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CHAPTER 57: Systemic Hypertension 399 both (Table 56-12). Major contraindications to thrombolytic therapy include intracranial disease, uncontrolled hypertension at presentation, recent major surgery or trauma (past 3 weeks), and metastatic cancer. Any patient with head trauma from syncope should have a CT scan prior to therapy to detect hemorrhage. Alteplase (tissue plasminogen activator) is the only currently approved agent for PE, dosed at 100 milligrams IV over 2 hours. Either enoxaparin (1 milligram/kg SC) or unfractionated heparin (80 units/kg IV bolus followed by 18 units/kg/h) is the anticoagulant, with the activated partial thromboplastin time kept at <120 seconds for unfractionated heparin. Heparin or low-molecular-weight heparin is typically started after the thrombolytic infusion. Use of 50 mg of alteplase may reduce bleeding risk with similar outcomes as 100 mg of alteplase, although the safety and efficacy of this approach remain controversial. 81,82 For further discussion of fibrinolytic agents, see Chapter 239, “Thrombotics and Antithrombotics. ”  CATHETER-DIRECTED THROMBOLYSIS Recent systematic reviews suggest that catheter-directed fibrinolysis for intermediate-risk PE produces good hemodynamic improvements and an intracranial bleeding rate <2%. 83-86 Catheter-directed thrombolysis for PE requires a far lower dose of alteplase (approximately 10 milligrams total), which may confer a lower bleeding risk. Catheter-directed thrombolysis is an option for patients over 65 years old, in whom intracranial bleeding risk is highest. 87 Because of the time delay needed to activate the vascular intervention suite, intrapulmonary fibrinolytic delivery should not be used in most patients with massive PE.  SURGICAL EMBOLECTOMY If available, surgical embolectomy is an option in young patients with large, proximal PE accompanied by hypotension. Because surgical embolectomy is often delayed, the reported mortality rate is approxi mately 30%. The amount of clot that can be extracted is often extensive, and removal may help limit later cardiopulmonary complications. SPECIAL POPULATIONS  PREGNANCY The clinical assessment of VTE in pregnant women is difficult because many signs and symptoms suggestive of VTE are seen in normal pregnancy. 89-91 Fewer than 2% of pregnant women with Wells’ score ≤4 had PE in prior retrospective studies. 92,93 In one prospective study, the revised Geneva score resulted in a stepwise increase in probability of PE (7 of 192 [3.6%] in the low–pretest probability group, 18 of 200 [9.0%] in the intermediate-probability group, and 3 of 3 [100%] in the high-probability group). 94 The PE rule-out criteria rule has not been adequately tested in pregnant patients to recommend its use in isolation to exclude PE. The d-dimer has low specificity in pregnant patients; by the third trimester, almost all healthy pregnant women have a positive d-dimer. 95,96 Studies that have examined the diagnostic sensitivity of the d-dimer have been hampered by low numbers and problems with d-dimer measurements made after systemic anticoagulation, which degrades test sensitivity. 97 Some have advocated for sequentially increasing the cutoff by approximately 50% for the d-dimer per trimester (first trimester, 750 nanograms/mL; second trimester, 1000 nanograms/mL; third trimester, 1250 nanograms/mL), although this approach has not been tested in a management study.

hich degrades test sensitivity. 97 Some have advocated for sequentially increasing the cutoff by approximately 50% for the d-dimer per trimester (first trimester, 750 nanograms/mL; second trimester, 1000 nanograms/mL; third trimester, 1250 nanograms/mL), although this approach has not been tested in a management study. 96,98-100 The diagnostic accuracy of US for DVT appears to be similar to that of nonpregnant patients. 101,102 The best choice of pulmonary vascular imaging in pregnancy is controversial and uncertain. 103 Both a normal CT pulmonary angiogram and V/Q  scanning have shown 100% diagnostic sensitivity for technically adequate studies. 91 MRI has not been adequately tested in pregnancy to provide any basis for recommenda tion, but it had too low of a sensitivity (78%) to rule out PE in nonpregnant patients.91,104 Pregnant patients diagnosed with VTE in the ED should be antico agulated with low-molecular-weight heparin. In the case of massive PE, options include systemic fibrinolysis, catheter-directed fibrinolysis, or the use of cardiopulmonary venoarterial extracorporeal membrane oxygenation. Current literature suggests a >80% probability of survival of both mother and fetus with the use of systemic fibrinolytics in the setting of massive PE. 105 For additional discussion, see Chapter 99, “Comorbid Disorders in Pregnancy. ”  ISOLATED SUBSEGMENTAL PULMONARY EMBOLISM Isolated subsegmental PE is a filling defect seen in one small pulmo nary artery, usually <3 mm in diameter and in the absence of DVT; radiologists often do not agree when viewing these images separately. The optimal treatment of subsegmental PE remains uncertain. Pooled data suggest that patients without high risk of recurrence (e.g., prior unprovoked VTE, active cancer, or other major active risk factor) may not benefit from anticoagulation. 106 However, no randomized trial has been performed to test this hypothesis. The author’s choice is to treat subsegmental PE as an outpatient with apixaban or rivaroxaban and check a d-dimer in 1 month and, if normal, stop anticoagulation. It is best to discuss the risks and benefits of treatment of subsegmental PE with patients and their physicians to help make the best decision about anticoagulation.  CANCER PATIENTS WITH VENOUS THROMBOEMBOLISM Current data and guidelines recommend treatment of patients with active cancer with low-molecular-weight heparin for at least 6 months. One randomized trial suggested that rivaroxaban can be used in patients with active cancer, with a reduction in VTE recurrence but increased risk of bleeding. REFERENCES The complete reference list is available online at www.TintinalliEM.com. Systemic Hypertension Brigitte M. Baumann INTRODUCTION AND EPIDEMIOLOGY Hypertension affects approximately 40% of the U.S. population, and 1% to 6% of all ED patients present with severe hypertension. 1-5 Of the latter, between one quarter and one half will have end-organ damage. 2-5 Risk factors for the development of acute hypertensive events include obesity, cigarette smoking, older age, lack of access to health care, and noncompliance with antihypertensive medications. Chronic hypertension is categorized into three classifications: prehypertension, stage 1 hypertension, and stage 2 hypertension (Table 57-1). Hypertensive crisis is an acute elevation of blood pressure, where the systolic blood pressure is >180 mm Hg and/or the diastolic blood pres sure is >120 mm Hg. There are two forms of hypertensive crisis. Hypertensive emergency is a hypertensive crisis (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >120 mm Hg) with concomitant end-organ damage; the targeted end organs include the brain, heart, aorta, kidneys, or eyes ( Table 57-2).

