INVITED REVIEW ARTICLE

Hypertensive Crisis Maria Alexandra Rodriguez, MD, Siva K. Kumar, MD, and Matthew De Caro, MD

Abstract: Hypertension is a common chronic medical condition affecting over 65 million Americans. Uncontrolled hypertension can progress to a hypertensive crisis defined as a systolic blood pressure ⬎180 mm Hg or a diastolic blood pressure ⬎120 mm Hg. Hypertensive crisis can be further classified as a hypertensive urgency or hypertensive emergency depending on end-organ involvement including cardiac, renal, and neurologic injury. The prompt recognition of a hypertensive emergency with the appropriate diagnostic tests and triage will lead to the adequate reduction of blood pressure, ameliorating the incidence of fatal outcomes. Severely hypertensive patients with acute end-organ damage (hypertensive emergencies) warrant admission to an intensive care unit for immediate reduction of blood pressure with a short-acting titratable intravenous antihypertensive medication. Hypertensive urgencies (severe hypertension with no or minimal end-organ damage) may in general be treated with oral antihypertensives as an outpatient. Rapid and short-lived intravenous medications commonly used are labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside, and clevidipine. Medications such as hydralazine, immediate release nifedipine, and nitroglycerin should be avoided. Sodium nitroprusside should be used with caution because of its toxicity. The risk factors and prognosticators of a hypertensive crisis are still under recognized. Physicians should perform complete evaluations in patients who present with a hypertensive crisis to effectively reverse, intervene, and correct the underlying trigger, as well as improve long-term outcomes after the episode. Key Words: hypertension, hypertensive crisis, hypertensive emergency, hypertensive urgency (Cardiology in Review 2010;18: 102–107)

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ystemic hypertension (HTN) is a common medical condition affecting over 1 billion people worldwide, and more than 65 million Americans. It is a risk factor for premature cardiovascular, renal, and cerebrovascular disease, and is responsible for up to 7 million deaths a year. Hypertension is defined as a systolic blood pressure (SBP) ⬎140 mm Hg or diastolic blood pressure (DBP) ⬎ 90 mm Hg in patients with known HTN or otherwise measured on 2 or more settings. Approximately 30% of the United States population age ⱖ18 have some form of HTN, making it one of the most common chronic medical conditions.1,2 The 2 principal categories of high blood pressure (BP) are essential (or primary) HTN and secondary HTN. Essential HTN has a more widespread presentation with an idiopathic source. This disease process occurs more commonly in patients with a variety of risk factors including black race, family history of HTN,3 dyslipidemia, alcohol intake, obesity, and personality traits, such as a hostile attitude.4 In contrast, secondary HTN accounts for 5% to 10% of hypertensive patients and is regularly caused by an underlying and frequently correctable etiolFrom the Department of Medicine, Cardiology Division, Jefferson Medical College/Thomas Jefferson University Hospital, Philadelphia, PA. Correspondence: Maria Alexandra Rodriguez, MD, Department of Medicine, Division of Cardiology, Thomas Jefferson University Hospital, Jefferson Heart Institute, 925 Chestnut St, Mezzanine, Philadelphia, PA 19107. E-mail: [email protected]. Copyright © 2010 by Lippincott Williams & Wilkins ISSN: 1061-5377/10/1802-0102 DOI: 10.1097/CRD.0b013e3181c307b7

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ogy, including primary renal disease, renovascular disease, and endocrine disorders such as a pheochromocytoma, Cushing syndrome or primary aldosteronism. It is estimated that 1% to 2% of the HTN population will present with an acute and severe elevation in BP termed “hypertensive crisis.”5 A hypertensive crisis is often described as a SBP ⬎180 mm Hg or a DBP ⬎120 mm Hg, with or without end-organ damage. It is further characterized as a hypertensive urgency or hypertensive emergency. The distinction is based on the degree of BP elevation and the presence or absence of target organ damage.6 Prompt recognition between a hypertensive urgency and hypertensive emergency could dictate management and triage. Treatment in the emergency room for an uncomplicated hypertensive urgency or admission to the intensive care unit with immediate BP reduction for a hypertensive emergency can prevent adverse outcomes that may include myocardial infarction (MI), stroke, renal failure, coma, and death. This article reviews hypertensive crisis—its identification, associated risk factors, pathophysiology, management, and treatment.

