I.Introduction
A.Epidemiology. More than 50 million people in the United States are diagnosed with systemic hypertension, many of whom are inadequately treated. Approximately 1% of those poorly treated progress to a crisis phase, accounting for more than 50% of all cases of hypertensive crisis. Unless promptly recognized and treated, hypertensive crisis can lead to acute central nervous system, renal, and cardiovascular dysfunction, and, possibly, death.
B.Definitions. Hypertensive crisis is defined as having either a hypertensive emergency or hypertensive urgency. According to the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure, normal blood pressure is defined as a systolic blood pressure <120 mm Hg and a diastolic blood pressure <80 mm Hg. Severe hypertension is defined as a systolic blood pressure >180 mm Hg and/or diastolic blood pressure >120 mm Hg.
1.Hypertensive emergency. Hypertensive emergency is defined as severe hypertension with evidence of acute end-organ damage, which can be manifested by a variety of syndromes (Table 34.1). Severe hypertension in the presence of chronic organ damage without associated acute manifestations does not constitute an emergency. Delineating hypertensive emergency from urgency is important because it implicates the need for immediate parenteral blood pressure lowering therapy in a monitored setting (typically intensive care unit [ICU]) to minimize tissue damage and long-term complications.
TABLE 34.1 Hypertensive Emergencies |
Severe hypertension (>180/120 mm Hg) with any of the following: |
Encephalopathy |
Acute stroke, intracranial hemorrhage, head trauma |
Acute aortic dissection |
Pulmonary edema |
Myocardial ischemia and/or infarction |
After coronary artery bypass surgery |
Postoperative bleeding at vascular suture lines |
Acute renal failure and/or hematuria and proteinuria |
Retinal hemorrhages, exudates, papilledema |
Eclampsia |
2.Hypertensive urgency. Hypertensive urgency, on the other hand, is generally defined as severe hypertension without acute end-organ damage. In the absence of symptoms or acute organ dysfunction, severe hypertension can be lowered over a period of days to weeks. Patients can be treated with oral medications and usually managed as outpatients.
3.Pseudoemergencies. Pseudoemergencies are acute rises in blood pressure attributed to a physiologic trigger, causing a massive sympathetic or catecholamine surge. These are typically seen as the result of pain, hypoxia, hypercarbia, hypoglycemia, anxiety, or a postictal state.
II.Pathophysiology
A.Autoregulation. Understanding autoregulation is the cornerstone of managing hypertensive crises safely while minimizing the risk of iatrogenic complications. The kidney, brain, fundi, and heart all possess autoregulatory mechanisms that maintain blood flow at near-constant levels despite fluctuations in blood pressure. There is a range of pressures for which the autoregulatory mechanism functions normally. In normotensive patients or in those with adequate hypertension management, this range of mean arterial pressures (MAPs) is approximately between 60 and 120 mm Hg. Loss of autoregulatory control at an MAP of 120 mm Hg in patients without preexisting chronic hypertension explains why a seemingly trivial elevation in blood pressure (160/100 mm Hg) can have severe end-organ damage. Classic examples of this phenomenon occur with acute illnesses such as acute glomerulonephritis, preeclampsia, and cocaine abuse. However, in chronically hypertensive patients the autoregulatory range is shifted to the right from arteriolar smooth muscle hypertrophy. This hypertrophy minimizes the transmission of pressure to the capillary bed, allowing tissue tolerance of higher blood pressures, but at the same time places the patient at risk for hypoperfusion if treated to normotensive pressures (Fig. 34.1). This is the reason that blood pressure should not be reduced too quickly in chronically hypertensive patients because this will result in relative hypotension causing tissue hypoperfusion. Gradual reduction in blood pressure allows the rightward-shifted autoregulatory curve to normalize as the arteriolar hypertrophy slowly regresses. Treatment must be tempered by the fact that abrupt overzealous blood pressure reduction may lead to hypoperfusion and ischemia, with potential for irreversible neurologic damage. Cerebrovascular accidents, blindness, paralysis, coma, myocardial infarction (MI), and death have been reported as consequences of overaggressive blood pressure reduction.
FIGURE 34.1 Autoregulatory cerebral blood flow response to changes in mean arterial pressure. Rightward shift of the autoregulation curve in chronically hypertensive patients. (Adapted from Strandgaard S, Olesen J, Skinhoj, Lassen NA. Autoregulation of brain circulation in severe arterial hypertension. Br Med J. 1973;1:507–510. With permission from BMJ Publishing Group Ltd.)