pres sure is >120 mm Hg. There are two forms of hypertensive crisis. Hypertensive emergency is a hypertensive crisis (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >120 mm Hg) with concomitant end-organ damage; the targeted end organs include the brain, heart, aorta, kidneys, or eyes ( Table 57-2). Hypertensive urgency is a controversial term—some believe it does not exist distinctly apart from severe hypertension—denoting a marked and acutely elevated blood pressure without acute or worsening target organ dysfunction. 7 Often, an arbitrary blood pressure of >180/120 mm Hg is cited as an indication for rapid pharmacologic intervention (typically parenteral) to reduce blood pressure within hours. There is no clinical CHAPTER Tintinalli_Sec07_p0329-0424.indd 399 8/2/19 6:42 PM

essure without acute or worsening target organ dysfunction. 7 Often, an arbitrary blood pressure of >180/120 mm Hg is cited as an indication for rapid pharmacologic intervention (typically parenteral) to reduce blood pressure within hours. There is no clinical CHAPTER Tintinalli_Sec07_p0329-0424.indd 399 8/2/19 6:42 PM 400 SECTION 7: Cardiovascular Disease outpatient follow-up.7 Gradual blood pressure reduction should occur over days to weeks. PATHOPHYSIOLOGY At baseline, chronic hypertensive patients have biochemical and structural changes in the arterial walls that shift the vascular autoregulatory curve, requiring higher arterial pressures to maintain end-organ blood flow, notably in the brain. 10-12 Eventually, the ability to adapt is passed. The resultant mechanical wall stress and endothelial injury lead to increased permeability and hyperperfusion of the cerebral, cardiac, and renal vascular beds. This may be followed by activation of the coagula tion cascade and platelets, and deposition of fibrin results in fibrinoid necrosis of the arterioles. Clinically, this produces hematuria (involvement of the renal vasculature), arterial hemorrhages, or exudates on funduscopic examination. 12 Further contributing to the damage are prostaglandins, free radicals, cytokines, and mitogenic, chemoattrac tant, and proliferation factors, causing endothelial damage, smooth muscle proliferation, and thrombosis. 10,12 The renin-angiotensin sys tem may also be activated, which leads to vasoconstriction. Pressure natriuresis occurs, leading to volume depletion, prompting additional release of vasoconstrictors from the kidney. These combined effects produce hypoperfusion, ischemia, and dysfunction of end organs. Endothelial dysfunction from such crises can persist for years after the acute event. CLINICAL FEATURES Measure blood pressure in both arms in a narrow time interval while the patient is quietly resting. Check blood pressure several times before starting antihypertensive therapy. Blood pressure differences between extremities can result from aortic dissection, coarctation, peripheral vascular disease, and some unilateral neurologic and mus culoskeletal abnormalities. Interarm blood pressure differences exist in some normal individuals, particularly the elderly, due to the loss of vascular elasticity or asymmetrical atheromatous narrowing of subclavian or brachial arteries. Although no guidelines regarding blood pressure disparities exist, an interarm difference >10 to 20 mm Hg is meaningful and increases long-term risks of cardiovascular events and mortality. 14,15 When an interarm blood pressure difference is detected, treat the higher blood pressure and ensure that subsequent measurements are made on the same arm. 15 Avoid wrist oscillometric devices as these give lower readings than upper arm measurements.16 A modest drop (up to 12 mm Hg) in systolic and diastolic blood pressures can occur absent therapy in patients presenting with elevated blood pressures. Conversely, do not discount a diagnosis of hypertensive TABLE 57-1 Categories of Blood Pressure in Adults* BP Category Systolic BP (mm Hg)   Diastolic BP (mm Hg) Normal <120 and <80 Elevated 120–129 and <80 Hypertension Stage 1 130–139 or 80–89 Stage 2 ≥140 or ≥90 Abbreviation: BP = blood pressure. *Data adapted from: 2017 High Blood Pressure Clinical Practice Guideline: Executive Summary, where BP is based on an average of ≥2 careful readings obtained on ≥2 occasions.

(mm Hg) Normal <120 and <80 Elevated 120–129 and <80 Hypertension Stage 1 130–139 or 80–89 Stage 2 ≥140 or ≥90 Abbreviation: BP = blood pressure. *Data adapted from: 2017 High Blood Pressure Clinical Practice Guideline: Executive Summary, where BP is based on an average of ≥2 careful readings obtained on ≥2 occasions. 7 TABLE 57-2 Hypertensive Emergencies Diagnostic Category Signs and Symptoms Evidence of Acute End-Organ Damage Acute aortic dissection Chest pain, back pain Unequal blood pressures (>20 mm Hg difference) in upper extremities Abnormal CT angiogram of chest and abdomen/pelvis or transesophageal echocardiogram of the aorta Acute pulmonary edema Shortness of breath Interstitial edema on chest radiograph Acute myocardial infarction Chest pain, nausea, vomiting, diaphoresis Changes on ECG or elevated levels of cardiac biomarkers Acute coronary syndrome Chest pain, nausea, vomiting, diaphoresis Clinical diagnosis, changes on ECG, or elevated levels of cardiac biomarkers Acute renal failure May have systolic or diastolic abdominal bruit Elevated serum creatinine level, proteinuria Severe preeclampsia, eclampsia Seizures, shortness of breath, headache, or vision abnormalities (blurred vision, flashing lights, scotomata) Proteinuria (no longer required for the diagnosis of preeclampsia), low platelet count, renal insufficiency, elevated liver enzyme levels, pulmonary edema Hypertensive retinopathy Blurred vision Retinal hemorrhages and cottonwool spots (Figure 57-1), hard exudates, and sausage-shaped veins Hypertensive encephalopathy Altered mental status, nausea, vomiting, headache May see papilledema or arteriolar hemorrhage or exudates on funduscopic examination, may note cerebral edema with a predilection for the posterior white matter of the brain on MRI Subarachnoid hemorrhage Headache, focal neurologic deficits Abnormal CT of the brain; red blood cells on lumbar puncture Intracranial hemorrhage Headache, new neurologic deficits Abnormal CT of the brain Acute ischemic stroke New neurologic deficits Abnormal MRI or CT of the brain Acute perioperative hypertension Bleeding unresponsive to direct pressure Clinical diagnosis; manifestations of other hypertensive emergencies Sympathetic crisis * Anxiety, palpitations, tachycardia, diaphoresis Clinical diagnosis in the setting of sympathomimetic drug use (i.e., cocaine or amphetamines) or pheochromocytoma (24-h urine assay for catecholamines and metanephrine or plasma fractionated metanephrines) *In this syndrome, acute end-organ dysfunction may not be measurable, but complications affecting the brain, heart, or kidneys may occur in the absence of acute treatment. FIGURE 57-1. Hypertensive retinopathy. Scattered flame (splinter) hemorrhages and cotton-wool spots (nerve fiber layer infarcts) in a patient with headache and a blood pressure of 234/120 mm Hg. benefit of such treatment (hence the concern about the term urgency), and precipitous drops in blood pressure can be harmful. 7-9 Current recommendations for patients with hypertensive urgency are reinsti tution or intensification of oral antihypertensive therapy and prompt Tintinalli_Sec07_p0329-0424.indd 400 8/2/19 6:42 PM

