Hello, this is Janice Zimmerman, and I will be discussing the management of hypertensive crisis in this presentation. When you approach the management of a patient with severe elevations of blood pressure, I would suggest that you consider three questions in determining your care. The first question is the most important. Does the blood pressure need to be lowered acutely? If the answer to this question is yes, then the second question is how much should you lower the blood pressure? Your response to this question will determine the answer to the last question, which is which medications should be used. So let's start with the first question. Which of the following patients requires an acute lowering of blood pressure? A 50-year-old with hypertension who's NPO for an upper endoscopy, blood pressure 188 over 110, patient two, an 87-year-old with an acute hip fracture waiting for surgery, blood pressure 178 over 112, or a 60-year-old with systolic heart failure, dyspnea, and arousal, blood pressures 180 over 118, or the last patient, a 45-year-old alcoholic with tachycardia and tremulousness, and a blood pressure of 180 over 102. So I'll give you just a few seconds to think about your response to this question. Well hopefully you chose patient number three, the patient with systolic heart failure. Patient one probably just needed to take his antihypertensive medications or may need anxiety addressed. The 87-year-old with the hip fracture likely has pain contributing to elevation of blood pressure, and the alcoholic probably needs some benzodiazepines. The key to the correct answer here in patient number three is the presence of decompensated heart failure. Progressive emergencies are defined by the presence of severe hypertension and the presence of new or progressive end-organ dysfunction. That organ dysfunction should be due to the hypertension and not to some other condition. In this situation, it indicates the need for an immediate lowering of the blood pressure. Although you may see other thresholds defined in literature, there really is no specific blood pressure value that defines an emergency. Factors that contribute include the baseline blood pressure, the rate of rise of the blood pressure, the absolute increase in blood pressure, and the duration of elevated blood pressure. Well the organs most commonly affected by elevations of blood pressure include the central nervous system, the cardiovascular system, and the renal system. That helps us define the conditions that are associated with hypertensive emergencies. In the central nervous system, we have encephalopathy, intracranial hemorrhage and stroke. In the cardiovascular system, we might see myocardial ischemia, heart failure with pulmonary edema, and less commonly, aortic dissection. Of course, in the renal system, it's acute renal insufficiency. Now there are a few other conditions that we have to at least mention, and you can see hypertensive emergencies with excess catecholamine states. And the most common is probably illicit sympathomimetic drugs, pheochromocytoma is on the list, monamine oxidase inhibitor tyramine interactions, and antihypertensive withdrawal. I want to just briefly mention scleroderma renal crisis because I'm not going to address that again. But if you see that on a board exam, the answer is to treat with an ACE inhibitor. Severe preeclampsia and eclampsia will be addressed in the obstetric presentations. Here's another question. So a 58-year-old with poorly controlled chronic hypertension presents with altered mental status, vomiting, and papilledema. No focal deficits are present, the blood pressure is 196 over 128, head CT findings are normal. So we're to our second question on that list, which is how much should the blood pressure be lowered initially? Decrease the systolic blood pressure to 150, decrease the mean arterial pressure by 20%, decrease the blood pressure to 140 over 90, or decrease the diastolic blood pressure to 100. I'll give you just a few seconds to think about this one. Well, I would suggest that the correct answer or the best answer is to decrease the mean arterial pressure by 20%. If you calculate the mean arterial pressure for 196 over 128, it's about 150. And if you looked at number one option and you lowered the systolic to 150, your mean arterial pressure is likely to be around 104, 105, which would be a 30% drop and probably too much. Decreasing the blood pressure to 140 over 90 is really too close to normal. And diastolic blood pressure alone is probably not a good target. So we usually target the mean arterial blood pressure. The goals of therapy in treating severe hypertension, of course, are to arrest and reverse that organ injury. But at the same time, you have to maintain organ perfusion and avoid complications. It's important to keep in mind that perfusion is very dependent on auto-regulation in the renal, cardiac, and in the brain. You're probably familiar with this graph of cerebral perfusion. As you see in a normal intensive individual, cerebral blood flow remains constant between mean arterial pressures of 50 and 150 due to auto-regulation. Now if the mean arterial pressure drops below 50, that patient is likely to be at risk for ischemia and infarction. But if it goes above a mean pressure of 150, then they're at risk for edema and hemorrhage. In the hypertensive patient, this curve is shifted to the right. And this is where determining the goal of lowering blood pressure is important. Because