Move fast, but sometimes not too fast, in hypertensive emergencies

Reducing blood pressure in stroke, aortic dissection, and other conditions.


Physicians looking for recent U.S. evidence-based guidelines on hypertensive emergency may find themselves out of luck, according to Gregary D. Marhefka, MD, FACP. The 2014 guidelines from the Eighth Joint National Committee (JNC8) on management of high blood pressure don't mention the topic at all, he noted during his talk on “Hypertension: Urgencies, Emergencies, and Refractory Hypertension” at Internal Medicine Meeting 2015.

“We have to go back to JNC7,” he said. Those guidelines, from 2003, recommend decreasing blood pressure in the first hour but no more than 25%. Within the first 6 hours, blood pressure should be decreased to a goal of about 160/100 mm Hg and then gradually normalized over time.

Gregary D Marhefka MD FACP Photo by Kevin Berne
Gregary D. Marhefka, MD, FACP. Photo by Kevin Berne

The guidelines call for that normalization to occur within 48 hours. “But I often tell the patients, ‘You know, your blood pressure may not be entirely normal when you leave the hospital in 3, 4, or 5 days, but it's going to be a continuum of outpatient follow-up,’” said Dr. Marhefka, who is an associate professor of medicine and associate director of the cardiovascular intensive care unit at Thomas Jefferson University Hospital in Philadelphia.

More recent guidelines from the European Society of Hypertension, which were published in 2013, don't offer as specific a timeline, but they also recommend a reduction of less than 25% in the first hours of treatment. Dr. Marhefka explained that a more drastic reduction could affect autoregulation.

He noted that the body can tolerate a fairly wide range of blood pressure fluctuations while maintaining normal pressure to the brain, heart, and kidneys, the 3 major organs that have microvascular or microcirculation. However, he said, “If somebody is chronically hypertensive … they're living at a microregulatory fashion, or in fact, they lose some of that autoregulation at the microvascular level. If their MAP [mean arterial pressure] is 120 [mm Hg] and you precipitously drop that MAP to 60 or 70 [mm Hg] … you're really dramatically reducing their cerebral perfusion pressure.”

For hypertensive emergencies associated with stroke, encephalopathy, or retinopathy, the agents of choice are intravenous nicardipine and labetalol, Dr. Marhefka said. Clevidipine, the ultra-short-acting dihydropyridine calcium-channel blocker, is also effective but cost-prohibitive, he noted.

“When it came out about 4 years ago, we started using it like crazy in the intensive care unit because it was very rapid in onset … it has a very nice wide range, it's very titratable, but incredibly expensive, so our pharmacy started restricting its use,” he said. “Until that price comes down, we'll probably have to do without it if we can.”

Drugs that are contraindicated in these clinical scenarios include nitroprusside, nitroglycerin, and hydralazine, all of which increase intracranial pressure, he said.

In acute stroke, 2013 guidelines from the American Heart Association (AHA)/American Stroke Association don't recommend treatment for blood pressure above 140 mm Hg but do recommend it once the blood pressure exceeds 220/120 mm Hg, Dr. Marhefka said. Also, he noted, tissue plasminogen activator shouldn't be given until blood pressure is controlled to below 185/110 mm Hg.

Dr. Marhefka pointed out that an evidence-based overall “ideal” blood pressure range is as yet unknown. “As a result of this, this is why when our neurology colleagues consult on some of our hypertensive emergency patients … the variability is quite wide in terms of what blood pressure range they recommend,” he said.

Another serious type of hypertensive emergency, aortic dissection, comes in 2 types, Dr. Marhefka said. Type A aortic dissection is any dissection that involves the ascending aorta, while type B involves only the descending aorta, he noted. With type A, he said, immediate surgery is the treatment of choice. “It's a 1% risk of mortality every hour that passes in the first 48 hours. So that means that 50% of patients are dead at 48 hours without any treatment,” he noted.

The treatment of choice for type B aortic dissection is medical therapy, “unless there's some malperfusion of one of the intestinal organs or spinal artery malperfusion or worsening dissection,” he said. The first-line medical treatment of choice is esmolol, but Dr. Marhefka said he often sees patients come up to the ICU on nitroglycerin, nitroprusside, or nicardipine, none of which is a good choice for first-line therapy in this situation.

“Though the blood pressure may look better, and everybody feels better, those medications do nothing to the contractility of the heart,” he said. “You want to decrease the contractility of the heart, so you must absolutely start these patients on a negative inotrope.”

Guidelines on hypertensive emergencies “go out the window” with an aortic dissection, Dr. Marhefka said. “With dissection, you want to get their blood pressure down as quickly as possible,” to a recommended level less than 120 mm Hg systolic, “not in the first hour, not in the first 6 hours, as quickly as possible,” he said. He also stressed that it's very important to monitor these patients closely for any neurologic changes.

