- Email: [email protected]
Hypertensive Emergencies in the Emergency Department
Hypertensive Emergencies in the Emergency Department Omoyemi Adebayo,
MD*,
Robert L. Rogers,
MD
KEYWORDS Hypertension Hypertensive emergency Hypertensive crisis KEY POINTS Hypertensive emergency cannot be diagnosed based only on the combination of severely increased blood pressure with symptoms such as headache, shortness of breath, and blurred vision. Hypertensive urgency is defined as severe hypertension in a patient with comorbidities that place the patient at higher risk of end-organ dysfunction. Hypertensive emergency is defined as objective findings of end-organ damage. Asymptomatic and otherwise healthy patients with severe essential hypertension should be referred to a primary care doctor within a week for nonurgent blood pressure control; treatment of this group with aggressive intravenous medications can precipitate hypotension and subsequent end-organ damage. Select a therapeutic agent that has rapid and reliable pharmacodynamics that can be turned on and off easily. The goal in treating most hypertensive emergencies is to reduce the blood pressure 25% within the first 24 hours after diagnosis. An exception is in patients with aortic dissection, which calls for much more rapid blood pressure reduction.
INTRODUCTION
In 2014, the American Heart Association (AHA) estimated that 77.9 million Americans older than 20 years of age have hypertension (HTN).1 That is approximately 1 in every 3 adults, which is a staggering figure compared with other common diseases such as diabetes and hyperlipidemia. In 2009, the AHA reported that almost a third of the population with HTN was unaware of their underlying diagnosis2; this percentage has decreased to 19% according to recent figures from the National Health and Nutrition
Disclosures: The authors have no relevant financial relationships to disclose. Department of Emergency Medicine, University of Maryland School of Medicine, 110 South Paca Street, 6th Floor, Suite 200, Baltimore, MD 21201, USA * Corresponding author. E-mail address: [email protected] Emerg Med Clin N Am - (2015) -–http://dx.doi.org/10.1016/j.emc.2015.04.005 0733-8627/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
emed.theclinics.com
2
Adebayo & Rogers
Examination Survey.1 Nearly 70% of all patients with a first-time myocardial infarction, stroke, or congestive heart failure have poorly controlled blood pressure.1 However, the 2014 Joint National Committee (JNC) guidelines for blood pressure management recommend a less aggressive treatment approach for older hypertensive patients than that proposed in the JNC 7 guidelines,3 which could increase the number of patients found to be in a hypertensive crisis in the emergency department (ED).4 HTN is associated with significant short-term and long-term morbidity and mortality. The effects of HTN often build to hypertensive crises that can affect numerous organ systems either individually or simultaneously. The JNC 7 recommendations laid the groundwork for the identification and treatment of hypertensive crisis, but they did not clearly distinguish hypertensive urgency from hypertensive emergency. This distinction is important because their treatment approaches for blood pressure control are different. Despite the lack of large randomized controlled trials designed to establish evidence-based guidelines for the management of hypertensive emergencies, general consensus exists regarding the need for a timely response to prevent adverse outcomes. This article discusses essential concepts in the evaluation and treatment of hypertensive emergencies that are encountered commonly in the ED. These emergencies include encephalopathy, pulmonary edema, myocardial ischemia, aortic dissection, nephropathy, and eclampsia (Box 1). DEFINITION
Hypertension is defined as a systolic blood pressure greater than 140 mm Hg or a diastolic pressure greater than 90 mm Hg.4 Hypertensive crises are separated into 2 broad categories of urgency and emergency. They are both defined by a systolic blood pressure greater than 180 mm Hg and a diastolic pressure greater than 120 mm Hg but are differentiated by the absence or presence, respectively, of endorgan damage.4 End-organ damage is typically manifested by dysfunction in the cerebrovascular, cardiovascular, pulmonary, or renovascular systems. Organ dysfunction is the sole element that dictates the rapidity and modality of treatment required in a hypertensive crisis. Hypertensive urgency is characterized by an acute increase of blood pressure that is not associated with end-organ damage. Recognition of hypertensive urgency can generate anxiety in emergency physicians (EPs), leading to the decision to administer intravenous (IV) medications. This therapeutic approach could inadvertently cause hypotension and organ hypoperfusion. In its definition of hypertensive urgency, the JNC includes symptoms such as headache, shortness of breath, and epistaxis. Many EPs are opposed to the term hypertensive urgency, citing its lack of meaningful definition. They prefer to refer to this entity as severe HTN. Patients with hypertensive urgency are typically either noncompliant with prescribed medications or have been lost to follow-up and therefore lack proper titration of their medication dosages. Optimal treatment in this population is close outpatient follow-up with a gradual move toward oral antihypertensive medications.5 No validated studies have shown that acutely reducing blood pressure in ED patients who present with severe HTN has any benefits in short-term risk reduction. In its 2013 clinical policy, the American College of Emergency Physicians discouraged initiation of blood pressure medication in the ED for asymptomatic patients with HTN.6 In contrast, hypertensive emergencies are associated with significant short-term and long-term morbidity and mortality: 5-year mortality approaches 100%.7 Hypertensive emergencies represent up to one-fourth of all ED visits.4 The JNC recommends
Hypertensive Emergencies in the ED
Box 1 Causes of hypertensive crises Essential hypertension Endocrine Pheochromocytoma Cushing syndrome Renin-secreting tumor Primary hyperaldosteronism Renovascular disease Renal artery stenosis Polyarteritis nodosa Takayasu arteritis Drugs Cocaine Phencyclidine Sympathomimetics Antihypertensive medication withdrawal Amphetamines Lead intoxication Tyramine reaction with use of monoamine oxidase inhibitors Serotonin syndrome from selective serotonin reuptake inhibitor use Central nervous system Cerebral edema Cerebral hemorrhage Brain tumor Spinal cord injury Coarctation of the aorta Pain Burns
the following therapeutic approach after a hypertensive emergency has been diagnosed: (1) mean arterial pressure reduction by w25% in the first 1 hour of treatment, and (2) avoidance of precipitously reducing blood pressure (except in patients with aortic dissection) to preclude organ hypoperfusion.4 EVALUATION History
Hypertensive emergencies can be identified based on the patient’s past and present history, results of the physical examination, laboratory analysis, and imaging. Any patient who presents to the ED with severely increased blood pressure should have a thorough evaluation. The EP’s evaluation and treatment algorithms are different for
3
4
Adebayo & Rogers
an acutely increased blood pressure in a patient with no history of HTN compared with another patient with known chronic HTN. For example, a previously normotensive woman who comes to the ED after her twentieth week of gestation with a severely increased blood pressure and headache raises concern for preeclampsia requiring emergent management; however, if the same gravid woman presents to the ED with chronic pregestational HTN and a headache, the level of concern and management approach are different than for the patient described earlier. The EP should obtain the patient’s current complete medication list: drug names, doses, any recent changes in their administration, and sudden discontinuations from previously taken prescriptions. Sympatholytic medications such as clonidine are notorious for causing severe rebound HTN. Another pertinent piece of information to obtain from the patient is the use of illicit substances. Cocaine and phencyclidine are sympathomimetics that cause severe increases in blood pressure, as well as other symptoms. A family history of sudden death, premature cardiac disease, or endocrine disorders should prompt the EP to consider pheochromocytoma, multiple endocrine neoplasm, and hyperthyroidism as possible causes of episodic blood pressure increase and tachycardia in a young healthy patient. The most vital part of the history is assessment of signs and symptoms associated with the patient’s chief complaint (eg, chest pain, shortness of breath, urine output, weakness, or sensory loss) and targeted evaluation of end organs. The presence of symptoms alone does not confirm a hypertensive emergency, but it suggests that an organ might be affected, requiring further assessment. Physical Examination
If high blood pressure is detected during the triage process, the measurement must be repeated in the examination room after the patient has rested for 5 minutes without perturbation. The one-size-fits-all approach to blood pressure cuffs can produce falsely high or low blood pressure readings; a cuff of appropriate size for each patient is required for accurate measurements.8 When examining a patient with suspected hypertensive emergency, several crucial parts of the examination indicate whether further testing is needed. Assessment of mental status is one of the first steps in a thorough neurologic examination. Confusion, delirium, or seizure without other cause or reason suggests hypertensive encephalopathy. Other telltale signs of neurologic impairment are motor or sensory deficits and papilledema on funduscopic evaluation. A complete ocular examination is vital; if not performed by the EP, ophthalmologic consultation is warranted to guard against permanent vision damage. The pulmonary examination should focus on evidence of rales, hypoxia, or tachypnea, which imply flash pulmonary edema. Murmurs heard on cardiac examination (specifically, a diastolic decrescendo murmur of aortic regurgitation that was not previously known to exist in the patient) could signify a type A aortic dissection. A careful vascular assessment of proximal and distal pulses and blood pressures allows stratification of the likelihood of this rare, and potentially deadly, diagnosis. Auscultation of an abdominal bruit should raise concern for renal artery stenosis. An often-overlooked part of the examination of a hypertensive patient is evaluation of volume status. An acute increase in blood pressure results in natriuresis, a physiologic response that decreases the blood volume in an effort to reduce the blood pressure. This response becomes extremely important when IV medications are administered to treat a hypertensive emergency; the combination of natriuresis and the effects of a potent antihypertensive agent could induce a dangerously fast reduction in blood pressure.
