Acknowledgments
The author thanks Shakaib U. Rehman, MD, the late Donald G. Vidt, MD, and Jan N. Basile, MD, for their contributions to previous editions of this chapter.
High blood pressure (BP), or hypertension, remains a major worldwide public health challenge, despite recent improvements in control rates in many developed nations. because it is a major contributor to cardiovascular disease (CVD), and is increasing in prevalence in developing nations. In the United States, approximately 80 million people had hypertension in 2012 ; fortunately, true “hypertensive crises” account for less than 1% of health care encounters involving elevated BP. Large U.S. claims databases have suggested that the annual incidence was about 1 to 2 per million population in the late 1990s, and may be decreasing recently, in the U.S. and other developed nations. However, as hypertension becomes more prevalent worldwide, case reports and case series of hypertensive crises continue to be reported.
In 1928, when “malignant hypertension” was first added to the medical lexicon, the prognosis of patients with grade IV hypertensive retinopathy was worse than that of many cancers (17% after 1 year in the 1939 case series, hence the name). About 40% of these deaths occurred from renal failure, with stroke (24%), myocardial infarction (11%), and heart failure (10%) accounting for most of the rest. This situation has markedly changed since the advent of effective chronic oral antihypertensive drug therapy ; the diagnoses of “malignant” or “accelerated” hypertension are now used nearly exclusively by coding personnel, and are no longer found in many national or international hypertension guidelines, except to redefine these terms in a more contemporary context.
Traditionally, hypertensive crises are divided into emergencies and urgencies. A hypertensive emergency is a very elevated BP in a patient with acute, ongoing target organ damage, and is a true medical emergency, requiring prompt BP reduction (although seldom into the normal range). Of less concern are “hypertensive urgencies” (except for perioperative hypertension, discussed later and in Chapter 44 ), which may be better termed “major elevations in BP without acute target organ damage.” Most patients with this problem are nonadherent to drug therapy or inadequately treated, and often present to the emergency department for other reasons. Such patients require neither hospital admission, nor acute lowering of BP, and can safely be treated in the outpatient setting with any one of a number of appropriate oral medications. It is the distinction between these two types of hypertensive crises that presents the greatest challenge to most physicians. This chapter will discuss the clinical presentation and appropriate evaluation and treatment of the patient with hypertensive crises, and suggest an algorithm to triage patients with major elevations of BP to in-hospital treatment or outpatient management.
Contemporary Definitions
Hypertensive Emergency
A hypertensive emergency is a major and often sudden elevation in BP, associated with progressive, acute target-organ dysfunction. It can present as an acute cerebrovascular event or disordered cerebral function, an acute coronary syndrome with ischemia or infarction, acute pulmonary edema, or acute renal dysfunction ( Box 46.1 ). Although the level of BP at presentation is often very high (systolic BP usually >180 mm Hg or diastolic BP > 120 mm Hg), it is not the degree of BP elevation, but rather the clinical status of the patient that defines the emergency. For example, a BP of 160/110 mm Hg in a 65- year-old man with an acute aortic dissection or a woman in her third trimester of pregnancy with eclampsia (despite a BP of only 145/95 mm Hg) are true hypertensive emergencies. Such patients almost always should be treated with parenteral medications in the intensive care unit or a monitored hospital bed. Risk factors for hypertensive emergencies include: low socioeconomic status, poor access to health care, nonadherence to prescribed antihypertensive drug therapy (including sudden withdrawal from an antihypertensive medicine, e.g., clonidine), substance (particularly cocaine) or alcohol use disorder, oral contraceptive use, and cigarette smoking.
- 1.
Hypertensive encephalopathy
- 2.
“Malignant hypertension:” elevated blood pressure with papilledema or acute retinal hemorrhages/exudates
- 3.
Intracranial hemorrhage (intracerebral or subarachnoid); ischemic stroke (rarely)
- 4.
Acute coronary syndrome (unstable angina/myocardial infarction)
- 5.
Acute left ventricular failure with pulmonary edema
- 6.
Acute aortic dissection
- 7.
Rapidly progressive renal injury, (e.g., systemic vasculitis, including scleroderma crisis)
- 8.
Eclampsia
- 9.
Life-threatening arterial bleeding
- 10.
Head trauma
- 11.
