E M PRACTICE - WordPress.com · Eclampsia/Preeclampsia Catecholamine-Induced States (sympathomimetics, pheo-chromocytoma, interactions with monamine oxidase inhibitors) Table 2. Joint

July 2005Volume 7, Number 7

Authors

Thomas T Nguyen, MDAssistant Professor, Mount Sinai School of Medicine, Department of Emergency Medicine—New York, NY.

Scott M Rohrback, MDSenior Resident, Mount Sinai School of Medicine, Department of Emergency Medicine—New York, NY.

Carrie Lenamond, MDDepartment of Emergency Medicine, University of Florida—Jacksonville, FL.

Peer Reviewers

Wyatt W Decker, MDChair and Associate Professor, Department of Emergency Medicine, Mayo Clinic College of Medicine—Rochester, MN.

Steven A Godwin, MD, FACEPAssistant Professor and Residency Director, Department of Emergency Medicine, University of Florida HSC/Jacksonville—Jacksonville, FL.

CME Objectives

Upon completing this article, you should be able to:Explain the underlying pathophysiology of hypertensive emergencies;Rationally direct the history, physical exam, and laboratory testing in patients presenting with a hypertensive emergency;Choose appropriate interventions for hyperten-sive emergency patients, based on etiology;In hypertensive emergency patients, use a rapid sequence intubation protocol to minimize ad-verse outcomes related to the intervention; and Decide which patients with elevated BP do not require immediate management in the ED.

Date of original release: July 25, 2005. Date of most recent review: July 18, 2005.

See “Physician CME Information” on back page.

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Editor-in-Chief

Andy Jagoda, MD, FACEP, Professor and Vice-Chair of Academic Affairs, Department of Emergency Medicine; Residency Program Director; Director, International Studies Program, Mount Sinai School of Medicine, New York, NY.

Associate Editor

John M Howell, MD, FACEP, Clinical Professor of Emergency Medicine, George Washington University, Washington, DC; Director of Academic Affairs, Best Practices, Inc, Inova Fairfax Hospital, Falls Church, VA.

Editorial Board

William J Brady, MD, Associate Professor and Vice-Chair, Department of EM, University of Virginia, Charlottesville, VA.

Peter DeBlieux, MD, LSUHSC Professor of Clinical Medicine; Director of Faculty and Resident Development, LSU Health Science Center, New Orleans, LA.

Wyatt W Decker, MD, Chair and Associate Professor, Department of EM, Mayo Clinic College of Medicine, Rochester, MN.

Francis M Fesmire, MD, FACEP, Director, Heart-Stroke Center, Erlanger Medical Center; Assistant Professor of Medicine, UT College of Medicine, Chattanooga, TN.

Valerio Gai, MD, Professor and Chair, Department of EM, University of Turin, Italy.

Michael J Gerardi, MD, FAAP, FACEP, Clinical Assistant Professor, Medicine, UMDNJ; Director, Pediatric EM, Children’s Medical Center, Atlantic Health System;

Department of EM, Morristown Memorial Hospital, NJ.

Michael A Gibbs, MD, FACEP, Chief, Department of EM, Maine Medical Center, Portland, ME.

Steven A Godwin, MD, FACEP, Assistant Professor and Residency Director, Department of EM, University of Florida HSC/Jacksonville, Jacksonville, FL.

Gregory L Henry, MD, FACEP, CEO, Medical Practice Risk Assessment, Inc; Clinical Professor of EM, University of Michigan, Ann Arbor, MI.

Keith A Marill, MD, Instructor, Department of EM, Massachusetts General Hospital, Boston, MA.

Charles V Pollack, Jr, MA, MD, FACEP, Chairman, Department of EM, Pennsylvania Hospital,

University of Pennsylvania Health System, Philadelphia, PA.

Michael S Radeos, MD, MPH, Assistant Professor of Emergency Medicine, Weill Cornell College of Medicine; Lincoln Medical and Mental Health Center, Bronx, NY.

Robert L Rogers, MD, FAAEM, , Assistant Professor and Program Director, Combined EM / IM Residency Program, University of Maryland School of Medicine, Baltimore, MD.

Alfred Sacchetti, MD, FACEP, Assistant Clinical Professor, Department of EM, Thomas Jefferson University, Philadelphia, PA; Research Director, Our Lady of Lourdes Medical Center, Camden, NJ.

Corey M Slovis, MD, FACP, FACEP, Professor and Chair, Department

of EM, Vanderbilt University Medical Center; Medical Director, Metro Nashville EMS, Nashville, TN.

Ron M Walls, MD, Chairman, Department of Emergency Medicine, Brigham & Women’s Hospital; Associate Professor of Medicine (Emergency), Harvard Medical School, Boston, MA.

Research Editors

Jack Choi, MD, Mount Sinai Emergency Medicine Residency.

Beth Wicklund, MD, Regions Hospital Emergency Medicine Residency, EMRA Representative.

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Distinguishing AndManaging HypertensiveEmergencies And UrgenciesIn the ED you examine a severely hypertensive man with chest pain, promptly diagnosing him with aortic dissection, properly lowering his blood pressure intra-venously, and obtaining a vascular consult. Your next 2 patients are a 41-year-old woman with a mild headache who is here for her C-section suture removal, and a 45-year-old woman with a finger laceration. They both happen to have the same BP of 170/95. Both are also treated and subsequently released. You advise them to follow up with their primary care doctors to have their BPs rechecked. Just 6 hours later, the first woman is brought back by EMS. She is actively seizing. After an angry call from her obstetrician, you realize you have missed diag-nosing preeclampsia in a woman only 9 days postpartum. Now you start to wonder about the second woman who had the high BP on incidental finding. You sent her home, too.... Did you do the right thing?

THERE is no absolute level of blood pressure that defines a hypertensive emergency. Hypertensive emergencies exist when there is acute end-or-

gan damage in the setting of hypertension.1,2 The presenting blood pressure can vary, depending on the chronicity of the hypertension, the patient’s age, and other related factors. For example, a systolic blood pressure of 160 mmHg in a pregnant patient is considered dangerously high, but the same blood pressure in a chronically hypertensive individual may be at baseline or even low for that patient. The magnitude of the blood pressure elevation is probably less important than the rapidity of the increase.3,4 Hypertensive emergencies stem from many causes and lead to a broad range of out-comes.5,6 Examples of hypertensive emergencies are presented in Table 1 on page 2. Hypertensive urgency is defined as elevated blood pressure, without evidence of acute, ongoing target organ damage, that requires urgent — but not emergent — blood pressure reduction. The definition of hypertensive urgency covers those patients who have known end-organ disease, but no active compromise. While no specific readings are used in this definition,

Emergency Medicine Practice © 2005 2 EMPractice.net • July 2005

patients are at a higher risk for hypertension-related ad-verse events in the short term.7,8 This situation is different than asymptomatic hypertensive patients. There is no evidence regarding the best time to lower blood pressure in hypertensive urgencies or among incidental hyperten-sives. Patients with incidental hypertension need to have timely follow-up with a primary care physician, usually within several days of the initial diagnosis.1,5

Critical Appraisal Of The Literature

A systematic review of the literature was performed via Ovid MEDLINE® and the Cochrane Database of System-atic Reviews (1966-present) using the terms hypertension, ED, hypertensive emergencies, hypertensive urgencies, and hypertensive crisis. Approximately 2000 articles were identified; from among these, about 130 were chosen, including the articles referenced here. Multiple review articles on hypertensive emergencies and urgencies were found. Many studies for specific antihypertensive agents and their clinical efficacy were also found. No guidelines specific to the ED were identified. However, there are sev-eral guidelines useful for the diagnosis and management of specific hypertensive emergencies. The first is from the Stroke Council of the American Stroke Association, which makes recommendations on BP management in isch-emic strokes. The second guideline is from the American College of Gynecology (ACOG) 2002 Practice Bulletin (number 33), entitled “Diagnosis and management of pre-eclampsia and eclampsia,” which offers recommendations on the diagnosis and treatment of these conditions. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is an important guideline. For more than 3 decades, the National High Blood Pres-sure Education Program (NHBPEP) Coordinating Com-mittee has issued guidelines and advisories designed to facilitate awareness, prevention, treatment, and control of hypertension. In April 2003, NHBPEP introduced JNC 7 — an update of JNC 6, which was published in 1997. The guideline is based on an extensive review of the hyperten-sion scientific literature from clinical trials, epidemiol-ogy, and behavioral sciences. The purpose of JNC 7 is

to provide a comprehensive guideline that is useful to clinicians and to simplify the classifications of normal and abnormal blood pressure measurements. (See Table 2.) JNC 7 is better suited for the primary care physician in the comprehensive care of the hypertensive patient than the emergency physician. Of a total 41 pages, only half of a single page is dedicated to hypertensive emergencies and urgencies. Specifically, JNC 7 states that hypertensive emergencies “require immediate BP reduction (not neces-sarily to normal) to prevent or limit end-organ damage.” These JNC 7 recommendations on hypertensive urgency and emergency are consensus-based; the authors provide no references to support their position.

Epidemiology, Etiology, And Pathophysiology

EpidemiologyHypertension is extremely common in the United States, requiring some form of treatment in more than 50 mil-lion Americans.5 Hypertensive emergencies will occur in approximately 1% of these individuals.3 Hypertensive urgencies and emergencies account for approximately 2-3% of all ED visits annually, with urgencies being more common than emergencies (70% vs 30%, respectively).9 Several risk factors increase the likelihood of developing a hypertensive emergency. Preexisting hypertension appears to be the most common risk factor, occurring in approxi-mately 75-90% of patients diagnosed with a hypertensive emergency.9,10 In one case series, hypertensive emergencies were found to occur more often in older black or Hispanic males with known hypertension who had previously been on antihypertensive therapy.10 Similarly, another case control study found hypertensive emergencies were more common among patients without a primary care physi-cian and those who did not comply with antihypertensive treatment.11,12 A retrospective study of 100 patients with severe hypertension admitted to a large urban hospital (of whom two thirds had end-organ damage) showed that less effective outpatient systolic blood pressure control was an independent risk factor for developing a hyper-tensive emergency.13 Finally, data from the Framingham Heart Study also confirmed that appropriate, monitored, long-term treatment of hypertension lowers the incidence of hypertensive complications.14

Table 1. Specific Diseases.