DEFINITION The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, with the most recent report in 2003,7 classifies 4 stages of BP: normal, prehypertension, stage 1 HTN, and stage 2 HTN. Pre-HTN is defined as a SBP of 120 to 139 mm Hg or a DBP of 80 to 89 mm Hg. Stage 1 is a SBP 140 to 159 or a DBP 90 to 99 mm Hg, while stage 2 is a SBP ⱖ160 mm Hg or a DBP ⱖ100 mm Hg. Although not a category in Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, a SBP ⬎179 mm Hg or a DBP ⬎109 mm Hg is termed “severe hypertension.” More significant than the BP rise is the briskness of the increase and the degree of target organ damage. The degree of BP elevation and length of time HTN has been present will determine the overall outcome.7 In 1914, clinician Franz Volhard and pathologist Theodor Fahr, who had completed extensive work on renovascular HTN, were the first to coin the term “malignant HTN”; the radical changes in BP that we recognize in the present day as a hypertensive urgency. They described this occurrence as a condition where individuals with severe HTN had parallel renal failure, retinopathy with papilledema, fibrinoid necrosis, uremia, and accelerated death.8 In 1921, Keith and Wagener identified similar patients who had papilledema and severe retinopathy with no findings of renal insufficiency, concluding that to have malignant HTN, symptoms could occur independently. They introduced the term “accelerated HTN.”9 In 1928 Oppenheimer and Fishberg were the first to describe a hypertensive encephalopathy associated with headaches, convulsions, and central nervous system deficits in the setting of accelerated HTN.10 Accelerated HTN is currently recognized as a severely elevated BP with a SBP ⬎179 mm Hg or a DBP ⬎109 mm Hg associated with ocular hemorrhages, exudates, and no papilledema (grade III Kimmelstiel-Wilson retinopathy).11 Malignant HTN may be used to define a marked HTN consisting of ocular hemorrhages and exudates with papilledema (grade IV Kimmelstiel-Wilson retinopathy).12 The term malignant HTN previously relating to encephalopathy or nephropathy is no longer used and has been removed from the National and International Blood Pressure Control guidelines. Cardiology in Review • Volume 18, Number 2, March/April 2010

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Medication noncompliance or the inadequate treatment of stage 1 or stage 2 HTN may lead to the development of hypertensive urgency, often defined as a SBP ⬎180 mm Hg or a DBP ⬎120 mm Hg in the absence of or minimal target end organ damage.7 These patients present with nonprogressive symptoms of headache, shortness of breath, epistaxis, or pedal edema.7 It is more desirable to reduce their BP within hours of presentation. Hypertensive emergency is severe HTN ⬎220/140 mm Hg and a DBP ⬎120 to 130 mm Hg, which irrevocably causes end-organ damage including but not limited to the cardiac, renal, and central nervous systems. Although the absolute BP elevation is not a criterion for diagnosis, a hypertensive emergency is most consistently seen with a DBP ⱖ120 mm Hg,13 and accounts for 25% to 30% of all hypertensive crises.14 Unlike hypertensive urgencies, with no end-organ damage, hypertensive emergencies may lead to acute MI, hypertensive encephalopathy, intracranial hemorrhage, dissecting aneurysm, acute renal failure, and pulmonary edema because of left ventricular dysfunction. Organ injury is most common with a DBP ⬎130 mm Hg unless the patient is a child or pregnant.15 In pregnant females a SBP ⬎169 mm Hg or DBP ⬎109 mm Hg is considered a hypertensive emergency and should be treated promptly.16