Less common situations:
- •
Pheochromocytoma crisis
- •
Tyramine interaction with monoamine oxidase (MAO)-inhibitors
- •
Overdose with sympathomimetic drugs, such as phencyclidine, lysergic acid diethylamide (LSD), cocaine, or phenylpropanolamines
- •
Rebound hypertension following the sudden withdrawal of antihypertensive agents, such as clonidine or beta-blockers
- •
Major Blood Pressure Elevation Without Ongoing Target-Organ Damage (So-Called “Hypertensive Urgencies”)
Traditionally, many physicians have been uncomfortable with hypertensive patients who had BP higher than 180/120 mm Hg, simply because such BP levels, if sustained, were first shown to benefit from antihypertensive drug treatment with a reduction in long-term morbidity. To acknowledge this, many older guidelines recognized “hypertensive urgencies:” major elevations in BP without acute, ongoing target organ dysfunction. Examples include major BP elevations associated with severe headache, shortness of breath, mild epistaxis, or severe anxiety. Other sources define a hypertensive urgency as a patient with diastolic BP (DBP) higher than 115 to 120 mm Hg, or systolic BP (SBP) higher than 180 mm Hg. Although such patients may have signs of chronic target organ damage, such as grade II hypertensive retinopathy, left ventricular hypertrophy, or chronic kidney disease with stable proteinuria, the absence of acute or progressively worsening hypertensive target organ damage differentiates these patients from those with hypertensive emergencies. Despite the very high BP, these patients have a low risk of cardiovascular events over the next few months (even if left untreated). Many now-classic case series gathered before antihypertensive drug therapy became available were validated by the first Veterans’ Administration Cooperative Trial (published in 1967), in which 70 patients with DBP between 115 and 129 mm Hg randomized to placebo had zero (95% confidence interval [CI] 0 to 5) major CVD or adverse events over the next 2 months. A descriptive meta-analysis of 86,137 hypertensive subjects in 590 randomized trials collected by the United States Food and Drug Administration (FDA) from 1973 to 2001 showed no significant difference (relative risk [RR]: 1.03, 95% CI: 0.71 to 1.47, p = 0.86) regarding short-term “irreversible harm” (a composite of death, stroke, and myocardial infarction [MI]) between subjects randomized to placebo or active drug treatment who dropped out of the trials. There is currently much more evidence showing harm, and little (if any) showing benefit, from acute BP lowering in asymptomatic patients with major BP elevations. Unfortunately, use of the term, “urgency,” has led some physicians to over-aggressively treat some patients in emergency departments with one or more parenteral medications, with the object of rapidly normalizing their BP. Although this procedure can impress the patient with the importance of BP-lowering, wild swings in BP have been associated with stroke, MI, and other tragedies. Even oral loading doses of antihypertensive agents can lead to cumulative effects, including hypotension, sometimes following discharge from the emergency department. A now-classic randomized clinical trial by Zeller et al, published in 1989, found no significant difference in BP control at 24 hours between groups of patients who had or had not received clonidine loading before initiation of appropriate chronic oral antihypertensive therapy. This conclusion was recently corroborated by the finding of no significant differences in any outcome for 435 emergency department patients with markedly elevated BPs, but without target-organ damage who received oral antihypertensive therapy, compared with 581 similar patients who received no acute therapy. Many believe that the traditional classification of “hypertensive urgency” needs to be updated (if not abandoned), and that more diagnostic importance should be placed on presenting signs and symptoms, rather than focusing on the BP level. Some have advocated replacing the term, “hypertensive urgency,” with “major BP elevation without ongoing target organ damage.”
Clinical Evaluation
Early triage of hypertensive emergency versus major BP elevation without ongoing target organ damage should limit the expenditure of scarce health care resources to those who truly need acute care and close monitoring, and reduce their morbidity and mortality. The evaluation of patients presenting with hypertensive crises should include a targeted history, focused physical examination and a limited laboratory examination to differentiate these two conditions. The main purpose of the diagnostic exercise is to assess whether target organ damage is acute and progressive.
The clinical presentation of hypertensive emergencies is most easily classified according to the target organ involved; the prevalence of each type is variable across the large reports. The most common of these include: cerebral infarction (20% to 25%), pulmonary edema (14% to 31%), hypertensive encephalopathy (0% to 16%), acute coronary syndrome (12% to 25%), intracerebral or subarachnoid hemorrhage (4% to 15%), eclampsia (0% to 4%), or aortic dissection (0% to 2%). A focused history should be obtained, especially regarding headaches, seizures, mental status changes, chest pain, shortness of breath, change in urination, and development of edema. A standardized sphygmomanometer with an appropriately sized cuff should be used to measure BP because many automated BP monitors are inaccurate at very high levels. All patients should have a funduscopic examination by an experienced clinician, looking carefully for hemorrhages, exudates, and/or papilledema. The value of this examination has been questioned because it is neither sensitive nor specific for hypertensive encephalopathy, and interexaminer reliability is low. However, a recent case-series using nonmydriatic ocular fundus photography documented grade III or IV hypertensive retinopathy in 33% of 21 subjects presenting to Emory University Hospital Emergency Department with DBPs 120 mm Hg or higher. A cardiovascular exam should document radial, femoral, and carotid pulses. Pulse deficits should raise the suspicion of aortic dissection. A thorough neurological examination, including mental status, should be conducted.
