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COLLABORATE | INVESTIGATE | EDUCATE HYPERTENSIVE EMERGENCIES: Emergency Department Evaluation and Management OCTOBER 2008 volume 3 Charles V. Pollack, Jr., MA, MD, FACEP, FAAEM, FAHA Dear Colleagues: Christopher J. Rees, MD Department of Emergency Medicine remains one of the most common processes in patients presenting to the Emergency Department (ED). While Pennsylvania Hospital sometimes symptomatic and associated with end organ damage University of Pennsylvania such as hypertensive encephalopathy, hemorrhagic , acute Philadelphia, PA coronary syndrome, , and renal insufficiency, many patients present without symptoms. Emergency physicians and Objectives: hospitalists should understand the appropriate classification of patients with hypertension, the pathophysiology of this disease 1. Describe the distinctions among hypertensive “crisis,” “urgency,” process, and appropriate treatment strategies. In this EMCREG- and “emergency” International Newsletter, Charles V. Pollack, Jr. MD and Christopher 2. Discuss the general approach to acute severe hypertension in the ED J. Rees, MD of Pennsylvania Hospital and the University of 3. Explain the limitations of typically used parenteral Pennsylvania discusses hypertension and parenteral medications antihypertensive agents in the ED used for treatment of these patients in the ED, including the Velocity 4. Summarize the potential role of clevidipine in ED management trial. This paper serves as a companion to the Hypertension of Consensus Panel publication as a supplement in the March 2008 Annals of Emergency Medicine and the EMCREG-International Newsletter published earlier this year by Drs. Judd Hollander and Introduction Anna Marie Chang. Hypertension is an extremely common Through collaboration with colleagues from a variety of specialties, illness, affecting 50 to 75 million people patients with hypertension can receive optimal therapy when in the US, many of whom are unaware that they even have hypertension.1-3 It is the presenting to an acute care setting such as the ED. For patients At some point in their receiving parenteral therapy, the natural transition of the patient most common primary medical diagnosis with hypertensive emergency through the ED to the intensive care in the US.4 Familiarity does not, however, lives, 1% of patients with unit or step-down bed involves careful collaboration between the equate to treatment success; some two- hypertension will have a emergency physician and hospitalists. It is our hope you will find thirds of hypertensive patients fail to hypertensive emergency. this EMCREG-International Newsletter helpful in the care of your achieve adequate control of their blood patients with hypertension. pressure (BP).2,3 Poor BP control often –––––––––––– prompts emergency department (ED) visits. About 5% of ED Sincerely, At some point in their lives, 1% of patients patients have at least with hypertension will have a hypertensive “emergency,” defined as severely elevated one (BP) blood pressure associated with target reading that is severely 1,2,5 organ dysfunction. elevated, although Meanwhile, about 5% of ED patients have most do not have a at least one BP reading that is severely hypertensive emergency. elevated, although most do not have a

Peer Reviewer for Commercial Bias: Douglas M. Char, MD; Associate Andra L. Blomkalns, MD W. Brian Gibler, MD Professor, Emergency Medicine; Program Director, Emergency Medicine Director of CME, President, Residency Program; Director, Emergency Cardiac Evaluation Unit. EMCREG-International EMCREG-International Washington University, St. Louis, MO Hypertensive Emergencies: Emergency Department Evaluation and Management

OCTOBER 2008 volume 3 Em e r g e n c y Medicine Ca r d i a c Re s e a r c h a n d Ed u c a t i o n Gr o u p