EPIDEMIOLOGY Hypertensive crisis affects 500,000 Americans or approximately 1% of hypertensive adults.17–19 Nearly 3.2% of patients presenting to the emergency room have a hypertensive crisis; with the decrease in incidence of HTN as a result of the advent of medications, the incidence has reduced substantially. Even so, the 5-year survival rate among all patients who present with a hypertensive crisis is 74%.20 Zampaglione et al evaluated the prevalence of hypertensive crisis in an emergency department during 12 months, and the frequency of end-organ damage during the first 24 hours after presentation. They found that 76% of the hypertensive crises were hypertensive urgencies and 24% were hypertensive emergencies, representing more than one-fourth of all medical urgencies-emergencies.21 Hypertensive crises were more prevalent among patients with renal disease, including renal artery stenosis and chronic kidney disease. Like HTN, hypertensive crises are more prevalent in the elderly and the non-Hispanic black population; yet men are affected 2 times more often than women.18,19 Severe HTN is seen more frequently in noncompliant individuals, black men, persons of lower socioeconomic status, and the elderly.18,22 A retrospective study of symptomatic patients who presented to a Brazilian emergency room with DBP ⬎120 mm Hg, found that hypertensive crises accounted for 0.5% of emergency cases studied, and 1.7% of clinical emergencies, with hypertensive urgencies being more common.23 The proportion presenting with hypertensive crisis was lower than the Zampaglione study because of the possibility of pseudocrisis in the latter. There was a high prevalence of hypertensive pseudocrisis (presenting emotionally charged, or in pain) when hypertensive crisis was suspected. Patients with hypertensive emergencies were older (59.6 ⫾ 14.8 vs. 49.9 ⫾ 18.6 years, P ⬍ 0.001) and had greater DBP (129.1 ⫾ 12 vs. 126.6 ⫾ 14.4 mm Hg, P ⬍ 0.05) than those with hypertensive urgencies. Cerebrovascular complications (39% ischemic stroke and 17% hemorrhagic stroke) and acute pulmonary edema (25%) were the most frequent target-organ lesions.23

ETIOLOGY Acute and severe BP elevation can occur as a complication of essential or secondary HTN, or it can happen idiopathically. The most common cause for a hypertensive crisis is chronic HTN with an acute exacerbation. One of the most common precipitants is medication noncompliance; although in general 8% of hypertensive © 2010 Lippincott Williams & Wilkins

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emergencies and 28% of hypertensive urgencies presenting to the emergency room are unaware of having a diagnosis of HTN.22 Other etiologies include withdrawal syndrome from centrally acting antihypertensives; peripheral ␣-blockers, or ␤-blockers causing an increased sympathetic flow. In previously normotensive individuals, the use of drugs such as oral contraceptives, cocaine, phencyclidine, monoamine oxidase inhibitors with tyramine or other agents such as linezolid, nonsteroidal anti-inflammatory drugs, or amphetamines puts them at jeopardy.24 Secondary causes of HTN can lead to a hypertensive crisis. This includes renal parenchymal disease, renovascular disease, renal infarction, pregnancy (preeclampsia), endocrine, and central nervous system disorders. Systemic illnesses with renal involvement, such as systemic lupus erythematosus, microangiopathic hemolytic anemia (TTP/HUS), endocrine disorders such as Cushing disease, primary aldosteronism, or a pheochromocytoma, and autonomic hyperactivity in spinal cord/head injuries, or cerebrovascular accident infarction/hemorrhage can precipitate a crisis.25 Many types of surgeries in patients with a known history of HTN can be associated postoperatively with HTN crisis including cardiac surgery, major vascular surgery, head and neck surgery and trauma. Postoperative HTN, defined as a SBP ⱖ190 mm Hg and a DBP ⱖ100 mm Hg on 2 consecutive readings have been reported in 4% to 35% of patients at least in part because of a high catecholamine state and increased vascular resistance26,27 (Table 1). In a retrospective cohort study on malignant HTN of a multiethnic population in Amsterdam between 1993 and 2005, racial differences were found in patients who developed hypertensive crisis. The incidence of malignant HTN and renal dysfunction was higher in blacks compared with whites. The data demonstrated that in blacks, as many as 40% of patients who presented with hypertensive emergencies developed renal failure. This may be due to ethnic disparities in BP control, noncompliance, and insurance status.28 Other risk factors associated consist of less effective control of SBP as an outpatient,29 the lack of a primary care physician and medical insurance,30 black males, lack of resources, smoking, diabetes, autumn season, and the morning hours between 6 AM and 12 PM.25