Hypertensive Emergencies in the ED
Diagnostic Testing
Laboratory analysis should be based on which organ system the EP thinks could be damaged. Any patient thought to have had a stroke, seizure, or any neurologic derangement secondary to hypertensive emergency should undergo computed tomography of the head as a priority. Based on a small study, Roque and colleagues9 concluded that measurements of optic nerve sheath diameter by bedside ultrasonography can accurately predict which patients have increased intracranial pressure. Every patient presenting with chest pain should have an electrocardiogram (ECG) to assess for signs of cardiac ischemia or infarct. If the patient’s history of present illness suggests acute coronary syndrome (ACS) (exertional chest pain, dyspnea, diaphoresis, fatigue, jaw/arm pain, and nausea with epigastric pain), cardiac biomarker measurements should also be obtained. Dyspnea has a myriad of causes (eg, an anginal equivalent, pulmonary edema, renal failure, and anemia), all of which could stem from a hypertensive emergency. Obtaining both a screening ECG and chest radiograph (CXR) in dyspneic patients is recommended. If renal dysfunction is suspected, urinalysis and a basic metabolic panel should be requested. Abnormalities that suggest hypertensive nephropathy include proteinuria, muddy casts, and an increased blood urea nitrogen or creatinine level. A complete blood count with manual differentiation showing schistocytes suggests microangiopathic hemolytic anemia, which is another sign of end-organ damage. Diagnostic testing should be tailored to focus on patient complaints and the end organ in question to both maximize ED efficiency and minimize costly unnecessary work-ups.10 MANAGEMENT OF HYPERTENSIVE EMERGENCIES
Definitive treatment of any hypertensive emergency is the acute reduction of blood pressure to prevent ongoing organ damage. The JNC 7 guidelines recommend that this be done within the first hour.4 Therapy decisions should be considered carefully, weighing risks and benefits and taking into account which end organ is compromised as well as the patient’s comorbidities. A patient in a hypertensive emergency should be admitted to an intensive or intermediate care unit for meticulous IV titration of antihypertensive medications and close cardiopulmonary monitoring. With the number of critically ill patients increasing and hospital overcrowding, EPs are likely to be responsible for managing patients with hypertensive emergencies for longer periods of time, including adjusting the therapeutic approach if the patient’s condition improves or deteriorates in the ED. For patients who improve, it is important for the EP to institute oral antihypertensive agents for long-acting therapy before discontinuation of IV agents. If the patient was already on an oral antihypertensive at home, restarting that medication is appropriate, keeping in mind its side effect profile, onset of action, and half-life, because iatrogenic hypotension is common in this population. Hypertensive Encephalopathy
The brain, like other organs, possesses an autoregulatory system to maintain a certain cerebral perfusion pressure. The autoregulatory system of a normotensive patient maintains a steady state, adequate for perfusion, by maintaining a mean arterial pressure (MAP) of 60 to 120 mm Hg. In normotensive patients who suddenly become hypertensive, the regulator system quickly becomes overwhelmed and can no longer maintain autoregulation through vasoconstriction and dilation. In contrast, in patients with long-standing hypertension, the autoregulatory system gradually adapts to severely increased blood pressures and accommodates a higher set-point and thus decreases the likelihood of a hypertensive emergency at moderately increased
5
6
Adebayo & Rogers
pressures. When the cerebral regulatory system becomes overwhelmed, the patient is at risk for cerebral edema. The subsequent syndrome is known as hypertensive encephalopathy. It can manifest in many ways, including acute delirium, lethargy, confusion, severe headache, or seizure. In addition, it is important to consider other equally dangerous causes of altered mental status (eg, infection and cerebrovascular accidents), because they have entirely different management strategies. In patients experiencing ischemic stroke, the blood pressure should not be reduced by more than 10% to 15% over the first 24 hours, because it is thought that HTN protects the ischemic penumbra of the brain.11–14 The treatment of hypertensive encephalopathy begins with symptom control. Expert opinion suggests that medications such as benzodiazepines, fosphenytoin, phenytoin, or barbiturates should be given for delirium and seizure control; they provide the added benefit of further blood pressure reduction.15 For blood pressure management of hypertensive encephalopathy not complicated by cerebral vascular accident, the MAP should be reduced by about 20% to 25% in the first 1 hour of treatment. Traditionally used medications include IV nitroprusside, labetalol, nicardipine, and enalapril (Table 1). Centrally acting medications such as clonidine should be avoided for the acute management of hypertensive emergencies because their sedative side effects can make it difficult to appreciate the resolution of encephalopathic symptoms.15 Pulmonary Edema
One of the most harrowing hypertensive emergencies is hypoxic respiratory failure with acute flash pulmonary edema. Certain patient populations (ie, those with congestive heart failure and end-stage renal disease) are unable to tolerate fluctuations in their blood pressure easily, resulting in volume overload and pulmonary edema. In recent years, attention has centered on the use of noninvasive ventilation therapy, such as bilevel positive airway pressure ventilation, to circumvent the likelihood of these patients progressing to intubation. Treatment of the underlying cause, along with blood pressure reduction, is key to clinical improvement. For patients with flash pulmonary edema, preload and afterload reduction remains the goal of treatment. One or more medications that work either alone or in conjunction with each other have been the traditional treatment. Nitrates such as nitroglycerin are effective in reducing preload because of their venodilatory effects. Afterload reducers, such as angiotensin-converting enzyme inhibitors, are also used as key treatment of flash pulmonary edema. Loop diuretics such as furosemide are often used to treat symptomatic dyspnea secondary to pulmonary edema. In a recent randomized, double-blind prospective study, Holzer-Richling and colleagues16 found that administration of furosemide versus placebo to a cohort of patients did not improve outcomes. Study participants who received furosemide required lower doses of antihypertensive agents, suggesting a role for loop diuretics in reducing blood pressure.16 Caution is needed when giving a diuretic during a hypertensive crisis, because more than half of patients with pulmonary edema are euvolemic or hypovolemic, not overloaded in terms of total body volume; in contrast, patients with renal or hepatic failure tend to be overloaded, so diuretics have benefit in the acute phase to excrete the excess fluid and off-load the lungs. Nitroprusside, one of the fastest acting agents in the treatment armamentarium, is considered ideal for patients with flash pulmonary edema.17 It has the profile benefit of being rapid in onset as well as a venous and arterial dilator. Its use carries a small risk of thiocyanate and cyanide toxicity, but that side effect is seen more commonly with excessive dosing and refractory blood pressure response. Clevedipine, one of the newest IV antihypertensive medications (approved by the US Food and Drug
Hypertensive Emergencies in the ED
Administration in 2008) has shown great promise in clinical trials for treatment of severe hypertension, particularly for pulmonary edema and postoperative hypertension.18 Clevedipine is a dihydropyridine calcium channel blocker that has the added benefit of not being metabolized by the kidney or liver.19–21 Myocardial Ischemia