t of such treatment (hence the concern about the term urgency), and precipitous drops in blood pressure can be harmful. 7-9 Current recommendations for patients with hypertensive urgency are reinsti tution or intensification of oral antihypertensive therapy and prompt Tintinalli_Sec07_p0329-0424.indd 400 8/2/19 6:42 PM CHAPTER 57: Systemic Hypertension 401 emergency in patients with no prior history of elevated blood pressure17,18 because up to 16% have no history of hypertension.4 Table 57-3 lists the proportion of patients who present with elevated blood pressure by stroke subtypes, aortic dissection subtypes, heart failure, and acute coronary syndrome. Although elevations in blood pressure accompany most of these presentations, note that severe elevations of blood pressure are far less common in presentations typically labeled as hypertensive emergencies.  CHEST PAIN AND SEVERE HYPERTENSION Rapid identification of acute aortic dissection is critical because delays in management increase mortality. Differentiating aortic dissection from the more common acute coronary syndromes is imperative given that blood pressure control differs in these two disorders and anticoagulation can prove catastrophic in acute aortic dissection. Acute aortic dissection presents with abrupt, sudden onset of pain, usually in the chest, often described as tearing or ripping, and radiating to the interscapular region 22,23,28-30 (see Chapter 59, “ Aortic Dissection and Related Aortic Syndromes, ” for more discussion).  ACUTE NEUROLOGIC SYMPTOMS AND SEVERE HYPERTENSION Elevated blood pressure, headache, and focal neurologic deficits are associated with either ischemic or hemorrhagic strokes (see Chapter 167, “Stroke Syndromes”) (Figure 57-2). Hypertensive encephalopathy is a clinical diagnosis made after excluding focal ischemia or bleeding. Patients with this condition have altered mental status, headache, vomiting, seizures, or visual distur bances, and most patients will have papilledema. When MRI findings demonstrate reversible edema that is predominantly posterior (occipital), the posterior reversible encephalopathy syndrome ( Figure 57-3) exists, which carries a poor prognosis.  ACUTE RENAL FAILURE, PERIPHERAL EDEMA, AND SEVERE HYPERTENSION Patients with new-onset renal failure may have peripheral edema, oliguria, loss of appetite, nausea and vomiting, orthostatic changes, or con fusion. However, some patients have few or no specific symptoms (see Chapter 88, “ Acute Kidney Injury”). Elevated serum creatinine confirms the diagnosis, and urinary sediment is also abnormal.  PREECLAMPSIA AND ECLAMPSIA Preeclampsia presents with elevated blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) on two occasions at least 4 hours apart in pregnant patients beyond the 20th week TABLE 57-3 Specific Diseases Associated With Elevated Blood Pressures Disease Threshold Value Raising Risk % of Patients With Elevated Pressures Subarachnoid hemorrhage19 ≥140 mm Hg SBP 100% Ischemic stroke19,20 ≥140 mm Hg SBP ≥160 mm Hg SBP 77%–82% 47%–54% Intracerebral hemorrhage 19 ≥140 mm Hg SBP ≥160 mm Hg SBP 75% 27% Type B aortic dissection 21,22 ≥140 mm Hg SBP or ≥90 mm Hg DBP 67%–77% Type A aortic dissection23 >150 mm Hg SBP 36%–74% Acute heart failure24,25 >140 mm Hg SBP 52%–54% NSTEMI-ACS24,26 ≥140 mm Hg SBP ≥160 mm Hg SBP 57%–59% 31% Abbreviations: DBP = diastolic blood pressure; NSTEMI-ACS = non–ST-segment elevation myocardial infarction acute coronary syndrome; SBP = systolic blood pressure. FIGURE 57-2. Intracerebral hypertensive hemorrhage. Noncontrast head CT scan with acute intraparenchymal hemorrhage, mass effect, midline shift, and intraventricular exten sion. [Image used with permission of Todd Siegal, MD.] FIGURE 57-3.

on myocardial infarction acute coronary syndrome; SBP = systolic blood pressure. FIGURE 57-2. Intracerebral hypertensive hemorrhage. Noncontrast head CT scan with acute intraparenchymal hemorrhage, mass effect, midline shift, and intraventricular exten sion. [Image used with permission of Todd Siegal, MD.] FIGURE 57-3. Axial fluid-attenuated inversion recovery MRI showing white matter hyperintensity in the occipital lobes bilaterally consistent with posterior reversible encepha lopathy syndrome. The patient’s confusion improved with blood pressure control. Repeat MRI after several days of therapy demonstrated remarkable improvement. [Image used with permission of Michael Farner, MD.] Tintinalli_Sec07_p0329-0424.indd 401 8/2/19 6:42 PM

s bilaterally consistent with posterior reversible encepha lopathy syndrome. The patient’s confusion improved with blood pressure control. Repeat MRI after several days of therapy demonstrated remarkable improvement. [Image used with permission of Michael Farner, MD.] Tintinalli_Sec07_p0329-0424.indd 401 8/2/19 6:42 PM 402 SECTION 7: Cardiovascular Disease of gestation. Eclampsia is the progression of preeclampsia to new-onset grand mal seizures in the absence of other neurologic conditions that could account for the seizure 31 (see Chapter 100, “Maternal Emergencies After 20 Weeks of Pregnancy and in the Peripartum Period”).  SYMPATHETIC CRISIS AND SEVERE HYPERTENSION There are four settings in which an excess of catecholamines can result in a hypertensive emergency. An acute catecholaminergic syn drome may occur with abrupt discontinuation of oral or transdermal clonidine. This withdrawal syndrome is potentiated by concomitant β-blocker therapy due to unopposed α-mediated vasoconstriction. Pheochromocytoma is rare, and between 5% and 20% of tumors are malignant. Patients may experience life-threatening hypertension. Signs and symptoms of pheochromocytoma include asymptomatic periods punctuated by episodic headache, elevated blood pressure, tachycardia, and diaphoresis. Sympathomimetic drugs such as cocaine, amphetamines, phencyclidine hydrochloride, and lysergic acid diethylamide can precipitate a hypertensive emergency, with tachycardia, diaphoresis, chest pain, and mental status changes. 33 Patients receiving monoamine oxidase inhibitors who consume tyramine-containing foods may develop a hyperad renergic state.34 Autonomic dysfunction due to spinal cord or severe head injury or abnormalities such as spina bifida may also present as a hypertensive emergency, with the diagnosis made clinically. Often, the associated blood pressure measurements are marginally elevated in this condition; do not let “near normal” values falsely exclude this diagnosis.  ASYMPTOMATIC PATIENTS WITH SEVERE HYPERTENSION Formal recommendations for the evaluation of an ED patient presenting with asymptomatic but severe hypertension do not exist. 9 Commonly ordered tests include basic metabolic panel, ECG, chest radiograph, and urinalysis, but in the asymptomatic population, abnormal results attributable to acute hypertensive target organ injury are found in <6% of patients. 3,35 Until more data are available, base ED evaluation on the patient complaint, history, and review of systems, and perform selected testing. TREATMENT Patients presenting with a hypertensive emergency should be admitted to a critical care setting for continuous monitoring of blood pressure and target organ function. Use parenteral antihypertensive agents to reduce systolic blood pressure no more than 25% in the first hour; if stable, then reduce to 160/100 mm Hg over the next 2 to 6 hours and then to normal over the following 24 to 48 hours. Balance the reduction of blood pressure with avoidance of hypoperfusion of cerebral, coronary, and renovascular beds, which can exacerbate end-organ damage. More aggressive blood pressure control is needed for acute aortic dissection, pheochromocytoma crisis, severe preeclampsia or eclampsia, and acute intracerebral hemorrhage. 7 Table 57-4 lists agents used in the manage ment of hypertensive emergencies categorized by diagnosis. In selecting therapy, be familiar with the administration of the selected agent and establish a target range for blood pressure reduction.  AORTIC DISSECTION The therapeutic goal in acute aortic dissection is a systolic blood pressure between 100 and 120 mm Hg and a heart rate ≤60 beats/min, ideally within the first hour of presentation.