PATHOPHYSIOLOGY The precise pathophysiology of a hypertensive crisis is not well known. It is recognized that an individual is able to maintain organ perfusion with varying degrees of BP by autoregulatory mechanisms. Two general theories, the pressure hypothesis and the humoral hypothesis, suggest that when a critical imbalance of pressure and/or humoral factors occurs a series of pathologic events lead to myointimal proliferation and fibrinoid necrosis.31

TABLE 1.

Common Causes of a Hypertensive Crisis

Medication noncompliance Antihypertensive drug withdrawal (ie, clonidine) Renal parenchymal disease Renovascular disease Drugs (ie, cocaine, PCP) Collagen vascular diseases (SLE) Cushing disease Pheochromocytomas Preeclampsia and eclampsia Postoperative state PCP indicates phencyclidine; SLE, systemic lupus erythematosus.

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The renin-angiotensin system plays a central role in the homeostasis of BP.32 A rise in plasma renin activity (PRA) stimulates the production of angiotensin II, a vasoconstrictor that results in increased vascular resistance and BP. In severe HTN there is amplification of the renin-angiotensin system; a rise in levels of renin and angiotensin II leading to high aldosterone secretion, resulting in damage to the endothelium of blood vessels, as evidenced by fibrin thrombi in the vessels.33 It is proposed that high BP leads to high vascular reactivity and critical levels of vasoactive agents such as norepinephrine, angiotensin II, and vasopressin leading to natriuresis, which brings about hypovolemia, triggering even more elevation of the vasoconstrictive agents. This leads to arteriolar fibroid necrosis which precipitates endothelial damage followed by platelet deposition and release of thromboxane which can result in a microangiopathic hemolytic anemia. It further results in myointimal proliferation/damage with an endpoint of ischemia. Ischemia releases further vasoconstrictive agents as mentioned above, which propagates the cycle.33 Ultimately there is elevation of asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor.34 Asymmetric dimethylarginine may play an important role in the pathogenesis of preeclampsia. Whereas increased vascular resistance is the mediator of hypertensive crisis, both sodium overload and catecholamine excess can lead to severe vasoconstriction. Conditions that primarily involve increased sodium reabsorption in the kidney, such as primary hyperaldosteronism and genetic disorders such as glucocorticoid remediable aldosteronism (GRA), pseudohyperaldosteronsim (ie, Liddle syndrome), and 11-hydroxylase deficiencies would be expected to suppress renin secretion and thus limit the concentration of circulating angiotensin II. However, these sodium avid conditions may ultimately result in severe vasoconstriction through the classic Guytonian mechanism for autoregulation and thus manifest hypertensive crisis.35,36 Blumenfield et al suggest a hypertensive crisis can be stratified according to disorders that are caused by increased PRA levels ⱖ0.65 ng/mL/h, designated as R type HTN corrected by antihypertensives that suppress renin and angiotensin II, such as ACE inhibitors and ␤-blockers (R drugs), and sodium-volume dependent forms of HTN in which PRA is not a factor (PRA ⬍0.65 ng/mL/h). The latter are V type HTN, and respond to diuretics, aldosterone antagonists, calcium channel blockers, or ␣-adrenergic receptor blockers (V drugs)37 (Table 2).