B.Endothelial damage. The abrupt increase in systemic vascular resistance (SVR) caused by elevated levels of circulating vasoconstrictors (e.g., norepinephrine and angiotensin II) during hypertensive crises leads to arteriolar fibrinoid necrosis and endothelial damage. This endothelial damage causes loss of autoregulatory function and the accumulation of necrotic fibrinoid debris that narrows and obliterates the vascular lumen. Target organ dysfunction ensuing from these two processes leads to further release of vasoactive substances, producing a cycle of increasing SVR, elevated systemic blood pressure, vascular injury, and tissue damage.
C.Manifestations. The endothelial damage and escape from autoregulatory control during a hypertensive crisis leads to the classic acute end-organ complications. Because the brain is encased in a finite space in the skull, the excess blood flow results in cerebral edema and elevated intracranial pressure (ICP), leading to encephalopathy and seizures. In the kidney, the fibrinoid necrosis and the excess blood flow destroy glomeruli, resulting in proteinuria, hematuria, and acute renal failure. The acute injury to the fundi is manifested by exudates, hemorrhage, papilledema, and potentially blindness. The cardiovascular system can suffer from myocardial ischemia and pulmonary edema from the increased afterload state as well as aortic dissection and hemolysis from the shear stress.
III.Etiology. It is estimated that 30% to 40% of patients with a hypertensive crisis have an identifiable underlying cause compared with <5% of those with hypertension who have not had a crisis. Evaluation for such secondary causes and precipitants is indicated in all patients with a hypertensive crisis.
A.A common scenario is that of a patient inadequately treated for chronic hypertension or one that is medically nonadherent.
B.Risk factors for progression to hypertensive crisis include male gender, black race, low socioeconomic status, cigarette smoking or other tobacco abuse, and oral contraceptive use. Unlike primary hypertension, the incidence of which increases with age, the peak incidence of hypertensive crisis occurs among people aged 40 to 50 years.
C.Underlying pathologic states that can precipitate hypertensive crises include renal parenchymal disease, renovascular hypertension, collagen vascular disease and scleroderma, pheochromocytoma, vasculitis, preeclampsia, and neurologic disorders (Table 34.2).
TABLE 34.2 Conditions That May Precipitate a Hypertensive Crisis |
Essential hypertension from undiagnosed or poorly controlled hypertension (most common) |
Nonadherence to antihypertensive medication regimen |
Renovascular disease |
Acute, as well as chronic, renal parenchymal diseases |
Acute central nervous system insults (e.g., ischemic stroke and intracranial hemorrhage) |
Drug induced (e.g., interactions, idiosyncratic reactions, exaggerated effects, and abrupt withdrawal) |
Collagen vascular disease and vasculitis (classically scleroderma) |
Preeclampsia |
Pheochromocytoma |
Obstructive sleep apnea |
D.A number of medications and illicit drugs can cause marked elevations in systemic blood pressure. The most common offenders are cocaine, oral contraceptives, sympathomimetic agents (e.g., diet pills and amphetamines), cold remedies (especially pseudoephedrine), nonsteroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, and monoamine oxidase inhibitors. Withdrawal from medications and illicit drugs can also precipitate severe hypertension. Examples include alcohol, benzodiazepine, and clonidine withdrawal.
IV.Clinical Presentation
A.History
1.Symptoms. The history should focus on the organs that are known to suffer from end-organ damage: cardiovascular, neurologic, renal, and ocular. Cardiopulmonary symptoms include shortness of breath and chest pain. Neurologic symptoms include headache, confusion, lethargy, altered mental status, nausea, and vomiting. Oliguria and change in urine color to suggest hematuria may be the symptoms volunteered by the patient if there is renal damage. Blurred vision or change in vision suggests ocular involvement.
2.Symptom chronology. Among patients with severe hypertension, symptom chronology and the duration of uncontrolled blood pressure should be elicited, because this will guide the aggressiveness of blood pressure control.
3.History of hypertension. Most patients with hypertensive crises have an underlying history of chronic primary hypertension; however, a significant proportion have secondary forms of hypertension. Age of onset of hypertension as well as other potential clues to a secondary form of hypertension should be assessed.
4.Contributory medication history may include NSAIDs, oral contraceptives, erythropoietin, psychotropic agents, monoamine oxidase inhibitors, ephedrine, cyclosporine, tacrolimus, over-the-counter cold remedies, and many other medications. Withdrawal from clonidine is always a risk factor for a crisis in hypertensive patients to whom this medication has been previously prescribed. For those on antihypertensive medications, it is crucial to elicit administration history, because a frequent, and potentially catastrophic complication occurs when severe hypotension is induced by initiation of all outpatient medications in a patient with nonadherence.