, be familiar with the administration of the selected agent and establish a target range for blood pressure reduction.  AORTIC DISSECTION The therapeutic goal in acute aortic dissection is a systolic blood pressure between 100 and 120 mm Hg and a heart rate ≤60 beats/min, ideally within the first hour of presentation. 7,22,36 The resultant reduction in tachycardia decreases the shearing forces and aortic wall stress, limiting the progression of the dissection. 36 Pain control with opioids helps decrease sympathetic tone.  ACUTE HYPERTENSIVE PULMONARY EDEMA Tailor the treatment of hypertensive pulmonary edema to the under lying pathophysiology. Most patients have existing poorly controlled hypertension with cardiac remodeling and left ventricular hypertrophy, stiffness, and diastolic dysfunction. With an acute rise in blood pressure, there is an increase in afterload and a decrease in venous capacitance. This leads to fluid shifts from the splanchnic and peripheral vascular beds into the pulmonary circulation. Interventions that improve for ward flow, via afterload reduction, tend to work better than diuresis. Other causes of acute hypertensive pulmonary edema include transient left ventricular systolic or diastolic dysfunction, acute dyssynchrony, or ischemic mitral regurgitation. 39 For these reasons, one must provide individualized management. The mainstay of therapy is vasodilators, predominantly nitrates.39 IV , sublingual, and topical nitrates reduce blood pressure, decrease myocardial oxygen consumption, and improve coronary blood flow. 39,40 If adding diuretics, be careful using loop diuretics in combination with nesiritide because together these might worsen renal function. 40,41,60 In patients with systolic dysfunction, IV nicardipine or clevidipine may help by increasing both stroke volume and coronary blood flow.7,61,62  ACUTE MYOCARDIAL INFARCTION Patients presenting with severely elevated blood pressure and ischemic changes on ECG should be treated with sublingual or IV nitrates. 7,42,43 Currently, IV β-blockade is only recommended for patients presenting with severe hypertension. Oral β-blockade in patients presenting with ST-segment elevation myocardial infarctions and non–ST-segment elevation myocardial infarctions remains part of early care, but this route may not provide sufficient or rapid enough blood pressure control in a hypertensive emergency. 42,43  ACUTE SYMPATHETIC CRISIS Manage patients in acute sympathetic crisis due to either cocaine or amphetamines with an IV benzodiazepine, such as lorazepam or diaz epam, to decrease adrenergic stimulation. 33,44 Monitor patients for respiratory depression and sedation. If benzodiazepines are not effective, add nitroglycerin or phentolamine . A calcium channel blocker can serve as a third-line agent. 42,44 β-blockers can result in unopposed α-blockade, which then can worsen coronary vasoconstriction and increase blood pressure. 44 If a β-blocker is selected, labetalol, due to its α-adrenergic blocking effects, should be used in conjunction with a vasodilator.42 IV phentolamine is the first-line agent for patients with pheochromocytoma and a hypertensive emergency. Intramuscular administration is an option if venous access is absent. 32 Second-line agents include clevidipine and nicardipine. 7 Phenoxybenzamine, a long-acting oral adrenergic α-receptor blocker, is used only in the preoperative setting in patients who are hypertensive but not in crisis. Patients with monoamine oxidase inhibitor toxicity often respond to an IV benzodiazepine; if more therapy is needed, use phentolamine, nitroglycerin, or nitroprusside. Nitroglycerin is the preferred agent for these hypertension events associated with chest pain or cardiac isch emia.

are hypertensive but not in crisis. Patients with monoamine oxidase inhibitor toxicity often respond to an IV benzodiazepine; if more therapy is needed, use phentolamine, nitroglycerin, or nitroprusside. Nitroglycerin is the preferred agent for these hypertension events associated with chest pain or cardiac isch emia. Monitor patients closely after reaching a targeted blood pressure because the hypertensive phase is often followed by a hypotensive one.  ACUTE RENAL FAILURE Fenoldopam, nicardipine, and clevidipine are all suitable for acute hypertension-induced isolated renal failure, because they reduce sys temic vascular resistance while preserving renal blood flow. 7 Fenoldopam improves natriuresis and creatinine clearance in patients with elevated blood pressure and impaired renal function.  ECLAMPSIA AND PREECLAMPSIA Obstetrical hypertensive emergencies can occur well below the blood pressure threshold for other hypertensive emergencies. Hydralazine and labetalol have good safety profiles in pregnancy. Another option is oral nifedipine. 31 (See Chapter 100, “Maternal Emergencies After 20 Weeks of Pregnancy and in the Peripartum Period, ” for further details.)  NEUROLOGIC EMERGENCIES Hypertensive encephalopathy (defined as a change in sensorium or seizure from the blood pressure elevation) warrants rapid and uniform Tintinalli_Sec07_p0329-0424.indd 402 8/2/19 6:42 PM

100, “Maternal Emergencies After 20 Weeks of Pregnancy and in the Peripartum Period, ” for further details.)  NEUROLOGIC EMERGENCIES Hypertensive encephalopathy (defined as a change in sensorium or seizure from the blood pressure elevation) warrants rapid and uniform Tintinalli_Sec07_p0329-0424.indd 402 8/2/19 6:42 PM CHAPTER 57: Systemic Hypertension 403 TABLE 57-4 Treatment of Hypertensive Emergencies by Diagnosis Diagnosis Therapy Goals Agents Risks Comments Aortic dissection Reduce shear forces by ↓ BP and PR Lower SBP to 100–120 mm Hg ↓ PR ≤60 beats/min 7,36 Esmolol* IV bolus, then continuous infusion7,36,37 OR Labetalol* IV bolus or continuous infusion7,36,37 Nicardipine IV continuous infusion (after β-blocker) 7,38 Nitroprusside continuous infusion (after β-blocker) β-blockers: Respiratory distress in asthma, COPD patients; test dose of esmolol recommended, switch to diltiazem if esmolol intolerant Measure BP in both arms and treat higher BP Always use β-blocker prior to vasodilators; nitroprusside alone increases wall stress from reflex tachycardia; cyanide and thiocyanate toxicity in patients with reduced renal function or therapy >24–48 h Acute hypertensive pulmonary edema Reduce BP by 20%–30%; diuresis through vasodilation; symptomatic relief Nitroglycerin* SL, topical, or IV continuous infusion7,39,40 Clevidipine IV continuous infusion7 Nitroprusside IV continuous infusion 7,39,40 Enalaprilat IV40 Nicardipine IV continuous infusion7 Nesiritide IV41 ACE inhibitors, can worsen renal function ACE inhibitors: Avoid hypotension and use with caution; some patients experience a negative inotropic effect Nitroprusside: Cyanide and thiocyanate toxicity in patients with reduced renal function or therapy >24–48 h IV nitrates dilate capacitance vessels at low doses; higher doses dilate arterioles and lower BP Mixed outcomes (favorable and unfavorable) with nesiritide, with most recent ASCEND-HF trial showing no difference in dyspnea and mortality when compared to placebo Acute myocardial infarction Reduce ischemia; avoid ≤25% reduction of MAP Nitroglycerin* SL, aerosol, or IV continuous infusion7,42,43 Esmolol* IV continuous infusion7 Labetalol or metoprolol IV bolus7,42,43 Do not give nitrates in patients who have taken phosphodiesterase inhibitors for erectile dysfunction ≤24 h for sildenafil and 48 h for tadalafil Do not give β-blockers in CHF, low-output states, or other contraindications to β-blockers β-blockers: Monitor for hypotension; consider RV infarct and volume depletion if this occurs SBP >180 mm Hg or DBP >110 mm Hg is a relative contraindication for thrombolytics Acute sympathetic crisis (cocaine, amphetamines, MAOI toxicity) Reduce excessive sympathetic drive and symptomatic relief Aim for SBP <140 mm Hg in the first hour Benzodiazepine* IV bolus33,44 Nitroglycerin SL, topical, or IV continuous infusion42,44 Phentolamine* IV or IM32 Nicardipine or clevidipine IV continuous infusion7 Benzodiazepines may induce respiratory depression; monitor patients closely Labetalol remains controversial, especially for cocaine-induced hypertension; if given, administer along with a nitrate Benzodiazepines are first-line agents for cocaine-induced hypertension Phentolamine is first-line therapy for pheochromocytoma Calcium channel blockers in cocaineinduced hypertension are considered third-line agents, after benzodiazepines and nitroglycerin Acute renal failure Reduce BP by no more than 20% acutely Fenoldopam IV continuous infusion 7,45 Nicardipine IV continuous infusion7,45 Clevidipine IV continuous infusion7 Avoid nitroprusside, as it results in cyanide and thiocyanate toxicity Avoid ACE inhibitors acutely Eclampsia, preeclampsia Aim for SBP <140 mm Hg in the first hour Hydralazine* IV bolus31 Labetalol* IV bolus31 Nifedipine* oral31 Hydralazine c