CLINICAL PRESENTATION AND ASSESSMENT Performing an adequate assessment is of utmost importance to determine whether a patient’s presentation is because of a hypertensive emergency or hypertensive urgency. This will indicate the appropriate treatment and its promptness. The symptoms will ultimately depend on the organ affected. The differentiation can be made from a thorough history, physical examination, and relevant studies including laboratory work, an electrocardiogram, echocardiogram, and radiographs. A detailed history is essential; it is vital to inquire about the onset, duration, and severity of HTN, prior organ damage, associated symptoms, recreational drug and alcohol use, a list of medications (antihypertensive regimen with dosing and over-the-counter preparations), compliance with the antihypertensive regimen, and time/dose of the most recent ingested treatment. Similarly, any patient who presents with a hypertensive crisis should be evaluated for secondary causes of HTN. A sudden rise in BP with undiagnosed HTN or the presentation in a young patient (⬍25 years of age) would suggest a secondary source. More important than the degree of BP elevation is the rise in BP compared with baseline; those who have become adapted to a BP of 200 mm Hg will 104 | www.cardiologyinreview.com

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TABLE 2. Hypertensive Crises According to the Plasma Renin Level Disorders with high renin Malignant hypertension Medium to high renin states Unilateral renovascular hypertension Renal vasculitis (scleroderma, lupus, polyarteritis) Renal trauma Renin secreting tumors Adrenergic crises: pheochromocytoma, cocaine abuse, clonidine Probable medium to high renin states (PRA ⱖ0.65 ng/mL/h) Hypertensive encephalopathy Hypertension with cerebral hemorrhage Hypertension with (impending) stroke Hypertension with pulmonary edema Hypertension with acute myocardial infarction or unstable angina Dissecting aortic aneurysm Perioperative hypertension Sodium-volume overload, low renin states: PRA ⬍0.65 ng/mL/h Acute tubular necrosis Acute glomerulonephritis Urinary tract obstruction Primary aldosteronism Low renin essential hypertension Preeclampsia/eclampsia Adapted from Blumenfield et al.37 PRA indicates plasma renin activity.

manifest fewer symptoms than a patient whose normal BP is lower than 130 mm Hg. There may be signs and symptoms associated with a hypertensive crisis, or its manifestation may be silent. Silent HTN crisis has been found to be especially common in young black men. In general, there is no precise BP rise for the presentation of a hypertensive emergency. Instead, the specific symptoms imply the presence of end-organ damage. These symptoms include chest pain (myocardial ischemia or MI), back pain (aortic dissection), dyspnea (pulmonary edema or congestive heart failure), neurologic symptoms, seizures, or altered consciousness (hypertensive encephalopathy).38 The most widespread signs and symptoms at presentation for hypertensive urgency are headache (22%), epistaxis (17%), faintness (10%), psychomotor agitation (10%), chest pain (9%), and dyspnea (9%).21 Other less common symptoms include arrhythmias and paresthesias. In contrast, most patients with hypertensive emergencies complain of chest pain (27%), dyspnea (22%), and neurologic deficits (21%) (Fig. 1). Associated end-organ damage includes cerebral infarction (24.5%), acute pulmonary edema (22.5%), hypertensive encephalopathy (16.3%), and congestive heart failure (12.0%).21 Less often patients present with intracranial hemorrhage, acute aortic dissection, acute MI, acute kidney injury, and eclampsia.20 The physical examination should initially focus on proper BP measurement in the bilateral upper limbs with an appropriately sized BP cuff, to evaluate for aortic dissection. Pulses should be palpated and compared in the upper, femoral, and lower extremities. BP readings in the supine, sitting, and standing positions are required to measure volume status. Carotid arteries and abdominal arteries should be auscultated for bruits, suggesting a cerebrovascular event. A comprehensive cardiovascular examination is of value. An elevated jugular venous pressure, third heart sound, gallop, and/or pulmonary rales are evidence of heart failure. A prominent/displaced © 2010 Lippincott Williams & Wilkins

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FIGURE 1. Common signs and symptoms of a hypertensive crisis on initial presentation (from Zampaglione et al).21 apical impulse or a harsh intrascapular murmur is suggestive of a coarctation of the aorta. Other significant tests include a fundoscopic examination for the presence of hemorrhages, papilledema, or exudates (confirming a hypertensive emergency), and a thorough neurologic examination to assess for stroke, somnolence, stupor, visual loss, focal deficits, seizures, or coma. Signs of hypertensive encephalopathy are seizure, nausea/vomiting, or renal manifestations such as oliguria and azotemia.14 Occasionally, hypertensive crises produce a clinical picture consistent with microangiopathic hemolytic anemia, because of direct endothelial damage. Determining whether microangiopathic hemolytic uremia is the primary cause of the hypertensive crisis (through renal ischemia) or a consequence of the hypertensive crisis is often difficult clinically, and only obvious in retrospect, after instituting treatment and lowering BP. Single-organ involvement is observed in approximately 83% of patients presenting with hypertensive emergencies. Two-organ involvement is found in 14% of patients, and multiorgan involvement (⬎3 organ systems) is found in approximately 3% of patients.21