hypertensive emergency (HE).6 Patients often present to the encephalopathy, acute hemorrhagic or ischemic stroke, ED for unrelated issues, only to be found to have severely acute , acute pulmonary , aortic elevated BP. Other patients present with complaints , acute renal failure with or without , clearly referable to a BP derangement. The incidence of and . It is essential to realize that most patients hypertensive emergency is disproportionately higher in the who present to the ED with severe hypertension do not elderly, male, and African-American populations.7,8 Rapid have a hypertensive emergency. recognition, evaluation, and treatment of hypertensive emergencies are necessary to prevent permanent or Hypertensive urgency is defined as “those situations worsened target organ damage. There are essentially associated with severe elevations in BP without 4 no evidence-based guidelines for treating hypertensive progressive target organ dysfunction.” Some authors use emergencies in general, although there are guidelines the term to include both hypertensive for the management of BP in stroke, , emergencies and hypertensive urgencies. This may not and eclampsia. The most recent periodic review by the be fruitful as the term “crisis” is often used to justify an Joint National Committee (JNC) on Prevention, Detection, acute intervention, which is not always necessary in the Evaluation, and Treatment of High Blood Pressure (JNC 7, ED when severe hypertension is detected. 2003) offers little in the form of evidence-based guidance Another important term in this discussion is autoregulation. on the management of hypertensive urgencies, defined as In normotensive people, there is ordinarily a broad range severe elevations of BP without target organ damage, or of pressures through which and can emergencies in general.4 dilate and constrict to maintain normal and consistent perfusion. Chronic hypertension causes arterial walls Definitions to accommodate chronically excessive pressures. This autoregulation limits the vessels’ ability to respond The JNC 7 describes hypertension using a baseline BP of appropriately to acute decreases or increases in BP. 115/75 mm Hg, reporting that the risk of cardiovascular When BP abruptly increases, regardless of stimulus, disease (CVD) doubles with each incremental increase larger arteries reflexively vasoconstrict in an effort to of 20/10 mm Hg. JNC 7 defines blood pressure and limit pressure reaching the tissues, which would interfere hypertension categories as follows: with normal cellular activity. In this situation, an acute lowering of BP by a clinician seeking to re-achieve a Normal: <120/80 mm Hg “normal” BP will reduce the blood flow to tissue without Pre-hypertension: 120-139/80-89 mm Hg prompt compensatory vessel dilation, which can lead to Hypertension: Stage 1: 140-159/90-99 mm Hg of end-organ tissue. Therefore, it is important Hypertension: Stage 2: > 160/100 mm Hg when treating hypertensive emergencies, to not decrease BP either too rapidly or by too great of an amount. Hypertensive emergencies almost always fall into stage 2,

although some patients, especially younger individuals, can have hypertensive emergencies at much lower BP Causes of Hypertensive Emergencies levels than those with chronic hypertension. The JNC 7 The most common origin of hypertensive emergency is an publication defines hypertensive emergency as “a severe abrupt increase in BP in patients with chronic hypertension, elevation in blood pressure (usually >180/120 mm Hg) most often as a result of medication noncompliance.3 complicated by evidence of impending or progressive Other relatively common causes of hypertensive target organ dysfunction.”4 Clinical manifestations of emergency include stimulant intoxication, including target organ damage usually involve derangements , methamphetamine, and phencyclidine as well as in the neurologic, cardiac, or renal systems. While withdrawal syndromes from the anti-hypertensives such as the myocardium is the most common target organ and beta blockers. Less common causes include damaged by hypertension with a clinical manifestation and adverse drug interactions with as acute coronary syndrome (ACS)3, other examples of monoamine oxidase inhibitors (MAO-I). target organ dysfunction include, but are not limited to,

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Clinical Syndromes of Hypertensive Evaluation of the Patient with Emergencies Hypertensive Emergency

