make them worse. So knowledge of that is really important, and consideration that that, in my mind, would be a complete contraindication giving lebay law, yeah. Dr. Khyati Patel 19:48 But somebody who has aortic dissection, we need to drop that heart rate. You know, this might be a good one to go to Dr. Sean Kane 19:55 exactly and again, the flip side is that if their heart rate is low, which is fairly unusual. Because many of these patients are fairly anxious, but if their heart rate is currently 60, they're probably not a good candidate for labetalol, because whether you want to or not, labetalol will work on both the heart rate and the blood pressure, and it's going to drop that Dr. Khyati Patel 20:11 heart rate down. All right. Dr. Kane, are you ready for this one? The second one is hydralazine. I think this is your favorite. Dr. Sean Kane 20:17 This is such a controversial drug, and I love talking about it. So its mechanism is a direct vasodilator. So we don't exactly know beyond that how it works, but it doesn't impact your heart rate, which is good. And generally speaking, this is going to be pulled out when you can't use le beta law. So that COPD exacerbation patient, the acute heart failure patient, the patient with a low heart rate already. And the reason that hydralazine becomes controversial is it has a more unpredictable kinetic profile than most people would like. So it does two things that are unpredictable. One, when you give a dose to a patient, you can see high variability in terms of the blood pressure reduction response for a patient, so in terms of how much their blood pressure will lower, it can be variable. And then two, it has an unpredictable duration. So it lasts a couple hours in some patients, it can last up to 12 hours in other patients, and you don't know until you give it to the patient. So that unpredictability makes this a very controversial drug, where, if you get in a room with like, a bunch of critical care cardiology pharmacists, and you mentioned hydralazine, everyone has an opinion. Dr. Khyati Patel 21:22 Dr. Kane, so that's interesting. You said that. What are some of the things you've heard people arguing about this? Dr. Sean Kane 21:29 So I do frequent Twitter in terms of pharmacy Twitter accounts, and some of the quotes that I pulled about this kind of Hot Topic include things like, hydralazine is the coding of IV meds, meaning that you know its metabolism is highly variable, or hydralazine, for when you want it to use Nicardipine, but in an unpredictable manner. And we'll talk about Nicardipine is a very commonly used one that's fairly predictable. Hydralazine is clearly not. And then, if you don't much care about what your vitals will be or when you'll get there, give IV hydralazine, again, emphasizing the unpredictable nature of the onset, duration and clinical effect of that, blood pressure reduction. Dr. Khyati Patel 22:08 These are pretty sarcastic remarks, but it seems like we will still go with the agent is labetalol is a no go, yeah. Dr. Sean Kane 22:17 And I would say lebedell All probably should be your first choice, but if you can't pick it. I do think hydralazine can be used in an effective manner if you pick the right dose. So one of the problems is that the vial comes in 20 milligram. I've never given 20 milligrams ever. So 10 milligrams, maybe even five milligrams. So giving a smaller dose and kind of titrating, you can always give more, but you can't take it back once you give it. So I think acknowledging that unpredictable nature and dosing it as such, I think that you can still use this as an effective option. And really all of the other IV push options are not very good, so you're kind of stuck here between le beta law and hydralazine. And I acknowledge lebetal Law is going to be your first choice, but there are certain patients that should not get le beta law, and that's where hydralazine comes in, right? Dr. Khyati Patel 22:59 And then talking about, you know, unpredictable outcomes with hydralazine, your patient is hooked up to this telemetry monitoring, so you're going to have an ability to keep a close eye on them to titrate the dose up or down as needed. Exactly. Yep. So moving on from IV push, we have a few agents to discuss in the IV infusion category, like you said, Dr. Kane earlier, Nicardipine is one of the agents and the brand name is Cardene; in the category of IV infused medication, this will be the most common one to be given in hypertensive emergency Dr. Sean Kane 23:33 situations, for sure. I mean, this is going to be the workhorse Nicardipine or cardine is. It's a dihydropyridine calcium channel blocker. So it causes peripheral vasodilation. It either causes no change in your heart rate, or can cause maybe a reflex tachycardia, and it has no impact on cardiac inotrophy, so it's not going to worsen heart failure. Dr. Khyati Patel 23:54 A similar agent in this category, the dihydropyridine calcium channel blocker, a newer one is clevidipine; that one has an even shorter half‑life than nicardipine, so maybe a little bit more titratable. But you have to think about it. It's actually available