Chapter 14. Hypertensive Crises

Hypertension is a common finding in patients presenting to the emergency department. The clinical context in which this is seen can represent a broad spectrum of disease: from asymptomatic individuals incidentally noted at triage to have elevated blood pressures to critically ill patients with hypertension-induced damage to critical organs. Determining the best management approach to such patients represents a significant challenge, as well as a frequent source of controversy, to emergency medicine and critical care clinicians.

A number of questions face the practitioner, including whether or not blood pressure reduction will be helpful or harmful, how quickly and to what level the blood pressure should be reduced, and what the appropriate agent is to use for a given situation. Additionally, the presence of preexisting conditions needs to be considered when making treatment decisions, as well as the patient's baseline blood pressure.

The diagnostic and therapeutic approach should not be algorithmic, guided strictly by numbers. Instead, clinicians should base their clinical decisions on a number of principles, most importantly the presence or absence of end-organ damage. Always treat the patient, not the number.

Hypertension is an increasingly important health care issue, with more than 50 million people in the United States having high blood pressure needing treatment.1 The prevalence increases with age, with more than half of people between the ages of 60 and 69 affected, increasing to more than three quarters of people over the age of 70.1 Elevated blood pressures are noted in more than 25% of all patients presenting to the emergency department.2,3 The ability to rapidly recognize and, when necessary, appropriately treat hypertension is therefore a critical skill for any practitioner in the emergency department or the intensive care unit (ICU).

Essential to appropriate management is first obtaining an accurate measurement. Patients should be seated for at least 5 minutes prior to the measurement being taken, with feet on the floor and arm supported at heart level. The auscultatory method should be used, and should be performed by a trained practitioner. The cuff bladder should encircle at least 80% of the arm, and at least two measurements should be performed with the average recorded.1

Hypertension can be broadly divided into primary (“essential”) and secondary hypertension. Essential hypertension, for which no cause is found, accounts for more than 90% of the cases of hypertension.4 Many pathophysiologic causes have been hypothesized, but generally it is believed that the primary cause is through renal mechanisms amplified by sympathetic nervous system activity and vascular remodeling. Essential hypertension has a tendency to cluster in families, often in association with other genetically inherited syndromes.4

Secondary hypertension can occur through a variety of causes. Renovascular disease, such as that due to renal artery stenosis or fibromuscular dysplasia, should be suspected in any young patient with hypertension or any patient with rapidly progressive symptoms. Decreased pressures in the lower extremities or delayed femoral pulses should raise the suspicion for coarctation of the aorta. Excessive glucocorticoids, most commonly a result of iatrogenic steroid administration, are also associated with hypertension. Physical signs and symptoms such as truncal obesity, glucose intolerance, and purple striae should suggest the diagnosis. Labile blood pressures with associated paroxysmal headaches, palpitations, pallor, and diaphoresis should raise the suspicion of pheochromocytoma.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), released in 2003, introduced a new classification for defining hypertension.1 Blood pressure between 120 and 139 mm Hg systolic, and/or between 80 and 89 mm Hg diastolic, is now termed “prehypertension.” Stage 1 hypertension is now defined as systolic between 140 and 159 mm Hg and/or diastolic between 90 and 100 mm Hg. And systolic greater than 160 mm Hg and/or diastolic greater than 100 mm Hg is now classified as stage 2 hypertension.

Acute severe elevations in blood pressure can be classified in a number of ways. Most commonly, practitioners consider hypertensive “emergency” to be uncontrolled hypertension in the setting of end-organ damage, particularly damage to the renal, cerebral, or cardiovascular systems. Hypertensive “urgency,” on the other hand, is generally defined as severe acutely elevated BP without evidence of acute organ damage. What constitutes “severely elevated” varies among practitioners, but is defined by JNC 7 as blood pressure greater than 180/120 mm Hg.1

The distinction between hypertensive emergency and urgency is critical as it dictates the timing and goals of blood pressure reduction, the need for parenteral versus oral agents, and the appropriate disposition on leaving the emergency department.