Hypertensive Encephalopathy

Cerebral Infarction/Hemorrhage

Acute Aortic Dissection

Acute Myocardial Infarction

Acute Left Ventricular Failure

Eclampsia/Preeclampsia

Catecholamine-Induced States (sympathomimetics, pheo-

chromocytoma, interactions with monamine oxidase

inhibitors)

Table 2. Joint National Committee On Prevention, Detection, Evaluation, And Treatment Of High Blood Pressure (JNC 7).Normal < 120/80

Prehypertension 120-139/80-89

Hypertension > 140/90

Stage 1 140-159/90-99

Stage 2 > 160/100

3 Emergency Medicine Practice © 2005July 2005 • EMPractice.net

Etiology/PathophysiologyThe pathophysiology of hypertensive emergencies has not been fully delineated. It is generally agreed that an abrupt rise in blood pressure initiates a series of vascular events that eventually manifest as end-organ dysfunction. Two theories presently define the debate: the pressure hypothesis and the humoral hypothesis. The pressure hypothesis posits that, as blood pressure rises, mechani-cal stress causes damage to the vascular endothelium, focal vasodilatation, and leakage of plasma proteins and fibrinogen. This eventually leads to fibrinoid necrosis of the vessel wall and proliferative endarteritis.15-17 The humoral hypothesis proposes that hypertensive emergen-cies occur as a result of an imbalance in the action of the renin-angiotensin system and other local mediators on the vasculature. The vasodilators nitric oxide and prostacyclin largely balance the effects of the vasoconstrictors angioten-sin II, norepinephrine, and vasopressin.18 However, when a critical pressure is reached, there is a loss of sodium and water through a pressure natriuresis. The resulting relative hypovolemia causes local vascular mediators to be acti-vated, leading to vasoconstriction and increased vascular permeability. This results in myointimal proliferation and fibrinoid necrosis of the endothelium, and a vicious cycle ensues.15-17 It is likely that the vascular and end-organ changes that define hypertensive emergencies represent a combination of these 2 theories working in concert. The concept of autoregulation is central to effective management of hypertensive emergencies and urgencies. Autoregulation functions to maintain constant blood flow and perfusion pressure to so-called target organs (brain, kidneys, heart, large arteries) even in the presence of large variations in blood pressure. As blood flow is equal to pressure divided by resistance, changes in blood pressure will not affect flow, as long as a parallel change in resis-tance via either vasoconstriction or vasodilation occurs. The most widely studied system of autoregulation involves the cerebral circulation. Cerebral blood flow in

Figure 1. Autoregulation Curve.

atche

Table 3. Pathophysiology For Hypertensive Emergencies.Organ or Disease Pathophysiology/Risk Factors

Hypertensive Encephalopathy Hypertension leading to endothelial dysfunction and cerebral edema

Intracerebral Hemorrhage Hypertension causing pseudoaneurysms and microbleeds

Cerebral Infarction Hypertension and atherosclerosisThrombosis, embolism, or hypoperfusion

Aortic Dissection Hypertension or congenital anomalyIntimal tear with dissection into media

AMI/ACS Thrombus or plaques in the coronary arteries leading to ischemia or infarction

Acute LV Failure Activation of the neurohormonal cascade, salt and water retention, increased vascular resis-tance, decreased cardiac output, increased pulmonary pressures

Renal Hypertension causing benign nephrosclerosisVascular, glomerular, and tubulointerstitial changes

Preeclampsia/Eclampsia Primarily a disorder of first pregnanciesUnknown etiology, likely related to incomplete trophoblastic invasion and alterations in immune responses

Catecholamine-Induced States Either direct or indirect effects on the sympathetic system

normotensive individuals is maintained via vasoconstric-tion and vasodilation when the mean arterial pressure (MAP) is between 70 and 120 mmHg. MAP is Diastolic Blood Pressure (DBP) + 1/3 [Systolic Blood Pressure (SBP) - DBP]. In this MAP range the cerebral perfusion pressure remains relatively constant. Beyond this range of auto-regulation, no further vasodilation or vasoconstriction can occur, and further changes in blood pressure lead to either hypoperfusion or hyperperfusion, respectively.19 In hypertensive individuals, the range of autoregulation has been shown to shift to the right, so that higher BPs are better tolerated and lower BPs more poorly tolerated. This is a result of the arteriolar hypertrophy that accompanies chronic hypertension, causing the arteries to lose their ability to adequately vasodilate. Thus, in chronically hy-pertensive individuals, the lower limit of MAP is 100-120 mmHg and the upper limit is 150-160 mmHg.20,21

An understanding of the pathophysiology provides the basis for management recommendations in hyper-tensive emergencies — initially blood pressure should be lowered by no more than 25% of the initial MAP. A marked BP drop in a right-shifted autoregulation curve causes hypoperfusion and relative brain ischemia.22 (See Figure 1.)


For females of child-bearing age, assess for a history of preeclampsia or gestational hypertension. The clinician should investigate specific symptoms related to acute end-organ damage. These may include neurological symptoms, such as altered mental status and seizures, which may represent hypertensive encephalopa-thy; chest pain (myocardial infarction, aortic dissection); back pain (aortic dissection); dyspnea (pulmonary edema, congestive heart failure); anuria (renal failure); and visual changes (papilledema, retinal hemorrhages). For patients more than 20 weeks pregnant (and usually in the last trimester until 14 days postpartum) elicit signs and symp-toms of preeclampsia, such as visual changes, headaches, oliguria, and altered mental status.24

Physical ExamThe exam should assess whether specific end-organ dam-age is present. Beginning with the head, start out with the fundoscopic exam, evaluating for papilledema, hemor-rhages, or exudates. The neurological exam should assess the mental status and evidence of focal neurologic deficits. The cardiovascular exam should focus on identifying the signs of heart failure, such as increased jugular venous pressure, pulmonary rales, an S3 gallop, and peripheral edema. The lung exam should elicit signs of heart failure, mainly pulmonary rales and crackles. The volume status of the patient should also be assessed. Volume overload may be a sign of renal or heart failure.25

Ancillary TestsTesting in patients with hypertensive emergencies is driven by the suspected etiology of the condition. There are few studies on specific recommendations for what tests to order in the setting of hypertensive emergencies. Chronic hypertension causes 30% of cases of end-stage re-nal disease; therefore it is reasonable to obtain electrolytes, creatinine (Cr), and blood urea nitrogen (BUN) to evaluate renal function.7,26 A hemoglobin can support an underly-ing diagnosis of renal disease, and in select cases, a blood

See Table 3 on page 3 for pathophysiologic character-istics of various types of hypertensive emergencies.

Prehospital Care

Patients with presumed hypertensive emergencies should be transported immediately with IV access, supplemental oxygen, and cardiac monitoring. Depending on the sce-nario, EMS personnel should notify the receiving facility of a potentially unstable patient (eg, pregnant patients with preeclampsia or patients with stroke symptoms).

ED Management Of Hypertensive Emergencies

Patients with presumed hypertensive emergency are tri-aged to the critical care area of the ED. Manual ausculta-tion is an accurate measurement method, since automatic cuffs are reportedly less accurate in the setting of patient movement or cardiac arrhythmia.7,23 Using an appropriate-sized cuff (cuff bladder encircling at least 80% of the arm) is important to ensure accuracy, and at least 2 separate measurements should be obtained.2,8

Clinical EvaluationThe key to the evaluation is to differentiate whether the acute situation is a hypertensive emergency or urgency. This distinction is made through a focused history, physi-cal exam, and ancillary tests to identify end-organ dam-age. Assess whether the patient is comfortable, making sure they are not hypoxic, in urinary retention, or in severe pain. Refer to the clinical pathway to sort out patients with potential hypertensive emergencies.

HistoryThe history should include details of the duration and severity of the preexisting hypertension, if any. What was the degree of success with blood pressure control in the past? What medications are being used to control the hypertension presently? Are there any other over-the-counter medicines being used (including cold medications or any illicit drugs, such as cocaine) that may have caused the hypertensive crisis? Table 4 provides a list of medica-tions that can cause increased blood pressure. A history of previous end-organ damage, such as renal disease or atherosclerotic disease, may be helpful. (See Table 5.)

Table 4. Drugs That May Precipitate A Hypertensive Emergency.

Oral contraceptives

Monoamine oxidase inhibitors

Tricyclic antidepressants

Steroids

Nonsteroidal anti-inflammatory drugs

Nasal decongestants

Cold remedies

Appetite suppressants

Table 5. Identifiable Causes Of Hypertension.

Sleep apnea

Thyroid or parathyroid disease

Renovascular hypertension

Primary aldosteronism

Pheochromocytoma

Obstructive uropathy

Chronic kidney disease

Coarctation of the aorta

Cushing’s syndrome

Drug-induced

*Source: Vidt, DG. Current concepts in treatment of hypertensive emer-gencies. Am Heart J 1986. See Reference 2.


upon the territory involved. Patients with hypertensive emergencies in the setting of an ischemic or hemorrhagic stroke generally have focal neurological deficits. On the ECG, pathologic, deep symmetrical T-wave inversions may be present.30,31 Patients with possible stroke require a neuroimaging study. It is important to distinguish acute ischemic stroke from hypertensive encephalopathy, because the decision to lower the BP may be catastrophic in acute ischemic strokes, but appropriate in hypertensive encephalopathy and hemorrhagic stroke.32

Acute Aortic DissectionHypertension is seen in about 50% of patients with acute aortic dissection.33 Hypertension can accentuate the propa-gation of the dissection, due to shearing forces (ie, dP/dT) from the high-pressure blood flow. Persons with aortic dis-section are often of advanced age and have hypertension, atherosclerotic diseases, or connective tissue diseases.34 Abrupt and severe retrosternal pain or interscapular chest pain is reported by approximately 90% of the patients with acute aortic dissection.34,35 The location and progression of the pain depends upon the location and propagation of the dissection. Compression of arterial branches of the aorta by an intimal flap or expanding hematoma can result in a pulse deficit in the affected limb and has been described in up to 30% of patients with an acute dissection.27,36 As a result, the limbs, kidneys, or mesentery may become isch-emic. Ischemia may also occur in the heart, if the coronary arteries become occluded by a dissection of the ascending aorta.37 In a case series of 464 patients, ECG evidence of acute myocardial infarction was present in 5% of cases, while ischemic changes were present in 15%.27 The goal of the clinician is to recognize acute aortic dissection and to lower the BP acutely (SBP 90-120 mmHg) without com-promising end-organ perfusion, to prevent propagation and rupture.38,39 This recommendation to lower the BP to a specific level is not evidenced-based. However, some authors do conclude that lowering BP in descending aortic dissection decreases mortality.40

Acute Left Ventricular FailureSevere hypertension may cause or exacerbate acute left ventricular failure. On exam, these patients may have elevated blood pressure, tachypnea, tachycardia, cyanosis, pulmonary rales, jugular venous distension, and a gal-lop.41 The ECG may show strain, left ventricular hypertro-phy, or even ischemia/infarction.

Acute Myocardial Infarction/Unstable AnginaPatients with myocardial ischemia at times present with severe hypertension. Presumably this is due to a sympa-thetic reflex initiated in the left ventricle.42,43 The high BP results in elevated afterload and causes the heart to work harder. This results in a higher cardiac oxygen demand and may worsen infarction size. These events may then lead to acute left ventricular failure and pulmonary edema, as described above. Patients with cardiac ischemia present with sypmtoms of angina, dyspnea, and diapho-

smear may be indicated to evaluate for microangiopathic hemolytic anemia. Urinalysis is done for the evaluation of proteinuria and red cell casts and may point to a diagnosis of glomerulonephritis. Proteinuria (> 300 mg a day) or +1 on dipstick may indicate preeclampsia in a pregnant patient with elevated blood pressure.24 Troponin and CPK levels should be sent in patients suspected of having an acute myocardial infarction. A chest x-ray is done to assess for pulmonary edema and cardiomegaly (signs of long-term, uncontrolled hypertension). A chest radiograph may be used to screen for evidence of aortic dissection — in one case series of 464 patients, widening of the mediasti-num was noted on chest radiography in approximately 60% of patients, depending on the type of dissection pres-ent.27 These patients may need a CT angiogram to further evaluate for aortic dissection. The ECG is done for signs of ischemia, left ventricular strain, hypertrophy, or myocardi-al infarction.2,4 A CT scan of the head should be performed if historical or exam features raise concern for ischemic or hemorrhagic stroke.

Differential Diagnosis

The diagnosis of a hypertensive emergency requires the demonstration of acute end-organ dysfunction that is directly attributable to an elevation of blood pressure. End-organ dysfunction reflects an individual’s inability to regulate flow at a given pressure, and can therefore occur in the setting of mild systemic hypertension in a previ-ously normotensive individual, because these individuals have not adapted to the chronically high BP (eg, right shift in the cerebral autoregulation curve). As treatment of hy-pertensive emergencies should be tailored to the affected organ system, diagnostic clues to the involvement of each organ system are discussed below.