in a lipid formulation like your propofol. So you're worried about somebody who already have high lipids, especially triglycerides. Dr. Sean Kane 24:16 Yeah, so most institutions are going to have either nicardipine or clevidipine. And honestly, it's primarily going to come down to cost. Clevidipine has a shorter half life, and it's more titratable, but again, it has that lipid, so it's kind of institution specific. Dr. Khyati Patel 24:31 The second agent in this category is the nitric oxide based therapy. There's a couple of them, nitro plus side, but we're going to focus on nitroglycerin instead. Yeah. Dr. Sean Kane 24:40 And the way that this works is that it gives nitric oxide to your smooth muscle, and that causes smooth muscle relaxation in your vasculature, dropping your blood pressure. We really only use nitroglycerin in hypertensive emergencies that have target organ damage of acute MI or acute heart failure with pulmonary edema, so we don't use it for other. Types of hypertensive emergencies, and the reason that we like it for those is that most of its effect on the vasculature is in coronary blood vessels. So it improves oxygen supplied to the myocardium, and then it has lots of venous dilation, especially in your pulmonary vasculature, and that can improve pulmonary edema. So if you don't have an acute MI or acute heart failure with pulmonary edema, we typically will not use nitroglycerin for those hypertensive emergencies. Dr. Khyati Patel 25:26 And that makes sense. And that dilation that can happen elsewhere too. That's why nitrates are affiliated with that headache, because headache usually happens when you're you know, vasculature in the brain is dilated. So that's one of the common side effect with it. Another thing to worry about this one is tachyphylaxis, meaning the dose kind of maxes out with the effects. So tolerance can happen. But usually this happens after a day or two of use, and by that time, we have normalized the patient's blood pressure, and perhaps they're even, you know, transition to oral therapy. So we might not get to practicality see this tachyphylaxis happening, but we need to keep that in the back of our mind. Dr. Sean Kane 26:07 And then, of course, we worry about the drug interaction of nitrates with PD five inhibitors like Viagra, Cialis. So we always need to ask our patient, did you take something like Viagra in the last 24 to 48 hours? And if they did, we will not use a nitrate in them, because it can dangerously drop their blood pressure. Again. The name of the game here is this, Goldilocks, slow and steady blood pressure reduction for these patients, and if we overdo it because of auto regulation concerns, we can actually cause them to have complications of too rapidly dropping their blood pressure. Dr. Khyati Patel 26:38 So the last, but not least, in the IV infusion categories, we have esmolol. It's also a beta blocker. The brand name is Brevibloc Dr. Sean Kane 26:48 block, and Dr. Patel, I love I adore this brand name because it is an uber short‑acting beta blocker. That's why the name Brevibloc is such a clever brand name for it. This is a beta one selective beta blocker, and it can lose some selectivity at higher doses, but we more or less consider this a beta one selective beta blocker, so it shouldn't cause as much reactive airway issues, especially in patients with COPD, as something like labetalol does. Dr. Khyati Patel 27:16 But again, if you're giving enough high doses, then it may lose that selectivity, however, hopefully, like by that time, we have converted patient to other oral agents, so kind of in the same category. But we're gonna use this to lower the heart rate, like that beta blocker action would give us, so somebody coming in with aortic dissection, we need to lower the heart rate to that primary less than 60. Goal, that's where this is going to be primarily used. Yeah. Dr. Sean Kane 27:45 So it will drop your blood pressure, but heart rate is the main reason that you're reaching for esmolol. So again, you're not going to use esmolol for someone with, you know, ischemic stroke, with hypertensive emergency, because you don't really care about their heart rate. It's not a primary issue. So in aortic dissection, that's a primary issue, which is why we typically will use it, Dr. Khyati Patel 28:06 and because it's a beta blocker, just like Le beta law, we're going to avoid in somebody who has acute heart failure, or obviously the you know, heart rate is really low. Tell us a little bit more about its dosing in the ICU setting that you have seen. Dr. Kane, yeah. Dr. Sean Kane 28:22 So at least in my experience, I don't associate esmolol, even at the max dose, as being an incredibly potent beta blocker. So when we use it to reduce heart rate, it does reduce heart rate, but it doesn't drop patients as much as you might expect at the maximum dose. And the problem is that when you give them the maximum dose, the amount of fluid you give the patient is actually quite high. So it depends on body weight, but roughly, patients can get up to, like, 100 mls per hour of an almost normal saline. It's point 7% sodium