MANAGEMENT/TREATMENT Laboratory work in the nonclinic setting should include a serum chemistry panel to test for hypokalemia or hypomagnesemia, which would predispose to arrhythmias, renal and hepatic function tests, along with a complete blood count and peripheral smear to check for hemolysis and microangiopathic anemia, urinalysis with microscopic examination of the urinary sediment for proteinuria, red blood cells, and/or cellular casts. An electrocardiogram to assess for coronary ischemia or left ventricular hypertrophy should be completed. A chest radiograph for those who present with chest pain or shortness of breath would be indicative of pulmonary edema or a widened mediastinum. Imaging studies, such as a head CT or MRI for abnormal neurologic examinations, mental status changes, or headaches and a chest CT scan or transesophageal echocardiogram to rule out aortic dissection should also be performed. Of some usefulness are plasma aldosterone and renin levels. Proper management of severe HTN is essential to prevent target organ injury of the brain, heart, kidneys, and vascular system. The treatment goal should aim at reducing BP according to the presentation type. Hypertensive urgency can be managed with an oral medical regimen and gradual BP control over 12 to 24 to 48 hours; patients should not have their BP rapidly lowered to their normal base© 2010 Lippincott Williams & Wilkins

Hypertensive Crisis

line.39,40 The goal is to reduce the BP to 160/100 mm Hg over hours to days with low doses of short-acting oral antihypertensive medications. These include oral labetalol (␣- and ␤-adrenergic blocker) or clonidine (central ␣-2 agonist).41,42 Captopril has also been suggested as a first-line agent in the treatment of hypertensive urgency, but it needs to be used with caution.43 Aggressive parenteral antihypertensives and high loading doses of oral medications should be strictly avoided. This could cause hypoperfusion of the major arterial beds of the brain, heart, and kidneys, leading to cerebral ischemia, cerebral infarction, myocardial ischemia, and blindness.44 – 46 Instead, the patient may be discharged home after observation, with instructions to increase the dose of their existing antihypertensive regimen, adding an additional antihypertensive medication or reinstituting the medication if noncompliant. These patients should subsequently be followed on an outpatient basis within 24 to 48 hours of discharge. Only those who are at higher risk for adverse outcomes, such as patients with diabetes, history of stroke, or coronary artery disease, should be considered for inpatient observation. Similarly, patients who present with medication noncompliance are at risk for progressing to hypertensive emergency (ie, developing end-organ damage) and benefit from an inpatient observation. Hypertensive emergencies require immediate admission to an intensive care unit for prompt BP control with a parenteral, titratable antihypertensive agent while continuously monitoring BP, neurologic status, and urine output. BP should be efficiently reduced within minutes to an hour, and not immediately to normal levels. The goal is to correct the BP to no less than 20% to 25% in the first hour and then if stable to 160/100 to 160/110 mm Hg within the next 2 to 6 hours.7 An alternative is to reduce DBP by 10% to 15% or to approximately 110 mm Hg in 30 to 60 minutes;47 with a goal reduction to normal within 24 to 48 hours. The aggressive lowering of BP may aggravate hypoperfusion and worsen end-organ damage.48 Specific therapies are targeted to the end-organ damage present. The rapid-acting antihypertensives preferred in hypertensive emergencies are labetalol, esmolol, fenoldopam, clevidipine, nitroprusside, and nicardipine.47 In addition, some patients, particularly those with normal kidney function, may have some element of volume depletion because of the preceding pressure natriuresis that occurred in the setting of very high BPs. Thus, in the absence of clinical signs of volume overload, some volume expansion with intravenous saline solution will help to suppress renin secretion and to prevent significant hypotension once the vasodilating medications begin to act.48 In patients with aortic dissection, however, a rapid reduction of SBP ⬍120 mm Hg and mean arterial pressure ⬍80 mm Hg should be achieved within 5 to 10 minutes, initially with ␤-blockers, to decrease the pressure impulse (dP/dT).49 Various short-acting medications are available for hypertensive emergencies. Enalaprilat is an ACE inhibitor that is not recommended for use in hypertensive crisis because of its slow onset of 1 hour and long duration of action of approximately 6 hours.46 Moreover, renal failure is common in patients with hypertensive crises, either as a trigger for, or as a result of the crisis50 and this could be further exacerbated by the use of an ACE inhibitor.47 It can be used cautiously in the later stages of therapy in patients with heart failure in the setting of a hypertensive crisis. Labetalol is a combined ␣1 adrenergic receptor blocker and nonselective ␤-blocker with an elimination half-life of about 5.5 hours. It maintains cardiac output and reduces total peripheral resistance with conservation of cerebral, renal, and coronary flow.51 Hypertensive encephalopathy patients may benefit from labetalol, and it is the preferred choice for acute myocardial ischemia, aortic dissection, acute ischemic stroke, and hypertensive encephalopathy. Esmolol, on the other hand, is a very short-acting ␤-blocker that decreases heart rate, www.cardiologyinreview.com | 105