5 Nicardipine IV continuous infusion7,45 Clevidipine IV continuous infusion7 Avoid nitroprusside, as it results in cyanide and thiocyanate toxicity Avoid ACE inhibitors acutely Eclampsia, preeclampsia Aim for SBP <140 mm Hg in the first hour Hydralazine* IV bolus31 Labetalol* IV bolus31 Nifedipine* oral31 Hydralazine c an lead to reflex tachycardia and hypotension Labetalol may cause fetal bradycardia, and there is risk in patients with asthma, COPD, and heart failure Nifedipine may cause maternal tachycardia and overshoot hypotension Hydralazine, labetalol, and nifedipine are all considered first-line agents. Nifedipine is ideal if IV access cannot be established Contraindicated: ACE inhibitors, ARBs, renin inhibitors, and nitroprusside Hypertensive encephalopathy Decrease MAP 20%–25% in the first hour of presentation 46; more aggressive lowering may lead to ischemic infarction Labetalol IV bolus or continuous infusion Nicardipine IV continuous infusion47 Clevidipine IV continuous infusion47 Avoid β-blockers in sympathetic crisis from drugs Autoregulation of cerebral perfusion may be significantly impaired, so avoid rapid BP lowering to prevent cerebral hypoperfusion Do not give nitroglycerin 48 as it may worsen cerebral autoregulation Subarachnoid hemorrhage SBP <160 mm Hg to prevent rebleeding BP parameters have not yet been defined 49,50 Nicardipine IV continuous infusion49,51 Labetalol IV bolus, 10–20 milligrams IV, or continuous infusion 49,52 Esmolol IV bolus, then continuous infusion Clevidipine IV continuous infusion Avoid hypotension to preserve cerebral perfusion Nimodipine is used to decrease mortality. BP control is not its primary goal, but some decrease in BP may be seen Clazosentan is used with success in lieu of nimodipine and has similar hypo tensive effects53 (Continued) Tintinalli_Sec07_p0329-0424.indd 403 8/2/19 6:42 PM

Avoid hypotension to preserve cerebral perfusion Nimodipine is used to decrease mortality. BP control is not its primary goal, but some decrease in BP may be seen Clazosentan is used with success in lieu of nimodipine and has similar hypo tensive effects53 (Continued) Tintinalli_Sec07_p0329-0424.indd 403 8/2/19 6:42 PM 404 SECTION 7: Cardiovascular Disease blood pressure reduction once other neurologic emergencies, notably ischemic or hemorrhagic stroke, are excluded.46,63 Management includes cessation of inciting agents, such as che motherapy and immunosuppressants, and blood pressure control in hypertensive patients with IV nicardipine, clevidipine, labetalol, or fenoldopam. 7,47,64 Avoid nitroglycerin because it dilates cerebral arteries and alters both global and regional blood flow, which may worsen the autoregulation failure. The ideal targets for blood pressure control in subarachnoid hemorrhage and ischemic stroke are not clear and should be bal anced to avoid worsening ischemia or rebleeding. For subarachnoid hemorrhage, recommended agents include IV labetalol, nicardipine, nitroprusside, and clevidipine, with no superior agent identified to date. 49 Oral nimodipine is a good choice for those with modest blood pressure elevations because it lowers blood pressure and reduces vaso spasm and subsequent cerebral infarction rates, improving neurologic outcomes. 49,50,65 High-dose clazosentan can also decrease the incidence of vasospasm-related delayed ischemic neurologic deficits and has similar blood pressure–lowering effects as nimodipine.53 If an anticonvulsant that can also reduce blood pressure is used, such as IV phenytoin or a benzodiazepine, be cautious with additional blood pressure reduction attempts. The treatment of hypertension in patients with intracerebral hemorrhage includes labetalol, nicardipine, and esmolol. 52,55,66 Enalaprilat may also be used, but due to concerns of precipitous blood pressure drop, start with a smaller test dose (0.625 mg).66 Lowering systolic blood pressures from >180 mm Hg to 130 to 160 mm Hg may improve clinical outcomes. 54-58 In ischemic stroke, moderately elevated blood pressure may be beneficial in preserving cerebral perfusion of ischemic areas. Conversely, it may also worsen edema and contribute to hemorrhagic transformation. Ideal blood pressure ranges for ischemic stroke subtypes have not yet been determined. For the treatment of ischemic stroke, labetalol, nicar dipine, and clevidipine are the recommended agents; however, the route and degree of blood pressure reduction depend on whether the patient is a candidate for reperfusion therapy (Table 57-4). 59 Fibrinolytic therapy is contraindicated in patients with ongoing blood pressure >185/110 mm Hg after antihypertensive therapy. In patients who maintain blood pressures ≤185/110 mm Hg (with or without antihypertensive therapy) and undergo fibrinolytic therapy, blood pressure goal is ≤180/105 mm Hg for the first 24 hours. Monitor blood pressure closely from the start of recombinant tissue plasminogen activator therapy for 24 hours. PHARMACOLOGIC AGENTS Parenteral agents used for hypertensive emergencies, including dosage, mechanisms, and warnings, are listed in Table 57-4 and Table 57-5. See Chapter 19, “Pharmacology of Antiarrhythmics and Antihypertensives, ” for detailed discussion of individual agents.