chloride. So these patients get a lot of fluid. And of course, giving fluid increases your blood pressure, so not kind of ignoring the fact that the bag will last probably two to three hours, and then you have to replace it. You're giving all this fluid the cost of it that can become an issue with eczema, and that would be a good argument to maybe transition those patients to other therapies to avoid giving them so much fluid If blood pressure becomes an issue, Dr. Khyati Patel 29:18 so good until the heart rate comes under control, but then probably may need to transition for blood pressure control to another agent that does not bring in all this fluid Exactly. Well, those were kind of like the short summary of the agents that we go after. However, it's important that we talk about certain patient population that we consider special, meaning we don't either drop their blood pressure too fast, or agents that we go and select for treatment are a little bit different. Dr. Sean Kane 29:49 Yeah, so ischemic stroke, and this is, you know, the patient case we had at the beginning of the episode, this patient would fall into that category. And what's unique about ischemic stroke is that we allow for what's called permit. Of hypertension. And essentially, the concern is that when you have brain tissue that is damaged, auto regulation may also be impaired, and perhaps in order to perfuse, especially some of the ischemic areas of the brain, you may need higher blood pressures, because auto regulation may not be effective in maintaining good perfusion, especially to that area of the brain that is ischemic Dr. Khyati Patel 30:22 so then, after having a patient, we establish the fact that the patient had ischemic stroke, then we decide whether patient deserves TPA or patient is not eligible for TPA. And depending on whether they're receiving or not receiving TPA, their blood pressure goals are a little bit different. Can you tell us a little bit more about it? Dr. Kane, yeah. Dr. Sean Kane 30:45 So if they don't get TPA, their blood pressure goal is less than 220 over 120 Yes, you heard it right. A crazy high blood pressure goal, 220, over 120, or less. And really, the reason, again, is dealing with the perception that auto regulation may be impaired if you give TPA the pre TPA blood pressure goal. So your blood pressure in order to qualify for TPA is less than 185 over 110 and then once you've given TPA, at least for the next 24 hours, you have to maintain them less than 180 over 105 so they took five off of systolic and diastolic of pre TPA versus post TPA, just to make it harder, I guess. But the concern here is that if a patient gets a thrombolytic and they're too hypertensive, the risk of having a hemorrhagic conversion, where they bleed in their brain is higher. That's why the blood pressure goal is different based on if you give TPA or not, right? Dr. Khyati Patel 31:41 And that pre and post TPA goal, you know, the difference of phi, it's very specific. And so you have to think about this. Patients are kind of fragile, you know, patient population in general, and we have to just do that much more rigorous monitoring and making sure these goals are maintained Exactly. Dr. Sean Kane 31:58 And you know, a similar patient population, Dr. Patel, is those with hemorrhagic strokes, so bleeds in the brain that give them stroke symptoms. And the concern here is that higher blood pressures are associated with the bleeds getting bigger or getting worse. And that kind of makes sense, right? So if you think of a garden hose with a hole in it, the higher the pressure in that garden hose, the more water is going to leak out of the hole. Similarly, in someone with a hemorrhagic stroke, the higher their blood pressure is, the bigger that bleed could get. So historically, we used a blood pressure goal less than 140 and we thought that that could reduce the size of the hemorrhage and potentially improve clinical outcomes. And that's actually what the guidelines currently have. However, there has been newer literature that kind of called this into question a little bit, and it seems like and it seems like a blood pressure around 140 to 160 is as good as less than 140 certainly a blood pressure above 160 is not acceptable. So somewhere around the 140 to 160 mark is probably okay. But again, the guidelines currently suggest a systolic BP less than 140 Dr. Khyati Patel 33:00 and moving on, we have aortic dissection patient population. We kind of talked about earlier how we're going to drop blood pressure as well as heart rate pretty fast in this patients, and we're going to go after that as a beta blocker like esmolol, therapy that blocks the AV node conduction, bringing the heart rate below 60 before any of the vasodilators are started. And again, in this patients, we're going to have to drop the blood pressure to less than 120 in the first hour. So it's a it might appear a big drop from where patient is. However, this is done irregardless of the auto regulation concern, because the mortality is really, really high. Dr. Sean Kane 33:40 And Dr. Patel, just to put a number to it, in patients with aortic