if you lower that mean arterial pressure even to what's considered normal, you may drop them off the bottom end of their auto-regulation curve. So the recommendation in the setting of a hypertensive emergency is to lower to a safer level in a few hours. And you should individualize that treatment goal based on comorbidities of your patient and their response to treatment. There are consensus recommendations out there, and keep in mind that these are all based on expert opinion. But what you'll see is a range of lowering the mean arterial pressure by 15 to 25%. So approximately 20% is a good goal in most situations. But if you know the baseline blood pressure, that may be a helpful goal as well, at least to not go any lower than their baseline blood pressure. When choosing a medication, the last step in this process, you should take several factors into consideration. Coexisting conditions in your patient, such as renal failure, cardiac disease, the extent and rate of blood pressure reduction that you're aiming for, because that will help you choose the right potency of drugs. You do have to know a little bit about the pharmacology of drugs to maintain safety in your patient. And also the availability of facilities and personnel to monitor the patient may play a role in determining which medication you choose. You should always choose a single parenteral agent initially. And we want a titratable, a potent, and a safe medications. And we're actually coming close in the options that we have today. Once the blood pressure has been lowered to a safer level, oral agents can actually be instituted within 8 to 24 hours. This is a list of the drugs we now have available to treat hypertensive emergencies. As you can see on this list, there's some very old drugs that are really not used anymore, some drugs that we used in the past that have gone out of favor, and then some newer drugs. So we actually do have quite a few options today. So let's start with choosing a medication for this patient. This patient is very similar to the last one, the 58-year-old with poorly controlled chronic hypertension, presents with altered mental status, vomiting, and papilledema. Blood pressure is 196 over 128, CT of the head is negative. And the question is, which of the following IV drugs is most appropriate for lowering the blood pressure? Labetalol, hydralazine, enalaprilat, or esmolol. I would suggest that of this list, labetalol is probably the best drug. Clearly this patient has a hypertensive emergency, and in this case, it looks like hypertensive encephalopathy. Now, hydralazine, I will tell you, is not a drug that we typically would use because of its variable effects in patients. And it has precipitated ischemic events due to precipitous drops of blood pressure. Enalaprilat also has variable results, and not all patients respond, and it's not very potent. And we'll talk a little bit about esmolol again, but keep in mind that the underlying pathophysiology in hypertensive emergency is vasoconstriction. So esmolol has no vasodilating effects. It lowers blood pressure by decreasing cardiac output. So it wouldn't typically be the best drug in the setting of hypertensive encephalopathy. Well, hypertensive encephalopathy has a range of clinical symptoms. Headache is always the gray zone, but they may have visual symptoms, and they progress all the way to altered mental status, seizures, and coma. We now know that this is a syndrome associated with particular MRI findings that we now call the posterior reversible encephalopathy syndrome, or PRESS. MRI shows bilateral hyperintensities on the MRI T2, and this is associated with basogenic subcortical edema. And although it is usually in the occipital areas, it can occur in other areas of the brain. And there are also cases where it's not always reversible. But in most cases, this resolves in five days to weeks. Of course, PRESS is also associated with a lot of other conditions with chemotherapy and other causes of hypertension. So the most commonly used drugs in hypertensive encephalopathy would likely be nicartipine and labetalol. Labetalol has a more rapid decrease in blood pressure and less variability. It is a shorter-acting drug, and it has really no toxic metabolites, but it is metabolized in the liver, which in those with significant liver dysfunction may require some monitoring. Labetalol has both alpha and beta blocking activity, so it does have some basal dilating activity, but you do have to be careful in patients with bradycardia and systolic heart failure. Clavitapine probably comes the closest to nitroprusside as far as being rapid onset, short duration. But the unique aspects of clavitapine is that it has no toxic metabolites. Only problem is it's more expensive. And you also have to avoid this drug in anyone who has a soy or egg allergy, and you may also see atrial fibrillation. Now nitroprusside and nitroglycerin have been used historically, but they are less commonly used today. Let's look at another patient. A 48-year-old patient presents with severe substernal chest pain. Blood pressure is 210 over 150. The electrocardiogram shows ST elevation. Which of the following is the most appropriate IV drug for lowering blood pressure? Nicardipine, nitroprusside, and naloprilat, or nitroglycerin? Well, I think most of you would probably choose nitroglycerin. In this case, the patient has ongoing chest pain, so nitroglycerin would address both the chest pain as well as the