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In hemorrhagic stroke, the aim is to minimize bleeding with a target mean arterial pressure of < 130 mm Hg. In acute subarachnoid hemorrhage, as long as the bleeding source remains uncorrected, a compromise must be struck between preventing further bleeding and maintaining cerebral perfusion in the face of cerebral vasospasm.

In this situation, blood pressure goals depend on the patient's usual blood pressure. In normotensive patients, the target should be a systolic blood pressure of 110-120 mm Hg; in hypertensive patients, blood pressure should be treated to 20% below baseline pressure. In the treatment of hypertensive emergencies complicated by (or precipitated by) central nervous system injury, labetalol or nicardipine are good choices, since they are nonsedating and do not cause significant cerebral vasodilation, which can increase intracranial pressure (a potential problem with sodium nitroprusside). In hypertensive emergencies arising from catecholaminergic mechanisms, such as pheochromocytoma or cocaine use, β-blockers can worsen the hypertension because of unopposed peripheral vasoconstriction; phentolamine is a better choice. Labetalol is useful in these patients if the heart rate must be controlled.

Pharmacologic Management

A. PARENTERAL AGENTS
A growing number of agents are available for management of acute hypertensive problems. (Table 11-12 lists drugs, dosages, and adverse effects.) Sodium nitroprusside is the agent of choice for the most serious emergencies because of its rapid and easily controllable action, but continuous monitoring is essential when this agent is used. In the presence of myocardial ischemia, intravenous nitroglycerin or an intravenous β-blocker, such as labetalol or esmolol, is preferable.

1. Nitroprusside sodium - This agent is given by controlled intravenous infusion gradually titrated to the desired effect. It lowers the blood pressure within seconds by direct arteriolar and venous dilation. Monitoring with an intra-arterial line avoids hypotension. Nitroprusside - in combination with a β-blocker - is especially useful in patients with aortic dissection.

2. Nitroglycerin, intravenous - This agent is a less potent antihypertensive than nitroprusside and should be reserved for patients with accompanying acute ischemic syndromes.

3. Labetalol - This combined β- and α-blocking agent is the most potent adrenergic blocker for rapid blood pressure reduction. Other β-blockers are far less potent. Excessive blood pressure drops are unusual. Experience with this agent in hypertensive syndromes associated with pregnancy has been favorable.

4. Esmolol - This rapidly acting β-blocker is approved only for treatment of supraventricular tachycardia but is often used for lowering blood pressure. It is less potent than labetalol and should be reserved for patients in whom there is particular concern about serious adverse events related to β-blockers.

5. Nicardipine - Intravenous nicardipine is the most potent antihypertensive agent and the longest acting of the parenteral calcium channel blockers. As a primarily arterial vasodilator, it has the potential to precipitate reflex tachycardia, and for that reason it should not be used without a β-blocker in patients with coronary artery disease.

6. Fenoldopam - Fenoldopam is a peripheral dopamine-1 (DA1) receptor agonist that causes a dose-dependent reduction in arterial pressure without evidence of tolerance, rebound, or withdrawal or deterioration of renal function. In higher dosage ranges, tachycardia may occur.

7. Enalaprilat - This is the active form of the oral ACE inhibitor enalapril. The onset of action is usually within 15 minutes, but the peak effect may be delayed for up to 6 hours. Thus, enalaprilat is used primarily as an adjunctive agent.

8. Diazoxide - Diazoxide acts promptly as a vasodilator without decreasing renal blood flow. To avoid hypotension, it should be given in small boluses or as an infusion rather than as the previously recommended large bolus. One use of diazoxide has been in preeclampsia-eclampsia. Hyperglycemia and sodium and water retention may occur. The drug should be used only for short periods and is best combined with a loop diuretic.

9. Hydralazine - Hydralazine can be given intravenously or intramuscularly, but its effect is less predictable than that of other drugs in this group. It produces reflex tachycardia and should not be given without β-blockers in patients with possible coronary disease or aortic dissection. Hydralazine is now used primarily in pregnancy and in children, but even in these situations, newer agents are supplanting it.

10. Trimethaphan - The ganglionic blocking agent trimethaphan is titrated with the patient sitting; its activity depends on this. The patient can be placed supine if the hypotensive effect is excessive. The effect occurs within a few minutes and persists for the duration of the infusion. This agent has largely been replaced by nitroprusside and newer medications.

11. Diuretics - Intravenous loop diuretics can be very helpful when the patient has signs of heart failure or fluid retention, but the onset of their hypotensive response is slow, making them an adjunct rather than a primary agent for hypertensive emergencies. Low dosages should be used initially (furosemide, 20 mg or bumetanide, 0.5 mg). They facilitate the response to vasodilators, which often stimulate fluid retention.

B. ORAL AGENTS
Patients with less severe acute hypertensive syndromes can often be treated with oral therapy. Abrupt blood pressure lowering is not usually necessary in asymptomatic individuals, and the use of agents such as rapid-acting nifedipine probably causes more adverse effects than benefits.

1. Clonidine - Clonidine, 0.2 mg orally initially, followed by 0.1 mg every hour to a total of 0.8 mg, will usually lower blood pressure over a period of several hours. Sedation is frequent, and rebound hypertension may occur if the drug is stopped.

2. Captopril - Captopril, 12.5-25 mg orally, will also lower blood pressure in 15-30 minutes. The response is variable and may be excessive.

3. Nifedipine - Fast-acting nifedipine capsules are commonly used in the emergency department or urgent care setting because they usually provide a rapid reduction in blood pressure. However, the nifedipine effect is unpredictable and may be excessive, resulting in hypotension and reflex tachycardia. Because myocardial infarction and stroke have been reported in this setting, the use of nifedipine without concomitant β-blocker therapy is not advised.

C. SUBSEQUENT THERAPY
When the blood pressure has been brought under control, combinations of oral antihypertensive agents can be added as parenteral drugs are tapered off over a period of 2-3 days. Most subsequent regimens should include a diuretic.

Bibliography

Cherney D et al: Management of patients with hypertensive urgencies and emergencies. J Gen Intern Med 2002;17:947.
Devlin JW et al: Fenoldopam versus nitroprusside for the treatment of hypertensive emergency. Ann Pharmacother 2004; 38:755.
Khanna A et al: Malignant hypertension presenting as hemolysis, thrombocytopenia, and renal failure. Rev Cardiovasc Med 2003;4:255.
Migneco A et al: Hypertensive crises: diagnosis and management in the emergency room. Eur Rev Med Pharmacol Sci 2004; 8:143.
Phillips RA et al: Hypertensive emergencies: diagnosis and management. Prog Cardiovasc Dis 2002;45:33.