5.History of use of recreational drugs such as cocaine and amphetamines, nonprescription stimulants including sympathomimetic weight loss pills, and performance-enhancing substances for athletes is important to elicit.
6.Smoking history. Smokers are at increased risk for progression to severe hypertension, perhaps because of endothelial dysfunction and dysfunctional autoregulation.
1.Vital signs. Blood pressure is measured in both upper and lower extremities to evaluate for stenosis or dissection of the aorta or great vessels. Severe hypertension is confirmed by taking two blood pressure measurements separated by 15 to 30 minutes. No absolute level of blood pressure differentiates an emergency from an urgency. The distinction is based upon the assessment of acute end-organ damage.
2.Optic fundi are examined for signs of retinopathy, including exudates, hemorrhages, or papilledema.
3.Neurologic assessment is performed to assess mental status and neurologic motor deficits. Patients with hypertensive encephalopathy may manifest neurologic signs of confusion or seizure activity.
4.Cardiovascular and pulmonary systems are examined for the presence of an S3, S4, new murmur, and/or pulmonary edema. Total volume status should be assessed, because certain treatments can cause severe hypotension in the setting of volume depletion and other medications are less effective in the setting of fluid overload.
5.Vascular system is examined by palpation of pulses and auscultation for bruits, especially renal bruits.
V.Diagnostic Evaluation. If a hypertensive emergency is suspected, appropriate arrangements for ICU admission and parenteral treatment should not be delayed while waiting for the results of further tests. Chest pain, shortness of breath, headache, blurred vision, signs of altered mental status, focal neurologic deficits, retinal exudates and hemorrhages, crackles, an S3 gallop, and pulse deficits all point toward an emergency. Diagnostic testing can be performed after treatment has been instituted.
A.Complete blood count and blood smear. The presence of anemia with schistocytes should raise concerns for hemolysis and microangiopathic hemolytic anemia.
B.Blood chemistries to evaluate for renal function and electrolyte levels. Hypokalemia and other electrolyte disturbances may give a clue to a secondary cause of hypertension (e.g., primary hyperaldosteronism and Cushing syndrome).
C.Urinalysis to look for proteinuria, hematuria, and casts. Hematuria and moderate to severe proteinuria are surrogate markers for glomerular damage.
D.Finger-stick glucose test should be performed to exclude hypoglycemia as the cause of altered mental status in the setting of suspected hypertensive encephalopathy as well as a cause of pseudoemergency.
E.Electrocardiogram to evaluate for myocardial ischemia and chronicity of hypertension with evidence of left ventricular hypertrophy. Cardiac markers of ischemia (creatine kinase and troponin) should be checked, but troponin is a very sensitive marker and will commonly be slightly above the upper limit of normal in severely hypertensive patients. This, in isolation, should not be considered acute end-organ damage.
F.Chest radiograph assesses heart size, can confirm auscultatory findings of pulmonary edema, and may show a widened mediastinum to suggest an aortic dissection.
G.Computed tomography and/or magnetic resonance imaging (MRI) of the brain may be indicated to evaluate neurologic deficits and altered mental status, especially in the setting of suspected primary stroke, hemorrhage, or trauma.
H.A urinary toxicology screen should be collected, because cocaine and other illicit drugs frequently cause severe hypertension.
I.Prior to initiating treatment, especially in hypertensive urgencies, obtaining renin and aldosterone level measurements as well as serum and urine metanephrine samples assists with retrospective analysis for a secondary cause of hypertension. Many of the medications used to treat hypertension (β-blockers, diuretics, and angiotensin-converting enzyme [ACE] inhibitors) confound the interpretation of these tests. This diagnostic evaluation should never delay treatment of a patient presenting with hypertensive emergency.
J.After appropriate management and resolution of the crisis, workup for common secondary causes of hypertension should be performed. Renovascular hypertension is very commonly seen in these patients. In addition, primary hyperaldosteronism, coarctation of the aorta, obstructive sleep apnea, and Cushing syndrome are frequently undiagnosed and should be investigated if the particular patient has suggestive features.
VI.Therapy. The presence of acute or rapidly progressive end-organ damage, and not the absolute blood pressure reading, determines whether the situation is an emergency or an urgency. This determination dictates the type of treatment (i.e., parenteral or oral) and the setting (i.e., ICU, hospital ward, or outpatient) in which it is implemented. Management of acute hypertensive syndromes should be tailored to each patient and based on the presence, absence, and type of end-organ damage. For example, a blood pressure of 130/90 mm Hg may represent a hypertensive emergency for a patient with an aortic dissection, whereas a blood pressure of 200/120 mm Hg for a patient with asymptomatic chronic hypertension without acute end-organ dysfunction does not necessitate emergent parenteral therapy.