asminogen activator therapy for 24 hours. PHARMACOLOGIC AGENTS Parenteral agents used for hypertensive emergencies, including dosage, mechanisms, and warnings, are listed in Table 57-4 and Table 57-5. See Chapter 19, “Pharmacology of Antiarrhythmics and Antihypertensives, ” for detailed discussion of individual agents. TABLE 57-4 Treatment of Hypertensive Emergencies by Diagnosis Diagnosis Therapy Goals Agents Risks Comments Intracerebral hemorrhage If SBP >220 mm Hg, consider aggressive management with IV infusion If SBP 150–220 mm Hg, IV boluses of antihypertensive medications should be used to acutely lower SBP to 140 mm Hg Labetalol IV bolus or continuous infusion 52,55 Nicardipine IV continuous infusion52,55 Esmolol IV bolus, then continuous infusion Drops in SBP <150 mm Hg are not associated with increased morbidity Early hemorrhage growth often occurs in first 6 h. Recent data suggest that at this time, aggressive BP control (SBP 130–139 mm Hg) diminishes hematoma growth, morbidity, and mortality 56-58 Acute ischemic stroke, rtPA candidate (BP ≤185/110 mm Hg) If fibrinolytic therapy planned, treat if BP remains >185/110 mm Hg after 3 measurements The following antihypertensive recommendations (agents section) are for immediate BP control prior to reperfusion; BP management during and after reperfusion therapy is outlined in comments section Labetalol * 10–20 milligrams IV over 1–2 min; may repeat once 55 Nicardipine* 5 milligrams/h IV infusion, titrate up by 2.5 milligrams/h every 5–15 min until desired BP is reached; maximum 15 milligrams/h Clevidipine* 1–2 milligrams/h IV infusion, double the dose every 2–5 min until desired BP is reached; maximum 21 milligrams/h Nitroprusside may be used if BP is not controlled with above agents or DBP >140 mm Hg Excess BP lowering may worsen ischemia Management of BP during and after reperfusion therapy If SBP >180–230 mm Hg or DBP >105–120 mm Hg, then consider: Labetalol 10 milligrams IV bolus followed by continuous IV infusion 2–8 milligrams/min Nicardipine 5 milligrams/h IV infusion, titrate up by 2.5 milligrams/h every 5–15 min to desired effect; maximum 15 milligrams/h Clevidipine 1–2 milligrams/h IV infusion; titrate up by doubling the dose every 2–5 min to desired effect; maximum 21 milligrams/h Acute ischemic stroke, hypertension excludes reperfusion therapy Treat if ≥220/120 mm Hg on third of 3 measurements, spaced 15 min apart; BP should be reduced by ~15% in the first 24 h Early treatment of hypertension is indicated if required by other comorbid conditions (i.e., acute coronary syndrome, aortic dissection, preeclampsia/eclampsia). Lowering by 15% acutely is probably safe Same agents and doses as above acute ischemic stroke rtPA candidate Be careful with BP control efforts in patients taking oral β-blockers or clonidine; antihypertensive withdrawal syndrome may occur. Do not lower SBP by >15% in first 24 h BP that is lower during the acute isch emic stroke than the premorbid pressure could be considered hypotension Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; BP = blood pressure; CHF = congestive heart failure; COPD = chronic obstructive pulmonary disease; DBP = diastolic blood pressure; MAP = mean arterial pressure; MAOI = monoamine oxidase inhibitor; PR = pulse rate; rtPA= recombinant tissue-type plasminogen activator; RV = right ventricular; SBP = systolic blood pressure; SL = sublingual. *Preferred agents. (Continued ) Tintinalli_Sec07_p0329-0424.indd 404 8/2/19 6:42 PM

= diastolic blood pressure; MAP = mean arterial pressure; MAOI = monoamine oxidase inhibitor; PR = pulse rate; rtPA= recombinant tissue-type plasminogen activator; RV = right ventricular; SBP = systolic blood pressure; SL = sublingual. *Preferred agents. (Continued ) Tintinalli_Sec07_p0329-0424.indd 404 8/2/19 6:42 PM CHAPTER 57: Systemic Hypertension 405 TABLE 57-5 IV Agents Used for Hypertensive Emergencies Drug Dosage Mechanism/Comments Warnings β-Blockers Labetalol Bolus: 10–20 milligrams (0.25 milligram/kg for an 80-kg patient) IV over 2 min; may administer 40–80 milligrams at 10-min intervals, up to 300 milligrams total dose. Continuous infusion: initially, 2 milligrams/min; titrate to response up to 300 milligrams total dose, if needed. Combined selective α 1-adrenergic and nonselective β-adrenergic receptor blocker with an α- to β-blocking ratio of 1:7. 67 Effect in 2–5 min, peaking by 15 min, duration 2–4 h. Renal, cerebral, and coronary blood flow maintained; minimal placental transfer. Safe in pregnancy. Avoid use in patients with bradycardia, greater than firstdegree heart block, uncompensated cardiac failure, or active bronchospasm, and in patients receiving IV verapamil or diltiazem. Caution in patients with liver impairment (effects may be prolonged); the elderly have a less predictable response and more toxicity. Esmolol Loading dose: 250–500 micrograms/kg infused over 1–3 min IV, follow with: Maintenance infusion: 50 micrograms/kg/min IV over 4 min; if adequate effect not observed, repeat loading dose and increase infusion rate using increments of 50 micrograms/kg/min IV (for 4 min). This regimen can be repeated for 4 bolus doses and to an infusion rate of 300 micrograms/kg/min. Ultra-short-acting, cardioselective, β-adrenergic receptor blocker. Onset within 60 s, duration 10–20 min. Ideal for use in patients at risk for complications from β-blockers, especially patients with mild to moderately severe left ventricular dysfunction or peripheral vascular disease. Duration 10–20 min; easily stopped. Avoid use in patients with bradycardia, heart block, car diogenic shock, decompensated cardiac failure, or active bronchospasm, and in patients receiving IV verapamil or diltiazem. Caution in patients with asthma, COPD, uncompensated cardiac failure; extravasation can lead to skin necrosis and sloughing; anemic patients will have a prolonged half-life, because drug is metabolized by red blood cell esterases. Calcium Channel Blockers Nicardipine Continuous infusion: start at rate of 5 milligrams/h. If target BP not achieved in 5–15 min, increase dose by 2.5 milligrams/h every 5–15 min until target pressure or the maximum dose of 15 milligrams/h is reached. Second-generation dihydropyridine calcium channel blocker with vascular selectivity for the cerebral and coronary arteries. Onset of action is 5–15 min; duration is 1–4 h. Avoid in patients with advanced aortic stenosis. Caution in decompensated heart failure. Avoid in patients receiving IV β-blockers. Common side effects are headache, hypotension, vomiting, and tachycardia. Clevidipine Continuous infusion: initiate infusion at 1–2 milligrams/h. Dose titration: double dose at short (90-s) intervals ini tially. As BP approaches goal, increase dose by less than doubling and lengthen time between dose adjustments to every 5–10 min. Maximum dose 32 micrograms/h; maximum duration is 72 h. Very rapid onset and offset of effect due to its ultra-short half-life, approximately 2–4 min. Clevidipine is rapidly hydrolyzed to its inactive metabolite in blood and extravascular tissues. It exerts a selective vasodilating action on arteriolar resistance vessels but has no effect on venous capacitance vessels. Its metabolism is independent of the kidney or liver.