Classically, ACS develops as the result of an acute coronary thrombus. Cardiac ischemia can also be the result of other uncommon causes, such as hypertensive emergency. Patients with cardiac ischemia typically present with chest pain, dyspnea, diaphoresis, vomiting, and, especially in the elderly, generalized fatigue. Severe hypertension is usually associated with increased myocardial work and oxygen demand. Patients with previously diseased hearts are at increased risk of further myocardial ischemia. Electrocardiographic abnormalities and increased cardiac biomarkers indicate hypertension-induced cardiac ischemia or infarction. Treatment of ischemic chest pain is 3-fold: (1) reduction in myocardial work, (2) reduction in myocardial oxygen consumption, and (3) improvement in coronary artery perfusion. The first intervention that should be performed in a patient with suspected ACS is administration of aspirin.22 Severely hypertensive patients with suspected ACS should be given an IV b-blocker (class IIa recommendation by the AHA).23 Other commonly recommended agents are nitroglycerin and labetalol. Nitroglycerin is often titrated to resolution of chest pain or hypotension, whichever occurs first. Nitroglycerin has the added effect of coronary vasodilation, which improves cardiac tissue perfusion. No specific recommendations exist on which b-blocker is preferred, but it is best to use a medication with a quick pharmacokinetic profile so that it can be titrated easily. Care should be used with medications such as hydralazine and nitroprusside. Hydralazine causes reflex tachycardia, which increases myocardial work and oxygen consumption. It also has an extremely variable dose response curve from patient to patient, which can cause a precarious situation for EPs when the blood pressure decreases precipitously. Nitroprusside has the potential to cause coronary steal syndrome, which worsens ischemia and could increase risk of death if it is given after acute myocardial infarction (AMI).24,25 Similarly, b-blockers should not be administered after AMI because of the risk that they could worsen underlying congestive heart failure and cause cardiogenic shock. Aortic Dissection
When a patient describes the sudden-onset chest pain that radiates to the back, the EP should put aortic dissection (AD) at the top of the differential diagnosis. However, more subtle presentations should not be overlooked: chest pain accompanied by pain in any extremity, neurologic symptoms, abdominal or back pain, or gastrointestinal bleeding should raise concern for AD. The mortality for AD increases 1% to 2% every hour during the first 24 hours after the onset of symptoms. The Stanford classification distinguishes dissections as either type A or type B. Type A involves the aortic arch only; type B involves the descending aorta. Most type B dissections and some type A dissections can be managed with medical therapy but that determination should be made by the vascular surgeon. All type A dissections should be referred to a vascular surgeon for likely surgical repair. Whenever AD is suspected, it is important to measure the blood pressure in both arms and to assess the pulses in all 4 extremities. It is critical not to rely on classic findings: w19% of patients with type A dissections and w9% of those with type B dissections have no identifiable pulse deficits.26 More reliable is identification of a new diastolic murmur suggestive of aortic regurgitation, which is seen in up to 44% of type A
7
8
Adebayo & Rogers
Table 1 Pharmacologic agents for hypertensive emergencies Drug
Dose
Onset of Action (min) Duration of Action
Adverse Effects
Indications
Nitroglycerin
5–100 mg/min as IV infusion
2–5
5–30 min
Cardiac ischemia; flash Headache, vomiting, pulmonary edema; caution methemoglobinemia; with recent use of caution in right ventricular phosphodiesterase infarct inhibitors
Sodium nitroprusside
0.25–10 mg/kg/min as IV infusion
Immediate
1–2 min
Nausea, vomiting, muscle twitching, sweats, thiocyanate and cyanide toxicity
5–10
15–30 min, may last Tachycardia, headache, several hours flushing, local phlebitis
Most hypertensive emergencies; caution of coronary steal with cardiac ischemia
Vasodilators
Nicardipine 5–15 mg/h IV hydrochloride
Most hypertensive emergencies; caution with high intracranial pressure or azotemia
Fenoldopam mesylate
0.1–0.3 mg/kg per min IV fusion
<5
30 min
Tachycardia, headache, nausea, flushing
Best for hypertensive nephropathy emergencies
Enalaprilat
1.25–5 mg every 6 h IV
15–30
6–12 h
Significant reductions in blood pressure in highrenin states
Acute left ventricular failure and flash pulmonary edema; avoid in AMI
10–20 IV 20–30 IM
1–4 h IV 4–6 h IM
Tachycardia, flushing, headache, vomiting, worsening angina
Eclampsia; caution given erratic response
Hydralazine 10–20 mg IV hydrochloride 10–40 mg IM
5–15 min
Headache, nausea, vomiting, Postoperative hypertension, hypertensive emergency in hypotension, rebound renal dysfunction or acute hypertension, reflex heart failure tachycardia
Esmolol 250–500 mg/kg/min IV bolus, 1–2 hydrochloride then 50–100 mg/kg/min by infusion; repeat bolus after 5 min if needed or increase infusion to 300 mg/min
10–30 min
Hypotension, nausea, asthma Aortic dissection, perioperative exacerbation, first-degree heart block, heart failure
Labetalol 20–80 mg IV bolus every hydrochloride 10 min; alternatively, 0.5– 2 mg/min IV infusion
5–10
3–6 h
Vomiting, scalp tingling, bronchoconstriction, dizziness, nausea, heart block, orthostatic hypotension
Most hypertensive emergencies except acute heart failure; ideal for preeclampsia
Phentolamine
1–2
10–30 min
Tachycardia, flushing, headache
Pheochromocytoma and other catecholamine excess states
Clevidipine
Initial infusion of 1–2 mg/h, titrate every 5–10 min
2–4
Adrenergic Antagonists
5-mg to 15-mg IV bolus
Hypertensive Emergencies in the ED
Abbreviations: AMI, acute myocardial infarction; IM, intramuscular. Adapted from Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52.
9
10
Adebayo & Rogers
dissections.26 A CXR obtained as part of the work-up might show a widened mediastinum, but as many as 15% of patients with AD have normal chest radiographs.27 The goal of medical therapy for AD is rapid and large reduction of vascular sheer stress and blood pressure. The initial medication should be able to reduce the sheering force; a b-blocker is typically used for this purpose, because this drug group both decreases the heart rate (HR) and prevents reflex tachycardia when arteriodilators are introduced. Esmolol is an ideal agent for this purpose because of its rapid on/off qualities and its ability to reduce the HR to less than 60 beats per minute. A medication is also needed to reduce the systolic blood pressure to less than 120 mm Hg. Nitroprusside has long been used for this purpose and is a reasonable option for fast and reliable blood pressure control.27 Acute Renal Failure
Acute renal failure (ARF) can be either the direct cause or an observed effect of a hypertensive emergency. A patient’s history, specifically renal transplant and renal function, can help differentiate cause from effect. Assessment of the patient’s volume status is also important to determine the need for adjunctive therapies, such as positive-pressure ventilation or diuretics for patients who present with dyspnea from fluid overload. Calcium channel blockers (eg, nicardipine) are typically preferred in ARF because they do not affect renal perfusion or clearance. Nitroprusside and fenoldopam are also commonly used. Nitroprusside is effective in reducing blood pressure, but it places the patient at risk of cyanide toxicity because it decreases renal clearance and thus causes a buildup of metabolites. Fenoldopam is a more desirable secondline medication. An arterial vasodilator, it not only decreases blood pressure but also promotes renal excretion via its specific effects on the dopamine receptors in the nephron. It produces no toxic metabolites and has been shown to be as effective in blood pressure reduction as nitroprusside.28,29 In the special case of scleroderma renal crisis, angiotensin-converting enzyme inhibitors (eg, captopril and enalapril) are first-line agents for effect management.30 Sympathomimetic Crisis
This category encompasses severe increases in blood pressure secondary to many causes: cocaine, phencyclidine, or amphetamine abuse; pheochromocytoma; interaction of monoamine oxidase inhibitor drugs with selective serotonin reuptake inhibitors or with wine and cheese (tyramine reaction); abrupt cessation of sympatholytic medications such as clonidine; and alcohol withdrawal. The treatment of all these crises is similar. The sole use of b-blockers is not recommended because of the reflex tachycardia that it induces, which could precipitate a rapid increase in blood pressure and cardiovascular collapse.31,32 Phenoxybenzamine, phentolamine, nitroprusside, and labetalol are good first-line medications.33,34 In cocaine-induced crisis, benzodiazepines should be used in conjunction with antihypertensive drugs. In a study involving 378 patients with cocaine-induced chest pain, Ibrahim and colleagues35 found no difference in the troponin levels of patients who received b-blockers and those who did not. This observation challenges convention, which has created a culture of fear around using such drugs in these patients. More studies are needed to validate or challenge these controversial findings. In the treatment of a hypertensive emergency in patients with clonidine withdrawal, the first step is to administer clonidine. Hypertensive Emergency in Pregnancy