A.Hypertensive emergencies
1.Goals of therapy include immediate but controlled reduction of the MAP. The pharmacologic characteristics and potential toxic side effects of antihypertensive agents must be understood and anticipated.
a.Patients are treated in an ICU, where clinical status and vital signs can be constantly monitored with the aid of an intra-arterial line.
b.Blood pressure is reduced in a controlled and predictable manner. It is recommended that blood pressure be reduced initially by no more than 25% of MAP over minutes to hours. After the first 24 hours, further reductions should occur over days to weeks in order to allow the autoregulatory mechanisms to reset. Exceptions include aortic dissection, postoperative bleeding, and pulmonary edema, all of which demand more aggressive blood pressure reduction to prevent catastrophic complications.
2.Medical therapy. A number of parenteral antihypertensive medications are available to manage hypertensive emergencies. Characteristics of an ideal agent include rapid onset and cessation of action, a predictable dose–response curve, and minimal side effects. Table 34.3 lists parenteral antihypertensive agents, dosages, side-effect profiles, and specific indications.
TABLE 34.3 Parenteral Medications Used to Manage Hypertensive Emergencies |
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Drug |
Dosage |
Onset/Duration |
Indications |
Side Effects |
Nitroprusside sodium (Nipride, Nitropress) |
Infusion: 0.25–10 µg/kg/min |
Immediate/3–5 min |
Most emergencies |
Nausea, vomiting, sweating, thiocyanate, and cyanide poisoning |
Nitroglycerin (a.k.a. glyceryl trinitrate) (Nitro-Bid) |
Infusion: 5–200 µg/min |
Immediate/3–5 min |
Myocardial ischemia, MI, left ventricular failure |
Headache, methemoglobinemia, tolerance with prolonged infusion |
Labetalol (Normodyne, Trandate) |
Bolus: 20 mg/5 min until desired effect (max 80 mg) Infusion: 1–2 mg/min |
5–10 min/1–8 h |
Most emergencies except those complicated by left ventricular failure |
Heart block, orthostatic hypotension |
Nicardipine (Cardene) |
Infusion: 5–15 mg/h |
5–10 min/1–4 h |
Most emergencies except those complicated by left ventricular failure |
Reflex tachycardia, headache, nausea, flushing Avoid in heart failure |
Clevidipine (Cleviprex) |
Bolus: 1–2 mg/h with potential doubling every 90 s for desired effect |
2–4 min/5–15 min |
Most emergencies except those complicated by left ventricular failure |
Avoid in heart failure |
Phentolamine (Regitine) |
Bolus: 5–15 mg IV Infusion: 0.2–5.0 mg/min |
1–2 min/3–10 min |
Pheochromocytoma crisis Crisis because of catecholamine excess |
Tachycardia, headache, flushing |
Hydralazine (Apresoline) |
Bolus: 10–20 mg IV every 30 min until desired effect achieved or side effects occur |
10–20 min/3–8 h |
Eclampsia |
Marked hypotension, tachycardia, flushing. Contraindicated in myocardial ischemia, aortic dissection, and elevated ICP |
Enalaprilat (Vasotec IV) |
1.25–5 mg every 6 h |
15 min/6 h |
Scleroderma crisis, left ventricular failure |
Marked decreases in blood pressure in high-renin states, renal failure, hyperkalemia |
Fenoldopam (Corlopam) |
Infusion: 0.1–0.3 µg/kg/min |
<5 min/30 min |
Most emergencies, renal insufficiency |
Tachycardia, headache, nausea, flushing Caution with glaucoma |
ICP, intracranial pressure; IV, intravenous; MI, myocardial infarction.
a.Sodium nitroprusside is the drug of choice for most hypertensive emergencies. This is due to its favorable hemodynamic profile, rapid onset, and rapid cessation of action. A potent, direct vascular smooth muscle relaxant, nitroprusside decreases afterload and preload by means of dilating arterioles and increasing venous capacitance. Hemodynamic effects include a decrease in MAP, afterload, and preload; renal blood flow and renal function may improve if cardiac output improves. Although the direct cerebral vasodilation by nitroprusside may cause an adverse increase in cerebral perfusion, this is counteracted by a potent effect on MAP. Most patients with a neurologic crisis who need blood pressure control tolerate nitroprusside without a worsening of neurologic status. Unlike intravenous nitroglycerin, nitroprusside does not raise ICP or cause headaches. However, the theoretical possibility of an increase in cerebral blood flow as well as increased ICP must be kept in mind if there is further clinical deterioration despite a decrease in the MAP when using this agent.