Hypertensive EncephalopathyPatients with hypertensive encephalopathy may have acute or subacute lethargy, confusion, headache, visual disturbance, or seizures. Other symptoms are somnolence, stupor, nausea, and vomiting.28 Papilledema, hypertensive retinopathy, and occasionally focal neurologic symptoms may occur.17 Encephalopathy can occur with or without proteinuria. When seizures occur, they can be focal or generalized. Other causes of acute confusion, eg, infection or mass lesions, should be investigated before attributing the etiology to hypertension. Improvement of the patient’s mental status with careful lowering of the blood pressure likely supports the diagnosis of hypertensive encepha-lopathy.29

Acute StrokeSevere hypertension is often seen in the setting of acute strokes. The elevation in BP could be from the stress of the stroke, a physiologic response to hypoxia, or the result of the body’s attempt to increase and maintain cerebral per-fusion in the setting of an ischemic stroke. Alternatively, severe hypertension may have caused the acute stroke.30 Stroke presentations are somewhat predictable, depending


or foods containing large quantities of tyramine. Pheo-chromocytomas can also present with severe paroxysmal hypertension, since the majority of them secrete norepi-nephrine. Abdominal imaging and 24-hour urine catechol-amines are sufficient in the diagnosis of pheochromocyto-mas.49,50 The classic presentation of catecholamine-induced hypertension includes paroxysmal episodes of headache, diaphoresis, anxiety, palpitations, nausea, vomiting, and abdominal pain.51 Finally, consider catecholamine excess in acute, unexplained, or paroxysmal hypertension refrac-tory to treatments, especially in young patients and those without a history of hypertension.52

ED Management Of Nonemergent Hypertension

Typically, hypertensive urgency patients present to the ED for vague symptoms, eg, mild headache relating to their elevated BP. These are patients who have a history of end-organ damage from chronic hypertension, but are assessed to not be experiencing acute end-organ damage, as is the case with hypertensive emergency patients.15,25 Hyperten-sive urgency patients may be asymptomatic or may have only mild symptoms, such as a slight headache, that occur when the BP is uncontrolled. Note that the case of the asymptomatic, incidentally diagnosed hypertensive in the ED will be addressed in the Controversies section.

Specific Agents Used To Lower Blood Pressure

See Table 6 for a summary of drugs used to treat hyperten-sive emergencies.

NitroglycerinNitroglycerin is a potent venodilator and, to a lesser extent, an arteriole dilator. Nitroglycerin dilates vascular smooth muscles, and dilates peripheral capacitance and

resis. Ischemic chest pain should decrease as nitroglycerin lowers the blood pressure.44 Lowering the BP and heart rate and increasing coronary perfusion limit infarction size and improve outcomes in cardiac function.42,45

Eclampsia and Preeclampsia Hypertension — of any reading — in pregnant patients between 20 weeks gestation and 2 weeks postpartum should always sound an alarm for the clinician, because of the potential for maternal and infant morbidity and mortality. Preeclampsia occurs in approximately 2-9% of healthy, nulliparous women.46 The diagnosis of preeclamp-sia requires new-onset hypertension after 20 weeks gesta-tion (> 140/90 in a patient with previously normal BP) and proteinuria (> 0.3 g in 24 hours).47 Associated symptoms may include headaches, visual disturbances, epigas-tric pain, oliguria, depression of consciousness, and/or the HELLP syndrome. HELLP syndrome is defined as hemolysis, elevated liver enzymes (≥ 2x normal), and low platelets (< 100,000/uL).48 The eclamptic patient presents with seizures in the setting of preeclampsia.24 Prompt recognition and treatment of preeclampsia/eclampsia decreases fetal and maternal morbidity/mortality. (For a thorough discussion of hypertension in the pregnant patient, see Emergency Medicine PRACTICE, Volume 6, Num-ber 12, Emergencies In The Second And Third Trimesters: Hypertensive Disorders And Antepartum Hemorrhage, December 2004.)

Catecholamine-Induced StatesSevere hypertension from catecholamine-induced states is rare. Examples are pheochromocytoma, use of sympatho-mimetics (eg, cocaine, phenylephrine), antihypertensive withdrawal (eg, clonidine), and monoamine oxidase inhib-itor (MAOI) interactions. MAOIs cause hypertensive crisis in those who consume either sympathomimetic drugs

Table 6. Parenteral Drugs Used In Hypertensive Emergencies.

Drug Mechanism of Action Adverse Effects

Sodium Nitroprusside

Arteriolar and venous dilatorActs via release of nitric oxide

Hypotension, nausea, vomiting, muscle twitching, thiocyanate, and cyanide intoxication

Nitroglycerin Potent venodilator, reduces preloadCoronary vasodilatorAt higher doses, acts as arteriolar dilator

Headache, tachycardia, nausea, vomiting

Hydralazine Direct relaxation of vascular smooth muscle cells Reflex tachycardia, headache, nausea, vomiting, cardiac ischemia

Enalapril Angiotensin-converting enzyme (ACE) inhibitor Renal failure, hypotension

Fenoldopam Selective postsynaptic dopaminergic receptor (DA1) agonist, causing both vasodilation and natriuresis

Reflex tachycardia, may raise intraocular pressure, headache, and nausea

Labetalol Competitive blocker of α1- and β-adrenergic receptors

Nausea, vomiting, bronchospasm, heart block, orthostatic hypotension

Esmolol Short acting β1-selective adrenergic blocker Hypotension, bronchospasm, heart failure

Phentolamine Nonselective α-adrenergic blocker Reflex tachycardia, headache

Nicardipine Calcium channel antagonist Reflex tachycardia, headache, nausea, vomiting, flushing, hypotension


resistance vessels. Nitroglycerin decreases preload, thus decreasing left ventricular diastolic volume and increasing coronary flow to the subendocardium. In the acute setting, nitroglycerin can be given intravenously or sublingually. Intravenous nitroglycerin has a half-life of 1-4 min-utes and is slowly titrated up from initial doses of 5-15 mcg/min every 2-5 minutes. Nitroglycerin is considered the drug of choice in severely hypertensive patients with cardiac ischemia, left ventricular dysfunction, and pulmo-nary edema, because it is rapid in onset, easily titratable, improves coronary blood flow, and decreases left ven-tricular filling pressures. Caution is required in patients with aortic stenosis or left ventricular outlet obstruction to avoid precipitating cardiovascular collapse.3,53

Nitroprusside Sodium nitroprusside decreases preload and afterload by dilating arteries and veins. This drug stimulates the formation of cyclic guanosine monophosphate that relaxes smooth muscles via nitric oxide. Nitroprusside is rapid in onset, usually within seconds, its duration of action is 1-2 minutes, and its half-life is about 3-4 minutes.2,3 This allows rapid titration of blood pressures with the use of an infusion pump. Nitroprusside is indicated for most hy-pertensive emergencies. There are concerns about cyanide toxicity (with prolonged use in renal failure), reflex tachy-cardia, and possible coronary steal in the setting of acute coronary syndrome. One molecule of sodium nitroprus-side consists of a ferric center, 5 cyanide ions, and a nitric oxide group. Cyanide is released nonenzymatically from nitroprusside and is metabolized into thiocyanate in the liver, which is then excreted by the kidney.54 Therefore cau-tion is called for in patients with renal and liver diseases. A beta-blocker should be added to prevent reflex tachy-cardia, especially in the treatment of aortic dissection. Since nitroprusside can precipitously decrease the blood pressure, it is recommended to begin at 0.25 mcg/kg/min and titrate to clinical response. In comparison studies of nitroprusside to nitroglyc-erin, both were equally efficacious in lowering blood pres-sure.55,56 The study by Fremes et al, though, was conducted in postoperative cardiothoracic patients with hypertension and may not be applicable to ED patients.55 Nitroglycerin appeared to be superior in the setting of acute myocardial infarction, since nitroprusside appeared to worsen the infarction via coronary steal and worsen lactate acid influx into the cells.2,55,56 Nitroprusside is safe in patients with left ventricular dysfunction.2

Side effects of nitroglycerin include hypotension, headaches, nausea, and vomiting. Tolerance to its clinical effect occurs and is often seen within 24 hours of contin-ued use.57 Methemoglobinemia is a rare but dangerous complication that occurs when nitrite ions interfere with hemoglobin’s oxygen-carrying capacity.3,4

Hydralazine Hydralazine is a favorite of obstetricians in the treatment of preeclampsia and eclampsia.4,47 Hydralazine can be

given intramuscularly or intravenously via injection or infusion. The dose is 10-50 mg IM or 5-10 mg IV (at 0.5-1 mg/min). Its onset of action is 5-15 minutes, and the dura-tion of action is 3-6 hours.2,58 Only rarely does hydralazine cause hypotension, which is why it has been the pre-ferred drug used in obstetrics.46 Adverse effects are reflex tachycardia and palpitations — thus it is best avoided in patients with coronary artery disease. Long-term use may result in rheumatoid arthritis or lupus-like syndromes. EnalaprilEnalapril is the only available angiotensin-converting enzyme (ACE) inhibitor that can be used intravenously. It is most effective in lowering blood pressure in patients with an active renin angiotensin system (eg, atheroscle-rotic disease, concomitant renal disease, and high catechol-amine states).59,60 The degree of blood pressure reduction is correlated with pretreatment levels of plasma renin and angiotensin II. The blood pressure response is more vari-able when compared to nitroprusside or nitroglycerin.25 Enalapril’s onset of action is 15 minutes, and its duration is 12-24 hours. The intravenous dose is 1.25 mg over 5 minutes every 6 hours. Enalapril is indicated in hyper-tensive emergencies involving congestive heart failure. It causes coronary vasodilation and decreases in systemic arterial pressure, pulmonary capillary pressure, heart rate, and stroke volume index. Because ACE inhibitors do not significantly impair cerebral blood flow, enalapril may also be useful for hypertensive patients at risk for cerebral hypotensive episodes.61,62 Enalapril is contraindicated in pregnancy and patients with ACE–inhibitor-associated angioedema. In patients with renal insufficiency, the dose must be adjusted.3 One study by Rutledge et al demon-strated that intravenous enalapril was significantly better at reducing BP than placebo in stage 2 hypertensives.63 However, this was done in the setting of hypertensive urgency. In another study of hypertensive emergency and urgency patients by Hirschl et al, enalapril was less effective than urapidil in lowering SBP to 180 and SDP to 95 after 45 minutes. The clinical significance of this is not known.64

FenoldopamFenoldopam is a selective dopamine agonist acting upon the dopamine DA1 receptor, causing both vasodilation and natriuresis.65 Unlike dopamine, fenoldopam has no action at DA2, α, or β receptors. Fenoldopam is indi-cated for the management of hypertensive emergencies and hypertension in the perioperative period.66 The side effects of administration include increased intraocular pressure, along with the same side effects associated with all vasodilators (ie, nonspecific T-wave changes without ischemia, headache, flushing, dizziness, and tachycardia or bradycardia).67 The safety of fenoldopam has been confirmed in numerous studies.68-70 Fenoldopam has been shown to be equivalent to sodium nitroprusside in a prospective, randomized, open-label study69 and in one retrospec-


tive study.68 In another randomized study comparing fenoldopam and nitroprusside, both drugs were shown to be efficacious.70 However, fenoldopam has been shown to improve renal function (through diuresis and sodium excretion), making it a possibly superior agent in the set-ting of renal diseases or congestive heart failure.68,69 More studies are needed to confirm this. The advantages of fenoldopam over sodium nitro-prusside are its lack of thiocyanate and cyanide toxicity, light-stability, and low incidence of inducing hypoten-sion.67 The disadvantage of fenoldopam compared to sodium nitroprusside is fenoldopam’s cost.70 In the future, a comparison of total costs of treatment needs to be done, as fenoldopam may be given without an arterial line, and even possibly without intensive care monitoring, depend-ing upon nursing support.