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myocardial contractility, and cardiac output.52 It can be used cautiously in patients with an acute MI concomitantly with nitroglycerin. Nicardipine is a dihydropyridine derivative calcium channel blocker with cerebral and coronary vasodilatory activity. This drug has therapeutic benefits in increasing stroke volume and coronary blood flow, making it useful for patients with coronary artery disease. It is also recommended for the treatment of acute ischemic stroke when DBP and SBP are not at goal.53 Clevidipine is a new short-acting intravenous third-generation dihydropyridine calcium-channel blocker, which is a selective arterial vasodilator available for intraoperative and critical care settings.54 –56 It is a safe and effective alternative in the acute management of moderate-to-severe HTN.56 –58 Its potential advantages consist of its short half-life, affording greater acute titratability. Fenoldopam is a dopaminergic DA1 receptor agonist that is a peripheral vasodilator and a diuretic.57 It has been found to be a rapid-acting, well-tolerated, and highly effective intravenous substance for the treatment of severe HTN.58 Sodium nitroprusside is a potent arterial and venous dilator that decreases preload and afterload. Potential drawbacks include its ability to decrease cerebral perfusion while increasing intracranial pressure, the development of coronary steal (increasing mortality if used in the setting of acute MI),59 and cyanide toxicity. Its use has been limited typically for patients with acute pulmonary edema and/or severe left ventricular dysfunction, and in patients with aortic dissection.60 It should be administered with care in the setting of renal insufficiency, because of the higher risk of cyanide accumulation. Immediate release nifedipine, nitroglycerin, and hydralazine should not be considered first-line drugs in the management of hypertensive emergencies because of toxicity and side effects.61 The use of short-acting nifedipine (either oral or sublingual) is no longer considered appropriate or safe because of a rapid unpredictable fall in BP, which may precipitate cerebral, renal, and cardiac ischemic events.62,63 Nitroglycerin is a venodilator that reduces preload and cardiac output. It is often used in conjunction with other antihypertensive agents, primarily in acute MI and pulmonary edema. Hydralazine is a direct-acting arteriolar vasodilator with a half-life of approximately 10 hours.64 It is commonly used in pregnant women because of its ability to increase uterine perfusion (ACE inhibitors are teratogenic and contraindicated). Other options in this patient population include labetalol, nicardipine, methyldopa, nifedipine, and prazosin. Studies have shown that all these drugs lower BP in the intravenous or oral form, with no evidence that any one is better than the other65 (Table 3).