hypertension. Now nicardipine is a calcium channel blocker would not be a first choice in the setting of myocardial ischemia. Nitroprusside is unlikely to be used, and as mentioned previously, naloprilat is not a great drug for hypertensive emergencies. So if someone has ongoing chest pain, nitroglycerin would be the first choice. The only caveat with nitroglycerin is that it is not a very potent arterial dilator, so you have to use higher doses. Labetalol, its beta-blocking effects would be very helpful in ischemia. You could use esmolol here, and nicardipine really last choice in dealing with hypertension in the setting of myocardial ischemia. Here is another patient, a 42-year-old with chronic kidney disease presents with dyspnea and bilateral arousal. Blood pressure is 190 over 128, heart rate is 110, his saturation is 91% on 5-liter nasal cannula, and the electrocardiogram shows left ventricular hypertrophy. Most recent creatinine was 2.8. Which of the following IV agents is most appropriate to lower his blood pressure? Hydralazine, furosemide, nicardipine, or esmolol? Well, I think out of this list, probably most of you would choose nicardipine. We have to keep in mind that when we're dealing with hypertensive heart failure, we have to think about what type it is. Is it with reduced ejection fraction? In these individuals, they tend to have lower elevations of blood pressure, and they usually have significant clinical signs of volume overload. And those patients with preserved ejection fraction, what we used to call diastolic dysfunction, they often have more clinical signs of hypertension that's been of longer duration. So they can mount a higher elevation of blood pressure, they may have retinopathy, and they often have left ventricular hypertrophy. And many of these patients have very thickened left ventricular walls, and that's important to keep in mind when you think about medications for these patients. When choosing a drug for severe hypertension with left ventricular dysfunction, nicardipine is probably a drug that many of you would choose first. Labetalol can be used in those with preserved ejection fraction and works excellently. You do have to be cautious in those with reduced ejection fraction. Nitroglycerin can be used and has been used, but you have to be cautious in those with preserved ejection fraction. And in this graph on the screen, you can see the difference in potency. Nitroglycerin just is not as potent as nicardipine or clovidipine. So you're going to have to use much higher doses, and it will take longer to lower the blood pressure. Clovidipine is another choice, but again, it may be restricted in your institutions due to the cost. Nitroprusside historically has been used, but there is concern that this may cause some coronary artery steel, and so it is not typically used. Diuretics really should be reserved after the blood pressure has been lowered, and only in those patients who have significant clinical signs of volume overload. Most patients with hypertensive emergencies will have a pressure diuresis due to the elevated blood pressure, and they're actually intravascularly volume depleted. Here's another patient to think about, a 55-year-old with hypertension who describes a tearing pain radiating to his back. The electrocardiogram shows left ventricular hypertrophy. Blood pressure's 180 over 112. Which of the following are the most appropriate therapy and target blood pressure for this patient? So we have two parts that you have to get right here. Would it be using nitroprusside aiming for 110 over 80, nitroprusside plus propranolol aiming for 140 over 90, nitroprusside plus esmolol aiming for 160 over 100, or labetalol aiming for 100 over 70? Well, here I think the best answer is the last one, using labetalol, and the key issue here is the target blood pressure, which is 100 over 70. There was no issue with determining that this was likely an aortic dissection. So your options are really to use a vasodilator and a beta blocker. So historically, this has been nitroprusside plus propranolol. You can use nitroprusside plus esmolol, but labetalol with its alpha and beta blocking activity can fulfill the roles of two agents and its single use. I will also mention that clavitabine plus esmolol has been reportedly used in aortic dissection as well. Now, the previous gold standard historically was trimethophan, but most institutions do not even have this drug available. So I don't think anyone would be asking you that on a board exam. The other key issue is to institute the beta blocker first, control the heart rate, and then add a vasodilator. Now, the gold blood pressure is an exception to what we said at the beginning, which is the goal of lowering by 20%. Here, the gold blood pressure is the blood pressure that results in relief of pain, and aiming for a systolic of 100 to 120, and a heart rate of about 60 or less. Okay, this is going to start a series of questions, four questions with CT scans. So we're gonna go through this fairly quickly, and then we're gonna come back and talk about these different conditions. Here you have a 65-year-old man who presents with left hemiparesis. He responds appropriately to questions. Blood pressure is 196 over 105, and you see his non-contrast CT. So the question is, should his blood pressure be lowered immediately? Yes or no? Okay, the answer here is yes. Here you have the next patient. Very similar patient, a 65-year-old with left hemiparesis and depressed