LabetalolLabetalol can be used in most hypertensive emergencies and blocks α1- and β-adrenergic receptors. The beta effects predominate. Unlike other vasodilators, labetalol causes little reflex tachycardia due to its β-blocking activ-ity. Labetalol can be given either by bolus injections or as an infusion; infusions are associated with fewer episodes of hypotension than bolus dosing.3 Side effects include nausea, vomiting, paresthesias, and sweating. Labetalol is contraindicated in patients with asthma, emphysema or chronic obstructive pulmonary disease, acute heart failure, or atrioventricular block. Parenteral labetalol has been compared to other medications for hypertensive emergen-cies in 2 clinical trials.71,72 The first study was a prospective randomized trial comparing intravenous labetalol to oral nifedipine in patients with hypertensive emergencies asso-ciated with pregnancy. Both were found to be efficacious, but nifedipine controlled blood pressure in a significantly shorter time than labetalol.71 The clinical significance of this benefit is unknown. Two limitations to the use of nife-dipine as compared to labetalol include relaxing uterine smooth muscle that could lead to uterine atony, and dan-gerous interactions with magnesium sulfate (ie, enhance-ment of blood pressure response leading to hypotension and cases of neuromuscular blockade).73 The second study compared labetalol to nicardipine in a prospective ran-domized trial of the treatment of severe hypertension of pregnancy. The drugs were equally efficacious.72 Labetalol is one of the preferred agents for acute ischemic stroke.30 Labetalol is favored because it reduces peripheral vascular resistance without reducing cerebral blood flow.74

EsmololEsmolol is a short-acting β1-selective adrenergic blocker with a rapid onset of action, short duration of action, and easy titration. Esmolol is indicated for supraventricular tachycardias, but is widely used in the perioperative period to treat hypertension in cardiovascular surgical patients. Esmolol has been used to blunt the reflex tachy-cardia associated with the treatment of aortic dissection with sodium nitroprusside. Beta-blockers are agents used

for limiting the force and velocity of contraction, known as dP/dT, which, if left unchecked, can lead to propagation of dissection. Esmolol has the same contraindications as all beta-blockers, and there have been no clinical trials study-ing esmolol specifically in hypertensive emergencies.

Phentolamine Phentolamine is an α1,2-adrenergic antagonist used to treat hypertensive crisis associated with increased cat-echolamine states. The main side effects are headache and tachycardia. There have been no clinical trials comparing phentolamine to other agents in the treatment of hyperten-sive emergencies.

Nicardipine Nicardipine is a calcium channel antagonist that is indi-cated for the treatment of perioperative hypertension. Its main side effects include headache, flushing, nausea, and vomiting. Nicardipine has proven equivalent to sodium nitroprusside in randomized trials of the treatment of severe hypertension and postoperative hypertension.75,76 Nicardipine was found to be equivalent to labetalol for the treatment of severe hypertension of pregnancy.72 It also was found to be effective in children with severe hyperten-sion in a retrospective cases series.77

Oral AgentsSee Table 7 for a summary.

Captopril Captopril is an oral ACE inhibitor that has been used for hypertensive urgencies for over a decade. It has been shown to be effective in lowering BP in 15-30 minutes. Some of the long-term side effects are angioedema, cough, and renal failure in patients with bilateral renal artery ste-nosis. A trial comparing oral nifedipine, nicardipine, and captopril in 65 patients by Komsuoglu et al demonstrated similar efficacy in decreasing BP after 6 hours.78

Clonidine Clonidine is a centrally acting alpha-adrenergic agonist that has an onset of action within 30 minutes and peak effect in 2-4 hours. The typical dose is 0.1-0.2 mg orally, followed by 0.1 hourly dose up to 0.7 or until BP level is achieved. Side effects are sedation and a dry mouth.3 A ret-rospective trial of oral nifedipine versus clonidine showed equal efficacy in lowering BP, but nifedipine had a more rapid onset of action.79

Labetalol Oral labetalol has been found to be effective for hyperten-sive urgencies. A randomized trial of 34 patients by Gon-zales et al showed that 100-, 200-, and 300-mg doses were equally effective in lowering BP at 1, 2, 3, and 4 hours after the initial dose. No differences in heart rates were found.80 In another trial, oral labetalol and clonidine showed equal efficacy in lowering BP in severe hypertension.81


NicardipineOral nicardipine at 30 mg has been shown to be effective in lowering BP in a randomized, placebo-controlled study of 53 patients.84 Some side effects are tachycardia and hypotension.

Nifedipine Nifedipine is a short-acting calcium channel antagonist that was initially found to be a promising oral agent to treat hypertensive emergencies. However, further use of this medication led to cases of cerebral ischemia, syncope, and myocardial ischemia due to precipitous and unpre-dictable hypotension.82,83 Thus short-acting nifedipine should not be used in therapy of either hypertensive urgencies or emergencies, due to its dangerous and some-times life-threatening side effects.

Novel TherapiesUrapidil Urapadil is a selective α1-adrenergic antagonist and sero-toninergic 5HT1A receptor antagonist that acts as a vaso-dilator with no reactive tachycardia, presumably because of its central action. It is given at a dose of 12.5-25 mg/L every 5-15 minutes up to 75-100 mg total, with a response in 5-10 minutes and duration of action of approximately 60 minutes.85 Urapidil was found to be equally safe and efficacious when compared to sodium nitroprusside in a prospective randomized trial.86 Urapidil has not received FDA approval, but has a proven safety record in patients abroad.

MagnesiumMagnesium may be important in the physiological regulation of blood pressure. Magnesium dilates smooth muscles, possibly via modulation of intracellular calcium, sodium, and ATPase. Small changes in magnesium levels may have significant effects on cardiac excitability and on vascular tone, contractility, and reactivity. For the most part, epidemiological and experimental studies demon-strate an inverse association between magnesium and blood pressure. However, data from clinical studies have been less convincing, and the therapeutic value of mag-

nesium in the prevention and management of essential hypertension remains unclear. The greatest therapeutic po-tential for magnesium in hypertension is in the treatment of preeclampsia and eclampsia, which will be discussed further below.87,88 More randomized studies are needed on the use of magnesium in the acute setting to lower BP in hypertensive crises, before any recommendations can be made.

Treatment of Hypertensive Emergencies

Management of a hypertensive emergency begins with making the patient comfortable, thus eliminating contrib-uting factors to the elevated blood pressure; this includes treatment of any underlying cause that may exacerbate the current situation, such as pain, urinary retention, and hypoxia. Patients with hypertensive emergencies require immediate lowering of blood pressures within minutes to hours, to terminate any ongoing end-organ damage.2 This process is initiated in the ED and continues in the inten-sive care unit setting. See Table 8 on page 11 for a sum-mary of recommended interventions.

Hypertensive Encephalopathy The goal of therapy is to initially decrease the BP by not more than 20-25% of the mean arterial pressure. The basis of this goal is that hypoperfusion occurs at the lower end of the cerebral perfusion autoregulation curve, which approximates about 25% of the baseline mean arterial pressure. On the other hand, hyperperfusion occurs at the upper limit of the autoregulatory curve, which is the basis for cerebral damage.3 The recommended agent of choice is nitroprusside, followed by labetalol.

Cerebral Infarction/Hemorrhage There is controversy as to whether blood pressure needs to be treated in ischemic stroke, as blood pressure generally decreases over time without treatment.29,89 However, with extremely elevated blood pressures, cautious lowering of the blood pressure can be done. Based on the guideline from the Stroke Council for the American Heart Associa-

Table 7. Oral Agents For Treating Hypertensive Urgencies.

Drug Mechanism of Action Dose Onset/Duration Adverse Effects

Captopril Angiotensin enzyme inhibitor 25 mg 15-30 min/4-6 hr Angioedema, renal failure

Clonidine Centrally acting alpha-adrenergic agonist

0.1-0.2 mg 30-60 min/4-6 hr Headache, tachycardia, nausea, vomit-ing

Labetalol Competitive blocker of α1- and β-adrenergic receptors

100-400 mg 30-120 min/4-6 hr Bronchospasm, bradycardia, ortho-static hypotension

Nicardipine

NifedipineCalcium channel antagonist

30 mg

10-20 mg15-30 min/3-6 hr

Hypotension, reflex tachycardia, and ischemiaNifedipine is no longer recommended due to precipitous hypotension.

*Adapted from: Mansoor G. Comprehensive Management of Hypertensive Emergencies and Urgencies. Heart Disease. 2002. See Reference 3.

Continued on page 11


The evidence for recommendations is graded using the following scale. For complete definitions, see back page. Class I: Definitely recommended. Definitive, excellent evidence provides support. Class II: Acceptable and useful. Good evidence provides support. Class III: May be acceptable, possibly useful. Fair-to-good evidence provides support. Indeterminate: Continuing area of research.

This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual needs. Failure to comply with this pathway does not represent a breach of the standard of care.

Copyright © 2005 EB Practice, LLC. 1-800-249-5770. No part of this publication may be reproduced in any for-mat without written consent of EB Practice, LLC.

Clinical Pathway: Hypertensive Emergencies And Urgencies

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➤➤

➤

Hypertensive Urgency

Daignosis: Cathecholamine excess? Possibilities:

PheochromocytomaCocaine/sypmathomimeticsAntihypertensive withdrawal

(For each, see Table 8 for treatment)(All Class II)

•••

Emergent labor & deliveryEmergent OB consultSee treatment table (Class II)

Toxidrome present?Flushing, increased BP/HR?

Diagnosis: ConsiderEclampsia vs preeclampsia•

Is the patient pregnant or up to 2 weeks postpartum?

Chest pain or SOB present?

Diagnosis: ConsiderAcute myocardial infarctionAortic dissectionAcute left ventricular failure

See treatment table for each(Class I, II)

•••

Mental status changes with a focal neurological deficit?

Diagnosis:Hypertensive encephalopathySee treatment table(Class II)

Diagnosis:StrokeSee treatment table(Class III)

➤

1. Repeat BP elevated2. Active, ongoing end-organ damage ruled out3. History of HTN-related end-organ damage

Treatment options for patients on HTN meds:1. Restart if noncompliant2. Increase dose3. Add another antihypertensive(Indeterminate)

1. Observe for several hrs2. Repeat BP3. Follow-up in 24-72 hrs

Treatment options for patients not on HTN meds:1. Give oral meds (See Table 7 for options)2. Not starting any meds(Indeterminate)

➤

➤

➤

➤

➤

➤ ➤

➤

YES

NO

YES

NO

NO YES

YESNO


Beta-blockers also limit the force and velocity of contrac-tion, which, if left unchecked, can lead to propagation of the dissection.

