Traditionally, hypertensive crises have been divided into emergencies and urgencies. Hypertensive emergencies are severe elevations in blood pressure (BP) that are complicated by evidence of progressive target organ dysfunction, and will require immediate BP reduction (not necessarily to normal ranges) to prevent or limit target organ damage. Examples include: hypertensive encephalopathy, intracranial hemorrhage, unstable angina pectoris, or acute myocardial infarction, acute left ventricular failure with pulmonary edema, dissecting aneurysm, or eclampsia. While the level of BP at the time of presentation is usually very high (greater than 180/120 mm Hg), keep in mind that it is not the degree of BP elevation, but rather the clinical status of the patient that defines a hypertensive emergency. For example, a BP of 160/100 mm Hg in a 60-year-old patient who presents with acute pulmonary edema represents a true hypertensive emergency.

Hypertensive urgencies are severe elevations of BP but without evidence of progressive target organ dysfunction and would be better defined as severe elevations in BP without acute, progressive target organ damage. A traditional term "urgency" has led to aggressive and often excessive treatment of the majority of patients who present to Emergency Departments (ED) with severe hypertension. While these patients may present with levels of BP similar to the hypertensive emergency, and may have evidence of target organ involvement, they do not display evidence of ongoing progressive target organ damage. Most of these patients are, in fact, nonadherent to drug therapy or are inadequately treated hypertensive patients and often present to the ED for other reasons. Patients with severe elevations of BP can be managed in the ED with oral agents and appropriate follow-up within 24 hours to several days depending upon the individual characteristics of the patient. It is the correct differentiation of these two forms of hypertensive crises, however, that presents the greatest challenge to the physician.

Hypertensive crisis affects upward of 500,000 Americans each year. Although the incidence of hypertensive crisis is low, affecting fewer than 1% of hypertensive adults, more than 50 million Americans suffer from hypertension. Based on the definitions in JNC VI,¹ one recent study found that hypertensive crises accounted for more than 25% of all patient visits to the medical section of an ED.² Hypertensive emergencies accounted for one third of these cases. Although the BP level is not considered a criterion for the diagnosis of a hypertensive emergency, all patients in that study had diastolic BPs exceeding 120 mm Hg. The most prevalent associated complications included cerebral infarction (24.5%), encephalopathy (16.3%), and intracerebral or subarachnoid hemorrhage (4.5%). Acute congestive heart failure with pulmonary edema was seen in 36.8%, acute myocardial infarction or unstable angina in 12%, aortic dissection in 2%, and eclampsia in 4.5%. When considered together, hypertensive crises represented a common presentation to a large city ED. Early triage to establish the appropriate therapeutic strategies for these patients is critical to limiting morbidity and mortality.

Initial Assessment
A brief but thorough history should address the duration as well as the severity of hypertension, all current medications including prescription and nonprescription drugs and, of particular importance, the use of recreational drugs. A history of other comorbid conditions and prior cardiovascular or renal disease is essential to the initial evaluation. Direct questioning regarding the level of compliance with current antihypertensive medications may establish inadequacy of treatment or frank noncompliance.

Frequent or continuous monitoring of BP should be established. Look for historical information suggestive of neurologic, cardiovascular, and/or renal symptoms. Check for specific manifestations such as headache, seizures, chest pain, dyspnea, and edema. The clinical characteristics of a hypertensive emergency are listed in Table 1. The level of BP alone does not determine a hypertensive emergency; rather, it is the degree of target organ involvement that will determine the rapidity with which BP should be reduced to a safer level to prevent or limit target organ damage. Initial therapy will be for a presumptive diagnosis based on the information available during the initial triage evaluation.

The attached algorithm Table 2 can help the clinician identify those patients who meet the criteria of a hypertensive emergency that requires immediate admission to an ICU for continuous monitoring of BP and initiation of parenteral antihypertensive therapy.³ For patients with uncontrolled hypertension (urgency), evidence of target organ damage may or may not be present but these patients do not demonstrate any evidence of deterioration of target organ function. They can be observed for several hours in the ED during which time their oral medications can be resumed, if discontinued, or if untreated, an oral regimen can be initiated. On occasion, increasing presently inadequate dosages of medication may be appropriate. Appropriate outpatient follow-up can then be arranged within 24 hours to several days as needed, and if no prior evaluation has been performed on this patient for hypertension, an outpatient appointment should be established. Failure to follow-up on this large group of patients is a missed opportunity from the standpoint both of keeping patients in the healthcare system, and establishing optimal BP.