For hypertension associated with congestive heart failure, the treatment of choice is a diuretic, nitroglycerin, or nitroprusside, Dr. Marhefka said. Medications with negative inotropes are contraindicated, including labetalol, esmolol, and diltiazem. Even nicardipine and clevidipine have a very mild negative inotrope effect and involve large volume, so they are usually best avoided, he noted.

“Last week, a patient was put on nicardipine in the middle of the night by the housestaff; in the morning the patient was intubated because they got 150 cc an hour overnight, and nobody observed that they were getting hypoxic,” he said. “So just be careful with the volume load, not to mention the negative inotrope, for these medications.”

Dr. Marhefka also addressed the question of screening for renal artery stenosis in the setting of hypertension. Class I indications for screening from the American College of Cardiology Foundation (ACCF)/AHA include onset of hypertension at an age younger than 30; accelerated, resistant, or malignant hypertension; acute kidney injury after angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) therapy; discrepant kidney size; or flash pulmonary edema. In patients with these indications, ultrasonography, computed tomography angiography (CTA), or magnetic resonance angiography (MRA) should be performed.

“If you can get an ultrasound, that's ideal, because there's no radiation. Unfortunately, some patients don't lend themselves to adequate ultrasound studies. They need to be NPO for that as well. But if you can't visualize the renal arteries or get a nice comfortable view, then CTA or MRA can also be used,” Dr. Marhefka said. “Depending on the findings there, you may need to go to a catheter-based angiogram.” Captopril renal scintigraphy and selective renal vein sampling are no longer recommended screening methods for this condition, he said.

The 2013 ACCF/AHA guidelines recommend pharmacologic treatment for unilateral renal artery stenosis, Dr. Marhefka noted, such as ACE inhibitors, ARBs, calcium-channel blockers, and beta-blockers. However, stents can be considered for patients with flash pulmonary edema (a class I indication) or unstable angina (a class IIa indication).

Asymptomatic renal artery stenosis isn't found much anymore because there is less enthusiasm for stenting it and physicians are less likely to screen for it, Dr. Marhefka said. However, he noted, “If you've got hemodynamically significant bilateral or solitary viable kidney—and this is usually in [consultation] with a nephrologist—this might be somebody you would consider [stenting].” Stents might also be considered in patients with malignant hypertension or patients with renal insufficiency. “Some of these [are] sort of lesser indications, but ones to think about,” he said.

Hypertension associated with scleroderma renal crisis “is something which you won't see often,” Dr. Marhefka said. “I only saw it 5 years ago and I haven't seen it since, but about 5% of patients with systemic sclerosis can present with scleroderma renal crisis, and it can be impressive.”

Patients in scleroderma renal crisis can present with malignant hypertension and end-organ damage or renal failure. The condition is more common in patients being actively treated with steroids, Dr. Marhefka said. Other possible features include acute heart failure, encephalopathy, and microangiopathic hemolytic anemia, he noted.

“The acute treatment for this, completely independent of creatinine, is ACE inhibitor,” for example, captopril, Dr. Marhefka said. “They do say in the guidelines here if the patient is in renal failure or even if they're about to be on dialysis, or if you start this captopril and the renal failure gets worse, continue the captopril, even if hemodialysis is needed,” he noted. The prognosis for systemic scleroderma is poor, with a 5-year survival rate of 65%, Dr. Marhefka said. He also noted that although ACE inhibitors are recommended for treatment, they don't prevent the condition.

Dr. Marhefka pointed out that pregnant patients have a lower threshold for hypertensive emergency, according to 2015 guidance from the American Congress of Obstetricians and Gynecologists (ACOG): a repeated value of 160/110 mm Hg persisting for more than 15 minutes of rest in the setting of preeclampsia, gestational hypertension, HELLP syndrome, or preexisting hypertension with acute worsening. The ACOG guidelines recommend intravenous labetalol, 20 mg; intravenous hydralazine, 5 to 10 mg; or oral nifedipine, 20 mg. ACE inhibitors cannot be used because they are contraindicated in all trimesters of pregnancy, Dr. Marhefka said.

Although intravenous hydralazine is recommended for these patients, Dr. Marhefka offered a general warning about its use as a first-line agent in most hypertensive emergencies because of its unpredictability.

“It has about a 5- to 6-hour half-life, so you can really get into trouble with a patient on the floor,” he said. “Their blood pressure is 190 [mm Hg], and somebody gives them hydralazine, and all of a sudden their blood pressure is 100 [mm Hg]. …You might cause more problems.”