Acute Myocardial Infarction The goal of antihypertensive therapy in acute MI is to de-crease cardiac work by decreasing afterload and increasing coronary perfusion pressures. The agents used to achieve these goals are nitrates and β-blockers. Morphine can be used to lower the blood pressure associated with the pain and anxiety of the infarction.90

Acute Left Ventricular Failure The management goal in acute pulmonary edema with hypertension is to decrease preload and afterload, and to lower the blood pressure, thereby “unloading” the failing heart. This is accomplished by using vasodilating agents, eg, nitroprusside or nitroglycerin. Concomitant use of diuretics, such as a loop diuretic, may be indicated for optimal results in cases of volume overload in the set-

Continued from page 9

Table 8. Treatment For Hypertensive Emergency.

Emergency First Line* Dose Medications to Avoid

Caveats

Hypertensive Encephalopathy

NTPLabetalolFenoldopamNicardipine

0.25-10 µg/kg/min20-80 mg IV bolus every 10 min, 0.5-2 mg/min 0.1-0.6 µg/kg/min5-15 mg/hr

TrimethophanClonidine

Must rule out strokes

Cerebral Infarction or Hemorrhage

LabetalolNTPNicardipine

20-80 mg IV bolus every 10 min, 0.5-2 mg/min 0.25-10 µg/kg/min5-15 mg/hr

Hydralazine Avoid ↓ cerebral perfusionTreatment only if BP:> 220/120 no thrombolytics> 185/110, thrombolytic cases

Aortic Dissection

LabetalolNTP +Esmolol

20-80 mg IV bolus every 10 min, 0.5-2 mg/min 0.25-10 µg/kg/minloading dose 500 µg/kg over 1 min, infusion 25-50 µg/kg/min titrate every 10-20 min

Hydralazine ↓ dP/dT (decrease shearing forces)

Acute Myocardial Infarction

NTGLabetalolNTPβ-blockers (eg, Lopressor)

5-100 µg/min20-80 mg IV bolus every 10 min, 0.5-2 mg/min 0.25-10 µg/kg/min5 mg IVP

Hydralazine ↑ coronary perfusion↓ afterload

Eclampsia LabetalolNicardipineMagnesiumHydralazine

20-80 mg IV bolus every 10 min, 0.5-2 mg/min 5-15 mg/hr6g loading dose, then 2 g/hr10-20 mg IV

EnalaprilatNTP

Consider emergent delivery

Acute Left Ventricular Failure

NTGNTPEnalaprilalFenoldopam(+ diuresis)

5-100 µg/min0.25-10 µg/kg/min1.25-5 mg every 6 hours0.1-0.6 µg/kg/min

LabetalolEsmolol

↓ afterload

Catecholamine Excess

PhentolamineLabetalol NTP + Esmolol

5-10 mg/min20-80 mg IV bolus every 10 min, 0.5-2 mg/min0.25-10 µg/kg/minloading dose 500 µg/kg over 1 min, infusion 25-50 µg/kg/min titrate every 10-20 min

Avoid unopposed β-blocker

Consider benzodiazepams for cocaine toxicity

*NTP=sodium nitroprusside, NTG=nitroglycerinFrom the Stroke Council of the American Heart Association. See Reference 30.

tion for acute ischemic strokes, if the patient is not eligible for thrombolytic therapy, treatment starts only with blood pressures greater than 220/120.30 With patients who are eligible for thrombolytic therapy, then treatment is initi-ated when the blood pressure is greater than 185/110.30 Treatment is with nicardipine, sodium nitroprusside, or labetalol. In general the agent used should be short-acting, easily titratable, and should not dilate cerebral vessels.

Aortic Dissection The goal of therapy is to prevent progression of the dis-section. The arterial pressure should be maintained as low as possible without compromising end-organ perfu-sion.33 This is typically done with a combination of sodium nitroprusside and a β-blocker, eg, esmolol; however, labetalol can also be used as a single agent. Beta-blockers are used to blunt the reflex tachycardia associated with the treatment of aortic dissection with sodium nitroprusside.


ting of acute left ventricular failure.29 There is a paucity of clinical data on the use of ACE inhibitors in patients with acute left heart failure, though ACE inhibitors are effective vasodilators.91 Intravenous enalapril is effective in rapidly lowering blood pressure in patients with hypertensive emergencies with chronic heart failure.59,63,92 Oral capto-pril is also effective in rapidly lowering blood pressure in hypertensive crises, but its maximal effect may be delayed for up to 2 hours.29,92

Preeclampsia/EclampsiaThe elevated blood pressure seen in eclampsia/pre-eclampsia can be quickly and safely lowered to “normal levels” at no increased risk for inducing cerebral or

cardiac ischemia. Control of the blood pressure is im-portant to help prevent cerebral vascular complications; however, evidence for the prevention of the progression of preeclampsia into eclampsia is not clear.46 The classic agent used is hydralazine, although labetalol has recently gained favor. Labetalol had similar efficacy and fewer side effects.46 Magnesium sulfate is added to the regimen for seizure prophylaxis and has been shown to lower the progression of preeclampsia to eclampsia in randomized trials.93 A randomized study of 135 patients by Witlin et al showed that magnesium may not be so effective in preventing seizures in mild preeclamptics.94 Magnesium sulfate has also been observed to lower the blood pressure transiently when given to severely hypertensive pregnant

Ten Pitfalls To Avoid6. Failing to elicit the use of cocaine or other sympathomimetics in young patients with extremely elevated BP without a history of hypertension.

Always ask for a history of illicit drug use. Cocaine, along with other sympathomimetics, can both lead to hypertension and precipitate a serotonin syndrome.

7. Failing to recognize that relatively high BP may be a compensatory mechanism to maintain cerebral perfusion pressures in stroke patients.

Based on the guideline for acute ischemic strokes from the Stroke Council for the American Heart Association, if the patient is not eligible for thrombolytic therapy, treatment to lower BP starts only with blood pressures greater than 220/120. With patients who are eligible for thrombolytic therapy, treatment is initiated when the blood pressure is greater than 185/110.

8. Using nifedipine to treat a patient with a hypertensive emergency.

Oral nifedipine has been associated with inducing acute cerebral and acute myocardial ischemia, because it leads to precipitous hypotension.

9. Failing to recognize simple causes of hypertension that could be easily addressed in the ED.

Try to ensure that patients (especially those who are demented, aphasic, or severely mentally retarded) are not in pain, urinary retention, or hypoxia. All these could cause agitation and elevated BP.

10. Focusing on the blood pressure and failing to treat the whole patient.

Get a good history and do a thorough exam to evaluate for acute, ongoing end-organ damage. Lowering the BP may cause more harm than good (as in strokes) and may not even be necessary. For example, there is strong evidence that patients with an incidental finding of elevated BP could be discharged from the ED with good follow-up. However, for patients with aortic dissection, the recommendation remains that blood pressure be lowered as much as possible (to SBP 90-120 mmHg). ▲

1. Failing to consider a postpartum (up to 14 days) patient for the evaluation of preeclampsia/eclampsia.

Pregnant patients — usually in the third trimester and up to 14 days postpartum — with elevated blood pressure, headache, and proteinuria should be evaluated for preeclampsia.

2. Failing to differentiate between hypertensive encephalopathy and cerebral ischemia.

The treatment for hypertensive encephalopathy is to lower the BP by 25% of the baseline MAP. However, the same treatment for a CVA may worsen the neurological deficits, due to a drop in the high compensatory cerebral perfusion pressures commonly present.

3. Using nitroprusside at large doses in patients with liver and renal disease.

Each molecule of nitroprusside has 5 molecules of cyanide. Cyanide is released nonenzymatically from nitroprusside and is metabolized into thiocyanate in the liver, which is then excreted by the kidney.

4. Failing to consider the use of beta-blockers in patients with aortic dissection.

Beta-blockers are an excellent choice to decrease the shearing force. Add beta-blockers to nitroprusside to blunt reflex tachycardia, which could cause more shearing of the arterial lumen wall and worsen the dissection.

5. Failing to differentiate between a hypertensive emergency and a hypertensive urgency.

Hypertensive emergencies have evidence of acute, ongoing end-organ damage due to extremely elevated BP, whereas hypertensive urgencies have a history of end-organ damage, but no active compromise. For hypertensive emergencies, immediate lowering of the BP (within minutes to hours) is needed to stop the ongoing end-organ damage. For urgencies, patients could probably be discharged with follow-up in 24-72 hours. Oral hypertensives may be considered in the ED.


patients. However, further studies are indicated, since the effect may simply be the result of bed rest, or a change in position.95 A small study of 35 patients by Rudnicki et al did show that magnesium was more effective than meth-yldopa in lowering BP in pregnant patients.96 Definitive therapy for eclampsia is delivery of the fetus.

Cathecholamine-Induced States The goal of therapy is blood pressure control without exacerbation of the condition. Several agents are recom-mended, including phentolamine, nitroprusside, and labetalol. Pure β-blockers are contraindicated, since they may exacerbate the condition due to unopposed alpha activity.50

In the setting of cocaine-induced catecholamine excess, benzodiazepines have been shown to decrease the centrally mediated and peripheral sympathomimetic outflow that contribute to the symptoms of cocaine, such as elevated blood pressure, chest pain, and agitation.97 Benzodiazepines help to lower the systemic arterial pres-sure, lower the heart rate, and decrease psychomotor hyperactivity.98 Benzodiazepines treat both the central and peripheral manifestations of cocaine intoxication, with few side effects. (For an extensive review of ED treat-ments for cocaine abuse, as well as toxidromes associated with other street drugs, see Emergency Medicine PRACTICE, Volume 7, Number 5, Drugs Of Abuse: Providing The Best In Evidence-Based Care To “Self-Medicated” Patients, May 2005.)

Hypertensive UrgenciesJNC 7 makes the following recommendations (based on consensus): hypertensive urgency patients should have their medications thoroughly reviewed. If noncompliance was the problem, then reinstitution of the antihyperten-sive drug is recommended. The next option is to increase the dose of the antihypertensive, if the patient is already taking one. The third option is the addition of combination drugs. JNC 7 also states that some hypertensive-urgent patients may benefit from treatment with an oral, short-acting agent, such as captopril, labetalol, or clonidine, followed by several hours of observation. The question

is — which patients? A prospective, double-blind, pla-cebo-controlled, randomized study by Hirschl et al on 40 hypertensive urgency patients showed that oral urapidil initiated in the ED lowered BP more effectively than pla-cebo 12 hours after patient discharge from the ED. How-ever, there are no conclusions on the clinical implications of this, and all patients in the study initially received IV urapidil!99 There is no evidence to suggest that failure to aggressively lower the BP in the ED is associated with any short-term increased risk for hypertension-related com-plications to the patient in this situation. Patients should be observed for several hours after administration of an antihypertensive drug to assure responsiveness. Whether treatment was initiated or not in the ED, patients should have prompt follow-up in 24-72 hours for BP recheck.5,25

Controversies/Cutting Edge

ED Evaluation and Management of Asymptomatic HypertensionPatients presenting to the ED with incidental hypertension pose a dilemma that is encountered by emergency physi-cians often multiple times a day. The health risks due to prolonged, untreated hypertension are well documented in the literature. However, there is no clear consensus on how to evaluate and manage such patients in the acute-care setting. The assessment of a patient with elevated blood pres-sure should be aimed at identifying evidence of end-organ damage. A search for evidence to validate the use of spe-cific screening tests revealed little data. At least one study has suggested that a negative urine dip for both protein and hematuria in 143 ED patients with hypertension ruled out an acute elevation in creatinine (sensitivity, 100%; 95% CI, 83-100). Despite achieving a high degree of sensitiv-ity, the wide confidence interval, unfortunately, does raise some concerns over using this test alone as a screening tool to identify acute renal damage.100 An abstract of a ret-rospective study, including 195 asymptomatic ED patients with diastolic blood pressures greater than 110, reported that ECG abnormalities were found in 43 (22%), and 13% were found to have serum creatinine levels more than 1.5. ECG abnormalities included T-wave inversions, Q waves, or ST-segment elevations or depressions.101 Peters et al concluded that ECG and serum creatinine were valuable screening tools in the evaluation of asymptomatic hyper-tension. An older chart review from 1978 demonstrated little impact on patient management with routine chest films and ECGs in 116 patients with hypertension. Only 2 of the 116 patients had therapeutic or diagnostic interven-tions based on the chest film or ECG, and none influenced hypertensive management. The authors concluded that routine chest films and ECGs could not be defended in the workup of hypertension.102 These studies suggest that a serum creatinine may be beneficial in evaluating the asymptomatic hypertensive patient, especially when fol-low-up care is a concern. However, routine chest films and electrocardiograms are controversial. There is little data directly addressing the need for

Key Points For Hypertensive Emergencies And Urgencies1. Evidence of acute, ongoing end-organ damage must be

present in order to make the diagnosis of a hypertensive emergency.