Cardiac manifestations of hypertensive emergencies All patients with severely elevated BP should undergo usually present with either ACS or acute cardiogenic a thorough history and physical examination in the . Central nervous system syndromes ED. A complete past medical history with attention to usually manifest as subarachnoid hemorrhage, hypertension is obviously important. A review of all the intraparenchymal hemorrhage, , patient’s medications which includes review of dosages, or hypertensive encephalopathy. Hypertensive length of use, compliance, and last time taken should encephalopathy is often more difficult to diagnose and is be obtained. The patient must be questioned about in the differential not only with the other three syndromes recreational drug use, as several drugs of abuse, such as noted, but also with substance abuse. Hypertensive cocaine, amphetamines, and phencyclidine, can cause encephalopathy is potentially fully reversible with hypertensive emergencies. appropriate treatment.1,9,10 Renal failure can both cause and be precipitated by hypertensive emergency. Blood pressure should be taken in both arms with Typically, renal damage from acute severe BP elevation an appropriately sized BP cuff. A thigh cuff may be manifests as non-oliguric acute renal failure, often necessary for the obese patient. Direct ophthalmoscopy associated with hematuria. Reducing BP helps to should be attempted, with attention given to evaluation for minimize further renal damage, but because of renal papilledema and hypertensive . A brief focused autoregulation, abrupt or overly aggressive correction neurologic examination to assess mental status and the should be avoided. presence or absence of focal deficits should be performed. The cardiopulmonary system should be evaluated, looking Aortic dissection deserves special attention, as it has particularly for signs of pulmonary edema. Abdominal much higher short-term morbidity and mortality than examination should include palpation for abdominal other clinical syndromes associated with hypertensive masses and tenderness, and auscultation for abdominal emergency, requires more urgent and rapid reduction in bruits. Peripheral pulses should be palpated. BP, and also necessitates specific and vigorous inhibition of reflex tachycardia as the BP is lowered. Aortic All patients should have an electrocardiogram to dissection classically presents with severe, tearing chest evaluate for left , acute ischemia pain radiating to the back. There may be a difference in or infarction, and . Urinalysis should be BP between the upper extremities; this should be checked performed to evaluate for hematuria and . and documented when the diagnosis is considered. Women of child-bearing age require a pregnancy test. Patients often have a history of chronic hypertension. It Laboratory studies should include a basic metabolic is recommended that patients with aortic dissection have profile with assay of BUN and creatinine as well asa their systolic BP (SBP) reduced to at least 120 mm Hg complete blood count with peripheral smear to evaluate within 20 minutes, which is a more rapid reduction than for microangiopathic hemolytic anemia. If ACS is that recommended for other syndromes associated with suspected, cardiac biomarkers should be assayed. severe hypertension. Typically, BP normally declines Radiographic studies may be ordered based on during the first trimester of pregnancy, so hypertensive presentation and diagnostic considerations. Often a emergencies are diagnosed at much lower BP levels in chest x-ray is required to evaluate for pulmonary edema, pregnancy. Pre-eclampsia is a syndrome which includes cardiomegaly, or mediastinal widening. If any focal hypertension, peripheral edema, and proteinuria in neurologic signs are present, or a decrease in mental women after the twentieth week of pregnancy. Eclampsia status is noted, a CT scan of the head is needed to is the more severe form of this disease with substantial evaluate for hemorrhage or infarct. hypertension, edema, proteinuria, and seizures. These diagnoses pose grave risks to mother and fetus and must be aggressively treated. Table 1 lists parenteral drugs used for acute BP management according to presenting hypertensive syndrome.

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General Treatment of the Patient with Hypertensive Emergency

According to the JNC 7 report, the immediate goal for treating hypertensive emergency is to reduce the SBP by 10-15%, but by no more than 25%, within the first hour and if the patient is then stable, to 160/100-110 mm Hg over the ensuing 2-6 hours.4 Aortic dissection is a special situation which requires reduction of the SBP to at least 120 mm Hg within 20 minutes, with commensurate protection against reflex tachycardia.4 It must be remembered Hypertensive emergency is a clinical diagnosis and the clinical state of the patient is that hypertensive more important than the absolute value of the BP.

emergency is a clinical Because of autoregulation, too-rapid reduction BP can lead to worsening tissue perfusion diagnosis, and that and ischemia and infarction. There are many agents used for treating acute severe the clinical state of the elevations of BP, and despite having been used for years, most are not ideal across the broad range of comorbidities seen in an ED population. Parenteral agents used for the patient is more important treatment of HE fall into several classes, as shown in Table 2. There are few clinical than the absolute value of trials or comparative studies to help guide the choice among drugs. Instead this decision is based upon physician and institutional preference and policies, underlying medical the blood pressure. conditions, and target organ involvement.