dissection, 40% of them die before they even get to the ER and then five to 20% die during or shortly after surgery. And the faster the heart rate is and the higher the blood pressure is, the more likely they are to have a rupture of their aortic dissection. So that is why we are so aggressive with them, and basically dropping their pressure and heart rate buys time for them to make it to the or to be able to have a repair done before it ruptures. Dr. Khyati Patel 34:11 And that makes very much a sense another fragile population like that, where we drop blood pressure really fast we talked about earlier is patients who have eclampsia or preeclampsia with severe symptoms, and you know, it's a little bit of a different ball game here. We're dealing with almost sort of two people, you know, mother and the fetus, and so we have to be extra careful with the monitoring. But in cases of preeclampsia with severe symptoms, you know your IV labetalol therapy, if not IV labetalol, nifedipine and hydralazine are alternatives in the eclampsia situation. However, if the patient is presenting with seizures, we are looking to terminate those seizures, and usually the more safety‑and‑efficacy‑established therapy is IV magnesium sulfate; we do a pretty large loading dose and then give an IV infusion thereafter. But that's, that's that's not an anti hypertensive agent, but that is agent to terminate seizures in a classic situations. And the thought is that once the seizures are controlled, the blood pressure does normally reduce, and Dr. Sean Kane 35:21 Dr. Patel, we could have a whole episode just on eclampsia and preeclampsia. I think one of the more important take home points is that magnesium sulfate is used in that patient population. You know, yes, we give it for seizures, but it's also going to drop their blood pressure as well. So there's a lot more going on here. And again, very different ball game, as you said, yeah. Dr. Khyati Patel 35:40 So this, this is probably off to my alley thinking about, you know, transitions of care and stuff, but let's say we have a patient we started on the IV therapies. Their blood pressure is getting to be controlled. They're at that 48 hour mark, and they're kind of ready to be converted to an oral agent. What is the usual approach here? Dr. Kane, Dr. Sean Kane 36:04 so you know, you can't leave the ICU with a continuous titrated antihypertensive, because the amount of monitoring required really requires the ICU care. So typically, what we're going to do is, again, once we kind of get the patient stable in a day or two, we'll start initiating oral therapies, if possible, we try to select stuff that would be the normal preferred outpatient therapy based on that patient's comorbidity. So one of the four preferred anti hypertensives, or if they have some compelling indication for a beta blocker or an ACE inhibitor, then we'll initiate those. But again, typically we're starting these oral therapies a day or two days once we've kind of stabilized them with these IV therapies with the intent that they can continue to be titrated out of the ICU setting. Dr. Khyati Patel 36:46 And it's very likely that they're going to be reinitiated on maybe if they were already taking oral agents prior to coming through this admission, back on that agent. But maybe their dose will be modified, or if we deem that that therapy did not work out for the patient, then an alternative agents, like you said, will be converted to Dr. Kane, and Dr. Sean Kane 37:07 if they worked on an antihypertensive beforehand, they're definitely going to be on one, you know, when they leave the hospital, Dr. Khyati Patel 37:12 absolutely, with all the education that goes behind it, exactly. So going back to our case, we had, you know, in your setting, Doctor K 55, year old patient who came in with acute CVA. Obviously, it's 12 hours since the symptoms started. So this patient is outside of that TPA window. And if you recall, the blood pressure was 260 over 150 with the heart rate of 110 what do we do for this gentleman. Dr. Sean Kane 37:41 So again, you know, we're going to briefly review key points here, but in that first hour, we're going to decrease that blood pressure by up to 25% so for me, I like 20% so 20% off would be 50 over 30 off. So that means that we want to take their BP of 260, over 150 and drop it down to 210, over 120 Dr. Khyati Patel 38:02 and this will be in the first hour. And then our goal for reduction of blood pressure within the next two to six hours will be around 160, over 100 However, remember, this patient has a stroke, and in the acute ischemic stroke, we want to make sure we don't drop the blood pressure too much, thinking the auto regulation is not doing what it needs to do. And so here that goal will be less than 220 over 120 however, you know the first hour goal was already below that, so obviously this goal will be further below 220 or 120 Dr. Sean Kane 38:40 Yeah, and that'll be for the first 24 hours. Then after that point, you can start dropping them slowly over the period of a day or two. And obviously, if a patient's stroke symptoms get worse as you drop