(1)Administration. Sodium nitroprusside must be administered by constant intravenous infusion in an intensive care setting with invasive arterial blood pressure monitoring. It has a very rapid onset of action, and its effect ceases within 1 to 5 minutes of stopping the infusion.
(2)Side effects. Red blood cells and muscle cells metabolize nitroprusside to cyanide, which is converted to thiocyanate in the liver and excreted in the urine. Thiocyanate levels rise in patients with renal insufficiency, and cyanide accumulates in patients with hepatic disease. Signs of thiocyanate toxicity include nausea, vomiting, headache, fatigue, delirium, muscle spasms, tinnitus, and seizures. Monitoring for signs and symptoms of toxicity and maintaining thiocyanate levels at <12 mg/dL allow safe use of nitroprusside. Risk factors for cyanide poisoning include treatment time >48 hours, renal insufficiency, and doses greater than 2 µg/kg/min. Severely affected patients can be treated with a sodium thiosulfate infusion. Thiocyanate toxicity is extremely rare in the extensive experience with nitroprusside at our institution.
b.Labetalol is useful in most hypertensive crises. The main disadvantage is its relatively long duration of action. Labetalol is an α-blocker and nonselective β-blocker. When given through continuous intravenous infusion, the relative β- to α-blocking effect of labetalol is 7:1.
(1)The hemodynamic effects of labetalol include a decrease in SVR, MAP, and heart rate and a decrease or no change in cardiac output. Cardiac output is often spared because the decrease in stroke volume from the β-blockade is offset by the decrease in afterload from the α-blockade. Labetalol has little direct effect on cerebral vasculature, does not increase ICP, and is considered by some to be the drug of choice in situations characterized by markedly elevated ICP. Labetalol begins to lower blood pressure within 5 minutes, and its effects can last 1 to 3 hours after cessation of the infusion.
(2)Contraindications. Labetalol is contraindicated for patients with acutely decompensated heart failure, cardiogenic shock, bradycardia, second- or third-degree heart block, and severe reactive airway disease known to be exacerbated by β-blockers. Labetalol should not be used without prior α-blockade in patients with heightened adrenergic tone including pheochromocytoma and cocaine overdose because inadequately blocked α-activity can increase blood pressure when β-blockade is incomplete.
c.Nitroglycerin is an important drug for managing hypertension in the setting of myocardial ischemia, acute MI, and acute cardiogenic pulmonary edema (ACPE). It is primarily a venodilator and has modest effects on afterload at high doses. The decrease in preload and afterload decreases myocardial oxygen demand. Nitroglycerin also dilates the epicardial coronary arteries, inhibits vasospasm, and favorably redistributes blood flow to the endocardium. Nitroglycerin directly increases cerebral blood flow, raises ICP, and is not used in situations initially characterized by high ICP. Tachyphylaxis to nitroglycerin is well known, and it is not uncommon for the blood pressure to rebound after prolonged administration. Headache is the most frequent side effect. Tachycardia resulting from reflex sympathetic activation may also occur.
d.Fenoldopam is a selective peripheral dopamine-1-receptor agonist approved for the management of severe hypertension. Fenoldopam is an arterial vasodilator with a rapid onset of action and a relatively short half-life when administered intravenously. It may be of particular benefit in patients with renal insufficiency, because it has been shown to improve renal perfusion. Fenoldopam may cause reflex tachycardia, which can be blunted by the concomitant use of a β-blocker. Fenoldopam is contraindicated in patients with glaucoma, because it can increase intraocular pressure. It is a potent systemic vasodilator and is used primarily by anesthesiologists to control blood pressure intraoperatively.
e.Nicardipine. As a dihydropyridine calcium channel blocker, nicardipine inhibits vascular smooth muscle contraction but has little to no activity on the heart’s atrioventricular or sinus nodes. It is particularly useful in the setting of postoperative hypertensive crises and neurologic scenarios, because it does not raise ICP and directly reduces cerebral ischemia. It is contraindicated in advanced heart block, acute MI, and renal failure. It is administered via a continuous intravenous infusion. In headtohead comparisons, nifedipine has shown similar safety and efficacy to labetalol, although nifedipine appears to provide more predictable and consistent BP control. Clevidipine is a short-acting dihydropyridine calcium channel blocker administered as a continuous infusion that does not cause reflex tachycardia. Its benefit over nicardipine is that the half-life is shorter and thus relative hypotension can be reversed quickly with cessation of the infusion. Clevidipine is contraindicated in patients with disordered lipid metabolism and should be used with caution in combination with propofol because it is administered in a lipid-laden emulsion.