ultra-short half-life, approximately 2–4 min. Clevidipine is rapidly hydrolyzed to its inactive metabolite in blood and extravascular tissues. It exerts a selective vasodilating action on arteriolar resistance vessels but has no effect on venous capacitance vessels. Its metabolism is independent of the kidney or liver. Cautions: Clevidipine contains approximately 0.2 gram of lipid per mL (2.0 kcal). Lipid restrictions may be necessary for patients with significant disorders of lipid metabolism. Clevidipine may produce hypotension and reflex tachycardia. Contraindicated in patients with severe aortic stenosis and egg or soy hypersensitivity. Use caution and lower doses in elderly. Vasodilators Hydralazine 10 milligrams slow IV infusion (maximum initial dose is 20 milligrams). Repeat every 4–6 h as needed. Potent direct arteriolar vasodilator with minimal effect on venous circulation. Onset begins at 10–30 min (can be sooner and precipitous); duration is 2–4 h. Safe in pregnancy. Avoid in patients with myocardial ischemia, pulmonary edema, and aortic dissection. Reflex tachycardia increases myocardial demand. Nitroglycerin Sublingual: 0.4 milligram. Paste: 1–2 in. Continuous infusion: start 5 micrograms/min, increase by 5 micrograms/min every 3–5 min to 20 micrograms/ min; if no response at 20 micrograms/min, increase by 10 micrograms/min every 3–5 min, up to 200 micro grams/min (note: many clinicians initiate with a higher infusion rate). Potent venodilator and only affects arterial tone at high doses. Onset begins at 2 min; duration is 10–20 min (paste duration 3–4 h, unless removed). Reduces BP by reducing pre load and cardiac output. Decreases coronary vasospasm and cardiac workload. Avoid in cases of compromised cerebral and renal perfusion; avoid concurrent use (within past 24–48 h) with phosphodi esterase-5 inhibitors (sildenafil, tadalafil, or vardenafil). Caution: may cause hypotension with reflex tachycardia, which is exacerbated by volume depletion. Nitroprusside Continuous infusion: 0.3–0.5 microgram/kg/min IV initial infusion, increase in increments of 0.5 micro gram/kg/min; titrate to desired effect. Rates >2 micrograms/kg/min may lead to cyanide toxicity. Use lowest possible dose. For infusions ≥4–10 micrograms/kg/min, institute a thiosulfate infusion. Arterial and venous vasodilator due to its interaction with oxyhemoglobin to produce nitric oxide. It decreases preload and after load. Onset of action is in seconds; duration is 1–2 min. Cerebral blood flow is decreased, whereas ICP is increased. Avoid in patients with kidney or hepatic failure, arteriove nous shunts, hereditary optic nerve atrophy (increases nerve ischemia), or elevated ICP. Caution: intra-arterial monitoring is recommended; must be protected from light. Nitroprusside is recommended only when other agents fail. Coronary steal syndrome may occur. Other Agents Phentolamine Bolus load: 1–5 milligrams IV; may repeat every 10 min. Continuous infusion: 0.2–0.5 milligram/min. 1- and α 2-adrenergic blocking agent; effective for pheochromocytoma and hypercatecholaminergic-induced hypertension. Myocardial infarction, cerebrovascular spasm, and cerebrovascular occlusion have occurred after administration. Fenoldopam Continuous infusion: start 0.1–0.3 microgram/kg/min, titrate by 0.05–0.1 microgram/kg/min every 15 min to desired BP. Maximum infusion rate: 1.6 microgram/kg/min. Dopamine 1 receptor agonist. Onset of action in 5 min; peak effect at 15 min; duration 30–60 min. Metabolized by liver, without P450 system. Improves creatinine clearance, urine flow, and sodium excretion. Caution: causes reflex tachycardia at higher dosages. Con current use of acetaminophen may increase fenoldopam levels. May cause flushing, dizziness, vomiting.

in 5 min; peak effect at 15 min; duration 30–60 min. Metabolized by liver, without P450 system. Improves creatinine clearance, urine flow, and sodium excretion. Caution: causes reflex tachycardia at higher dosages. Con current use of acetaminophen may increase fenoldopam levels. May cause flushing, dizziness, vomiting. Caution in patients with increased ocular pressures and ICP; caution in patients who have sulfite sensitivity (it is con tained in a solution of sodium metabisulfite). (Continued) Tintinalli_Sec07_p0329-0424.indd 405 8/2/19 6:42 PM

in 5 min; peak effect at 15 min; duration 30–60 min. Metabolized by liver, without P450 system. Improves creatinine clearance, urine flow, and sodium excretion. Caution: causes reflex tachycardia at higher dosages. Con current use of acetaminophen may increase fenoldopam levels. May cause flushing, dizziness, vomiting. Caution in patients with increased ocular pressures and ICP; caution in patients who have sulfite sensitivity (it is con tained in a solution of sodium metabisulfite). (Continued) Tintinalli_Sec07_p0329-0424.indd 405 8/2/19 6:42 PM 406 SECTION 7: Cardiovascular Disease TABLE 57-5 IV Agents Used for Hypertensive Emergencies Drug Dosage Mechanism/Comments Warnings Enalaprilat Bolus: 1.25 milligrams IV over 5 min every 4–6 h; titrate at increments of 1.25 milligrams every 12–24 h, with a maximum of 5 milligrams every 6 h. Angiotensin-converting enzyme inhibitor. Test dose of 0.625 milligram recommended when concern for first-dose hypotension exists. AVOID in pregnancy. Avoid in pregnancy and those with myocardial ischemia or bilateral renal artery stenosis. Caution: first-dose hypotension is common, especially in high-renin states; may cause dizziness and headache. Abbreviations: BP = blood pressure; COPD = chronic obstructive pulmonary disease; ICP = intracranial pressure. (Continued )  β -BLOCKERS Labetalol is unique among commonly used β-blockers because it also has modest selective α 1-inhibitory effects, with an α- to β-blocking ratio of 1:7. 67,68 It is recommended for nearly all hypertensive emergencies with the exception of cocaine intoxication and systolic dysfunction in association with decompensated heart failure. In the latter, nicardipine and clevidipine are preferred when nitroglycerin fails. Oral metoprolol use is common in patients presenting with acute coronary syndromes. Oral β-blockers improve survival, whereas mortality data are conflicting with IV formulations. 42,43 However, if blood pressure control is needed in a patient with acute coronary syndrome, use the IV formulation first, then change later. Esmolol has a short duration of action and is titratable, an advantage in patients at risk for the adverse effects of β-blockers, such as those with severe asthma and chronic obstructive pulmonary disease.  CALCIUM CHANNEL BLOCKERS Clevidipine is a third-generation dihydropyridine calcium chan nel blocker with ultra-short-acting selective arteriolar vasodilator properties. 68-70 Its advantage is its ability to be titrated with a half-life less than a minute. Nicardipine has a rapid onset of action and can be titrated at 5- to 15-minute intervals. It is safe and effective in neurologic hypertensive emergencies and has a favorable effect on myocardial oxygen balance, increasing both stroke index and coronary blood flow. Compared to labetalol, nicardipine achieves physician-specified tar geted blood pressure goals more often within 30 minutes of therapy. 67 Use oral nifedipine (10 milligrams) only in peripartum patients.31  VASODILATORS Hydralazine is a potent vasodilator with a rapid onset of action that can have an unpredictable effect on blood pressure, which may not always be dose dependent. A potentially adverse effect is reflex tachycardia, which can worsen myocardial ischemia. Given the availability of other, more easily titratable agents, it is limited to pregnancy-related care. Nitroglycerin is a potent venodilator, showing arterial dilatation only at very high doses. Use may cause hypotension and reflex tachycardia, both worsened by the volume depletion characteristic of hypertensive emer gencies. Nitroglycerin is a first-line agent only in the treatment of heart failure and acute coronary syndromes due to its favorable effects on coronary blood flow and cardiac workload. 7 Its hypotensive effects are due to its reduction of preload and cardiac output, which makes it a poor choice in other hypertensive emergencies. Sodium nitroprusside is best used when other agents fail.