The majority of patients presenting to the emergency department with hypertensive urgency have previously diagnosed hypertension and most often present in the setting of various painful symptoms.5 The level of hypertension necessitating treatment, and the choice of agent used, varies among practitioners.5 However, most would agree that, in the absence of end-organ damage, blood pressure should not be normalized in the emergency department but instead should be controlled over a period of several days through the use of oral agents.33

The treatment strategy in the emergency department should begin with attempts to alleviate pain and anxiety, including providing patients with a quiet room if possible. These interventions alone may decrease the blood pressure to acceptable levels. If the patients are already being treated for hypertension, their home blood pressure medications should be given if they have not already taken them that day. If they have been compliant with their home medications, an increase in dosage can be considered or an additional agent added to their home regimen, although this should ideally be done in coordination with their primary physician.

If a decrease in blood pressure is desired over a period of hours to acceptable levels in the emergency room, oral agents such as clonidine (0.1–0.2 mg) or captopril (12.5–25 mg) may be given. However, such patients should be observed for several hours in the emergency department after drug administration.

Discharge home may be considered if the patient can be relied upon to closely follow up with his or her primary doctor within the next several days and no other compelling reason exists to admit to the hospital. All patients should be counseled on lifestyle modifications including weight loss, dietary sodium restriction, and regular aerobic activity.

It is important to note that absence of end-organ damage does not necessarily signify the absence of symptoms. Patients with hypertensive urgency may present with headache, epistaxis, anxiety, or other symptoms attributable to the elevated blood pressure. However, excessive and overly rapid correction of blood pressure elevations in such patients could precipitate ischemia to vital organs and should be avoided.

Hypertensive emergency is generally defined as uncontrolled hypertension in the setting of end-organ damage, and treatment with titratable intravenous (IV) agents should be instituted immediately. The choice of agent and the goals of therapy should be based on the specific clinical presentation and are summarized in Table 14-1. Patients with a hypertensive emergency should receive an ICU consultation.

Critical to the management of any hypertensive emergency is understanding the concept of autoregulation. Autoregulation is the ability of an organ to maintain a near-constant blood flow despite variations in perfusion pressure. The autoregulatory response is intrinsic to the specific organ's vascular bed, and is independent of neural or humoral factors. Although examples of autoregulation can be seen throughout the body, it is most prominent in the cerebral, coronary, and renal vascular beds.

However, autoregulation is only maintained over a certain range of perfusion pressures. Outside of this range, changes in blood pressure are directly reflected in the microvasculature. This leads to ischemia in the setting of hypotension, and hyperperfusion injury in the setting of hypertension. Additionally, chronic hypertension can cause this autoregulatory range to be shifted to a higher range of pressures. Attempting to rapidly normalize elevated blood pressures in such patients may in fact lead to hypoperfusion and ischemia.

Hypertensive Encephalopathy

Under normal conditions, cerebral perfusion is maintained relatively stable over a wide range of blood pressures, due to the ability of the brain to autoregulate its blood flow. Hypertensive encephalopathy results from a cerebral perfusion pressure above this level of autoregulation, and represents a true medical emergency.

The precise pathophysiology of hypertensive encephalopathy is not completely understood. With sudden elevations of blood pressure, the ability of the brain to autoregulate its blood flow is lost, resulting in vasodilation, breakdown of the blood–brain barrier, and cerebral edema. It has been linked to the reversible posterior leukoencephalopathy syndrome,7 in which acute elevations in blood pressure lead to white matter edema mostly in the posterior parietal–temporal–occipital regions of the brain. In both conditions, symptoms can be rapidly reversed with appropriate and timely lowering of blood pressure. However, if inadequately treated, these symptoms can progress to cerebral hemorrhage, coma, and death.6

No exact value of blood pressure is pathognomonic for hypertensive encephalopathy, although cerebral autoregulation can be overwhelmed at mean arterial pressures (MAPs) as low as 120 mm Hg in previously normotensive individuals.6 However, individuals with chronic hypertension often have autoregulatory curves that have been shifted to higher pressures, and may not develop symptoms of hypertensive encephalopathy until MAPs have exceeded 150 mm Hg or higher.