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Studied in post-operative hypertension, post-cardiac surgery, and emergency department treatment of HE. Potentially useful for all types of HE syndromes.

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Specific Parenteral Agents for Treatment is a combined α and β-adrenergic receptor of Hypertensive Emergencies inhibitor (α:β activity ratio, 1:3 to 1:7). It controls reflex tachycardia as BP drops. It does not affect cerebral blood Choosing an appropriate agent for use in the ED is flow, does not decrease cardiac blood flow or reduce difficult, and too often not based on objective criteria, cardiac output, or have any appreciable effect on renal but on institutional and individual experiences. Often, function. The effect can persist 2-4 hours after stopping the “resource” issues take precedence over “medical” issues infusion. Labetalol can be given as repeated IV boluses, in choosing an agent. The ideal agent for use in the or as a short-term IV infusion. It is especially useful in ED would be one that had a very quick onset of action aortic dissection, in combination with a vasodilator. The matched by an equally quick offset of effect when the most recent American Heart Association/ American infusion is stopped. Offset of effect is very important in Stroke Association guidelines specifically recommend the ED, as overshoot of target BP does occur and can be labetalol or for patients with hypertension associated with poor outcomes if persistent. An ideal who are candidates for r-tPA or other acute reperfusion agent would also be easy to administer, not requiring strategies.11 ED Bottom Line for labetalol: mixed alpha/ central venous access, intra-arterial monitoring, or special beta receptor blocker; rapid onset of action; repeated set-up and delivery systems, and therefore may differ from bolus or titrated infusion dosing; activity may persist up to the model agent for the intensive care unit or surgical four hours after cessation of infusion; particularly useful in suite. Given the incomplete histories and complex stroke and aortic dissection patients. comorbidities of many ED patients, an agent should also have a limited side-effect profile and broad applicability, Nicardipine is a dihydropyridine calcium channel with limited renal, hepatic, or cardiac contraindications blocker. It selectively blocks L-type, voltage-sensitive or adverse impact. calcium channels of the heart, thereby dilating coronary arteries and causing relaxation of peripheral arteriolar Esmolol is a beta-adrenergic blocker that selectively smooth muscle and reduced peripheral . inhibits beta-1 receptors in the heart and peripheral Abrupt withdrawal can cause rebound angina and vasculature. It is short acting, with an onset of action of hypertension. ED Bottom Line for nicardipine: calcium 6-20 minutes after bolus, and a maximal effect occurring channel antagonist; rapid onset of action; infusion about 5 minutes after bolus. Activity may persist for up dosing; coronary -friendly; activity may persist up to 20 minutes after discontinuing the infusion. Dosing is to six hours after cessation of infusion; caution in hepatic reviewed in Table 2. ED Bottom Line for esmolol: beta- and renal patients. 1 receptor blocker; rapid onset of action; bolus/infusion dosing; activity may persist up to 20 minutes after Nitroprusside is a direct venous and arterial cessation of infusion; caution in renal patients. vasodilator. Due to its combined venous and arterial effects, nitroprusside decreases both preload and is a peripheral dopamine-1 receptor afterload. Its use often results in a reflex tachycardia due agonist. It causes selective predominately to activation of baroreceptors. In comparison to the other in the renal, cardiac, and splanchnic vascular beds. agents discussed so far, it has the quickest onset of action This causes decreased peripheral vascular resistance, and the shortest half-life. It is therefore easily titratable increased renal blood flow, and inhibition of sodium and reversible. No type of hypertension is refractory to reabsorption; the latter results in natriuresis and diuresis. nitroprusside. Fenoldopam lowers BP but also improves creatinine clearance and urine flow. It is short-acting with an onset of Use of nitroprusside, however, is problematic for many action of about 10 minutes and a half-life of 7-9 minutes. reasons. It can cause precipitous drops in BP, leading ED Bottom Line for fenoldopam: dopamine-1 receptor to overshoot of the target BP and tissue perfusion blocker; rapid onset of action; titrated infusion dosing; compromise because of autoregulation. It is difficult activity may persist up to 60 minutes after cessation to administer, as in most institutions it requires BP of infusion; may be especially useful in renal patients; monitoring with an intra-arterial line. Furthermore, the contraindicated in glaucoma patients. drug is inactivated by light, so the infusion bag and all IV