2. Preeclampsia and eclampsia can be present up to 2 weeks postpartum, and the blood pressure may be only mildly elevated.

3. Avoid precipitous drops in blood pressure in cases of cerebrovascular hypertensive emergencies; target for a ≈25% decrease of the mean arterial pressure. ▲


Special Circumstances

Airway Management in Hypertensive EmergenciesThere are principles of airway management that the clini-cian needs to consider when intubating in the setting of hypertensive emergencies. Stimulation of the well-inner-vated larynx, carina, and supraglottic structures during laryngoscopy and endotracheal intubation activates the sympathetic nervous system, with a subsequent release of catecholamines. This adrenergic surge increases the systolic blood pressure and the mean arterial pressure up to 100%, and the diastolic blood pressure up to 50%. These increases in physiologic parameters can have detrimental consequences in cases of cardiovascular (ischemia, failure, or dissection) and cerebrovascular (strokes) hypertensive emergencies. To prevent this adrenergic surge, the intuba-tion should be carried out as quickly and atraumatically as possible, with attention to proper depth of placement of the endotracheal tube to avoid stimulation of the carina. In addition to these nonpharmacologic methods, 2 medica-tions, fentanyl and esmolol, have been studied as pretreat-ment medications to attenuate the reflex sympathetic response from laryngoscopy and endotracheal intubation. Esmolol, at a dose of 1.4-3.0 mg/kg, or fentanyl, at a dose of 2-3 mcg/kg, can be given 3 minutes before induction during airway management. Esmolol has been shown to be effective in controlling the heart rate and blood pres-sure during laryngoscopy and intubation.107-109 Fentanyl will blunt the rise in blood pressure associated with intu-bation, but it is not clear from the literature that fentanyl is as effective at controlling the heart rate.107,110,111

Disposition

Patients with hypertensive emergency should be admit-ted to a monitored setting, preferably an intensive care unit. Depending on the diagnosis, the appropriate service should be consulted and should follow the patient. Patients with hypertensive urgencies can be discharged with timely follow-up.5 If an antihypertensive is initi-ated, then patients receiving these medications should be observed for a few hours to observe for its effects. If the patient is unable to access follow-up elsewhere, a return to the ED for follow-up would be prudent. ED patients with an incidental finding of hypertension should be referred for outpatient therapy and further workup after a basic screening for end-organ damage is done.

Summary

The management of acutely elevated blood pressure re-quires the clinician to differentiate hypertensive emergen-cies from hypertensive urgencies. Hypertensive emergen-cies have evidence of acute, ongoing end-organ damage, while hypertensive urgencies do not involve ongoing end-organ compromise. Hypertensive emergencies require an immediate lowering of the blood pressure in order to prevent further deterioration from end-organ damage; hypertensive urgencies only rarely need to be acutely

rapidly lowering elevated blood pressure in asymptom-atic patients in the ED. Much of the available evidence is extrapolated from long-term trials or studies done in ambulatory care settings, and this does not directly ad-dress the impact of acute management in asymptomatic patients. A landmark 1967 randomized, placebo-controlled trial, known as the VA Cooperative Trial, enrolled 143 patients with diastolic blood pressures (DBPs) of 115-130. This well done study demonstrated no adverse outcomes with treatment versus placebo over the initial 3 months of study.103 Another prospective, randomized controlled trial compared the blood pressure response in 64 asymptomatic patients with DBPs 116-139 mmHg who were receiving oral clonidine. Patients were loaded with clonidine, fol-lowed by further dosing with clonidine or placebo, to a predetermined blood pressure prior to discharge, versus discharge with maintenance dosing as an outpatient only. There was no clinically important difference in blood pres-sure response or clinical outcome between study groups over 7 days.104 To date there is no evidence demonstrating improved patient outcomes, including decreased mortality or morbidity, with acute management of elevated blood pressure in the ED. Interestingly, there are a number of well-documented cases of patients with poor outcomes, including hypoten-sion, myocardial ischemia and infarction, strokes, and death precipitated by rapidly lowering elevated blood pressures in asymptomatic patients.7,83,89,105 The majority of these cases are associated with documented complications from the acute use of oral nifedipine. So, should the emergency physician even worry about identification of hypertension in the ED? There are data to suggest the need for definitive follow-up, as patients treated with placebo in the VA Cooperative Trial did de-velop significant complications within 4 months of enroll-ment, including sudden death, ruptured aortic aneurysm and death, severely elevated BUN, and congestive heart failure.103

Despite the lack of supportive evidence, previously undiagnosed patients with severely elevated blood pres-sure in the ED may warrant initiation of therapy, when access to follow-up or primary care is not readily avail-able. Prior to initiating this therapy, the treating physician should consider that as many as a third of patients with diastolic blood pressures above 95 mmHg upon initial ED visit have been found to normalize prior to the arranged follow-up. However, these results also serve to under-score the complexity of this dilemma — two thirds of the patients did require initiation of long-term therapy by their primary care physicians.106 Ultimately in the ED set-ting, perhaps the greatest benefit that can be provided to these patients is identifying the hypertensive episode and educating the patients about the need for further evalu-ation and potential management. Ideally, this workup is best performed through definitive follow-up with their primary physicians.


Minority Population. N Engl J Med 1992; 327:776-781. (Case control study, 207 patients)

12. Tisdale JE, Huang MB, Borzak S. Risk factors for hyper-tensive crisis: importance of out-patient blood pressure control. Family Practice 2004;21:420-424. (Retrospective, case-controlled study, 143 patients)

13. Bennett N, Shea S. Hypertensive emergency:case criteria, sociodemographric profile, and previous care of 100 cases. Am J Public Health 1988;78:636-640. (Retrospective case series, 100 patients)

14. Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate man-agement of blood pressure in a Hypertensive population. N Engl J Med 1998;339:1957-1963. (Retrospective, 800 patients)

15. Houston M. Hypertensive emergencies and urgen-cies: Pathophysiology and clinical aspects. Am Heart J 1986;111(1):205-210. (Review)

16. Ault MJ, Ellrodt AG. Pathophysiological Events Leading to the End-organ Effects of Acute Hypertension. Am J Emerg Med [Suppl] 1985;3:10-15. (Review)

17. Kitiyakara C, Guzman NJ. Malignant Hypertension and Hypertensive Emergencies. J Am Soc Nephrol 1998;9:133-142. (Review)

18. Vaughan CJ, Norman D. Hypertensive emergencies. Lancet 2000;356:411-417. (Review)

19. Reed WG, Anderson RJ. Effects of rapid blood pres-sure reduction on cerebral blood flow. Am Heart J 1986;111(1):226-228. (Review)

20. Strandgaard S, Olesen J, Skinhoj E, et al. Autoregulation of Brain Circulation in Severe Arterial Hypertension. BMJ 1973;1:507-510. (Observational study, 13 patients)

21. Strandgaard S. Autoregulation of Cerebral Blood Flow in Hypertensive Patients. Circulation 1976;53(4):720-727. (Observational study, 36 patients)

22. Gifford RW. Effect of Reducing Elevated Blood Pressure on Cerebral Circulation. Hypertension 1983 Sep-Oct;5(5 Pt 2):III17-20. (Review)

23. World Hypertension League. Measuring your blood pressure. Available at: www.mco.edu/org/whl/blood-pre.html. World Hypertension League. Accessed July 13, 2005.

24. Lipstein H, Lee CC, Crupi RS. A Current Concept of Eclampsia. Am J Emerg Med 2003;21:223-226. (Review)

25. Kaplan, NM. Treatment of Hypertensive Emergencies and Urgencies. Heart Disease and Stroke 1992;1:373-378. (Review)

26. Pastan S, Baily J. Dialysis Therapy. N Eng J Med 1998;338:1428-1437. (Review)

27. Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. JAMA 2000;283-897. (Review)

treated, although close outpatient follow-up is required. Treatment of hypertensive emergencies requires an under-standing of the pathophysiology and etiology, in order to select the most appropriate intervention. Physicians need to avoid merely treating the blood pressure reading, and instead treat each patient individually, carefully weighing each new set of clinical circumstances as they arise. ▲

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The find-ings of a large, prospective, randomized, and blinded trial should carry more weight than a case report. To help the reader judge the strength of each refer-ence, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available.

1. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, The JNC 7 Report. JAMA 2003;289:2560-2572. (Practice guideline)

2. Vidt, DG. Current Concepts in treatment of hypertensive emergencies. Am Heart J 1986;111:220-225. (Review)

3. Mansoor GA, Frishman WH. Comprehensive Manage-ment of Hypertensive Emergencies and Urgencies. Heart Disease 2002;4:358-371. (Review)

4. Varon J, Marik PE. The Diagnosis and Management of Hypertensive Crises. Chest 2000;118:214-227. (Review)

5. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pres-sure. Hypertension 2003;42:1206-1252. (Practice guideline)

6. Prisant LM, Carr AA, Hawkins DW. Treating Hyperten-sive Emergencies: controlled reduction of blood pressure and protection of target organs. Postgrad Med 1993;92-96:101-104. 108-110. (Review)

7. Shayne PH, Pitts SR. Severely Increased Blood Pres-sure in the Emergency Department. Ann Emerg Med 2003;41:513-529. (Review)

8. Pitts SR, Adams RP. Emergency Department Hyper-tension and Regression to the Mean. Ann Emerg Med 1998;31:214-218. (Historical cohort study, 195 patients)

9. Zampaglione B, Pascale C, Marchisio M, et al. Hy-pertensive Urgencies and Emergencies. Hypertension 1996;27:144-147. (Review)

10. Bennett NM, Shea S. Hypertensive Emergency: Case Cri-teria, Sociodemographic Profile, and Previous Care of 100 Cases. Am J Public Health 1988;78:636-640. (Retrospective case series, 100 patients)

11. Shea S, Misra D, Ehrlich MH et al. Predisposing Factors For Severe, Uncontrolled Hypertension In An Inner-city


guidelines for the management of patients with acute myocardial infarctions: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 1999. Available at: http://www.acc.org/clinical/guidelines/ami.html. (Practice guide-line)

46. Sibai B, Dekker G, Kupferminc M. Preeclampsia. Lancet 2005;365:785-799. (Review)

47. ACOG Practice Bulletin No. 33 Diagnosis and Manage-ment of Preeclampsia and Eclampsia. Int J Gynaecol Obstet 2002;77:67-75. (Practice guideline)

48. Sibai BM. The HELPP syndrome: much ado about noth-ing? Am J Obstet Gynecol 1990;162:311-316. (Review)

49. Andreoli TE, Bennett JC, Carpenter CC. Cecil Essentials of Medicine. 4th ed. Philadelphia, Pa: WB Saunders Co; 1997:502-503. (Textbook)

50. Walther MM, Keiser HR, Linehan WN. Pheochromocy-toma: Evaluation, diagnosis and treatment. World J Urol 1999;17:35-39. (Review)

51. Calhoun DA, Oparil S. Treatment of Hypertensive Crisis. N Engl J Med 1990;323:1177-1183. (Review)

52. Grossman S, Gunnells JC. Recognition and Treatment of Hypertensive Emergencies. Cardiovasc Clin 1981;11(3):97-116. (Review)

53. Cohn JN, Franciosa JA, Francis GS, et al. Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administra-tion cooperative study. N Engl J Med 1982;306:1129-1135. (Randomized, double-blind, placebo-controlled trial, 812 patients)

54. Hall VA, Guest JM. Sodium nitroprusside-induced cya-nide intoxication and prevention with sodium thiosulfate prophylaxis. Am J Crit Care 1992;1(2):19-27. (Review)

55. Fremes SE, Weisel RD, Mickle DA, et al. A comparison of nitroglycerin and nitroprusside: I. Treatment of post-operative hypertension. Ann Thorac Surg 1985;39:53-60. (Randomized, crossover trial, 33 patients)

56. Mann T, Cohn PF, Holman LB. Effect of nitroprusside on regional myocardial blood flow in coronary artery dis-ease:result in 25 patients and comparison with nitroglyc-erin. Circulation 1978;57:732-738.