Clinically, hypertensive encephalopathy is manifested by symptoms of headache, nausea, lethargy, altered mental status, and seizures. When associated with the reversible posterior leukoencephalopathy syndrome, symptoms may also include visual abnormalities, including cortical blindness, homonymous hemianopsia, and blurred vision.7 On physical exam, signs of increased intracranial pressure (ICP) such as papilledema may be seen. Focal neurologic deficits are generally not found on exam, although they may occur if hemorrhage or infarction occurs. The differential diagnosis is wide and includes intracerebral hemorrhage, brain tumor, meningoencephalitis, toxidromes, and CVA.

Hypertensive encephalopathy represents a true medical emergency, and efforts at blood pressure reduction should begin immediately when this is suspected. An initial goal blood pressure reduction of 20–25% is generally advised, or a goal diastolic of 100–110 mm Hg. A titratable agent such as nitroprusside should be used, preferably with arterial line monitoring to avoid overshoot hypotension. Other agents such as fenoldopam and labetalol are acceptable alternatives.

Stroke Syndromes

Antihypertensive therapy in the setting of stroke remains an area of considerable controversy. In these scenarios, hypertension may represent both a contributing factor and a physiologic response to the stroke syndrome. Despite the widespread prevalence of stroke syndromes, an optimal treatment strategy regarding blood pressure management has not been established.8,9

Elevated blood pressures have been shown to be a prognostic indicator of stroke mortality,9,10 but it is not clear whether this is a causal relationship or a measure of stroke severity. In the setting of ischemic stroke, there are several theoretical reasons why antihypertensive therapy would be beneficial. Lowering blood pressure could reduce edema around the damaged area, decrease the risk of hemorrhagic transformation, and lessen further vascular damage. However, aggressive treatment of hypertension in the setting of ischemic stroke could also reduce perfusion in ischemic areas. This risk of causing harm, combined with the lack of data supporting benefit, suggests that aggressive lowering of blood pressure should be avoided in the acute phase of stroke.

The Stroke Council of the American Stroke Association has offered guidelines8 for the management of hypertension in the setting of ischemic stroke. The consensus is to withhold treatment unless the hypertension is severe, defined by this council as systolic >220 mm Hg or diastolic >120 mm Hg. The recommendation in these scenarios is treatment with labetalol 10–20 mg IV boluses every 1–2 minutes or with a nicardipine infusion of 5–15 mg/h.

These recommendations change for those patients who are candidates for thrombolytic therapy. In these patients, elevated blood pressures represent an increased danger of intracerebral hemorrhage and should thus be controlled. Blood pressure should be lowered to <185 mm Hg systolic and <110 mm Hg diastolic prior to administration of a thrombolytic agent, and should be maintained below these levels for 16 hours after therapy.8 Again, labetalol boluses and nicardipine infusion are the recommended agents, although nitroprusside may be necessary in refractory cases.

In most cases of ischemic stroke, elevated blood pressures decrease spontaneously without treatment. Additional measures to lower ICP, such as raising the head of the bed, and measures to reduce pain and anxiety can also lower blood pressure through nonpharmacologic means.

For hemorrhagic stroke, representing approximately 15% of all strokes, the optimal treatment strategy is equally controversial.11–13 Hypertension in the setting of intracranial hemorrhage is often severe due to increased ICPs and irritation of the autonomic nervous system. Similar concerns exist for initiating therapy including the balance between decreasing the risk of further bleeding and hemorrhagic enlargement, with the concern for decreasing cerebral perfusion pressure. As a result, no general consensus exists suggesting a compelling need to initiate antihypertensive therapy in the patient with acute intracranial hemorrhage.11–13

Current guidelines for patients with intracerebral hemorrhage, released in 2007 from the American Heart Association/American Stroke Association Stroke Council,12 recommend considering aggressive therapy if the systolic is greater than 200 mm Hg or the MAP is greater than 150 mm Hg. If systolic is above 180 mm Hg or the MAP is above 130 mm Hg, and if elevated ICP is suspected, recommendations are to consider establishing ICP monitoring and maintaining a cerebral perfusion pressure between 60 and 80 mm Hg. In the absence of evidence of increased ICP, for patients with a systolic greater than 180 mm Hg or an MAP greater than 130 mm Hg, a modest reduction in blood pressure, to an MAP of 110 mm Hg or target blood pressure of 160/90 mm Hg, should be considered. However, at present, little prospective data exist to definitively recommend a specific blood pressure threshold.