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tubing must be protected Nitroglycerin is a direct venous dilator which reduces from light. In addition, preload and cardiac output. It is an ineffective arterial it can cause , dilator and is not specifically useful for hypertensive , diaphoresis, emergencies. Its use is generally limited to myocardial and muscle twitching. ischemia and pulmonary edema because of its Most importantly, dilatory effect on coronary vessels. ED Bottom Line for cyanide (CN) is released nitroglycerin: Not generally useful for hypertensive Clevidipine was shown from nitroprusside non- emergencies except in the setting of acute cardiac to be safe and effective enzymatically in a dose- ischemia. In this setting, it may reduce BP and is given d e p e n d e n t f a s h i o n . more for symptom relief. for the treatment of acute Cyanide is metabolized Enalaprilat is the IV form of the angiotensin converting hypertension during in the liver to thiocyanate in a reaction that requires enzyme inhibitor enalapril. It has an onset of action of an 18-hour infusion in thiosulfate. Thiocyanate is about 15 minutes, but it has multiple disadvantages that a recent clinical trial 100 times less toxic than limit its usefulness for hypertensive emergencies. The peak effect does not occur for up to 4 hours, and its duration of performed in the ED. CN, and thiocyanate is excreted largely through action can last for up to 12-24 hours. It is contraindicated the kidneys. Even with in pregnancy. ED Bottom Line for enalaprilat: Not normal renal and liver function, therapeutic dosages generally useful for hypertensive emergencies in the ED of nitroprusside can lead to toxic accumulation of CN due to inconsistent and prolonged onset and offset of within 24 – 48 hours. In the setting of renal and hepatic effect. dysfunction, toxic levels can accumulate much more is a direct arterial vasodilator that is often rapidly. Cyanide toxicity is largely asymptomatic but can used for hypertensive emergencies of pregnancy. It is not cause cardiac arrest, coma, encephalopathy, seizures, teratogenic and it actually increases uterine blood flow. It and focal neurologic damage. is not used or recommended for hypertensive emergencies; Nitroprusside can cause several other serious problems. recent studies have shown that nicardipine and labetalol 14 Because it causes significant afterload reduction, it can are superior. ED Bottom Line for hydralazine: Not cause “coronary steal” in patients with coronary artery generally useful for hypertensive emergencies in the ED, disease. Its use is not recommended in patients with ACS as multiple better agents are available. or known severe . Precipitous after- Clevidipine is a new, third generation, ultra-short load reduction in these patients can cause reduction of acting dihydropyridine calcium-channel antagonist coronary artery blood flow as coronary arteries fill during which has recently been approved by the FDA for use diastole, leading to cardiac ischemia.12 In one randomized, in hypertensive emergencies. Clevidipine has been placebo-controlled trial, nitroprusside increased mortality shown to be an effective parenteral agent for use in when infused early in acute .13 With hypertensive emergencies without many of the problems nitroprusside, there is also a dose-dependent decrease associated with older agents. It blocks L-gated calcium in cerebral blood flow, so it must be used cautiously in channels leading to relaxation of the smooth muscle of patients with increased intracranial pressure and at times small arteries, resulting in decreased peripheral vascular may initially worsen hypertensive encephalopathy. ED resistance. It reduces after-load without affecting preload Bottom Line for nitroprusside: Useful for any type and causes little to no reflex tachycardia. It is the first of hypertensive emergency; long clinical experience with new parenteral antihypertensive agent to be approved use; rapid onset and offset of effect. Multiple limitations by the FDA in over ten years, and it is the first parenteral including reflex tachycardia, overshoot of target BP, antihypertensive ever to include an ED-based study in its cyanide and thiocyanate toxicity; not suggested for use new drug application. in ischemic or hemorrhagic stroke; careful use in renal insufficiency; logistically challenging in ED.