Physical Examination
The physical examination should begin with an assessment of BP, with an appropriate-size cuff in both upper extremities and in a lower extremity if peripheral pulses are markedly reduced. Brachial, femoral, and carotid pulses should be assessed. A careful cardiovascular examination as well as a thorough neurologic examination, including mental status, should be conducted. This assessment will aid in establishing the degree of involvement of affected target organs and should provide clues to the possible existence of a secondary form of hypertension, such as renovascular hypertension. If a secondary cause of hypertension is suspected, appropriate blood and urine samples should be obtained before aggressive therapy is initiated. A careful funduscopic examination should be performed to detect the presence of hemorrhages, exudates, and/or papilledema.

Initial Laboratory Studies
Initial laboratory studies should be limited and rapidly expedited. A urinalysis with microscopic examination of the urinary sediment, an immediate chemistry panel, and an electrocardiogram should be obtained. The urinalysis may reveal significant proteinuria, red blood cells, and/or cellular casts. Cellular casts are suggestive of renal parenchyma disease. Electrolyte abnormalities, particularly hypokalemia or hypomagnesemia, increase the risk of cardiac arrhythmias, and the chemistry panel will also provide evidence of renal and/or hepatic dysfunction. The electrocardiogram should identify evidence of coronary ischemia and/or left ventricular hypertrophy and may reveal pulse deficits, raising the question of aortic dissection. When the clinical examination suggests cerebrovascular ischemia or hemorrhage, or if the patient is comatose, a computed tomographic scan of the head should be immediately obtained.

Initial Treatment of the Hypertensive Emergency
The initial goal for BP reduction is not to obtain a normal BP but rather to achieve a progressive, controlled reduction in BP to minimize the risk of hypoperfusion in cerebral, coronary, and renovascular beds. Under normal conditions, blood flow to these organs remains relatively constant despite wide fluctuations in BP. In the presence of severe hypertension, the autoregulatory range is shifted upward so that higher levels of BP are tolerated, but organ circulation may be put at risk with sudden reductions in BP. As an example, studies on the autoregulation of cerebral blood flow suggest that the lower limit of autoregulation is about 25% below the resting mean arterial pressure in normotensive subjects and in those with uncomplicated essential hypertension. These observations have led to the suggestion that initial reduction in mean arterial pressure should not exceed 20% to 25% below the pretreatment BP. As an alternative, mean arterial pressure can be reduced within the first 30 to 60 minutes to 110 to 115 mm Hg. If this level of BP is well tolerated and the patient is clinically stable, further gradual reductions toward a normal BP can be implemented over the next 24 hours. Excessively rapid reductions in BP have been associated with acute deterioration in renal function, ischemic cardiac or cerebral events, and occasional retinal arterial occlusion and acute blindness.

A significant exception to the above recommendations should be recognized for patients with ischemic stroke, with the awareness that cerebral autoregulation is disrupted in ischemic tissue. There is no clear evidence from clinical trials to support the use of antihypertensive treatment during an acute stroke in the absence of other concurrent disorders such as aortic dissection or heart failure. Antihypertensive treatment may adversely affect cerebral autoregulation in acute stroke. Hypertension associated with an acute ischemic stroke spontaneously decreases to pre-stroke levels within several days.

How Urgent is Urgent Hypertension?
Historically, most patients seen in the ED with severe hypertension did not meet the criteria for hypertensive emergency and were therefore classified as having hypertensive urgencies. Most were treated aggressively in the ED and many were, in fact, admitted to the hospital for control of BP. The important caveat is that elevated blood pressure alone rarely requires emergency therapy. Initial triage should identify those patients who have an elevated BP without any evidence of significant target organ damage or any other impending cardiovascular events, and these patients clearly represent the majority of those seen in the ED. They are often asymptomatic and can be observed for a brief period in the ED to initiate or resume medication in the noncompliant patient or to increase dosages for those being inadequately treated. Follow-up can be arranged within several days in the outpatient department.

The occasional patient who presents to the ED with uncontrolled hypertension and symptoms such as headache, shortness of breath, or epistaxis, may benefit from observation in the ED over a period of several hours and/or an increase in current medications or added medication to further lower BP under observation and monitoring of current symptoms. When clinically stable, the patient may safely be sent home with oral agents and arrangements for follow-up. There are several oral agents available that can provide rapid response in blood pressure within one to several hours. These include agents such as the short-acting ACE inhibitor, captopril, clonidine, Labetalol, or in selected patients the alpha-adrenergic blocking agent prazosin. Some of the pharmacologic characteristics of these oral agents are listed below.