In the case of aneurysmal subarachnoid hemorrhage, recommendations are to maintain the systolic blood pressure below 160 mm Hg and the MAP below 130 mm Hg.13 However, pain control, sedation, and ICP-lowering measures, such as raising the head of the bed, should be instituted prior to administering antihypertensive agents. Additionally, the use of oral nimodipine, to prevent delayed cerebral vasospasm, will have a modest hypotensive effect, although it is not used for this purpose.

As with ischemic stroke, when the decision is made to lower blood pressure, the agents used should be rapid acting and easily titratable such as labetalol, nicardipine, or esmolol. Blood pressure monitoring should be continuous, via arterial line monitoring, or every 5 minutes.12

Other situations where aggressive antihypertensive therapy may be indicated in the setting of acute stroke include aortic dissection, hypertensive encephalopathy, and myocardial infarction. The systemic effects of hypertension must always be taken into account when making the decision to initiate antihypertensive therapy.

Congestive Heart Failure

Congestive heart failure (CHF) represents a clinical syndrome of inadequate cardiac output with a resulting cascade of events, primarily mediated through increased catecholamines, leading to increased peripheral vascular resistance, increased intravascular and interstitial volumes, and pulmonary edema. The hypertension associated with CHF can be both a cause and effect of this process and needs to be lowered rapidly, although carefully, to relieve symptoms and improve clinical outcome. Nitroglycerin is generally the first-line agent, although nitroprusside may be necessary in severe or refractory cases. Additionally, angiotensin-converting enzyme (ACE) inhibitors such as captopril or, if unable to tolerate PO, enalapril or enalaprilat may be helpful.

β-Blockers are widely used in patients with chronic CHF, but are generally avoided in acutely decompensated states due to the negative inotropic and chronotropic effects. The only exception to this would be in the case of known or suspected diastolic dysfunction. With these patients, CHF is a function of inadequacy of ventricular filling during diastole. β-Blockers may allow for additional cardiac relaxation and better filling. The ejection fraction is not typically reduced in these patients. Diastolic dysfunction is typically diagnosed with an echocardiogram, but may be suspected in a patient with decompensated heart failure without evidence of cardiomegaly.

Diuretics such as furosemide should be used to reduce fluid overload and improve work of breathing. Additional measures, including supplemental oxygen, BiPAP, and even mechanical ventilation, are often also necessary. With an improvement in respiratory status, the catecholamine surge is often relieved, subsequently lowering blood pressure and breaking the pathologic cycle.

Cardiac Ischemia

Myocardial ischemia or infarction associated with hypertension warrants immediate blood pressure–lowering therapy to minimize myocardial damage. Agents of choice include nitroglycerin and IV β-blockers such as metoprolol. ACE inhibitors are also an important part of the therapy in the setting of an acute coronary syndrome; however, care should be taken to avoid overshoot hypotension when coadministered with nitroglycerin and β-blockers.

Renal Failure

Hypertension can be seen as both a consequence of and a cause of renal failure. Renal disease leads to hypertension both through increased salt retention and through the renin–angiotensin system. Additionally, uncontrolled hypertension may cause acute kidney injury and can accelerate the progression of injury in patients with chronic renal failure. Worsening kidney function in the setting of elevated blood pressures should be considered a hypertensive emergency and warrants immediate treatment.

Nitroprusside is considered a first-line agent for hypertension-induced acute renal failure, although labetalol is often preferred due to the decreased risk of overshoot hypotension. ACE inhibitors, although highly effective in controlling chronic renal disease, should be used cautiously in the setting of acute renal failure as they may worsen the process acutely.

Emergent dialysis may be indicated in patients with end-stage renal disease with acute uncontrolled hypertension in the setting of volume overload or any evidence of other end-organ dysfunction.

