Extremely Elevated Blood Pressures: An Update on Hypertensive Urgencies and Emergencies

ABSTRACT: Acute elevations in blood pressure (also known as hypertensive crises or severe hypertension) can cause significant morbidity and mortality. The key to management of these episodes is to keep in mind that damage to particular organs from an elevated blood pressure is more important than the absolute level of blood pressure per se. A hypertensive emergency involves target organ injury and thus requires immediate (within 30 to 60 minutes) blood pressure reduction of between 10% and 20% with easily titratable intravenous medications. If target organ manifestations are not present, the severe hypertension can be approached as a hypertensive urgency, with a cautious reduction in blood pressure over 24 to 48 hours, usually with oral medications. After the hypertensive crisis, patients often continue to have difficulty with blood pressure control; in such cases, workup for secondary causes of refractory hypertension may be warranted.

 Key words: hypertensive urgency, hypertensive emergency, severe hypertension

Although most patients who are evaluated and treated in primary care practice for hypertension are ambulatory and achieve target blood pressure with 1 to 3 medications, about 1% require hospitalization consequent to more alarming elevations in blood pressure (usually higher than 180/110 mm Hg).¹ Some of these patients are seen in consultation for severe hypertension after strokes, myocardial infarctions, or surgery; occasionally during complicated pregnancies; or because of sudden, dramatic elevations in blood pressure (eg, as a result of nonadherence, antihypertensive withdrawal, or cocaine abuse) discovered in an office setting or emergency department. Primary care physicians are often asked to assist in the care of persons who experience a so-called inpatient “hypertensive crisis,” or what may be called a hypertensive urgency or emergency, often followed or preceded by ambulatory resistant hypertension.

The workup and pharmacological management of patients with strikingly elevated blood pressure have changed significantly over the past decade. There was a time when diazoxide, nitroprusside, and hydralazine were the only treatment options. All of these medications can have serious adverse effects; some, such as diazoxide, are not used anymore. Gradually, medications such as fenoldopam, labetalol, nicardipine, and clevidipine, as well as others, have proved their efficacy and safety in this setting. Recently, the workup of resistant or severe hypertension has expanded to include aldosterone/renin ratios, renin profiling, and polysomnography for obstructive sleep apnea, while renal artery interventions, such as dilatation and stenting for blood pressure control, have been questioned.² 

In this article, we will define a terminology that will be applied to acute, severe hypertension. We will also present 2 cases representative of the spectrum seen by primary care physicians: a hypertensive crisis in the perioperative period (Case 1) and severe hypertension during a CNS ischemic event (Case 2). We will discuss the appropriate primary care workup of patients with suspected resistant hypertension and possible changes in ambulatory treatment based on the results.

in the accompanying Primary Care Update, “Treatment Choices for Severe Hypertension,” we will review the updated armamentarium and outline the indications and potential complications of commonly used agents. 

TERMINOLOGY FOR
SEVERE HYPERTENSION
Chronic hypertension is a known risk factor for cardiovascular, cerebrovascular, and renal disease. Acute elevations in blood pressure, called hypertensive crises or “severe hypertension,” can also cause significant morbidity and mortality.

Although acute, severe hypertension was not specifically addressed in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), it is generally defined as a systolic blood pressure greater than 179 mm Hg or a diastolic pressure greater than 109 mm Hg respectively. This definition of severe hypertension will be used throughout this article. Some experts make adjustments to this range with systolic pressures as low as 160 mm Hg (especially during pregnancy or even lower with aortic dissection) and diastolic pressures as low as 100 mm Hg.

As we will emphasize throughout this article, it is not only the level of blood pressure that is critical, it is whether the elevated pressure has caused target organ damage. Table 1lists the most significant organ injuries. Even minimal hypertension (150/100 mm Hg, for example) is dangerous if the target organ of injury is the aorta during an aortic dissection. An elevated blood pressure accompanied by hemorrhages and exudates on funduscopic examination (Box I) is severe hypertension and a hypertensive emergency; however, a level of 200/125 mm Hg without ophthalmoscopic changes or other target organ injury is serious, but constitutes a hypertensive urgency, not an emergency. In contrast—and an important caveat—during ischemic strokes, systolic elevations of less than 200 (in some guidelines, 220) mm Hg are usually not treated (see Case 2). Key to management in these disparate circumstances is that damage to particular organs from an elevated blood pressure (the aortic vasculature in dissection or the vessels manifesting eye ground changes in the fundus) is more important than the absolute level of blood pressure per se.

Various terms have been associated with severe, acute hypertensive syndromes:
•Malignant or accelerated hypertension (usually based on grade 3 or grade 4 retinopathy, ie, hemorrhages and exudates or hemorrhages and exudates with papilledema, respectively).
•Hypertensive emergency (a variety of target organ injuries consequent to elevated blood pressure).
•Hypertensive urgency (no apparent target organ injury).
In the ambulatory setting, patients with severe hypertension are frequently characterized as “difficult to control” or as “resistant hypertensives”; they often receive 3 or more antihypertensive medications simultaneously. Some may also be nonadherent or experience rebound after abruptly discontinuing their medications.