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Clevidipine has a very rapid onset of action, with a half- more of the agents previously discussed. As soon as the life of less than 1 minute. The usual dose is 2 µg/kg/min, pressure begins to respond to therapy, plans should be with upward doubling titration to effect. Blood pressure initiated for transitioning the patient to oral therapy. If control is often achieved within 5 minutes of starting the patient is already on BP medications and has been an infusion. It is rapidly cleared within 10 minutes. noncompliant, then those medications are often the Clevidipine is metabolized to an inactive metabolite by best choice at least for reinstitution of oral therapy. If esterases in blood and extravascular tissue, independent the diagnosis of hypertension is new, then a reasonable of renal or hepatic function. It is logistically simple to oral agent might be chosen from the same class as the use, being given through a peripheral IV line and with intravenous (IV) agent employed such as a calcium BP cuff monitoring instead of intra-arterial access. It has channel antagonist if clevidipine or nicardipine controlled a non-weight-based dosing regimen and no associated the BP, or an oral beta-blocker if labetalol or esmolol was myocardial depression, sino-atrial (SA) node suppression, used.1 The choice of oral agent may also be impacted by or atrio-ventricular (AV) node suppression. the nature of new or reinstituted therapy for the end-organ damage sustained by the patient. Clevidipine was shown to be safe and effective for the treatment of acute hypertension during an 18-hour infusion The overall management of acute hypertension was in a recent clinical trial performed in the ED. VELOCITY summarized in a recent supplement to Annals of was a Phase-III, open-label, single-arm study to confirm Emergency Medicine.16 This work is a handy reference the safety and efficacy of IV clevidipine for patients with for the emergency physician and ED nursing personnel. acute hypertension requiring parenteral treatment for at least 18 hours. Patients were enrolled in the trial if they Observation or “clinical decision” units (CDUs) may be had acute hypertension (SBP >180 mm Hg or DBP >115 suitable for the short-term monitoring and management mm Hg) on 2 successive occasions 15 minutes apart and of hypertensive urgency. Ordinarily, initiation of IV had evidence of acute or chronic end-organ damage, antihypertensive therapy is associated with the need for were 18 years of age or older, and could provide written, admission to an intensive care unit bed. On occasion, informed consent. Ninety percent (104/117) of patients when the suspected end-organ damage is avoided or reached their target BP within 30 minutes (median for all excluded in a short-term stay, such as the patient with patients, 10.9 minutes). No clinical hypotensive events angina and severe hypertension who does not have related to clevidipine were reported throughout the study, elevated serial cardiac biomarkers, the total hypertensive and there was no excessive reflex tachycardia. Transition emergency management might be effected in a CDU. to oral therapy was successful in 91.3% of patients.15 ED Bottom Line for clevidipine: Rapid onset and offset Conclusion of effect, limited side-effect profile, broadly applicable without renal or hepatic issues, limited-to-no reflex Treatment of hypertensive emergencies, especially in an tachycardia, easy to administer as requires no central ED, can be challenging and resource-intensive. Many access or monitoring. agents are available, but most are limited by side effects, pharmacologic and physiologic barriers, or resource- ED Management Strategies based barriers. Clevidipine, a new ultrashort-acting dihydripyridine calcium channel blocker appears to be Hypertensive urgencies can and should ordinarily be an important new addition to the armamentarium of the managed with oral antihypertensives only. Because the clinician. It has been shown to be safe, effective, and diagnosis confirms that no end-organ damage is ongoing or easy to administer in an ED setting. Labetalol continues incipient, most patients with hypertensive urgencies have had to enjoy wide applicability in the ED. Newer, safer, and their BP control deteriorate over days to weeks to months, easier-to-use agents may begin to replace nitroprusside. 1 and urgent correction is neither necessary nor advisable. In the case of patients with limited comorbidities, management in a CDU without formal hospital admission Hypertensive emergencies, again by definition with end may be possible, especially in hypertensive urgencies. organ damage, require parenteral therapy using one or