Pregnancy

Hypertensive disorders complicate between 6% and 8% of all pregnancies14 and represent a significant source of morbidity and mortality to both the mother and the fetus. Up to 15% of maternal deaths in the United States are attributable to hypertensive disorders, making it the second leading cause of maternal mortality after thromboembolic disease.14

Classification of pregnancy-associated hypertensive disorders is based on the level of blood pressure elevation, the presence of proteinuria, and physical signs and symptoms. Hypertension in pregnancy is defined as a systolic blood pressure ≥140 mm Hg or a diastolic pressure ≥90 mm Hg. The level of hypertension is classified as severe if the systolic blood pressure is ≥160 mm Hg or the diastolic pressure is ≥105–110 mm Hg.15 Hypertension in pregnancy occurring prior to 20 weeks' gestation is termed chronic hypertension, most likely antedating pregnancy. Hypertension occurring after 20 weeks, but without proteinuria or any signs or symptoms, is termed gestational hypertension. Preeclampsia is defined as hypertension occurring after 20 weeks with proteinuria (>300 mg in 24 hours) or other clinical or laboratory abnormalities. Eclampsia is the occurrence of seizures or coma in the presence of preexisting preeclampsia.

Severe preeclampsia or eclampsia, or pregnancy-associated hypertension with any signs or symptoms indicative of end-organ damage, represent true hypertensive emergencies and should be treated emergently. Treatment goals in the emergency department should include blood pressure reduction, seizure prevention and control, and early obstetric consultation.

The specific goals of blood pressure reduction are not well defined. Severe, acute elevations in blood pressure can be associated with cerebral and cardiovascular complications, as well as placental abruption and uteroplacental insufficiency.15 However, some evidence suggests a parallel between reduction in MAP and adverse effects on fetal growth.16 Some advocate withholding treatment unless diastolic blood pressure remains persistently elevated above 105–110 mm Hg.14

Hydralazine has traditionally been the frontline agent of choice, although this has come into question in the recent years.15 Nevertheless, it is still widely used and is an effective agent, although caution must be taken due to its unpredictable dose–response curve. Labetalol is now the drug of choice for pregnancy-associated hypertensive emergencies.17 Nicardipine may also be effective, although there has been some concern about administering it in patients also receiving magnesium sulfate for seizure prophylaxis, due to the combined calcium channel–blocking activity.15 Nitroprusside should be reserved to severe hypertension refractory to other agents, due to the potential for fetal cyanide toxicity and overshoot hypotension. ACE inhibitors are contraindicated in pregnancy.

Aortic Dissection

Aortic dissection should be suspected in any patients presenting with chest and/or upper back pain, particularly pain that is sharp or “tearing” in quality and maximal at onset. However, up to 20% may present with syncope without a history of typical pain or other findings.18 Physical exam findings pointing to a diagnosis of aortic dissection include pulse deficits, a diastolic murmur, and neurologic deficits. A high index of suspicion should always be maintained, as inappropriately treating for a presumed acute coronary syndrome or stroke could be devastating for patients with aortic dissection.

Aortic dissection represents a hypertensive emergency in which the treatment approach is two-pronged. Since propagation is dependent on both the level of hypertension and the left ventricular ejection force, therapy must be aimed at both lowering pressure and slowing the rate of pressure rise. Therefore, generally a β-blocker such as esmolol is used in combination with a vasodilator such as nitroprusside. Alternatively, labetalol, which has both α- and β-blocking effects, can be used as monotherapy.19 Goal blood pressure should be below 120–130 mm Hg systolic.

All patients with suspected aortic dissection require prompt surgical consultation. However, aneurysms involving only the descending aorta (Stanford type B) are generally medically managed.

Many of the agents used to treat hypertensive urgency and emergency are described below. Parenteral agents are summarized in Table 14-2.

Sodium Nitroprusside

Nitroprusside is an extremely powerful and effective pressure-lowering agent, acting as a potent vasodilator in both the arterial and venous systems. Due to its rapid onset of action (1–2 minutes), short half-life (3–4 minutes), and almost universal effectiveness, it is widely considered the standard drug of choice in hypertensive emergencies.

Due to its high potency, overshoot hypotension is the most common complication. Close hemodynamic monitoring, preferably with an intra-arterial line, is required. Infusion of sodium nitroprusside is generally begun at 0.3 mcg/kg/min and titrated up to goal MAP, with a maximum dose of 10 mcg/kg/min.20

Sodium nitroprusside is metabolized by the liver to thiocyanate that is then excreted by the kidneys. Cyanide is an intermediate metabolite in this process, although cyanide toxicity is rare. However, thiocyanate toxicity may occur in the setting of hepatic or renal failure or prolonged administration.20 Use of this agent is also complicated by the need for special handling, as it is unstable in the presence of ultraviolet light and must be wrapped in opaque material during administration.