Pregnancy causes many deviations from women’s pregravid physiology. Blood pressure decreases in the second trimester of pregnancy before increasing back to
Hypertensive Emergencies in the ED
baseline values in the third trimester. Preeclampsia is a poorly understood disorder of hypertension that occurs for unknown reasons in 2% to 6% of pregnancies after the 20th week of gestation. It can be a serious disorder, with consequences for both mother and fetus. The dramatic increase in maternal blood pressure affects the placenta, which is the end organ that is vital to fetal development. Preeclampsia has mild and severe forms. Mild preeclampsia and severe preeclampsia are essentially distinguished by the degree of hypertension that persists and not the degree of proteinuria because both forms can exist without proteinuria. The treatment of severe preeclampsia is 2-fold: (1) delivering the fetus as soon as possible (ideally after the administration of steroids for fetal lung maturity in viable fetuses), and (2) reducing the blood pressure and reversing end-organ damage. Preeclampsia can also lead to other end-organ dysfunction such as the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Failure to achieve rapid control of the blood pressure can lead to the potentially fatal progression to eclampsia, characterized by seizures, strokes, and death. The approach to blood pressure management in a preeclamptic patient is a balancing act. When the fetus is viable and delivery is not imminent, antihypertensive therapy must be chosen so that precipitous decreases in blood pressure do not cause placental hypoperfusion and compromise fetal blood flow. Labetalol, nifedipine, nicardipine, and hydralazine have been common choices for this condition for years. However, the safety of hydralazine and nifedipine in gravid patients has been questioned. Those medications, particularly hydralazine, should be considered second-line or third-line choices because of their unpredictability in duration of action and degree of hypotension. Labetalol and nicardipine are more predictable.36 Another hallmark in the treatment of severe preeclampsia and eclampsia is the use of magnesium sulfate, which is given as a bolus followed by an infusion. Patients should be monitored closely for the development of magnesium toxicity. Magnesium is thought to be neuroprotective to the mother, preventing the onset of eclampsia (or terminating seizures once eclampsia has set in), and possibly to the fetus.37 SUMMARY
Hypertension is a multifaceted disease process that affects the US and global populations in massive proportions. The most accurate indicator of hypertensive emergency is the presence of end-organ damage. The EP’s role is pivotal in rapidly identifying and differentiating hypertensive emergency from hypertensive urgency and providing the appropriate intervention. Actions that are fundamental to identifying individuals at risk include obtaining a targeted history, performing a careful physical examination, and requesting the appropriate laboratory and diagnostic screening. Many medications are available to treat hypertensive emergencies but none is universally recognized as being superior to the others. Important considerations in drug selection include an understanding of the underlying physiology of the crisis, the patient’s comorbid conditions, and associated risk factors. Once a drug is chosen, it should be given quickly because “time is tissue” in hypertensive emergency. Patients should be managed in an intensive care unit because critical care monitoring is required. With appropriate identification and management, hypertensive crises can be halted and reversed. REFERENCES
1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 2014;129:e28–292.
11
12
Adebayo & Rogers
2. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21–181. 3. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20. 4. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52. 5. Vaidya CK, Ouellette JR. Hypertensive urgency and emergency. Hosp Physician 2007;43:43–50. 6. Wolf SJ, Lo B, Shih RD, et al. Clinical policy: critical issues in the evaluation and management of adult patients in the emergency department with asymptomatic elevated blood pressure. Ann Emerg Med 2013;62:59–68. 7. Webster J, Petrie JC, Jeffers TA, et al. Accelerated hypertension—patterns of mortality and clinical factors affecting outcome in treated patients. Q J Med 1993;86:485–9. 8. Graves JW. Prevalence of blood pressure cuff sizes in a referral practice of 430 consecutive adult hypertensives. Blood Press Monit 2001;6:17–20. 9. Roque PJ, Wu TS, Barth L, et al. Optic nerve ultrasound for the detection of elevated intracranial pressure in the hypertensive patient. Am J Emerg Med 2012;30:1357–63. 10. Dedic A, ten Kate G, Nieman K, et al. Coronary CT angiography outperforms calcium imaging in the triage of acute coronary syndrome. Int J Cardiol 2013;167: 1597–602. 11. Papadopoulos DP, Votteas V. Role of perindopril in the prevention of stroke. Recent Pat Cardiovasc Drug Discov 2006;1:283–9. 12. Lavin P. Management of hypertension in patients with acute stroke. Arch Intern Med 1986;146:66–8. 13. Adams HP Jr, del Zoppo 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 Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655–711. 14. O’Connell JE, Gray CS. Treatment of post-stroke hypertension: a practical guide. Drugs Aging 1996;8:408–15. 15. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000;356:411–7. 16. Holzer-Richling N, Holzer M, Kerkner H, et al. Randomized placebo controlled trial of furosemide on subjective perception of dyspnea in patients with pulmonary edema because of hypertensive crisis. Eur J Clin Invest 2011;41:627–34. 17. Aggarwal M, Khan I. Hypertensive crisis: hypertensive emergencies and urgencies. Cardiol Clin 2006;24:135–46. 18. Aronson S, Dyke SM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg 2008;107: 1110–21. 19. Pollack CV, Varon J, Garrison NA, et al. Clevidipine, an intravenous dihydropyridine calcium channel blocker, is safe and effective for the treatment of patients with acute severe hypertension. Ann Emerg Med 2009;53:329–38.
Hypertensive Emergencies in the ED
20. Cleviprex (clevidipine butyrate) [package insert]. Clayton, NC: Hospira; 2008. 21. Marik P, Rivera R. Hypertensive emergencies: an update. Curr Opin Crit Care 2011;17:569–80. 22. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction. Lancet 1988; 2(8607):349–60. 23. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78–140. 24. Mann T, Cohn PF, Holman LB, et al. Effect of nitroprusside on regional myocardial blood flow in coronary artery disease: results in 25 patients and comparison with nitroglycerin. Circulation 1978;57:732–8. 25. 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 Administration cooperative study. N Engl J Med 1982;306:1129–35. 26. Hagan PG, Nienaber CA, Isselbacher EM, et al. International Registry of Acute Aortic Dissection (IRAD): new insights from an old disease. JAMA 2000;283: 897–903. 27. Braverman AC. Acute aortic dissection: clinician update. Circulation 2010;122: 184–8. 28. Elliott WJ, Weber RR, Nelson KS, et al. Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension. Circulation 1990;81:970–7. 29. Reisin E, Huth MM, Nguyen BP, et al. Intravenous fenoldopam versus sodium nitroprusside in patients with severe hypertension. Hypertension 1990;15:I59–62. 30. Mouthon L, Be´rezne´ A, Bussone G, et al. Scleroderma renal crisis: a rare but severe complication of systemic sclerosis. Clin Rev Allergy Immunol 2011;40: 84–91. 31. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Intern Med 1990;112: 897–903. 32. Pitts WR, Lange RA, Cigarroa JE, et al. Cocaine-induced myocardial ischemia and infarction: pathophysiology, recognition, and management. Prog Cardiovasc Dis 1997;40:65–76. 33. Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol 1998;9:133–42. 34. Rhoney D, Peacock W. Intravenous therapy for hypertensive emergencies, part 1. Am J Health Syst Pharm 2009;66:1343–52. 35. Ibrahim M, Maselli D, Hasan R, et al. Safety of b-blockers in the acute management of cocaine-associated chest pain. Am J Emerg Med 2013;31:613–6. 36. Magee LA, Cham C, Waterman EJ, et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ 2003;327:955–60. 37. Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulfate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009;(1):CD004661.