level of consciousness. Blood pressure is 196 over 105, and you have a non-contrast CT here to look at. Should the blood pressure be lowered immediately? Yes or no? The answer is yes. Another 65-year-old, again, same findings here, left hemiparesis and depressed level of consciousness that began one hour prior to arrival. The blood pressure is 196 over 105, and this is a non-contrast CT that you see. Should the blood pressure be lowered immediately? Yes or no? The answer is yes. This is the last question of the series. A 65-year-old presents with left hemiparesis and depressed level of consciousness. Blood pressure is 196 over 105, and you have a non-contrast CT shown and even has an arrow. Should the blood pressure be lowered immediately? Yes or no? The answer for this one is no. And hopefully, you'll be able to see that this shows the beginning of an ischemic stroke here. So let's look at these different situations. The first case that we looked at was an intracranial hemorrhage. And I wanted to mention the two studies that have actually had an impact on some of the guidelines. The first study was the InterACT2 study, which looked at treating patients within six hours and dividing them into groups aiming for a systolic blood pressure less than 140 in one group and less than 180 in the other group within one hour. And unfortunately, this showed no difference in death or major disability. They did find a better quality of life in the intensive blood pressure group, which doesn't really explain a whole lot or help us a lot. Now, the Attach2 trial was about 1,000 patients, and they treated these within four and a half hours of arrival, aiming for a systolic of 110 to 139 in the intensive group and 140 to 179 in the guideline group. They found no difference in the composite outcome of death or disability at three months. They did find more deaths in the intensive group when that was looked at as a single factor, and they also found more renal adverse events with intensive treatment. Well, these are the guidelines for spontaneous intracranial hemorrhage, and I want you to pay attention to the wording. So, if systolic blood pressure is 150 to 220 and there is more than 150, if systolic blood pressure is 150 to 220 and there is no contraindication to acute blood pressure treatment, acute lowering the systolic blood pressure 140 is safe. You will notice that it does not say you should lower the blood pressure, and this is important. You may in your institutions have people who say the guidelines say we must lower, and that's not exactly what it says, but it does say it is safe. Now, if the systolic blood pressure is greater than 220, it is reasonable to consider aggressive reduction of blood pressure with continuous IV infusions. Now, again, the level of evidence is much lower here, so that's why it is a suggestion using the word reasonable rather than saying you should do something. Now, an additional guideline recommendation was added to indicate that lowering a systolic blood pressure to less than 140 may be harmful. So, you can see it's a tight line here between lowering it to 140 but not going below 140 because of the potential for harm. So, these are the guideline recommendations that I think you'll be held to when it comes to a board exam. The second case that was presented was a subarachnoid hemorrhage, and when approaching a patient with subarachnoid hemorrhage and who has severe elevations of blood pressure, you have to keep in mind that you're going to use analgesics to relieve pain. You're also going to be administering nipromodipine, which will lower the blood pressure. So, those two factors have to be accounted for. But if the blood pressure is still elevated, then the recommendation, which is, again, expert opinion, is to control the blood pressure until the aneurysm is obliterated. And usually, you'll see a recommendation to decrease the systolic blood pressure to less than 160. And the agents that are recommended are the ones you're familiar with, nicortipine and labetalol probably at the top of the list, but also esmolol and clavitopine. Now, the third and fourth cases that we had for questions were strokes. And the interventions for the managing blood pressure depend on whether the patient is a candidate for reperfusion. So, again, these guidelines were initially developed for thrombolytic therapy. So, if the patient was eligible for reperfusion therapy, then you had to lower the blood pressure if it was greater than 185 over 110 before they were candidates for thrombolytic therapy. The recommendation is also to maintain the blood pressure less than or equal to 180 over 105 during and after reperfusion therapy. And after is usually referring to the first 24 hours. In other patients, and this is the key to that last case we had, in other patients who are not candidates for reperfusion, it may be reasonable to lower the blood pressure if it's greater than 220 over 120 or another indication exists. And in these cases, the recommendation is to lower initially by 15% in the first 24 hours. And the similar suggested agents, labetalol, nicartapine, and clavitopine. Well, what about blood pressure after thrombolysis? The guidelines did not address 48 to 72 hours after thrombolysis. So, is it reasonable to lower the blood pressure to a systolic of 140 in that situation? Well, the trial that addressed that was the ENCHANTED trial, which was reported in 2019, and they randomized patients within six hours of