heart failure and acute coronary syndromes due to its favorable effects on coronary blood flow and cardiac workload. 7 Its hypotensive effects are due to its reduction of preload and cardiac output, which makes it a poor choice in other hypertensive emergencies. Sodium nitroprusside is best used when other agents fail. It requires invasive monitoring to prevent “overshoot” in blood pressure control and has demonstrated higher mortality rates in cardiac surgery patients when compared to clevidipine. 7,71 Concerns about cyanide toxicity, heightened in patients with renal or hepatic insufficiency, and the potential for tachyphylaxis curtail use. 7 Combination therapy is the most common current use, as in aortic dissection patients who also receive esmolol to achieve blood pressure targets at lower doses.  OTHER AGENTS Fenoldopam is a unique peripheral dopaminergic-1 receptor agonist, and due to its ability to promote diuresis, natriuresis, and creatinine clearance, it is useful in renal hypertensive emergencies. 68 Phentolamine is used successfully in cocaine-, amphetamine-, and pheochromocytomarelated hypertensive emergencies and also to counteract soft tissue catecholamine injection extravasation and ischemia (by injecting in the same area). 32,68,72 Enalaprilat, the only available IV angiotensin-converting enzyme inhibitor, has special application in patients with heart failure or acute coronary syndrome, but monitor carefully because of first-dose hypotension. Clonidine, a central α 2-agonist, generally does not have a role in the treatment of patients with hypertensive emergencies except for those who have recently stopped taking the drug. The resultant rebound hypertension may be difficult to control with other agents. When used, 0.2-0.3 mg PO clonidine is a common start, with blood pressure reduction starting within 30 to 60 minutes and peaking at 2 to 4 hours. 68 In patients who are unable to take oral medications, a clonidine patch for dermal delivery is an option, although the onset of action may be delayed by 2 to 3 days and titration is challenging. For maximum absorption, apply the patch to the chest or upper arm. 68,73 Although abrupt cessation of either clonidine or a β-blocker may result in rebound hypertension, clonidine withdrawal tends to be more severe and often will not respond to therapy without reinstitution. TREATMENT OF ASYMPTOMATIC SEVERE HYPERTENSION Acute treatment of asymptomatic severe hypertension does not prevent or reduce short-term patient morbidity or mortality. 8 However, uncorrected hypertension is associated with an eventual increased risk of cardiovascular events and renal dysfunction. 74 In addition, if severe hypertension is not addressed in the ED setting, patients may not seek further outpatient blood pressure management. These considerations support initiating outpatient blood pressure reduction regimens prior to ED discharge. Table 57-6 lists oral agents commonly used for hypertension. The drugs listed are chosen for their relatively rapid onset of action and their potential use for ongoing control of chronic hypertension. Choosing an agent that can be used once daily and is inexpensive is often an ideal plan (e.g., generic hydrochlorothiazide, started at 25 milligrams daily). If choosing an angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist, check the patient’s creatinine and potassium first. DISPOSITION AND FOLLOW-UP OF ASYMPTOMATIC HYPERTENSION Table 57-7 provides a summary of the 2017 blood pressure management recommendations from the American Heart Association.

f choosing an angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist, check the patient’s creatinine and potassium first. DISPOSITION AND FOLLOW-UP OF ASYMPTOMATIC HYPERTENSION Table 57-7 provides a summary of the 2017 blood pressure management recommendations from the American Heart Association. 7 Although the American Heart Association recommendations are comprehensive, they fall short of providing common ED guidance and management of patients who present with severe hypertension with no prior history of hypertension. In all cases, reinforce the need for outpatient follow-up, with or without ED-initiated oral therapy, even if elevated blood pres sure was not part of the chief complaint. 7,75 Table 57-8 lists indications for recommended oral antihypertensive classes based on trial data and consensus guidelines. 7,75 Be sure to inform patients about potential adverse effects when pre scribing an antihypertensive medication. The most common side effects stratified by drug class are provided in Table 57-9. Pediatric regimens are in Table 57-10; start these in close consultation with a pediatrician. Tintinalli_Sec07_p0329-0424.indd 406 8/2/19 6:42 PM

m patients about potential adverse effects when pre scribing an antihypertensive medication. The most common side effects stratified by drug class are provided in Table 57-9. Pediatric regimens are in Table 57-10; start these in close consultation with a pediatrician. Tintinalli_Sec07_p0329-0424.indd 406 8/2/19 6:42 PM CHAPTER 57: Systemic Hypertension 407 TABLE 57-6 Oral Agents for Hypertensive Urgencies Agent Mechanism of Action Dosage Onset of Action Duration Contraindications Adverse Effects Carvedilol α 1-, β-Adrenergic blocker 6.25 milligrams PO 30–60 min 7–10 h Asthma, chronic obstructive pulmonary disease, bradycardia, heart block, heart failure, hepatic impairment Hypotension, bradycardia, syncope, dizziness Labetalol α 1-, β-Adrenergic blocker 200–400 milligrams PO, repeat every 2–3 h 30–120 min 6–12 h Asthma, chronic obstructive pulmonary disease, bradycardia, heart block, heart failure Bronchoconstriction, bradycardia, hyperkalemia Metoprolol β-Adrenergic blocker 50 milligrams PO Oral (IR): ≤1 h 3–4 h Asthma, chronic obstructive pulmonary disease, bradycardia, heart block, heart failure Bronchoconstriction, bradycardia, heart block, weight gain, hyperglycemia Captopril Angiotensinconverting enzyme inhibitor 12.5–25 milligrams PO 15–30 min 4–6 h Renal artery stenosis, pregnancy Acute renal failure, angioedema, side effect of chronic cough Losartan Angiotensin II antagonist 50 milligrams PO 60 min 12–24 h Second and third trimesters of pregnancy Allergic reaction (rare) Hydrochlorothiazide Ideal first choice medication in most patients, but onset of action is delayed Thiazide diuretic 25 milligrams PO 2 h; peak effect at 4 h 24 h Renal insufficiency, pregnancy Caution in diabetics; may raise glucose levels Hypokalemia, dehydration, increased uric acid levels (may precipitate gout attacks) Nifedipine (extended release) Indicated for preeclampsia only Calcium channel blocker 10 milligrams PO, may repeat every 30–60 min 5–15 min 3–6 h Angina, acute hypertension Myocardial infarction, cerebrovascular accident, syncope, heart block, CHF Clonidine Primary indication for rebound hypertension Central α 2-agonist 0.1–0.2 milligram PO 30–60 min 6–8 h CHF, second- or third-degree heart block Would not recommend as a new or singular antihypertensive agent Drowsiness, sedation, tachycardia, dry mouth Abbreviation: CHF = congestive heart failure; IR = immediate release. TABLE 57-7 Recommended Treatment Protocol for ED Patients With Increased Blood Pressure (BP)* SBP (mm Hg)   DBP (mm Hg) Follow-Up/Treatment 130–139 or 80–89 AND ASCVD † risk <10% Lifestyle modification and outpatient follow-up 130–139 or 80–89 AND ASCVD † risk ≥10% Lifestyle modification; initiate antihypertensive; follow-up in <1 month 140–179 or >90–109 Lifestyle modification; initiate antihypertensive therapy (ideally 2 agents); follow-up in <1 month ≥180 or ≥110 Evaluation for target organ damage; initiate lifestyle modification and antihypertensive therapy (ideally 2 agents); prompt outpatient follow-up (within a week) Abbreviations: ASCVD = atherosclerotic cardiovascular disease; DBP = diastolic blood pressure; SBP = systolic blood pressure. *To assess 10-year risk, please refer to http://tools.acc.org/ASCVD-risk-estimator/. †Use the lowest values for cholesterol, if unknown, to obtain a conservative risk value. Data adapted from: Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

e lowest values for cholesterol, if unknown, to obtain a conservative risk value. Data adapted from: Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 7 TABLE 57-8 Indications for Specific Antihypertensive Therapy Heart Failure Post–Myocardial Infarction High Coronary Artery Disease Risk Recurrent Stroke Prevention Diabetes Chronic Kidney Disease Blood pressure goal <130/80 mm Hg <130/80 mm Hg <130/80 mm Hg <140/90 mm Hg <130/80 mm Hg <130/80 mm Hg First-line therapy Diuretic with ACE inhibitor β-Blocker, ACE inhibitor or ARB β-Blocker, calcium channel blocker (if angina pectoris) Thiazide diuretic with ACE inhibitor or ARB Nonblack: Thiazide diuretic, ACE inhibitor, ARB, or CCB Black: Thiazide diuretic or CCB ACE inhibitor or ARB Second-line therapy β-Blocker Aldosterone antagonist ACE inhibitor, calcium channel blocker, or diuretic — Above alone or in combination Above alone or in combination with other drug class Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CCB = calcium channel blocker. Data adapted from: Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.7 Tintinalli_Sec07_p0329-0424.indd 407 8/2/19 6:42 PM