13
MD*,
Robert L. Rogers,
MD
KEYWORDS Hypertension Hypertensive emergency Hypertensive crisis KEY POINTS Hypertensive emergency cannot be diagnosed based only on the combination of severely increased blood pressure with symptoms such as headache, shortness of breath, and blurred vision. Hypertensive urgency is defined as severe hypertension in a patient with comorbidities that place the patient at higher risk of end-organ dysfunction. Hypertensive emergency is defined as objective findings of end-organ damage. Asymptomatic and otherwise healthy patients with severe essential hypertension should be referred to a primary care doctor within a week for nonurgent blood pressure control; treatment of this group with aggressive intravenous medications can precipitate hypotension and subsequent end-organ damage. Select a therapeutic agent that has rapid and reliable pharmacodynamics that can be turned on and off easily. The goal in treating most hypertensive emergencies is to reduce the blood pressure 25% within the first 24 hours after diagnosis. An exception is in patients with aortic dissection, which calls for much more rapid blood pressure reduction.
INTRODUCTION
In 2014, the American Heart Association (AHA) estimated that 77.9 million Americans older than 20 years of age have hypertension (HTN).1 That is approximately 1 in every 3 adults, which is a staggering figure compared with other common diseases such as diabetes and hyperlipidemia. In 2009, the AHA reported that almost a third of the population with HTN was unaware of their underlying diagnosis2; this percentage has decreased to 19% according to recent figures from the National Health and Nutrition
Disclosures: The authors have no relevant financial relationships to disclose. Department of Emergency Medicine, University of Maryland School of Medicine, 110 South Paca Street, 6th Floor, Suite 200, Baltimore, MD 21201, USA * Corresponding author. E-mail address: [email protected] Emerg Med Clin N Am - (2015) -–http://dx.doi.org/10.1016/j.emc.2015.04.005 0733-8627/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
emed.theclinics.com
2
Adebayo & Rogers
Examination Survey.1 Nearly 70% of all patients with a first-time myocardial infarction, stroke, or congestive heart failure have poorly controlled blood pressure.1 However, the 2014 Joint National Committee (JNC) guidelines for blood pressure management recommend a less aggressive treatment approach for older hypertensive patients than that proposed in the JNC 7 guidelines,3 which could increase the number of patients found to be in a hypertensive crisis in the emergency department (ED).4 HTN is associated with significant short-term and long-term morbidity and mortality. The effects of HTN often build to hypertensive crises that can affect numerous organ systems either individually or simultaneously. The JNC 7 recommendations laid the groundwork for the identification and treatment of hypertensive crisis, but they did not clearly distinguish hypertensive urgency from hypertensive emergency. This distinction is important because their treatment approaches for blood pressure control are different. Despite the lack of large randomized controlled trials designed to establish evidence-based guidelines for the management of hypertensive emergencies, general consensus exists regarding the need for a timely response to prevent adverse outcomes. This article discusses essential concepts in the evaluation and treatment of hypertensive emergencies that are encountered commonly in the ED. These emergencies include encephalopathy, pulmonary edema, myocardial ischemia, aortic dissection, nephropathy, and eclampsia (Box 1). DEFINITION
Hypertension is defined as a systolic blood pressure greater than 140 mm Hg or a diastolic pressure greater than 90 mm Hg.4 Hypertensive crises are separated into 2 broad categories of urgency and emergency. They are both defined by a systolic blood pressure greater than 180 mm Hg and a diastolic pressure greater than 120 mm Hg but are differentiated by the absence or presence, respectively, of endorgan damage.4 End-organ damage is typically manifested by dysfunction in the cerebrovascular, cardiovascular, pulmonary, or renovascular systems. Organ dysfunction is the sole element that dictates the rapidity and modality of treatment required in a hypertensive crisis. Hypertensive urgency is characterized by an acute increase of blood pressure that is not associated with end-organ damage. Recognition of hypertensive urgency can generate anxiety in emergency physicians (EPs), leading to the decision to administer intravenous (IV) medications. This therapeutic approach could inadvertently cause hypotension and organ hypoperfusion. In its definition of hypertensive urgency, the JNC includes symptoms such as headache, shortness of breath, and epistaxis. Many EPs are opposed to the term hypertensive urgency, citing its lack of meaningful definition. They prefer to refer to this entity as severe HTN. Patients with hypertensive urgency are typically either noncompliant with prescribed medications or have been lost to follow-up and therefore lack proper titration of their medication dosages. Optimal treatment in this population is close outpatient follow-up with a gradual move toward oral antihypertensive medications.5 No validated studies have shown that acutely reducing blood pressure in ED patients who present with severe HTN has any benefits in short-term risk reduction. In its 2013 clinical policy, the American College of Emergency Physicians discouraged initiation of blood pressure medication in the ED for asymptomatic patients with HTN.6 In contrast, hypertensive emergencies are associated with significant short-term and long-term morbidity and mortality: 5-year mortality approaches 100%.7 Hypertensive emergencies represent up to one-fourth of all ED visits.4 The JNC recommends
Hypertensive Emergencies in the ED
Box 1 Causes of hypertensive crises Essential hypertension Endocrine Pheochromocytoma Cushing syndrome Renin-secreting tumor Primary hyperaldosteronism Renovascular disease Renal artery stenosis Polyarteritis nodosa Takayasu arteritis Drugs Cocaine Phencyclidine Sympathomimetics Antihypertensive medication withdrawal Amphetamines Lead intoxication Tyramine reaction with use of monoamine oxidase inhibitors Serotonin syndrome from selective serotonin reuptake inhibitor use Central nervous system Cerebral edema Cerebral hemorrhage Brain tumor Spinal cord injury Coarctation of the aorta Pain Burns
the following therapeutic approach after a hypertensive emergency has been diagnosed: (1) mean arterial pressure reduction by w25% in the first 1 hour of treatment, and (2) avoidance of precipitously reducing blood pressure (except in patients with aortic dissection) to preclude organ hypoperfusion.4 EVALUATION History
Hypertensive emergencies can be identified based on the patient’s past and present history, results of the physical examination, laboratory analysis, and imaging. Any patient who presents to the ED with severely increased blood pressure should have a thorough evaluation. The EP’s evaluation and treatment algorithms are different for
3
4
Adebayo & Rogers
an acutely increased blood pressure in a patient with no history of HTN compared with another patient with known chronic HTN. For example, a previously normotensive woman who comes to the ED after her twentieth week of gestation with a severely increased blood pressure and headache raises concern for preeclampsia requiring emergent management; however, if the same gravid woman presents to the ED with chronic pregestational HTN and a headache, the level of concern and management approach are different than for the patient described earlier. The EP should obtain the patient’s current complete medication list: drug names, doses, any recent changes in their administration, and sudden discontinuations from previously taken prescriptions. Sympatholytic medications such as clonidine are notorious for causing severe rebound HTN. Another pertinent piece of information to obtain from the patient is the use of illicit substances. Cocaine and phencyclidine are sympathomimetics that cause severe increases in blood pressure, as well as other symptoms. A family history of sudden death, premature cardiac disease, or endocrine disorders should prompt the EP to consider pheochromocytoma, multiple endocrine neoplasm, and hyperthyroidism as possible causes of episodic blood pressure increase and tachycardia in a young healthy patient. The most vital part of the history is assessment of signs and symptoms associated with the patient’s chief complaint (eg, chest pain, shortness of breath, urine output, weakness, or sensory loss) and targeted evaluation of end organs. The presence of symptoms alone does not confirm a hypertensive emergency, but it suggests that an organ might be affected, requiring further assessment. Physical Examination
If high blood pressure is detected during the triage process, the measurement must be repeated in the examination room after the patient has rested for 5 minutes without perturbation. The one-size-fits-all approach to blood pressure cuffs can produce falsely high or low blood pressure readings; a cuff of appropriate size for each patient is required for accurate measurements.8 When examining a patient with suspected hypertensive emergency, several crucial parts of the examination indicate whether further testing is needed. Assessment of mental status is one of the first steps in a thorough neurologic examination. Confusion, delirium, or seizure without other cause or reason suggests hypertensive encephalopathy. Other telltale signs of neurologic impairment are motor or sensory deficits and papilledema on funduscopic evaluation. A complete ocular examination is vital; if not performed by the EP, ophthalmologic consultation is warranted to guard against permanent vision damage. The pulmonary examination should focus on evidence of rales, hypoxia, or tachypnea, which imply flash pulmonary edema. Murmurs heard on cardiac examination (specifically, a diastolic decrescendo murmur of aortic regurgitation that was not previously known to exist in the patient) could signify a type A aortic dissection. A careful vascular assessment of proximal and distal pulses and blood pressures allows stratification of the likelihood of this rare, and potentially deadly, diagnosis. Auscultation of an abdominal bruit should raise concern for renal artery stenosis. An often-overlooked part of the examination of a hypertensive patient is evaluation of volume status. An acute increase in blood pressure results in natriuresis, a physiologic response that decreases the blood volume in an effort to reduce the blood pressure. This response becomes extremely important when IV medications are administered to treat a hypertensive emergency; the combination of natriuresis and the effects of a potent antihypertensive agent could induce a dangerously fast reduction in blood pressure.