TABLE 3. Parenteral Agents Used in the Management of Various Hypertensive Crises Primary Condition Acute aortic dissection Hypertensive encephalopathy Acute myocardial ischemia Congestive heart failure Eclampsia Pheochromocytoma Acute pulmonary edema

Acute ischemic stroke/ intracerebral bleed Acute renal failure/MAHA

Therapy Labetalol or nicardipine ⫹ esmolol, nitroprusside ⫹ esmolol Labetalol, nicardipine, fenoldopam, clevidipine Nitroglycerin ⫾ esmolol, fenoldopam, labetalol Enalaprilat, loop diuretic Hydralazine, nicardipine, labetalol Phentolamine, labetalol Sodium nitroprusside, nicardipine, fenoldopam, loop diuretic, nitroglycerin Nicardipine, fenoldopam, labetalol, clevidipine Nicardipine, fenoldopam

Adapted from Varon et al.47 MAHA indicates microangiopathic hemolytic anemia.

survival in hypertensive crisis, with poorer outcomes for black patients.21 The 1-year mortality rate is 79% for patients with untreated hypertensive emergencies,68 and 5-year survival rate among all patients who present with hypertensive crisis is 74%.20 At times, cardiac enzymes are tested and found to be elevated. With little to no evaluation of underlying coronary artery disease, it becomes difficult to stratify patients for purposes of treatment and diagnosis. It is difficult to discern whether troponin elevation is a result of subendocardial ischemia because of extreme left ventricular wall stress from the increase in afterload versus coronary artery disease and unstable plaque that triggers a catecholamine surge with resultant severe HTN. Physicians should perform complete evaluations in patients who present with a hypertensive crisis to effectively reverse the crisis, intervene and correct the underlying trigger, to improve long-term outcomes after the episode. Efforts to reduce the incidence of hypertensive crisis should continue. For those unfortunate patients who do present with hypertensive crisis, strategies to risk-stratify, educate, and improve outcome after these events should be optimized.

PROGNOSIS

REFERENCES

There are few data regarding the outcomes of a hypertensive crisis. In a study of 315 patients with malignant HTN, 40% were alive after 33 months. The most common causes of death were renal failure (39.7%), stroke (23.8%), MI (11.1%), and heart failure (10.3%).20 Furthermore, studies of patients presenting to the emergency room with a hypertensive crisis have demonstrated that most do not receive the appropriate evaluation, medical regimen, and discharge instructions proposed by the current guidelines. Two studies of patients presenting to the emergency room with a hypertensive crisis found that serum chemistry was only obtained in 70% to 73% of patients, electrocardiogram in 53% to 70% of patients, chest x-ray in 24% to 46% of patients, and urinalysis in 43% to 44% of patients. Two-thirds of the total number of patients evaluated did not have a funduscopic examination in the emergency room, and only 19% discharged had modification of their antihypertensive regimen. Overall, only 6% obtained the tests recommended by the guidelines, and 10% had no tests performed.66,67 The known duration of HTN and procuring the serum urea level at presentation have been found to be the main predictors of

1. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988 –2000. JAMA. 2003;290:199 –206. 2. Center for Disease Control and Prevention. National Center for Health Statistics. Health, United States, 2005. Available at: http://www.cdc.gov/ bloodpressure/facts.htm. 3. Wang NY, Young JH, Meoni LA, et al. Blood pressure change and risk of hypertension associated with parental hypertension: the Johns Hopkins Precursors Study. Arch Intern Med. 2008;168:643– 648. 4. Yan LL, Liu K, Matthews KA, et al. Psychosocial factors and risk of hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study. JAMA. 2003;290:2138 –2148. 5. McRae RP Jr, Liebson PR. Hypertensive crisis. Med Clin North Am. 1986; 70:749 –767. 6. Gifford RW. Management of hypertensive crises. JAMA. 1991;266:829 – 835. 7. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206 –1252. 8. Volhard F, Fahr T. Die Brightsche Nierenkrankheit: Klinik Pahologie und Atlas. Berlin, Germany: Julius Springer; 1914:247–280. 9. Keith NM, Wagener HP, Keronohan JW. The syndrome of malignant hypertension. Arch Intern Med. 1928;4:264 –278.

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