Caution should be used in patients in whom increased cerebral pressure is a concern, as nitroprusside acts as a cerebral vasodilator. Additionally, nitroprusside should be avoided in pregnant patients due to its ability to cross the placenta and cause toxic effects on the fetus.

Fenoldopam

Fenoldopam mesylate is a selective postsynaptic dopamine-1 receptor agonist that functions both as a systemic and renal vasodilator and as a natriuretic. Like nitroprusside, fenoldopam has an onset of action within minutes and a short duration of action (less than 10 minutes). Additionally, it has been demonstrated to be as effective as nitroprusside in lowering blood pressure21 with less hypotension and no concerns of light sensitivity or thiocyanate or cyanide toxicity. For these reasons, fenoldopam is gaining favor by some as the drug of choice in treating hypertensive emergencies.

Fenoldopam is dosed initially at 0.1 mcg/kg/min and titrated in increments of 0.1 mcg/kg/min every 15 minutes until a desired pressure is reached. Side effects may include reflex tachycardia, headache, and facial flushing.

Nitroglycerin

Nitroglycerin is a rapidly acting vasodilator that lowers blood pressure in a dose-dependent fashion. It primarily acts on the venous system, thus decreasing preload more than afterload. It is therefore most useful in cardiac ischemia or heart failure associated with hypertension. When given intravenously, it is generally begun at 5–10 mcg/min titrating up in 5 mcg/min increments every 5 minutes until desired blood pressure is reached or the patient's symptoms have resolved.

The primary side effects of nitroglycerin are headache and tachycardia. It should be avoided in the setting of right heart failure, as a precipitous drop in cardiac output and blood pressure may result.

Hydralazine

Hydralazine is a direct arterial vasodilator, commonly used in pregnancy-induced hypertension. Onset of action is approximately 10 minutes when given intravenously with a duration of action of 4–6 hours. However, the effects can often be unpredictable, with an initial 5- to 15-minute latent period followed by an often precipitous drop in blood pressure, which may last up to 12 hours.22,25 Doses are generally begun at 5–10 mg IV, with repeated doses of 10 mg every 10–15 minutes until goal blood pressure is reached. Reflex tachycardia is a common complication, and thus should be avoided in patients with myocardial ischemia or aortic dissection. Other adverse effects include headache, nausea, and postural hypotension. Chronic use may lead to a lupuslike syndrome.

Labetalol

Labetalol is a combined α1-blocker and nonselective β-blocker. The ratio of α- to β-blockade is 1:7 in the IV form.23 As a result, labetalol is an effective blood pressure–lowering agent that has the advantage of not causing reflex tachycardia.

When given IV, onset of action is 5–10 minutes with a high volume of distribution and duration of action of approximately 6–8 hours. Dosing is usually begun at 20 mg IV for hypertensive emergencies with repeated doses of 20, 40, or 80 mg every 5–10 minutes until desired blood pressure is reached, up to a maximum of 300 mg. Alternatively, a continuous infusion of 1–2 mg/min can be begun after the initial bolus dose.

When goal blood pressure is reached, transition to oral form can be begun. Orally dosing is generally begun at 200 mg. Onset of effects with oral dosing is approximately 1–3 hours.

Labetalol has little effect on cerebral or coronary blood flow and can be used safely in patients with acute myocardial infarction. Due to its β-blockade effect, use with caution in patients with decompensated heart failure or in acute exacerbation of asthma or chronic obstructive pulmonary disease (COPD). It should also be avoided in patients with cardiac conduction system abnormalities. In low doses intravenously, due to the high ratio of β to α effects, there is a theoretical risk of paradoxical hypertension with administration to patients in high catecholamine-induced hypertension, such as that seen with pheochromocytoma or cocaine-induced hypertension.

Esmolol

Esmolol is a selective β1-antagonist with an ultrashort half-life of approximately 9 minutes. It is easily titratable, due to its short duration of action of approximately 10–20 minutes. Esmolol is metabolized by red blood cell esterases, making it additionally useful in patients with hepatic and renal failure.24

Infusion is generally begun with a bolus of 250–500 mcg/kg over 1 minute, followed by an initial infusion of 25 mcg/kg/min. This can then be titrated up by increments of 25–50 mcg/kg/min every 4 minutes until goal blood pressure, or heart rate, is reached or to a maximum of 300 mcg/kg/min.