Hypertensive Emergencies in the ED
Diagnostic Testing
Laboratory analysis should be based on which organ system the EP thinks could be damaged. Any patient thought to have had a stroke, seizure, or any neurologic derangement secondary to hypertensive emergency should undergo computed tomography of the head as a priority. Based on a small study, Roque and colleagues9 concluded that measurements of optic nerve sheath diameter by bedside ultrasonography can accurately predict which patients have increased intracranial pressure. Every patient presenting with chest pain should have an electrocardiogram (ECG) to assess for signs of cardiac ischemia or infarct. If the patient’s history of present illness suggests acute coronary syndrome (ACS) (exertional chest pain, dyspnea, diaphoresis, fatigue, jaw/arm pain, and nausea with epigastric pain), cardiac biomarker measurements should also be obtained. Dyspnea has a myriad of causes (eg, an anginal equivalent, pulmonary edema, renal failure, and anemia), all of which could stem from a hypertensive emergency. Obtaining both a screening ECG and chest radiograph (CXR) in dyspneic patients is recommended. If renal dysfunction is suspected, urinalysis and a basic metabolic panel should be requested. Abnormalities that suggest hypertensive nephropathy include proteinuria, muddy casts, and an increased blood urea nitrogen or creatinine level. A complete blood count with manual differentiation showing schistocytes suggests microangiopathic hemolytic anemia, which is another sign of end-organ damage. Diagnostic testing should be tailored to focus on patient complaints and the end organ in question to both maximize ED efficiency and minimize costly unnecessary work-ups.10 MANAGEMENT OF HYPERTENSIVE EMERGENCIES
Definitive treatment of any hypertensive emergency is the acute reduction of blood pressure to prevent ongoing organ damage. The JNC 7 guidelines recommend that this be done within the first hour.4 Therapy decisions should be considered carefully, weighing risks and benefits and taking into account which end organ is compromised as well as the patient’s comorbidities. A patient in a hypertensive emergency should be admitted to an intensive or intermediate care unit for meticulous IV titration of antihypertensive medications and close cardiopulmonary monitoring. With the number of critically ill patients increasing and hospital overcrowding, EPs are likely to be responsible for managing patients with hypertensive emergencies for longer periods of time, including adjusting the therapeutic approach if the patient’s condition improves or deteriorates in the ED. For patients who improve, it is important for the EP to institute oral antihypertensive agents for long-acting therapy before discontinuation of IV agents. If the patient was already on an oral antihypertensive at home, restarting that medication is appropriate, keeping in mind its side effect profile, onset of action, and half-life, because iatrogenic hypotension is common in this population. Hypertensive Encephalopathy
The brain, like other organs, possesses an autoregulatory system to maintain a certain cerebral perfusion pressure. The autoregulatory system of a normotensive patient maintains a steady state, adequate for perfusion, by maintaining a mean arterial pressure (MAP) of 60 to 120 mm Hg. In normotensive patients who suddenly become hypertensive, the regulator system quickly becomes overwhelmed and can no longer maintain autoregulation through vasoconstriction and dilation. In contrast, in patients with long-standing hypertension, the autoregulatory system gradually adapts to severely increased blood pressures and accommodates a higher set-point and thus decreases the likelihood of a hypertensive emergency at moderately increased
5
6
Adebayo & Rogers
pressures. When the cerebral regulatory system becomes overwhelmed, the patient is at risk for cerebral edema. The subsequent syndrome is known as hypertensive encephalopathy. It can manifest in many ways, including acute delirium, lethargy, confusion, severe headache, or seizure. In addition, it is important to consider other equally dangerous causes of altered mental status (eg, infection and cerebrovascular accidents), because they have entirely different management strategies. In patients experiencing ischemic stroke, the blood pressure should not be reduced by more than 10% to 15% over the first 24 hours, because it is thought that HTN protects the ischemic penumbra of the brain.11–14 The treatment of hypertensive encephalopathy begins with symptom control. Expert opinion suggests that medications such as benzodiazepines, fosphenytoin, phenytoin, or barbiturates should be given for delirium and seizure control; they provide the added benefit of further blood pressure reduction.15 For blood pressure management of hypertensive encephalopathy not complicated by cerebral vascular accident, the MAP should be reduced by about 20% to 25% in the first 1 hour of treatment. Traditionally used medications include IV nitroprusside, labetalol, nicardipine, and enalapril (Table 1). Centrally acting medications such as clonidine should be avoided for the acute management of hypertensive emergencies because their sedative side effects can make it difficult to appreciate the resolution of encephalopathic symptoms.15 Pulmonary Edema
One of the most harrowing hypertensive emergencies is hypoxic respiratory failure with acute flash pulmonary edema. Certain patient populations (ie, those with congestive heart failure and end-stage renal disease) are unable to tolerate fluctuations in their blood pressure easily, resulting in volume overload and pulmonary edema. In recent years, attention has centered on the use of noninvasive ventilation therapy, such as bilevel positive airway pressure ventilation, to circumvent the likelihood of these patients progressing to intubation. Treatment of the underlying cause, along with blood pressure reduction, is key to clinical improvement. For patients with flash pulmonary edema, preload and afterload reduction remains the goal of treatment. One or more medications that work either alone or in conjunction with each other have been the traditional treatment. Nitrates such as nitroglycerin are effective in reducing preload because of their venodilatory effects. Afterload reducers, such as angiotensin-converting enzyme inhibitors, are also used as key treatment of flash pulmonary edema. Loop diuretics such as furosemide are often used to treat symptomatic dyspnea secondary to pulmonary edema. In a recent randomized, double-blind prospective study, Holzer-Richling and colleagues16 found that administration of furosemide versus placebo to a cohort of patients did not improve outcomes. Study participants who received furosemide required lower doses of antihypertensive agents, suggesting a role for loop diuretics in reducing blood pressure.16 Caution is needed when giving a diuretic during a hypertensive crisis, because more than half of patients with pulmonary edema are euvolemic or hypovolemic, not overloaded in terms of total body volume; in contrast, patients with renal or hepatic failure tend to be overloaded, so diuretics have benefit in the acute phase to excrete the excess fluid and off-load the lungs. Nitroprusside, one of the fastest acting agents in the treatment armamentarium, is considered ideal for patients with flash pulmonary edema.17 It has the profile benefit of being rapid in onset as well as a venous and arterial dilator. Its use carries a small risk of thiocyanate and cyanide toxicity, but that side effect is seen more commonly with excessive dosing and refractory blood pressure response. Clevedipine, one of the newest IV antihypertensive medications (approved by the US Food and Drug
Hypertensive Emergencies in the ED
Administration in 2008) has shown great promise in clinical trials for treatment of severe hypertension, particularly for pulmonary edema and postoperative hypertension.18 Clevedipine is a dihydropyridine calcium channel blocker that has the added benefit of not being metabolized by the kidney or liver.19–21 Myocardial Ischemia