f.Enalaprilat. This is a short-acting intravenous ACE inhibitor that lowers blood pressure abruptly. It is not widely used in hypertensive emergencies, because it can precipitate hypotension, particularly in volume-depleted patients or those with renal artery stenosis. ACE inhibitors are first-line therapy for the management of scleroderma renal crisis.
g.Hydralazine. Although very commonly administered, the role of intravenous hydralazine in hypertensive emergency should be limited to the treatment of pregnant women with preeclampsia and eclampsia. Hydralazine is a direct arterial vasodilator with no effect on venous capacitance. It crosses the uteroplacental barrier but has minimal effects on the fetus. It is usually administered in intravenous boluses of 10 to 20 mg and has a long duration of action. Hydralazine decreases SVR, induces compensatory tachycardia, and increases ICP. It can exacerbate angina and is contraindicated in the care of patients with ongoing coronary ischemia, aortic dissection, or increased ICP.
h.Clonidine. Clonidine should be used primarily in cases where the cause of hypertensive emergency is clonidine withdrawal.
B.Oral agents. Once the blood pressure is controlled parenterally, switching to an oral regimen that benefits the patient in the long term, based on their particular comorbidities, is recommended. In chronically hypertensive patients, this usually requires at least two antihypertensive medications. Increasing the dose of existing medications or reinitiating therapy in nonadherent patients is appropriate.
C.Management of specific emergencies
1.Neurologic emergencies. Patients with neurologic findings and severe hypertension present a particular challenge. Neurologic emergencies can be the result of a hypertensive emergency that will then be exacerbated by the elevated blood pressure or the result of a primary neurologic insult that causes markedly elevated blood pressures to maintain necessary perfusion. One key differentiating point is that neurologic alterations caused by severe hypertension are reversed when blood pressure is controlled appropriately, whereas primary neurologic disorders typically do not improve with blood pressure control.
a.Hypertensive encephalopathy. This condition occurs when cerebral edema is induced by markedly elevated blood pressures that overwhelm the autoregulatory capabilities of the brain and is characterized by headache, irritability, and an altered state of consciousness. The treatment of choice is sodium nitroprusside or labetalol. Agents that depress the sensorium or increase ICP (i.e., intravenous nitroglycerin) should be avoided. Mental status will classically revert to normal within hours of blood pressure reduction. If there is no improvement despite an appropriate decrease in blood pressure, the diagnosis must be reconsidered and concern should be for a primary neurologic insult causing secondary hypertension. During the neurologic workup, an MRI of the brain may reveal white matter edema in the parieto-occipital regions, termed reversible posterior leukoencephalopathy syndrome. Occasionally, hypertensive encephalopathy will manifest as seizures. Along with appropriate blood pressure control, concurrent anticonvulsive therapy to terminate active seizures is appropriate; however, chronic antiepileptic therapy is not necessarily indicated because treatment of the hypertension prevents further events.
b.Ischemic stroke. Although hypertension is a risk factor for ischemic strokes, the management of hypertension in the setting of an acute stroke is controversial. The elevated blood pressure is thought to be protection from hypoperfusion because of vasodilation in the peri-ischemic regions. In general, patients should not be treated unless their blood pressure is >220/120 mm Hg or they have evidence of acute end-organ damage elsewhere (e.g., aortic dissection and myocardial ischemia). In addition, in those that are eligible for thrombolytic therapy, a blood pressure < 185/110 mm Hg is required. The goal reduction is 15% in the first 24 hours. Labetalol is the preferred agent, with calcium channel blockers being acceptable alternatives.
c.Intracranial hemorrhage. Intracerebral hemorrhage and subarachnoid hemorrhage (SAH) are often associated with severe hypertension. Similar to an ischemic stroke, the increased blood pressure is thought to be protective. Because of the blood within the skull, ICP increases. In order to maintain the necessary cerebral perfusion pressure (CPP) of 60 to 80 mm Hg in the setting of elevated ICP, an increase in MAP is necessary (CPP = MAP − ICP). Neurology consultation along with neuroimaging and intracerebral pressure monitoring is frequently used to guide blood pressure management. Nimodipine is considered the standard of care for SAH, because it prevents vasospasm commonly seen in this condition.