A hypertensive emergency requires immediate (within 30 to 60 minutes) blood pressure reduction of between 10% and 20% with easily titratable intravenous medications. An emergency diagnosed by appropriate eye ground changes can also be considered accelerated or malignant, if that is practical for the individual clinician. If target organ manifestations are not present, the severe hypertension can be approached as a hypertensive urgency, with a cautious reduction in blood pressure over 24 to 48 hours, usually with oral medications. Box II offers suggestions for choosing the optimal antihypertensive medication in the appropriate setting.

 

These concepts will be demonstrated in the following 2 cases.

CASE 1: 
SEVERE, PERIOPERATIVE
HYPERTENSION
A 56-year-old man with type 2 diabetes mellitus, stage 3 chronic kidney disease (a glomerular filtration rate between 30 and 59 mL/min for longer than 3 months as a result of nephrosclerosis), and cholecystitis/cholelithiasis underwent laparoscopic cholecystectomy. You have been asked to see him postoperatively for glucose control and a blood pressure of 190/118 mm Hg.

He has a 15-year history of hypertension; recently, his blood pressure has been more difficult to control. He initially met his target (lower than 130/85 mm Hg; because he did not have proteinuria, his blood pressure was not decreased to 120/80 mm Hg) on monotherapy (hydrochlorothiazide 25 mg a day), but his in-office blood pressure (150/100 mm Hg) is presently not at target on a 3-drug regimen (hydrochlorothiazide 25 mg, amlodipine 10 mg, and lisinopril
20 mg, all once a day). Other than an ultrasound of his kidneys (which revealed bilateral renal disease without obstruction and kidney sizes of 9.2 and 9.8 cm) and a spot urine protein and creatinine sample that showed minimal urine protein excretion (less than 500 mg/d), no further workup has been done.

In addition to severe hypertension, the physical examination reveals a body mass index of 31, no hypertensive or diabetic changes on dilated funduscopic examination, no evidence of acute or chronic cardiac disease, no bruits, and no significant neurological or mental status problems (see Table 1). You write orders to manage his glucose and then address his blood pressure. The following questions need to be considered:
•Since he has severe hypertension (190/118 mm Hg), which category (emergency or urgency) should he placed in?
•What are your treatment options? (See “Treatment Choices for Severe Hypertension” on page 449.)
•During what time interval should his pressure be lowered and by how much?
•How should this episode of severe hypertension and his recent in-office hypertension change his ambulatory workup and therapy?

This patient has severe hypertension without manifest target organ injury. He does not have eye ground changes, an acute cardiac syndrome (ischemia or heart failure), encephalopathy, focal neurological injury, or other key findings listed in Table 1. Therefore, this is a hypertensive urgency, not an emergency.

A number of drugs are appropriate in this setting. For instance, labetalol, bolus or drip; nicardipine; or fenoldopam can be used as well as other agents. Since he has had abdominal surgery and is not allowed to eat or drink, clonidine is not an optimal choice. Nitroprusside is not necessary.

A 10% to 20% reduction in blood pressure over the first 24 hours is a good target. Thus, his systolic blood pressure of 190 mm Hg can be lowered by about 19 to 38 mm Hg to a range of 150 to 170 mm Hg, and his diastolic pressure of 118 mm Hg can be lowered by about 12 to 24 mm Hg to a range of 110 to 98 mm Hg. When he begins to eat, the selected antihypertensive agent can be transitioned to an oral combination based on his home regimen.

This patient’s hypertensive crisis in the hospital and his failure to reach target blood pressure as an outpatient (assuming medication adherence) warrant a diagnosis of resistant hypertension. To determine further adjustments to his regimen after his hospitalization, refer to Box III, which addresses ambulatory workup and treatment. He will require an aldosterone/renin ratio, renin profiling, and changes to his treatment based on those results. For example, if aldosterone-mediated hypertension (an elevated aldosterone and aldosterone/renin ratio) is diagnosed, his antihypertensive regimen should include spironolactone.

CASE 2:
SEVERE HYPERTENSION
COMPLICATING A STROKE
The family of a 75-year-old man brings him to the emergency department after the sudden onset of right- (dominant-) sided weakness and difficulty in communicating. He has a history of poorly controlled hypertension (on a 3-drug regimen) and type 2 diabetes mellitus, which is treated with metformin and exenatide. His most recent hemoglobin A_1c level was 8.0%. CT findings are consistent with older lacunar infarcts and a possible, acute dominant hemispheric parietal lobe ischemic stroke. He has no history of atrial fibrillation.

The patient is admitted. His blood pressure is 200/108 mm Hg. You are asked to assist the neurologist in the management of his elevated blood pressure.