57. Elkayam U, Kulick D, McIntosh N, et al. Incidence of early tolerance to hemodynamic effects of nitroglycerin in patients with coronary artery disease and heart failure. Circulation 1987;76:577-584. (Randomized, placebo-con-trolled study, 31 patients)

58. Shepherd AH, Ludden TM, McNay JL, et al. Hydrala-zine kinetics after single and repeated oral doses. Clin Pharmacol Ther 1980;28:804-811. (Observational study, 8 patients)

59. DiPette DJ, Ferraro JC, Evans RR, Martin M. Enalaprilat, an intravenous angiotensin-converting enzyme inhibitor, in hypertensive crises. Clin Pharmacol Ther 1985;38:199-204. (Observational study, 7 patients)

28. Finnerty FA. Hypertensive Encephalopathy. Am J Med 1972; 52(5):672-678. (Review)

29. Tuncel M, Ram VC. Hypertensive Emergencies Etiology and Management. Am J Cardiovasc Drugs 2003;3(1):21-31. (Review)

30. Adams HP, Adams RJ, Brott T et al. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the stroke council of the Ameri-can Stroke Association. Stroke 2003; 4:1056-1083. (Practice guideline)

31. Oppenheimer HM, Hachinski HC. The Cardiac Conse-quences of Stroke. Neuro Clin 1992;10:167-176. (Review)

32. Oliveira-Filho J, Silva SC, Trabuco CC, et al. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology 2003;61:1047. (Retrospec-tive study)

33. Knaut A, Cleveland J. Aortic Emergencies. Emerg Med Clin N Am 2003;21:817-845. (Review)

34. Nienaber C, Eagle K. Aortic Dissection:New Frontiers in Management and Diagnosis. Circulation 2003;108:628-635. (Review)

35. Chen K, Varon J, Wenker OC et al. Acute Thoracic Aortic Dissection: The Basics. J Emerg Med 1997;15(6):859-867. (Review)

36. Bossone, E, Rampoldi, V, Nienaber, CA, et al. Usefulness of pulse deficit to predict in-hospital complications and mortality in patients with acute type A aortic dissection. Am J Cardiol 2002;89:851.

37. Pretre R, Von Segesser LK. Aortic Dissection. Lancet 1997;349:1461-1464. (Review)

38. Erbel R, Alfonso F, Boileau C, et al. Diagnosis and man-agement of aortic dissection. Eur Heart J 2001;122:1642-1681. (Review)

39. Crawford ES. The diagnosis and management of aortic dissection. JAMA 1990;264:2537-2541. (Review)

40. Nienaber CA, von Kodolitsch Y. Meta-analysis of the prognosis of thoracic aortic dissection: changing mortal-ity in the last four decades. Herz 1992;17(6):398-416. (Meta-analysis)

41. Fromm RE, Varon J, Gibbs LR. Congestive Heart Failure and Pulmonary Edema for the Emergency Physician. J Emerg Med 1995; 13(1):71-87. (Review)

42. Gifford RW. Management of Hypertensive Crises. JAMA 1991;266:829-835. (Review)

43. McRae RP, Liebson PR. Hypertensive Crisis. Med Clin North Am 1986;70(4):749-767. (Review)

44. Karlberg KE, Saldeen T, Wallin R et al. Intravenous ni-troglycerin reduces ichaemia in unstable angina pectoris double-blind placebo controlled study. J Intern Med 1998;243:25-31. (Randomized, double-blind, placebo-controlled trial, 162 patients)

45. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA


60. Rupp H. Excess Catecholamine Syndrome, Pathophysiol-ogy and Therapy. Ann NY Acad Sciences 1999;881:430-444. (Review)

61. Rajagopalan B, Raine AE, Cooper R, et al. Changes in cerebral blood flow in patients with severe congestive heart failure before and after captopril treatment. Am J Med 1984;76:86-90. (Abstract)

62. Paulson OB, Jarden JO, Godtfredsen J, et al. Cerebral blood flow in patients with congestive heart failure treated with captopril. Am J Med 1984;76:91-95. (Prospec-tive, controlled trial, 10 patients)

63. Rutledge J, Ayers C, Davidson R. et al. Effect of intrave-nous enalapril in moderate and severe hypertension. Am J Cardiol 1988;62:1062-1067. (Randomized, double-blind study, 65 patients)

64. Hirschl MM, Seidler D, Mullner M, et al. Efficacy of dif-ferent antihypertensive drugs in the emergency depart-ment. J Human Hypertens 1996 Sep;10 Suppl 3:S143-S146. (Prospective, controlled trial, 168 patients)

65. Post JB, Frishman WH. Fenoldopam. A New Dopamine Agonist for the Treatment of Hypertensive Urgencies and Emergencies. J Clin Pharmacol 1998; 8:2-13. (Review)

66. Oparil S, Aronson S, Deeb GM, et al. Fenoldopam: A New Parental Antihypertensive Consenses Roundtable on the Management of Perioperative Hypertension and Hypertensive Crisis. Am J Hypertens 1999;12:653-664. (Review)

67. Murphy MB, Murray C, Shorten GD. Fenoldopam-A Selective Peripheral Dopamine-Receptor Agonist for the Treatment of Severe Hypertension. N Engl J Med 2001;345:1548-1557. (Review)

68. Devlin JW, Seta ML, Kanji S, et al. Fenoldopam Versus Nitroprusside for the Treatment of Hypertensive Emer-gency. Ann Pharmacother 2004;38:755-759. (Retrospective, 43 patients)

69. Panacek EA, Bednarczyk EM, Dunbar LM, et al. Ran-domized, Prospective Trial of Fenoldopam vs Sodium Nitroprusside in the Treatment of Acute Severe Hyper-tension. Acad Emerg Med 1995;2:959-965. (Multicenter, prospective, randomized, open-label trial, 183 patients)

70. Tumlin JA, Dunbar LM, Oparil S, et al. Fenoldopam, a Dopamine Agonist, for Hypertensive Emergency: A Mul-ticenter Randomized Trial. Acad Emerg Med 2000;7:653-662. (Multicenter, randomized, double-blind trial, 117 patients)

71. Vermillion ST, Scardo JA, Newman RB, et al. A Ran-domized, Double-Blind Trial of Oral Nifedipine and Intravenous Labetalol in Hypertensive Emergencies of Pregnancy. Am J Obstet Gynecol 1999;181(4):858-861. (Ran-domized, double-blind trial, 50 patients)

72. Elatrous S, Nouira S, Ouanes Besbes L, et al. Short-term treatment of severe hypertension of pregnancy: prospec-tive comparison of nicardipine and labetalol. Intensive Care Med 2002;28:1281-1286. (Randomized, prospective study, 60 patients)

73. Drug interactions between nifedipine and magnesium

sulfate. Thomson Healthcare Series, Vol. 121. Available at: http://www.micromedex.com. Accessed July 13, 2005. (Online tool)

74. Olsen KS, Svendsen LB, Larsen FS, et al. Effect of labet-alol on cerebral blood flow, oxygen metabolism and auto-regulation in healthy humans. Br J Anaesth 1995;75:51-54. (Observational study, 8 patients)

75. Halpern NA, Goldberg M, Neely C, et al. Postopera-tive hypertension: a multicenter, prospective, random-ized comparison between intravenous nicardipine and sodium nitroprusside. Crit Care Med 1992;20(12):1637-1643. (Multicenter, prospective, randomized, open-label study, 139 patients)

76. Neutel JM, Smith DH, Wallin D, et al. A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hyper-tens 1994;7:623-628. (Randomized study, 121 patients)

77. Flynn JT, Mottes TA, Brophy PD, et al. Intravenous nicar-dipine for treatment of severe hypertension in children. J Pediatr 2001;139:38-43.

78. Komsuoglu V, Sengun B, Bayram A, et al. Treatment of hypertensive urgencies with oral nifidipine, nicardioine, and captopril. Angiology 1991;12:447-454. (Randomized study, 65 patients)

79. Just VL, Schrader BJ, Paloucek FP, et al. Evaluation of drug therapy for treatment of hypertensive urgencies in the emergency department. Am J Emerg Med 1991;9:107-111. (Retrospective, 94 patients)

80. Gonzales ER, Peterson MA, Rach EM, et al. Dose response evaluation of oral labetolol in patients present-ing to the emergency room department with accelerated hypertension. Ann Emerg Med 1991;20:333-338. (Random-ized, double-blind trial, 255 patients)

81. Atkin SH, Jaker MA, Beaty P, et al. Oral labetolol versus oral clonidine in the emergency treatment of severe hypertension. Am J Med Sci 1992;303:9-15. (Prospective, randomized, double-blind study, 36 patients)

82. Grossman E, Messerli FH, Grodzicki T, et al. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergen-cies? JAMA 1996;276(16):1328-1331. (Review)

83. Wachter RM. Symptomatic hypotension induced by nifedipine in the acute treatment of severe hypertension. Arch Intern Med 1987;147:556-558. (Case reports)

84. Habib GB, Dunbar LM, Rodrigues R, et al. Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: a mulitcenter, randomized double blind, parallel, placebo-controlled clinical trial. Am Heart J 1995;129:917-923. (Randomized, double-blind, pla-cebo-controlled trial, 57 patients)

85. Alijotas-Reig J, Bove-Farre I, Cabo-Frances FD, et al. Effectiveness and Safety of Prehospital Urapidil for Hy-pertensive Emergencies. Am J Emerg Med 2001;19:130-133. (Prospective study, 16 patients)

86. Hirschl MM, Binder M, Bur A, et al. Safety and efficacy of urapidil and sodium nitroprusside in the treat-


pressure within the first 12 h of hypertensive urgencies. J Hypertens 1998;16:251-255. (Randomized, prospective, double-blind, placebo-controlled study, 40 patients)

100. Karras DJ, Heilpern KL, Riley LJ, et al. Urine dipstick as a screening test for serum creatinine elevation in emergen-cy department patients with severe hypertension. Acad Emerg Med 2002;9:27-34. (Prospective observational, 143 patients)