2.Cardiovascular emergencies
a.Aortic dissection. As opposed to most other presentations of hypertensive emergency when appropriate care requires that blood pressure be normalized slowly, in the setting of an acute aortic dissection, blood pressure must be corrected immediately. Patients with a type A dissection have a mortality rate of 1% per hour in the first 48 hours unless medical therapy is instituted rapidly and the patient is referred for emergency surgical intervention. In the setting of an uncomplicated type B dissection, antihypertensive therapy aimed at reducing vascular resistance and shear force on the vessel wall is the treatment of choice. Aortic dissections require decreased vascular shear force by means of reducing the inotropic state of the heart and the ratio of change in ventricular pressure to the change in time (dP/dt). This should be accomplished via β-blockade prior to vasodilation in order to prevent reflex tachycardia and increases in dP/dt. Aggressive blood pressure reduction is indicated, even for patients with normal blood pressure, because shear force and afterload must be maximally reduced to prevent extension of the dissection and/or aortic rupture. A systolic blood pressure between 100 and 110 mm Hg (or lower if tolerated) with a heart rate between 50 and 60 beats/min is the goal. Suspect hemopericardium with tamponade or aortic rupture if hypotension is present prior to initiating therapy. Sodium nitroprusside with an intravenous β-blocker (metoprolol) is the treatment of choice at our institution. Continuous infusion with labetalol is sometimes used because of its combined effects on myocardial contractility as well as SVR but the fixed β-blockade to α-blockade ratio makes independent titration of blood pressure and heart rate challenging. Fenoldopam, esmolol, and diltiazem infusions are other options.
b.Acute cardiogenic pulmonary edema. Often termed flash pulmonary edema, ACPE because of severe hypertension is best treated with sodium nitroprusside or nitroglycerin. Because of the pulmonary edema, a common reflexive action is to administer intravenous loop diuretics; however, this may have deleterious effects downstream. Accepting this seemingly paradoxical statement requires insight into the pathophysiology of pulmonary edema in this particular setting. The patients at risk for ACPE tend to be older in age with long-standing hypertension or diabetes, all of which impair diastolic function. The acutely elevated blood pressure results in left ventricular afterload mismatch; left ventricular end-diastolic pressure suddenly rises with concomitant elevation of the pulmonary venous pressure. On the pulmonary capillary level, increased Starling forces cause transcapillary leak and, ultimately, pulmonary edema. If the patient is euvolemic prior to the acute pressure change, then the pulmonary edema is due to maldistribution of the intravascular volume and not due to total body volume overload. Intravenous loop diuretics may have an initial beneficial venodilatory effect, but the subsequent volume depletion can cause future hemodynamic side effects. Thus, treatment should be aimed at decreasing the acute pressure overload and afterload mismatch, which will reverse the fluid shift in a time frame similar to the rate of decompensation. If nitroprusside or nitroglycerin infusions are not immediately available in this setting, nitroglycerin tablets can be given sublingually with repeated administration until goal blood pressure is achieved. Because the ACPE is often due to rapid onset of pressure overload and not due to chronically elevated blood pressure, normalization of the blood pressure in this hypertensive emergency is well tolerated without ischemic risks. It is not uncommon to see immediate relief of dyspnea and hypoxia in a patient with florid pulmonary edema once the blood pressure is lowered. β-Blockers and calcium channel blockers must be avoided in the decompensated state because the impaired inotropy and chronotropy will exacerbate the already afterload-burdened ventricle.
c.Myocardial ischemia. Preload, afterload, contractility, and heart rate determine myocardial oxygen consumption. Elevated blood pressure, and thus afterload, can induce ischemia from the increased oxygen demand. In addition, the significantly elevated blood pressure can rupture stable coronary plaques, resulting in an MI. Blood pressure reduction with nitroglycerin is the treatment of choice. Nitroprusside is added if further blood pressure reduction is required. Heparin infusion should not be started with uncontrolled systolic blood pressures (190 mm Hg or greater), because the risk of intracerebral bleeding is significant.
d.Postoperative bleeding. Postoperative bleeding from vascular suture lines should be treated with immediate normalization of blood pressure, similar to an aortic dissection. Parenteral treatment with sodium nitroprusside, nicardipine, or labetalol is preferred. After coronary bypass grafting, nitroglycerin is considered the initial drug of choice to maximize cardiac perfusion.
3.Pregnancy. In addition to delivery of the fetus and placenta in preeclampsia, intravenous magnesium therapy is the treatment of choice to prevent progression to eclampsia. Labetalol or hydralazine, combined with a β-blocker to prevent reflex tachycardia, can be used safely in pregnancy. ACE inhibitors and angiotensin receptor antagonists are contraindicated. Target blood pressures in pregnancy are 130 to 150 systolic and 80 to 100 diastolic.