In either case, to discharge the patient from an ED without a confirmed follow-up appointment represents a missed opportunity to get that patient back into treatment for optimal control of BP, which should be a management goal. There is little justification today to admit patients with hypertensive urgency or high BP to a hospital for further evaluation and management when these issues can be efficiently and cost-effectively addressed in the outpatient setting.

Oral Agents for Severe Hypertensive
Several oral agents can be particularly appropriate for treating a hypertensive urgency in the ED.

Captopril, an angiotensin-converting enzyme inhibitor, is well tolerated and can effectively reduce BP in a hypertensive urgency.⁴ Given by mouth, captopril is usually effective within 15 to 30 minutes and may be repeated in 1 to 2 hours, depending on the response. The drug has been administered sublingually, in which case the onset of action is within 10 to 20 minutes, with a maximal effect reached within 1 hour. Responsiveness to captopril can be enhanced by the coadministration of a loop diuretic such as furosemide. Administration may lead to acute renal failure in patients with high-grade bilateral renal artery stenosis, and some reflex tachycardia may be observed.

Clonidine is a centrally acting alpha-adrenergic agonist with onset of action 30 to 60 minutes after oral administration, and maximal effects are usually seen within 2 to 4 hours. This agent is most commonly administered as a loading dose of 0.1 or 0.2 mg followed by 0.1 mg hourly for several hours until an appropriate BP level is attained. Evidence suggests that a comparable response may be seen with a single 0.2 mg dose.⁵ The most common adverse effect in the acute setting is drowsiness, affecting up to 45% of patients. Clonidine may be a poor choice when monitoring of mental status is important. Dry mouth is a common complaint, and light-headedness is occasionally observed.

Labetalol, a combined alpha- and beta-adrenergic blocking agent, can be effectively administered orally in a dose of 200 to 400 mg with BP response observed within 2 to 3 hours.⁶ However, the onset of effect may be observed within 1 to 2 hours. Like other beta-blocking agents, labetalol has the potential to induce heart block and to worsen the symptoms of bronchospasm in the asthmatic patient. Caution must be observed in patients who have more than first-degree heart block, symptomatic bradycardia, or congestive heart failure.

Prazosin is an alpha-adrenergic blocking agent that can have limited benefit in the early management of a patient with a pheochromocytoma. Side effects include first-dose syncope, palpitations, tachycardia, and orthostatic hypotension.

Parenteral Agents for Hypertensive Emergencies
Parental therapy may be initiated in the ED if suitable supervision and monitoring of BP can be provided. More appropriately, the patient should be admitted to an ICU where monitoring of BP is available. A number of parenteral agents are effective in treating hypertensive emergencies (Table 3). Labetalol is effective when administered as 20- to 40-mg bolus intravenous (IV) injections and can provide a step-wise, controlled reduction in BP to a predetermined goal. Once the goal BP is achieved, injections are stopped, and the long duration of action facilitates conversion to effective oral therapy. A continuous infusion of labetalol at 2 mg/min offers an alternative method of administration and is also associated with a gradual yet controlled reduction in BP. Since the beta-blocking effects predominate with this agent, bradycardia or heart block may be observed in patients with intrinsic heart disease.^7-9

Sodium nitroprusside has an extremely rapid onset of action, within seconds of initiating an infusion, and a rapid offset of effect within 1 to 2 minutes, which necessitates constant supervision of BP during administration. This agent is particularly effective in reducing preload and afterload in patients with impaired left ventricular function, and a carefully titrated infusion can achieve any desired goal BP. Nitroprusside does not cause sedation or somnolence but is rapidly degraded by light, requiring periodic exchange of solutions.

In patients with significant renal impairment, accumulation of a major metabolite, thiocyanate, may occur over several days with toxic effects. In the presence of poor tissue perfusion and depressed hepatic function, an intermediate metabolite in the form of cyanide can accumulate and occasionally lead to cyanide poisoning.

Nicardipine is an IV form of the dihydropyridine calcium antagonist and is effective in a high percentage of hypertensive emergencies, particularly at higher infusion rates. Its growing popularity can be attributed to its ease of administration. Infusion rates can be increased by 2.5 mg/hr at intervals of 15 to 20 minutes until the maximal recommended dosage of 15 mg/hr is obtained or until the desired reduction in BP is achieved. Dosing of nicardipine is not dependent on body weight. Nicardipine has been shown to reduce both cerebral and coronary ischemia although headache, nausea, and vomiting may occasionally be observed.