their blood pressure, you're going to stop doing that, and you'll go back to whatever blood pressure did not give them worsening stroke symptoms. What would be Dr. Khyati Patel 38:57 the ideal agent to use? That's something that we need to think about as well, right? This patient came in with ischemic stroke. Dr. Sean Kane 39:04 Yeah, so typically, again, to kind of get the party started, we're going to give an IV push option. They have no contraindication to getting labetalol, so that would typically be the preferred IV push therapy. So again, no heart failure, no COPD, no bradycardia, so there's no reason to reach for that controversial hydralazine. So labetalol IV push is going to get that party started. Dr. Khyati Patel 39:24 And if the initial IV push therapy with labetalol is not getting us to the goal, meaning patients requiring multiple labetalol IV pushes, we can consider changing the patient to IV nicardipine. We kind of thought about nicardipine over here, versus nitroglycerin or esmolol, because, again, we normally keep nitroglycerin for those who have MI or heart failure, and esmolol for those who need that rapid heart rate reduction, such as aortic dissection. Yeah. Dr. Sean Kane 39:56 And again, as we mentioned, there's a bunch of other anti hypertens. Those that are continuous IV infusions, but nicardipine, or at some institutions, clevidipine, is going to be your workhorse, and that's where you're going to start. And it'd be unusual to need more than that therapy. And you know, given that this patient has a fairly high blood pressure goal of 220, over 120, they probably could be maintained just on labetalol pushes. And, you know, titrating that based on their clinical effect. Again, if they need a lot, then sure we can give them a continuous infusion, but they may not need it. So Dr. Patel, what are some key take home points that you think the listeners should get away from today's episode? Dr. Khyati Patel 40:33 You know, one other thing that was important to discuss was the stark difference between hypertensive emergency and hypertensive urgency, not just so much the definition, but how we care for the patient. And so those who have hypertensive urgency, even though the word says urgent, it's kind of like a misnomer. Patient don't need to go to the ER to, you know, start the IV therapy. Patient just may be okay with titrating their home therapies, oral therapies on outpatient basis. Dr. Sean Kane 41:06 The number two point for me is that in most cases, and again, there are going to be exceptions, but generally speaking, your blood pressure goal is to decrease it by no more than 25% in the first hour, then try to get to around 160 over 100 and hours, two to six then over the next one to two days, you're going to drop them to a fairly normal blood pressure. Dr. Khyati Patel 41:26 And the beta law is going to be that preferred IV push therapy, unless we are looking at acute heart failure, bradycardia, some airway diseases. Then other options are available. Dr. Sean Kane 41:39 And then finally, Nicardipine is going to be your main workhorse, continuous IV infusion. Again, there's others out there. For the most part, many of the other therapies are going to be reserved for specific types of hypertensive emergencies. So pulmonary edema, you're going to reach for your nitroglycerin; aortic dissection, because we want to reduce their heart rate as well, maybe esmolol. And again, there's a variety of other anti hypertensives out there, but we've really tried to focus on the most clinically relevant and common therapies that you're going to see in clinical practice. Dr. Khyati Patel 42:11 And Dr. Kane, you know, they're going to be under good observation, good care, perhaps 48 hours, to control their blood pressure and bring it to the goal, but the next step is to then start prepping them for transitions of care, so perhaps changing them to their oral therapies. If they were not on any antihypertensives prior to admission, they will be on one. If they were on antihypertensives prior to the admissions, maybe the dose or the agents need to be readjusted Dr. Sean Kane 42:40 perfect well for the listeners that want to see some references, we have both the 2017 hypertension guidelines, in addition to the ACEP guidelines for asymptomatic elevated blood pressure, both of those guidelines are linked in our show notes. You can see those at HelixTalk com. Again, this is episode 134 we're also on Twitter at helixoc, where we release clinical pearls every now and again, about our previous episodes, and we still love those five star reviews and iTunes or Apple podcasts, so keep those coming so we can climb those rankings. So with that, I'm Dr. Kane Dr. Khyati Patel 43:15 and I'm Dr. Patel, and as always, study hard. Narrator - Dr. Abel 43:19 If you enjoyed the show. Please help us climb the iTunes rankings for medical podcasts by giving us a five star review in the iTunes Store. Search for HelixTalk and place your review there Narrator - ? 43:30 to suggest an episode or contact us. We're online at HelixTalk.com thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science.