4.Pheochromocytoma. Phentolamine is an intravenous α-adrenergic blocker useful in cases of pheochromocytoma because it is effective in cases of catecholamine excess. β-Blockers should never be used in isolation because they can cause a paradoxical increase in blood pressure because of the effects of unopposed α-receptor stimulation from circulating catecholamines.
D.Hypertensive urgencies. Most patients diagnosed with hypertensive urgency actually have chronically severe hypertension and are not in any immediate danger of progressing to hypertensive emergency. They are often people with chronic hypertension who are suboptimally treated or nonadherent. As previously mentioned, the key to distinguishing hypertensive emergency from urgency is to assess whether there is evidence of acute end-organ damage.
1.Goal of therapy
a.Hypertensive urgencies can often be managed with oral medication without admission to the hospital. End-organ damage is not imminent, and blood pressure can be lowered modestly over a period of hours as long as adequate follow-up care is ensured. The greatest danger lies in overtreating these patients and inciting hypotensive complications. However, even in the absence of acute end-organ dysfunction, hospital admission should be considered for patients with a diastolic blood pressure >140 mm Hg, those with a high risk of cardiovascular complications (known coronary disease or previous stroke), or those with uncertain outpatient follow-up.
b.Because hypertensive urgencies can have significant morbidity if treated aggressively, lower initial doses of antihypertensive medications are used to treat patients with known cerebrovascular disease or coronary artery disease or who are volume depleted. These patients tend to have exaggerated responses to drug therapy. In addition, they are also especially vulnerable to the effects of hypotension. Monitoring for 4 to 6 hours is necessary to judge treatment effect and to look for complications. Urgent follow-up care is mandatory within 24 to 48 hours. In general, blood pressure should be lowered to <160/<100 without overly rapid correction as noted above. Patient-specific optimal blood pressure goals can then by achieved over the next 2 to 3 months.
2.Drug therapy. In adherent patients already prescribed with antihypertensive medications, increasing the dose of a current medication is usually sufficient. If initiation of a new agent is required, the choice should be a medication that benefits the patient in the long term; therefore, underlying comorbidities should be taken into account. The medications commonly used for hypertensive urgencies include captopril, long-acting nifedipine, and oral labetalol.
a.Captopril. Considered by some to be the drug of choice, captopril is the fastest acting oral ACE inhibitor. At small doses, it rarely causes marked hypotension, although this potential exists in patients who are markedly volume depleted or who have renal artery stenosis. Captopril begins to work within 15 to 30 minutes of ingestion and the duration of activity is 4 to 6 hours. An initial dose of 6.25 mg should be given and if hypotension does not occur within 1 to 2 hours, the patient will tolerate doses of 12.5 to 25 mg three times daily.
b.Nifedipine. The short-acting and sublingual forms of nifedipine should not be used, because profound hypotension is easily precipitated. The long-acting form is a potent antihypertensive medication and should be initiated at 30 mg daily with uptitration as an outpatient. The onset of action is not as quick as labetalol or captopril but the daily dosing is favorable for adherence.
c.Labetalol. A combined α-blocker and β-blocker, labetalol taken orally has a relative β-blocking to α-blocking effect of approximately 3:1. Dosage begins at 100 mg (taken orally twice daily) and is titrated to the desired response. The onset of action is 30 minutes to 2 hours after administration; the duration of action is 8 to 12 hours.
VII.Prognosis. The prognosis of a patient with an untreated hypertensive crisis is poor. Before the introduction of effective antihypertensive agents, 1-year mortality exceeded 80% and 5-year mortality was approximately 99%. In the modern era of effective antihypertensive medications, 10-year survival has improved to 70%. However, patients presenting with hypertensive crises have increased risk for future cardiovascular events despite a lower prevalence of overall cardiac risk factors. Therefore, appropriate recognition of these clinical syndromes coupled with the treatment of blood pressure in a safe and controlled manner is paramount to significantly improve outcomes for these once mortal conditions.
ACKNOWLEDGMENTS: The author thanks Drs. John H. Chiu, Harpreet Bhalla, Daniel Cantillon, and Kia Afshar for their contributions to earlier editions of this chapter.
Key Reviews
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Landmark Articles
Amraoui F, Van Der Hoeven NV, Van Valkengoed IG, et al. Mortality and cardiovascular risk in patients with a history of malignant hypertension: a case-control study. J Clin Hypertens. 2014;16:122–126.
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Relevant Book Chapters
Victor RG. Systemic hypertension: mechanisms and diagnosis. In: Mann DL, Zipes DP, Libby P, Bonow RO, ed. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia, PA: WB Saunders; 2015:934–952.