Nitroglycerin may be of particular benefit in hypertensive emergencies with coexisting coronary ischemia. Since this agent dilates collateral coronary vessels and, like nitroprusside, has a rapid onset and offset of effect, its use requires close nursing supervision. Unfortunately, at low infusion rates, nitroglycerin has its primary effect on capacitance vessels in which much higher infusion rates are required to effect arteriolar vasodilitation. Infusion rates may be increased at 3- to 5-minute intervals until the desired effect is achieved. Nitroglycerin may be particularly useful in patients with severe coronary ischemia whose BPs are only modestly elevated or in patients with acute hypertension following postcoronary artery bypass surgery. Tolerance to IV nitroglycerin may be observed within 24 to 48 hours of instituting an infusion.

Fenoldapam is a selective, peripheral dopamine₁-receptor agonist that induces systemic vasodilation, particularly in the renal circulation.¹⁰ This agent also has effects on renal proximal and distal tubules. Fenoldapam does not bind to dopamine₂ receptors or beta-adrenergic receptors; it has no alpha-adrenergic agonist effects but is an alpha₁ antagonist. This drug does not cross the blood/brain barrier.

Fenoldapam's unique effects on the kidney provide increased urine flow rate, sodium and potassium excretion, and improved creatinine clearance, making this agent particularly attractive in hypertensive emergencies associated with significant renal impairment.

Fenoldapam provides clinical effects similar to those of nitroprusside in improving cardiac hemodynamics in patients with acute congestive heart failure.¹¹ Onset of clinical effect is seen within 5 minutes, and effects tend to dissipate within 30 minutes of discontinuing the infusion. The most common side effects include headache, flushing, tachycardia, and dizziness. A dose-related increase in intraocular pressure has been observed in normotensive and hypertensive patients.¹² Inactive metabolites are eliminated in the urine, and no dosage adjustments are required for patients with renal or hepatic impairment.

Hydralazine finds limited use today in pregnant women with preeclampsia. Five to 20 mg may be administered IV as a bolus injection, and may be repeated. The major advantage is this agent's ability to improve uterine blood flow. Hydralazine is contraindicated in patients who have coronary atherosclerosis, as administration is associated with reflex tachycardia and sodium and water retention, together with intense flushing. Headache and increased intracranial pressure have also been observed.

Other Parenteral Agents
Enalaprilat is administered in an IV dose of 1.25 mg and may be repeated at 6-hour intervals. Onset of action is within 30 minutes. Response to enalaprilat in hypertensive emergencies is unpredictable, in part because of variable degrees of plasma volume expansion. This agent may be particularly suitable in hypertensive emergencies associated with congestive heart failure or with high plasma angiotensin II concentrations.

Esmolol is an ultra-short-acting beta-adrenergic blocker that is administered intravenously. Onset of effect is seen within 1 to 5 minutes, with a rapid offset of effect within 15 to 30 minutes after discontinuation. Esmolol may be administered as a 500-µg/kg bolus injection, which may be repeated after 5 minutes. Alternatively, an infusion of 50 to 100 µg/kg/min may be initiated and increased to 300 µg/kg/min as needed. Adverse effects include increased heart block, precipitation of congestive heart failure, and bronchial spasm.

Phentolamine is a nonselective alpha-adrenergic blocking agent that is still used when excess catecholamine states, such as pheochromocytoma, are suspected. It is useful as a diagnostic agent when administered as a bolus injection of 5 to 10 mg in patients with suspected pheochromocytoma. Acute BP lowering will be seen within several minutes and may last 10 to 30 minutes. Tachycardia is common and on occasion may precipitate myocardial ischemia. Nitroprusside and labetalol are more easily titrated in the management of hypertensive emergencies associated with high circulating levels of catecholamines, and therefore phentolamine is rarely used therapeutically today.

Diazoxide is rarely used any longer in the treatment of hypertensive emergencies. Although a potent vasodilator, large doses of 300 mg were often associated with severe hypotension. Smaller miniboluses of 50 mg administered at 10- to 15-minute intervals can provide controlled reduction of BP but are usually associated with reflex tachycardia, hyperglycemia, hyperuricemia, and sodium and water retention. In view of these side effects, diazoxide offers little advantage over several other agents that have more acceptable adverse-effect profiles.

Patients presenting to the ED with severe hypertension deserve prompt triage to establish the presence of a hypertensive emergency as opposed to uncontrolled hypertension. Those with hypertensive emergencies warrant prompt admission to an ICU where continuous monitoring of BP is available as well as prompt initiation of therapy with parenteral antihypertensive drugs to prevent progression of target organ damage. Most patients with uncontrolled hypertension can be managed on an ambulatory basis with initiation or adjustment of appropriate oral antihypertensive therapy. One key to the management of crises is the ensurance of appropriate follow-up care to ensure continued, optimal hypertension management.

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