Few recent studies have determined the prognostic value of abnormal laboratory findings in asymptomatic patients with major elevations in BP, but this is a very valuable method of screening for, and documenting, acute target organ damage. The laboratory evaluation should include a complete blood count, including peripheral smear, to look for schistocytes (indicative of microangiopathic hemolytic anemia ), a metabolic profile (blood urea nitrogen, serum creatinine, electrolytes), and a urinalysis. Although proteinuria is important prognostically (particularly if acutely increased, compared with baseline), the most important findings are red blood cells (RBCs) and RBC casts, typical of acute glomerular and/or tubular injury. An electrocardiogram and portable chest radiograph should be performed for patients with chest pain or dyspnea, but not for asymptomatic individuals. For patients with an acute change in mental status or acute neurological signs and symptoms suggestive of cerebral encephalopathy, ischemia or hemorrhage, a computed tomographic (CT) scan of the head should be performed. Antihypertensive drug therapy may need to be initiated before all test results are obtained or the underlying cause of the emergency is determined.
One approach to therapy of hypertensive emergencies stratifies patients according to the patient’s plasma renin activity or direct renin level. In most hospitals, the laboratory turnaround time is too long for this strategy to be useful. Until this scheme is prospectively evaluated, empiric treatment for patients with a hypertensive emergency will remain the standard of care.
Clinical Management
Because it is no longer ethical to withhold antihypertensive treatment from patients presenting with hypertensive crises, any recent evidence-base for such therapy is lacking. Such treatment is, by definition, only provided in the short-term (minutes-to-hours), and is routinely followed by conventional oral antihypertensive agents; it is therefore unlikely that long-term CVD outcome differences could be demonstrated. No long-term data from randomized clinical trials of different drugs in hypertensive emergencies have been collected; instead, existing data come from long-term cohort studies, comparative trials of acute BP-lowering agents, and expert opinion. Nonetheless, all authorities agree that therapeutic decisions should be based on the presence of acute, ongoing target-organ damage and not solely on the level of BP. The first priority should be to diagnose each patient who presents with very high BP as shown in Fig. 46.1 .
Hypertensive Emergencies
When a hypertensive emergency has been diagnosed, antihypertensive drug therapy should be initiated immediately. This often occurs before the results of all laboratory studies are available. Once the patient is more clinically stable, investigation into the cause of the presentation should be performed.
The primary goal in treating the patient with a hypertensive emergency is to limit target organ damage, by allowing autoregulation to be reestablished in important vascular beds. In most patients with hypertensive emergencies, the BP-flow curve ( Fig. 46.2 ) is shifted, over time, upward and to the right. Lowering BP suddenly, or to a level that would otherwise be considered “normal” (e.g., downward arrow in Fig. 46.2 ) would leave the patient with an acutely underperfused vascular bed, and may lead to ischemia (cerebral, myocardial, renal, or other). Parenteral therapy is recommended because it can be precisely controlled, and its antihypertensive effect rapidly stopped, should the patient’s BP suddenly fall. Although many hospitals have protocols prohibiting the use of short-acting parenteral antihypertensive agents outside of intensive care units, such therapy can be started by a physician at the bedside (even in the Emergency Department), and continued during transfer to a monitored hospital bed. Although there is no clinical trial evidence, experience recommends a reduction in mean arterial pressure to no more than 25% below pretreatment level within the first 2 hours after presentation. Over the next 2 to 6 hours, BP can be reduced slowly toward 160/100 mm Hg. If this level of BP is well tolerated and the patient is clinically stable, further gradual reductions can be implemented in the next 24 to 48 hours. The most notable exceptions to these general targets (see later) are with acute aortic dissection (SBP target: <120 mm Hg over 20 minutes), and acute ischemic stroke-in-evolution (for which no BP lowering is generally recommended in the U.S.). Some of the agents often used in the management of the hypertensive emergencies are listed in Table 46.1 . Once BP has been lowered safely for a sufficient period to allow restoration of normal autoregulation (typically 12 to 24 hours), oral agents can be started as the parenteral agent is tapered, thus avoiding rebound hypertension. Typically, patients with hypertensive emergencies are volume depleted, so loop diuretics are not recommended, unless there is evidence of volume overload. The judicious use of diuretics may be necessary after many (typically >12) hours of intravenous vasodilator therapy because, with the exception of fenoldopam, use of these agents is accompanied by sodium and volume retention, and resistance to further BP reduction (so-called “tachyphylaxis”).