Classically, ACS develops as the result of an acute coronary thrombus. Cardiac ischemia can also be the result of other uncommon causes, such as hypertensive emergency. Patients with cardiac ischemia typically present with chest pain, dyspnea, diaphoresis, vomiting, and, especially in the elderly, generalized fatigue. Severe hypertension is usually associated with increased myocardial work and oxygen demand. Patients with previously diseased hearts are at increased risk of further myocardial ischemia. Electrocardiographic abnormalities and increased cardiac biomarkers indicate hypertension-induced cardiac ischemia or infarction. Treatment of ischemic chest pain is 3-fold: (1) reduction in myocardial work, (2) reduction in myocardial oxygen consumption, and (3) improvement in coronary artery perfusion. The first intervention that should be performed in a patient with suspected ACS is administration of aspirin.22 Severely hypertensive patients with suspected ACS should be given an IV b-blocker (class IIa recommendation by the AHA).23 Other commonly recommended agents are nitroglycerin and labetalol. Nitroglycerin is often titrated to resolution of chest pain or hypotension, whichever occurs first. Nitroglycerin has the added effect of coronary vasodilation, which improves cardiac tissue perfusion. No specific recommendations exist on which b-blocker is preferred, but it is best to use a medication with a quick pharmacokinetic profile so that it can be titrated easily. Care should be used with medications such as hydralazine and nitroprusside. Hydralazine causes reflex tachycardia, which increases myocardial work and oxygen consumption. It also has an extremely variable dose response curve from patient to patient, which can cause a precarious situation for EPs when the blood pressure decreases precipitously. Nitroprusside has the potential to cause coronary steal syndrome, which worsens ischemia and could increase risk of death if it is given after acute myocardial infarction (AMI).24,25 Similarly, b-blockers should not be administered after AMI because of the risk that they could worsen underlying congestive heart failure and cause cardiogenic shock. Aortic Dissection
When a patient describes the sudden-onset chest pain that radiates to the back, the EP should put aortic dissection (AD) at the top of the differential diagnosis. However, more subtle presentations should not be overlooked: chest pain accompanied by pain in any extremity, neurologic symptoms, abdominal or back pain, or gastrointestinal bleeding should raise concern for AD. The mortality for AD increases 1% to 2% every hour during the first 24 hours after the onset of symptoms. The Stanford classification distinguishes dissections as either type A or type B. Type A involves the aortic arch only; type B involves the descending aorta. Most type B dissections and some type A dissections can be managed with medical therapy but that determination should be made by the vascular surgeon. All type A dissections should be referred to a vascular surgeon for likely surgical repair. Whenever AD is suspected, it is important to measure the blood pressure in both arms and to assess the pulses in all 4 extremities. It is critical not to rely on classic findings: w19% of patients with type A dissections and w9% of those with type B dissections have no identifiable pulse deficits.26 More reliable is identification of a new diastolic murmur suggestive of aortic regurgitation, which is seen in up to 44% of type A
7
8
Adebayo & Rogers
Table 1 Pharmacologic agents for hypertensive emergencies Drug
Dose
Onset of Action (min) Duration of Action
Adverse Effects
Indications
Nitroglycerin
5–100 mg/min as IV infusion
2–5
5–30 min
Cardiac ischemia; flash Headache, vomiting, pulmonary edema; caution methemoglobinemia; with recent use of caution in right ventricular phosphodiesterase infarct inhibitors
Sodium nitroprusside
0.25–10 mg/kg/min as IV infusion
Immediate
1–2 min
Nausea, vomiting, muscle twitching, sweats, thiocyanate and cyanide toxicity
5–10
15–30 min, may last Tachycardia, headache, several hours flushing, local phlebitis
Most hypertensive emergencies; caution of coronary steal with cardiac ischemia
Vasodilators
Nicardipine 5–15 mg/h IV hydrochloride
Most hypertensive emergencies; caution with high intracranial pressure or azotemia
Fenoldopam mesylate
0.1–0.3 mg/kg per min IV fusion
<5
30 min
Tachycardia, headache, nausea, flushing
Best for hypertensive nephropathy emergencies
Enalaprilat
1.25–5 mg every 6 h IV
15–30
6–12 h
Significant reductions in blood pressure in highrenin states
Acute left ventricular failure and flash pulmonary edema; avoid in AMI
10–20 IV 20–30 IM
1–4 h IV 4–6 h IM
Tachycardia, flushing, headache, vomiting, worsening angina
Eclampsia; caution given erratic response
Hydralazine 10–20 mg IV hydrochloride 10–40 mg IM
5–15 min
Headache, nausea, vomiting, Postoperative hypertension, hypertensive emergency in hypotension, rebound renal dysfunction or acute hypertension, reflex heart failure tachycardia
Esmolol 250–500 mg/kg/min IV bolus, 1–2 hydrochloride then 50–100 mg/kg/min by infusion; repeat bolus after 5 min if needed or increase infusion to 300 mg/min
10–30 min
Hypotension, nausea, asthma Aortic dissection, perioperative exacerbation, first-degree heart block, heart failure
Labetalol 20–80 mg IV bolus every hydrochloride 10 min; alternatively, 0.5– 2 mg/min IV infusion
5–10
3–6 h
Vomiting, scalp tingling, bronchoconstriction, dizziness, nausea, heart block, orthostatic hypotension
Most hypertensive emergencies except acute heart failure; ideal for preeclampsia
Phentolamine
1–2
10–30 min
Tachycardia, flushing, headache
Pheochromocytoma and other catecholamine excess states
Clevidipine
Initial infusion of 1–2 mg/h, titrate every 5–10 min
2–4
Adrenergic Antagonists
5-mg to 15-mg IV bolus
Hypertensive Emergencies in the ED
Abbreviations: AMI, acute myocardial infarction; IM, intramuscular. Adapted from Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52.
9
10
Adebayo & Rogers
dissections.26 A CXR obtained as part of the work-up might show a widened mediastinum, but as many as 15% of patients with AD have normal chest radiographs.27 The goal of medical therapy for AD is rapid and large reduction of vascular sheer stress and blood pressure. The initial medication should be able to reduce the sheering force; a b-blocker is typically used for this purpose, because this drug group both decreases the heart rate (HR) and prevents reflex tachycardia when arteriodilators are introduced. Esmolol is an ideal agent for this purpose because of its rapid on/off qualities and its ability to reduce the HR to less than 60 beats per minute. A medication is also needed to reduce the systolic blood pressure to less than 120 mm Hg. Nitroprusside has long been used for this purpose and is a reasonable option for fast and reliable blood pressure control.27 Acute Renal Failure
Acute renal failure (ARF) can be either the direct cause or an observed effect of a hypertensive emergency. A patient’s history, specifically renal transplant and renal function, can help differentiate cause from effect. Assessment of the patient’s volume status is also important to determine the need for adjunctive therapies, such as positive-pressure ventilation or diuretics for patients who present with dyspnea from fluid overload. Calcium channel blockers (eg, nicardipine) are typically preferred in ARF because they do not affect renal perfusion or clearance. Nitroprusside and fenoldopam are also commonly used. Nitroprusside is effective in reducing blood pressure, but it places the patient at risk of cyanide toxicity because it decreases renal clearance and thus causes a buildup of metabolites. Fenoldopam is a more desirable secondline medication. An arterial vasodilator, it not only decreases blood pressure but also promotes renal excretion via its specific effects on the dopamine receptors in the nephron. It produces no toxic metabolites and has been shown to be as effective in blood pressure reduction as nitroprusside.28,29 In the special case of scleroderma renal crisis, angiotensin-converting enzyme inhibitors (eg, captopril and enalapril) are first-line agents for effect management.30 Sympathomimetic Crisis
This category encompasses severe increases in blood pressure secondary to many causes: cocaine, phencyclidine, or amphetamine abuse; pheochromocytoma; interaction of monoamine oxidase inhibitor drugs with selective serotonin reuptake inhibitors or with wine and cheese (tyramine reaction); abrupt cessation of sympatholytic medications such as clonidine; and alcohol withdrawal. The treatment of all these crises is similar. The sole use of b-blockers is not recommended because of the reflex tachycardia that it induces, which could precipitate a rapid increase in blood pressure and cardiovascular collapse.31,32 Phenoxybenzamine, phentolamine, nitroprusside, and labetalol are good first-line medications.33,34 In cocaine-induced crisis, benzodiazepines should be used in conjunction with antihypertensive drugs. In a study involving 378 patients with cocaine-induced chest pain, Ibrahim and colleagues35 found no difference in the troponin levels of patients who received b-blockers and those who did not. This observation challenges convention, which has created a culture of fear around using such drugs in these patients. More studies are needed to validate or challenge these controversial findings. In the treatment of a hypertensive emergency in patients with clonidine withdrawal, the first step is to administer clonidine. Hypertensive Emergency in Pregnancy