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References 1. Aggarwal M, Khan IA. Hypertensive crises: hypertensive 12. Pollack CV, Varon J, Garrison NA, et al. Clevidipine, an emergencies and urgencies. clinics intravenous dihydropyridine calcium channel blocker, is 2006;24:135-46. safe and effective for the treatment of patients with acute severe hypertension. Ann Emerg Med 2008 E-pub ahead 2. Marik PE, Varon J. Hypertensive crises: Challenges and of print Jun 4. management. Chest 2007;131:1949-62. 13. Mann T, Cohn RF, Holman LB, Green LH, Markis 3. Stewart DL, Feinstein SE, Colgan R. Hypertensive JE, Phillips DA. Effect of nitroprusside on regional urgencies and emergencies. Primary Care: Clinics in myocardial blood flow in coronary artery disease. Office Practice 2006;33: 613-23. Results in 25 patients and comparison with nitroglycerin. 4. National Heart, Lung, and Blood Institute. Seventh report Circulation 1978;57:732-38. of the Joint National Committee on prevention, detection, 14. Cohn JN, Franciosa JA, Francis GS, et al. Effect of short- evaluation, and treatment of high blood pressure (JNC-7) term infusion of on mortality rate in 2003. Publication No. NIH 03-5233. Bethesda (MD): NIH; acute myocardial infarction complicated by left ventricular 2003. failure: results of a Veterans Administration cooperative 5. Zampaglione B, Pascale C, Marchisio M, et al. study. NEJM 1982;306:1129-35. Hypertensive urgencies and emergencies: prevalence and 15. Walker JJ. Severe pre-eclampsia and eclampsia. Bailleres clinical presentations. Hypertension 1996;27:144-47. Best Prac Res Clin Obstet Gynaecol 2000;14:57. 6. Karras DJ, Ufberg JW, Harrigan RA, et al. Lack of 16. Hoekstra J, Qureshi A. Management of hypertension relationship between hypertension-associated symptoms and hypertensive emergencies in the emergency and blood pressure in hypertensive ED patients. Am J department: The EMCREG-International Consensus Panel Emerg Med 2005;23:106-10. Recommendations. Ann Emerg Med 2008;51 Suppl 3. 7. Bennett NM, Shea S. Hypertensive emergency: case 17. Flanigan JS, Vitberg D. Hypertensive emergencies and criteria, sociodemographic profile, and previous care of severe hypertension: what to treat, who to treat, and how 100 cases. Am J Public Health 1988;78:636-40. to treat. Med Clin N Am 2006;90:439-51. 8. Potter JF. Malignant hypertension in the elderly. Q J Med 18. Amin A. Parenteral medication for hypertension with 1995;88:641-47. symptoms. Ann Em Med 2008;51(Suppl):S1-S15. 9. Lavin P. Management of hypertension in patients with 19. Elliott, WJ. Clinical features in the management of acute stroke. Arch Int Med 1986;146:66-68. selected hypertensive emergencies. Prog Cardiovasc Dis 10. Gilmore RM, Miller SJ, Stead LG. Severe hypertension in 2006;48:316-25. the emergency department patient. Emerg Med Clin N Am 2005;23:1141-58. 11. Adams HP Jr., delZoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/ American Stroke Association, Clinical Cardiology council, Cerebrovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Stroke 2007;38:1655-1722.