101. Peters H, Baldwin M, Clarke M. The utility of laboratory data in the evaluation of the asymptomatic hypertensive workup. Ann Emerg Med 2002;40:S48. (Abstract)

102. Bartha GW, Nugent CA. Routine chest roentgenograms and electrocardiograms. Usefulness in the hypertensive workup. Arch Intern Med 1978;138:1211-1213. (Chart review)

103. Veterans Administration Cooperative Study Group. Veterans Administration Cooperative Study Group on Antihypertensive Agents. JAMA 1967;202:1028-1034. (Randomized placebo-controlled trial)

104. Zeller KR, Von Kuhnert L, Matthews C. Rapid reduction of severe asymptomatic hypertension. A prospective, controlled trial. Arch Intern Med 1989;149(10):2186-2189. (Randomized controlled trial, 64 patients)

105. O’Mailia JJ, Sander GE, Giles TD. Nifedipine-associated myocardial ischemia or infarction in the treatment of hypertensive urgencies. Ann Intern Med 1987;107:185-186. (Case reports)

106. Chernow SM IK, Criss E. Use of the emergency depart-ment for hypertensive screening: a prospective study. Ann Emerg Med 1987;162(2):180-182. (Prospective obser-vational, 239 patients)

107. Helfman SM, Gold MI, DeLisser EA, et al. Which drug prevents tachycardia and hypertension associated with tracheal intubation: lidocaine, fentanyl, or esmolol? Anesth Analg 1991;72:482-486. (Randomized placebo-controlled trial, 80 patients)

108. Feng CK, Chan KH, Liu KN, et al. A comparison of lido-caine, fentanyl, and esmolol for attenuation of cardiovas-cular response to laryngoscopy and tracheal intubation. Acta Anaesthesiol Sin 1996;34:61-67. (Randomized, single-blinded study, 80 patients)

109. Singh H, Vichitvejpaisal P. Comparative effects of lido-caine, esmolol, and nitroglycerin in modifying the hemo-dynamic response to laryngoscopy and intubation. J Clin Anesth 1995;7:5-8. (Randomized, placebo-controlled, double-blind study, 40 patients)

110. Splinter WM, Cervenko F. Haemodynamic responses to laryngoscopy and tracheal intubation in geriatric pa-tients: effects of fentanyl, lidocaine and thiopentone. Can J Anaesth 1989;36:370-376. (Abstract)

111. Adachi YU, Satomoto M, Higuchi H, et al. Fentanyl at-tenuates the hemodynamic response to endotracheal in-tubation more that the response to laryngoscopy. Anesth Analg 2002; 5:233-237. (Randomized controlled trial, 100 patients)

ment of hypertensive emergencies. Intensive Care Med 1997;23:885-888. (Randomized, prospective clinical study, 81 patients)

87. Touyz RM. Role of magnesium in the pathogenesis of hypertension. Mol Aspects Med Feb-Jun 2003;24(1-3):107-136. (Review)

88. Jee SH, Miller ER 3rd, Guallar E, et al. The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens 2002;15:691-696. (Meta-analysis)

89. Ram CV. Immediate management of severe hyperten-sion. Cardiol Clin 1995;13(4):579-591. (Review)

90. Graham C. Pharmacological Therapy of Acute Cardio-genic Pulmonary Edema in the Emergency Department. Emerg Med Australias 2004;16:47-54. (Review)

91. Annane D, Bellissant E, Pussard E, et al. Placebo-con-trolled, randomized double blind study of enalaprit ef-ficacy and safety in acute cardiogenic pulmonary edema. Circulation 1996;94:1316-1324. (Randomized, double-blind, placebo-controlled study, 20 patients)

92. Haude M, Steffan W, Erbel R, et al. Sublingual adminis-tration of captopril versus nitroglycerin in patients with severe congestive heart failure. Int J Cardiol 1990;27:351-359. (Randomized, crossover study, 24 patients)

93. Cotzee EJ, Dommisse J, Anthony J. A randomized controlled trial if Intravenous magnesium sulfate versus placebo in the management of women with severe pre-ecclampsia. Br J Obstet Gynaecol 1998;105:300-303. (Randomized double-blinded, 699 subjects)

94. Witlin AG, Friedman SA, Sibai BM. The effect of magne-sium sulfate therapy on the duration of labor in women with mild preeclampsia at term: A randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol 1997;176:623–627. (Randomized double-blind placebo, 135 patients)

95. Cotton DB, Gonik B. Cardiovascular alterations in severe pregnancy induced hypertension:acute effects of intravenous magnesium sulfate. Am J Obstet Gynecol 1984;148:162-165. (Case studies, 5 patients)

96. Rudnicki M, Frolich A, Pilsgaard K, et al. Comparison of magnesium and methyldopa for the control of blood pressure in pregnancies complicated with hypertension. Gynecol Obstet Invest 2000;49(4):231-235. (Randomized controlled trial, 35 patients)

97. Lange RA, Cigarroa RG, Yancy CW Jr, et al. Cocaine-

induced coronary-artery vasoconstriction. N Engl J Med 1989;321:1557-1562. (Observational study, 45 patients)

98. Baumann BM, Perrone J, Hornig SE, et al. Randomized, double-blind, placebo-controlled trial of diazepam, nitro-glycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes. Acad Emerg Med 2000;7:878-885. (Randomized, double-blind, placebo-controlled trial, 40 patients)

99. Hirschl MM, Herkner H, Bur A, et al. Course of blood


Physician CME Questions

1. The absolute BP required to make a diagnosis of hypertensive emergency is 220/120.a. true b. false

2. The mechanism of action of fenoldopam is:a. beta-blocker b. alpha-blocker c. dopamine agonist d. ACE inhibitor e. calcium channel blocker

3. The requirement(s) for the diagnosis of hyperten-sive emergencies is/are:a. age b. level of BP c. gender d. end-organ damage e. all of the above

4. All the following are examples of hypertensive emergencies, except:a. encephalopathy b. migraine headache c. preeclampsia d. aortic dissection e. pulmonary edema

5. Which of the following drug(s) can be used in acute ischemic strokes?a. nicardipine b. nitroprusside c. labetalol d. all of the above

6. Approximately what percentage of chronic hyper-tensives will develop a hypertensive emergency? a. 1% b. 5% c. 10%d. 15%

7. In chronic hypertensive patients, is the MAP higher or lower than in normotensive patients on the cere-bral autoregulation curve?a. higher b. lower

8. The best single agent for the treatment of aortic dis-section is?a. nitroprusside b. ACE inhibitor c. beta-blocker d. alpha-blocker e. none of the above

9. Minorities (African American, Hispanic) and male patients are at highest risk for hypertensive crisis.a. trueb. false

10. The side effects of nitroprusside include:a. cyanide toxicitiy b. tachycardia c. hypotension d. coronary steal e. all of the above

11. All of the following are treatments for eclampsia, except:a. hydralalazine b. magnesium c. labetalol d. ACE inhibitor e. prompt delivery of the fetus

12. All of the following can precipitate a hypertensive crisis, except:a. progesterone b. MAO inhibitors c. decadron d. pseudophedrine e. Tylenol®

13. Beta-blockers are the antihypertensive of choice for catecholamine-induced states.a. true b. false

14. Which of the following should not be used in the treatment of hypertensive crisis, due to abrupt falls in BP?a. nitroglyerin b. metoprolol c. enalapril d. nifedipine e. labetalol

Physician CME questions conclude on back page


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Date of Original Release: This issue of Emergency Medicine Practice was published July 25, 2005. This activity is eligible for CME credit through July 1, 2008. The latest review of this material was July 18, 2005.

Discussion of Investigational Information: As part of the newsletter, faculty may be presenting investigational information about pharmaceutical products that is outside Food and Drug Administration approved labeling. Information presented as part of this activity is intended solely as continuing medical education and is not intended to promote off-label use of any pharmaceutical product. Disclosure of Off-Label Usage: This issue of Emergency Medicine Practice discusses no off-label use of any pharmaceutical product.

Faculty Disclosure: In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement. The information received is as follows: Dr. Nguyen, Dr. Rohrback, Dr. Lenamond, Dr. Decker, and Dr. Godwin report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation.

Accreditation: Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.

Credit Designation: Mount Sinai School of Medicine designates this educational activity for up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those hours of credit actually spent in the educational activity. Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category 1 credit (per annual subscription). Emergency Medicine Practice has been approved by the American Academy of Family Physicians as having educational content acceptable for Prescribed credit. Term of approval covers issues published within one year from the distribution date of July 1, 2005. This issue has been reviewed and is acceptable for up to 4 Prescribed credits. Credit may be claimed for one year from the date of this issue. Emergency Medicine Practice has been approved for 48 Category 2-B credit hours by the American Osteopathic Association.

Earning Credit: Two Convenient Methods • Print Subscription Semester Program: Paid subscribers with current and

valid licenses in the United States who read all CME articles during each Emer-gency Medicine Practice six-month testing period, complete the post-test and the CME Evaluation Form distributed with the December and June issues, and return it according to the published instructions are eligible for up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition Award (PRA) for each issue. You must complete both the post-test and CME Evaluation Form to receive credit. Results will be kept confidential. CME certificates will be delivered to each participant scoring higher than 70%.

• Online Single-Issue Program: Paid subscribers with current and valid licenses in the United States who read this Emergency Medicine Practice CME article and complete the online post-test and CME Evaluation Form at EM-Practice.net are eligible for up to 4 hours of Category 1 credit toward the AMA Physician’s Recognition Award (PRA). You must complete both the post-test and CME Evaluation Form to receive credit. Results will be kept confidential. CME certificates may be printed directly from the Web site to each participant scoring higher than 70%.

Class IAlways acceptable, safeDefinitely usefulProven in both efficacy and ef-fectiveness

Level of Evidence:One or more large prospective stud-ies are present (with rare exceptions)High-quality meta-analysesStudy results consistently positive and compelling

Class IISafe, acceptableProbably useful

Level of Evidence:Generally higher levels of evidenceNon-randomized or retrospective studies: historic, cohort, or case-control studiesLess robust RCTsResults consistently positive

Class IIIMay be acceptablePossibly usefulConsidered optional or alternative treatments

Level of Evidence:Generally lower or intermediate

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levels of evidenceCase series, animal studies, consen-sus panelsOccasionally positive results

IndeterminateContinuing area of researchNo recommendations until further research

Level of Evidence:Evidence not availableHigher studies in progressResults inconsistent, contradictoryResults not compelling

Significantly modified from: The Emergency Cardiovascular Care Committees of the American Heart As-sociation and representatives from the resuscitation councils of ILCOR: How to Develop Evidence-Based Guidelines for Emergency Cardiac Care: Quality of Evidence and Classes of Recommenda-tions; also: Anonymous. Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcom-mittees, American Heart Association. Part IX. Ensuring effectiveness of com-munity-wide emergency cardiac care. JAMA 1992;268(16):2289-2295.

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Emergency Medicine Practice is not affiliated with any pharmaceutical firm or medical device manufacturer.

Class Of Evidence Definitions

Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions.

15. The magnitude of BP elevation is less important than the time course in the rise of the BP in hyper-tensive emergencies.a. true b. false

16. In general for a chronic hypertensive who has extremely elevated BP with a hypertensive cerebral encephalopathy, the MAP should be lowered by what percentage of baseline MAP? a. 5% b. 15% c. 25% d. 35% e. 45%

Coming in Future Issues:

Minor Head Trauma • Beta-Blocker Overdoses

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