Adverse effects may include bradycardia, hypotension, dizziness, somnolence, nausea, and bronchospasm. As with all β-blockers, use with caution in patients with CHF, asthma, COPD, heart block, and bradycardia, or in the setting of cocaine overdose or pheochromocytoma.

Nicardipine

Nicardipine is a parenteral calcium channel blocker of the dihydropyridine class. It acts as a powerful vasodilator, but, unlike other calcium channel blockers such as nifedipine, it has the advantage of lacking significant negative inotropic effects.25

Nicardipine is generally begun at a rate of 5 mg/h and titrated every 5 minutes to a maximum of 15 mg/h or until the desired blood pressure is reached. Onset of action is within minutes, and duration of action is 4–6 hours.

Headache is a common side effect, occurring in up to 20–50% of patients.26 Less commonly, tachycardia, nausea, and overshoot hypotension are seen. Caution should be used in patients with liver failure, as it is heavily metabolized by the liver.27

Enalaprilat

Enalaprilat is an IV ACE inhibitor that has been shown to be effective at lowering blood pressure without causing overshoot hypotension.34 It is the active metabolite of the oral ACE inhibitor enalapril. Dosing is generally begun with a dose of between 0.625 and 1.25 mg IV. Peak effects occur within 10–15 minutes with a duration of action of 12–24 hours. Adverse effects may include renal failure, angioneurotic edema, and cough. ACE inhibitors are contraindicated in pregnancy.28

Phentolamine

Phentolamine is an α-adrenergic blocking agent most useful in management of catecholamine-induced hypertensive emergencies. It is generally given as 5-mg boluses, with an onset of action within 1–2 minutes and a duration of action of 10–30 minutes. It is contraindicated in the setting of myocardial ischemia, except when associated with cocaine toxicity, and may cause reflex tachycardia and tachydysrhythmias as a side effect.

Clevidipine

Clevidipine is an ultrashort-acting IV calcium channel blocker that was approved by the FDA in 2008 for the treatment of severe hypertension. It is easily titratable, with blood pressure reduction seen within 2–3 minutes of administration and a duration of action of 5–15 minutes.29–31 Additionally, since it is cleared by plasma esterases, it requires no dosage adjustment for patients with hepatic or renal impairment. Dosing is begun at 1–2 mg/h and titrated up until desired blood pressure is reached. Titration is generally performed initially by doubling the dose every 90 seconds, although this titration should be done every 5–10 minutes if the blood pressure is near goal. A maximum of 16 mg/h is recommended; however, limited data exist for dosages up to 32 mg/h.29–31 Adverse effects include headache, nausea, and chest discomfort.

Clonidine

Clonidine is a centrally acting α2-agonist that lowers blood pressure through negative feedback on the vasomotor center of the brain, decreasing sympathetic discharge. It is an oral agent, and can be effective in cases of hypertensive urgency when blood pressure reduction is desired over a period of hours. Onset of action is between 30 minutes and 2 hours, with a duration of action of 6–8 hours. Dosing is begun at 0.1–0.2 mg orally, with additional doses 0.1 mg given hourly as necessary until goal blood pressure is reached. Side effects include sedation and dry mouth, and clonidine may sometimes cause orthostatic hypotension.32

Captopril

Captopril is an oral ACE inhibitor that, like clonidine, can be useful in situations of hypertensive urgency where a more gradual blood pressure reduction is desired. Dosing is 12.5–25 mg with an onset of action between 15 and 30 minutes, and a duration of action of 4–6 hours. Side effects may include cough or skin rash. A more rare, but serious, side effect to ACE inhibitor therapy is angioedema, which may be life-threatening. ACE inhibitors are contraindicated in pregnancy.

Hypertensive crises continue to represent a significant critical care challenge to the emergency physician. This will become increasingly more prevalent an issue as our population ages. Many factors must be considered when deciding on an appropriate treatment strategy. Therapy should always be specific to the patient and the situation, and never based on absolute values of blood pressure. The most important consideration, as always, is to remember to treat the patient, not the blood pressure.