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Support: This monograph is supported in part by an unrestricted bioMérieux, Bristol-Myers Squibb, Heartscape Technologies, educational grant from PDL BioPharma. Inovise, The Medicines Company, Millennium Pharmaceuticals, PDL BioPharma, Roche Diagnostics, Sanofi-Aventis, Schering- Author Disclosures Plough, and Scios (Significant). In accordance with the ACCME Standards for Commercial Support of CME, the author has disclosed relevant relationships CME Accreditation with pharmaceutical and device manufacturers. The University of Cincinnati designates this educational activity Dr. Pollack – Speaker for Cleviprex® which is marketed and for a maximum of (1) AMA PRA Category 1 credit(s)™. Physicians manufactured by The Medicines Company. should only claim credit commensurate with the extent of their participation in the activity. The University of Cincinnati College EMCREG Disclosures of Medicine is accredited by the Accreditation Council for EMCREG-International has disclosed relevant relationships with Continuing Medical Education (ACCME) to sponsor continuing pharmaceutical and device manufacturers. EMCREG-International, medical education for physicians. a medical education company, provides non-biased, high quality educational newsletters, monographs and symposia for Disclaimer emergency physicians and other health care providers providing This document is to be used as a summary and clinical reference tool emergency care. The EMCREG website (www.emcreg.org) and NOT as a substitute for reading the valuable and original source provides further detail regarding our policy on sponsors and documents. EMCREG-International will not be liable to you or anyone disclosures as well as disclosures for other EMCREG members. else for any decision made or action taken or not taken by you in EMCREG-International has received unrestricted educational reliance on these materials. This document does not replace grants from Abbott POC/i-STAT, ArgiNOx, Biosite, BRAHMS/ individual physician clinical judgment.

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PLEASE SEND THIS PAGE to: CME Post Test University of Cincinnati College of Medicine, After you have read the monograph carefully, record your Office of Continuing Medical Education answers by circling the appropriate letter answer for each PO Box 670556 Cincinnati OH 45267-0556 question. 1. The difference between “hypertensive OR FAX TO: 513-558-1708 emergency” and “hypertensive urgency” is CME Expiration Date: November 2009 based upon which ONE of the following? a. the actual magnitude of the systolic pressure On a scale of 1 to 5, with 1 being highly satisfied and 5 being highly b. the actual magnitude of the diastolic pressure dissatisfied, please rate this program with respect to: c. the presence or absence of symptoms Highly Highly d. the presence or absence of objective signs of satisfied dissatisfied end-organ damage Overall quality of material: 1 2 3 4 5 Content of monograph: 1 2 3 4 5 2. Which ONE of the following is NOT considered to be evidence of end-organ Other similar CME programs: 1 2 3 4 5 damage from acute, severe hypertension? How well course objectives were met: 1 2 3 4 5 a. acute coronary syndrome b. acute pulmonary edema What topics would be of interest to you for future CME programs? c. acute epistaxis d. acute renal failure

3. Which ONE of the following statements Was there commercial or promotional bias in the presentation? regarding the action of specific parenteral antihypertensive agents is TRUE? q YES q NO If YES, please explain a. sodium nitroprusside has a prolonged duration of action b. labetolol is not a preferred drug in the management of blood pressure elevations accompanying acute stroke How long did it take for you to complete this monograph? c. fenoldopam is contraindicated in patients with renal insufficiency d. although nitroglycerin may decrease blood pressure, it is usually not a sufficient Name (Please print clearly): antihypertensive therapy for patients with hypertensive emergency and acute myocardial infarction Degree:

4. Which ONE of the following statements about the VELOCITY study and clevidipine is FALSE? Specialty: a. patients treated for acute severe hypertension Academic Affiliation (if applicable): with clevidipine in the ED in VELOCITY required blood pressure monitoring with an arterial catheter b. the median time to successful control of acute Address: severe hypertension in VELOCITY was about 11 minutes c. there were essentially no safety concerns regarding “overshoot” of blood pressure control with clevidipine City: State: Zip Code: d. there was no excessive reflex tachycardia in Telephone Number: ( ) VELOCITY patients treated with clevidipine

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HYPERTENSIVE EMERGENCIES: Emergency Department Evaluation and Management

October 2008, Volume 3

HYPERTENSIVE EMERGENCIES: PRSRT STD Emergency Department Evaluation and Management U.S. Postage International PAID October 2008, Volume 3 Cincinnati, Ohio The Emergency Medicine Cardiac Research Permit No. 4452 and Education Group 4555 Lake Forest Drive Suite 650 Cincinnati, OH 45242