Pregnancy causes many deviations from women’s pregravid physiology. Blood pressure decreases in the second trimester of pregnancy before increasing back to
Hypertensive Emergencies in the ED
baseline values in the third trimester. Preeclampsia is a poorly understood disorder of hypertension that occurs for unknown reasons in 2% to 6% of pregnancies after the 20th week of gestation. It can be a serious disorder, with consequences for both mother and fetus. The dramatic increase in maternal blood pressure affects the placenta, which is the end organ that is vital to fetal development. Preeclampsia has mild and severe forms. Mild preeclampsia and severe preeclampsia are essentially distinguished by the degree of hypertension that persists and not the degree of proteinuria because both forms can exist without proteinuria. The treatment of severe preeclampsia is 2-fold: (1) delivering the fetus as soon as possible (ideally after the administration of steroids for fetal lung maturity in viable fetuses), and (2) reducing the blood pressure and reversing end-organ damage. Preeclampsia can also lead to other end-organ dysfunction such as the HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Failure to achieve rapid control of the blood pressure can lead to the potentially fatal progression to eclampsia, characterized by seizures, strokes, and death. The approach to blood pressure management in a preeclamptic patient is a balancing act. When the fetus is viable and delivery is not imminent, antihypertensive therapy must be chosen so that precipitous decreases in blood pressure do not cause placental hypoperfusion and compromise fetal blood flow. Labetalol, nifedipine, nicardipine, and hydralazine have been common choices for this condition for years. However, the safety of hydralazine and nifedipine in gravid patients has been questioned. Those medications, particularly hydralazine, should be considered second-line or third-line choices because of their unpredictability in duration of action and degree of hypotension. Labetalol and nicardipine are more predictable.36 Another hallmark in the treatment of severe preeclampsia and eclampsia is the use of magnesium sulfate, which is given as a bolus followed by an infusion. Patients should be monitored closely for the development of magnesium toxicity. Magnesium is thought to be neuroprotective to the mother, preventing the onset of eclampsia (or terminating seizures once eclampsia has set in), and possibly to the fetus.37 SUMMARY
Hypertension is a multifaceted disease process that affects the US and global populations in massive proportions. The most accurate indicator of hypertensive emergency is the presence of end-organ damage. The EP’s role is pivotal in rapidly identifying and differentiating hypertensive emergency from hypertensive urgency and providing the appropriate intervention. Actions that are fundamental to identifying individuals at risk include obtaining a targeted history, performing a careful physical examination, and requesting the appropriate laboratory and diagnostic screening. Many medications are available to treat hypertensive emergencies but none is universally recognized as being superior to the others. Important considerations in drug selection include an understanding of the underlying physiology of the crisis, the patient’s comorbid conditions, and associated risk factors. Once a drug is chosen, it should be given quickly because “time is tissue” in hypertensive emergency. Patients should be managed in an intensive care unit because critical care monitoring is required. With appropriate identification and management, hypertensive crises can be halted and reversed. REFERENCES
1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 2014;129:e28–292.
11
12
Adebayo & Rogers
2. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21–181. 3. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth Joint National Committee (JNC 8). JAMA 2014;311:507–20. 4. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52. 5. Vaidya CK, Ouellette JR. Hypertensive urgency and emergency. Hosp Physician 2007;43:43–50. 6. Wolf SJ, Lo B, Shih RD, et al. Clinical policy: critical issues in the evaluation and management of adult patients in the emergency department with asymptomatic elevated blood pressure. Ann Emerg Med 2013;62:59–68. 7. Webster J, Petrie JC, Jeffers TA, et al. Accelerated hypertension—patterns of mortality and clinical factors affecting outcome in treated patients. Q J Med 1993;86:485–9. 8. Graves JW. Prevalence of blood pressure cuff sizes in a referral practice of 430 consecutive adult hypertensives. Blood Press Monit 2001;6:17–20. 9. Roque PJ, Wu TS, Barth L, et al. Optic nerve ultrasound for the detection of elevated intracranial pressure in the hypertensive patient. Am J Emerg Med 2012;30:1357–63. 10. Dedic A, ten Kate G, Nieman K, et al. Coronary CT angiography outperforms calcium imaging in the triage of acute coronary syndrome. Int J Cardiol 2013;167: 1597–602. 11. Papadopoulos DP, Votteas V. Role of perindopril in the prevention of stroke. Recent Pat Cardiovasc Drug Discov 2006;1:283–9. 12. Lavin P. Management of hypertension in patients with acute stroke. Arch Intern Med 1986;146:66–8. 13. Adams HP Jr, del Zoppo 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 Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655–711. 14. O’Connell JE, Gray CS. Treatment of post-stroke hypertension: a practical guide. Drugs Aging 1996;8:408–15. 15. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000;356:411–7. 16. Holzer-Richling N, Holzer M, Kerkner H, et al. Randomized placebo controlled trial of furosemide on subjective perception of dyspnea in patients with pulmonary edema because of hypertensive crisis. Eur J Clin Invest 2011;41:627–34. 17. Aggarwal M, Khan I. Hypertensive crisis: hypertensive emergencies and urgencies. Cardiol Clin 2006;24:135–46. 18. Aronson S, Dyke SM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg 2008;107: 1110–21. 19. Pollack CV, Varon J, Garrison NA, et al. Clevidipine, an intravenous dihydropyridine calcium channel blocker, is safe and effective for the treatment of patients with acute severe hypertension. Ann Emerg Med 2009;53:329–38.
Hypertensive Emergencies in the ED
20. Cleviprex (clevidipine butyrate) [package insert]. Clayton, NC: Hospira; 2008. 21. Marik P, Rivera R. Hypertensive emergencies: an update. Curr Opin Crit Care 2011;17:569–80. 22. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction. Lancet 1988; 2(8607):349–60. 23. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78–140. 24. Mann T, Cohn PF, Holman LB, et al. Effect of nitroprusside on regional myocardial blood flow in coronary artery disease: results in 25 patients and comparison with nitroglycerin. Circulation 1978;57:732–8. 25. 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 Administration cooperative study. N Engl J Med 1982;306:1129–35. 26. Hagan PG, Nienaber CA, Isselbacher EM, et al. International Registry of Acute Aortic Dissection (IRAD): new insights from an old disease. JAMA 2000;283: 897–903. 27. Braverman AC. Acute aortic dissection: clinician update. Circulation 2010;122: 184–8. 28. Elliott WJ, Weber RR, Nelson KS, et al. Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension. Circulation 1990;81:970–7. 29. Reisin E, Huth MM, Nguyen BP, et al. Intravenous fenoldopam versus sodium nitroprusside in patients with severe hypertension. Hypertension 1990;15:I59–62. 30. Mouthon L, Be´rezne´ A, Bussone G, et al. Scleroderma renal crisis: a rare but severe complication of systemic sclerosis. Clin Rev Allergy Immunol 2011;40: 84–91. 31. Lange RA, Cigarroa RG, Flores ED, et al. Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade. Ann Intern Med 1990;112: 897–903. 32. Pitts WR, Lange RA, Cigarroa JE, et al. Cocaine-induced myocardial ischemia and infarction: pathophysiology, recognition, and management. Prog Cardiovasc Dis 1997;40:65–76. 33. Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol 1998;9:133–42. 34. Rhoney D, Peacock W. Intravenous therapy for hypertensive emergencies, part 1. Am J Health Syst Pharm 2009;66:1343–52. 35. Ibrahim M, Maselli D, Hasan R, et al. Safety of b-blockers in the acute management of cocaine-associated chest pain. Am J Emerg Med 2013;31:613–6. 36. Magee LA, Cham C, Waterman EJ, et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ 2003;327:955–60. 37. Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulfate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009;(1):CD004661.
13