Severe hypertension in acute CNS ischemic syndromes: caveats reviewed. The questions to consider in this episode of severe hypertension are:
•Does this presentation qualify as a hypertensive emergency?
•Are there special considerations in patients with severe hypertension in the setting of acute cerebral ischemia?
•What drugs are appropriate and which agents should be avoided? (See “Treatment Choices for Severe Hypertension.”)
•Are there special considerations for his blood pressure management after he is discharged?

Severe hypertension in the setting of an acute CNS ischemic episode is treated as a unique circumstance. By definition, a target organ injury (to the brain) is present, but there is more to the story.

The brain depends on adequate blood flow to carry out its complex functions; however, cerebral auto-regulatory ability is disrupted after an ischemic insult. Single photon emission tomography has demonstrated that decreases in blood pressure during ischemic strokes can impair cerebral blood flow.³ Reduced cerebral blood flow can lead to additional neuronal death beyond that caused by the stroke itself. There are vulnerable neurons surrounding the infarct zone called the penumbra. They are at risk of further injury or cell death if blood pressure is reduced to what we might consider normal or even “partially controlled” levels, such as 170/95 mm Hg.⁴

A varietyof studies have demonstrated a relationship between diastolic blood pressure reductions and stroke outcomes—the higher the blood pressure, the better. Independent of treatment, the odds of death or dependency at 21 days after an ischemic stroke were 2.6 times greater in patients with less than a 10% early decrease in diastolic blood pressure, approximately 3 times greater in those with a 10% to 20% decrease, and 4.36 times greater in those with a more than a 20% decrease in the elevated diastolic blood pressure.⁵Another study prospectively evaluated factors that affect the 3-month outcome in 115 patients with ischemic strokes; a poor outcome was independently associated with the degree of systolic blood pressure reduction during the first 24 hours. The odds ratio was 1.89 for a poorer outcome with every 10% decrease in systolic pressure.⁶

As a result of the data, a scientific statement from the Stroke Council of the American Stroke Association has recommended that blood pressure generally not be lowered in patients with acute ischemic stroke who are not otherwise candidates for thrombolysis.⁷ (Table 2 lists recommendations for the use of thrombolysis).Based on these considerations, this patient’s blood pressure should not be treated in the acute period. Exceptions to these recommendations include patients with an additional hypertensive encephalopathy, aortic dissection, acute renal failure, acute pulmonary edema, acute myocardial infarction, or other organ involvement consistent with target organ damage (see Table 1). By consensus, it has been recommended that acute blood pressure lowering be avoided in patients without these special conditions unless the systolic pressure is 220 mm Hg or higher or the diastolic pressure is 120 mm Hg or higher.⁷

The Cochrane Stroke Group performed a systematic review that assessed the effect of lowering or raising blood pressure in persons with acute stroke; data from 32 trials (5368 patients) were included. The investigators concluded that there was not enough evidence to reliably evaluate the effect of altering blood pressure on outcome after ischemic strokes. Further studies are required to determine the optimal management of blood pressure and the use of antihypertensive medication in patients with acute stroke.⁸

Hemorrhagic strokes and subarachnoid hemorrhages. These must be discussed separately from ischemic strokes. Despite similar recommendations regarding blood pressure lowering in the setting of acute cerebral hemorrhage, there are 2 large studies underway that may change this practice in the future. The first is the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT).⁹ The investigators reviewed previous small studies that demonstrated early blood pressure lowering in the setting of hemorrhagic stroke might be beneficial. Two hundred patients diagnosed within 6 hours of a hemorrhagic stroke with elevated blood pressure received guideline-based therapy (target systolic pressure lowered to 180 mm Hg)¹⁰ and 203 received intensive lowering (target systolic pressure lowered to 140 mm Hg). The intensively treated group had a significantly lower risk of hematoma growth. A similar study called Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) is addressing the same question with a similar design.¹¹ A reference is provided for additional information about subarachnoid hemorrhages.¹²

A CONSISTENT APPROACH IS CRUCIAL
A recent study demonstrated heterogeneity in care, blood pressure control, and outcomes for patients hospitalized for severe hypertension.¹³ Hospital mortality in this cohort was 6.9%, and the 90-day readmission rate was 37%. Funduscopic examination was performed in only 13% of the patients. Attempts to control severe hypertension varied significantly both in the quality of the agents used and in the success and timing in lowering dangerously elevated blood pressures. The authors were concerned enough about the results that they suggested ongoing studies to standardize diagnosis and treatment of severe, acute hypertension—in an effort to decrease mortality and readmission rates. Another study that focused on severe hypertension in patients treated at 4 academic center emergency departments was qualitatively similar in both its results and its conclusions.¹⁴ 

Severe hypertension is a life-threatening syndrome. Thus, differentiation of urgency from emergency (especially on the basis of funduscopic examination), appropriate medication use, cautious reductions in blood pressure, and attention to ambulatory adjustments should be consistent. The template provided in this article addresses all relevant issues relating to specific diagnoses, examination findings, target organ evaluations, pharmacological treatment, and appropriate attention to later ambulatory adjustments and additional workup. Consistency in application has the potential to decrease readmission rates as well as mortality.■

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