stroke onset to an intensive group aiming for a systolic blood pressure of 130 to 140 within one hour, or the guideline group, which was a systolic less than 180. They found no difference in death or disability at 90 days. And unfortunately, even though there were fewer intracranial hemorrhages in the intensive group, that didn't translate into a better outcome. So, in reality, we don't know the optimum blood pressure for 48 to 72 hours after thrombolysis. Well, as you know, patients are now having reperfusion with mechanical thrombectomy. So, what are the guidelines? Well, in the 28 stroke guidelines, you'll see some recommendations that are somewhat similar to thrombolytic therapy. They state it is reasonable to maintain the blood pressure less than 180 over 105 during and for 24 hours after the procedure. And in the patients who have successful reperfusion, it might be reasonable. Again, you can see it's a very soft recommendation to maintain the blood pressure less than 180 over 105. And you have to keep in mind in those patients who do not have successful recanalization of the target vessel, it is probably better to have the blood pressure on the higher side based on some observational and retrospective studies. One of the problems here is that the clinical trials were not addressing blood pressure goals. They were addressing the use of thrombectomy. And these trials use various blood pressure goals. So, it's very difficult to come up with a consensus based on those trials. There was a systematic review that found that a lower mean systolic blood pressure before and after the procedure was associated with better outcomes. However, they couldn't identify what that blood pressure threshold should be because there were so many variations in the studies that were examined. So, acute intracranial events. The workhorse drugs are going to be nicardipine and labetalol. Labetopine can be used. Esmolol has been used. But here you don't really want to use nitroprusside or nitroglycerin because they may increase cerebral blood flow and that could lead to worsening of cerebral edema. Let's finish up with some of those excess catecholamine states. The traditional choice has been fentolamine. Now, the key issue is if you know you're dealing with pheochromocytoma, and often this is for the anesthesiologist in the operating room, the key is to always give an alpha blocker, such as prazosin or doxazosin, before giving a beta blocker. For those patients with drug-induced hypertension, mostly from illicit drugs, then treat the agitation with benzodiazepines. And if they have still sustained severe hypertension, then labetalol or nicardipine can be used successfully. I want to take a few moments to just mention perioperative hypertension because this may also be viewed as a hypertensive emergency in specific patients. And here the goal blood pressure for the individual patient depends on the type of surgery and also the patient's comorbidities. Perioperative hypertension has been associated with more bleeding and transfusion, or acute renal injury, myocardial cerebral ischemia, and even intracranial hemorrhage. There are usually specific surgeries that have a higher risk for perioperative hypertension, and that includes cardiovascular surgeries, patients with head injury, neurosurgical procedures, head and neck surgeries, renal transplantation, and burn patients. When you approach these patients, you have to keep in mind that pain and anxiety must be addressed and treated first. If the patient has significant volume overload, diuresis may bring the blood pressure down. And don't forget about urinary retention. Since perioperative hypertension is transient, you want to use a very short-acting IV medication. And a variety have been used, nitroglycerin, nicardipine, clavidipine, labetalol, and again nitropresside historically, but probably not today. The very last thing I want to address is something that we probably see all the time in the ICU. That's the treatment of asymptomatic hypertension. So as you know, it's quite common practice that for a specified systolic blood pressure, there are orders to give IV hydralazine and or labetalol. I want to point out that there is actually no evidence of benefit with this practice, and there are actually no guidelines that address asymptomatic hypertension. I think the most important thing is when you are being called or you see a patient with elevated blood pressure in the ICU is to examine the patient. Consider that they may have pain or anxiety. They may be cold, or as we often see, the measurement may be incorrect, or it may be a transient number that comes right back down normal. So in general, if you could refrain from treating a number, the patient is likely to have better outcomes. I want to leave you with a few take-home points. Use the right patient for lowering the blood pressure acutely. When you do lower the blood pressure, aim for modest initial blood pressure reductions with monitoring of the effects so that you can make the correct next steps. Tailor the medication to the patient and their condition, and keep in mind that the optimum blood pressure for intracranial events still requires further studies, and you're likely to see changes with time as we get more information. Thank you very much for listening to this presentation.

hypertensive crisis

blood pressure management

acute blood pressure reduction

hypertensive emergencies

organ injury

autoregulation

medication choice