No large clinical trials have investigated optimal drug therapy in patients with hypertensive emergencies. The choice of pharmacologic agent should be individualized based on drug properties, patient comorbidities, and the end-organ(s) involved.
Selected pharmacologic agents: Sodium nitroprusside (SNP) is a short-acting, potent arterial and venous dilator that has been used extensively in the treatment of hypertensive emergencies. Despite its familiarity, there are several important limitations to its use. SNP can increase intracranial pressure (ICP), worsen myocardial ischemia through coronary steal, and is associated with cyanide and/or thiocyanate toxicity. Although used broadly across many types of hypertensive emergencies, SNP should be considered a first-line agent in acute left ventricular (LV) failure and, when combined with beta-blockers, in acute aortic dissection.
Labetalol is an alpha-1 and nonselective beta-blocker that reduces systemic vascular resistance while preserving cerebral, renal, and coronary blood flow. It is considered a first-line agent in most hypertensive emergencies, with the exception of acute LV failure.
Esmolol is a short-acting, selective beta-blocker that decreases heart rate, myocardial contractility, and cardiac output.
Nicardipine is a second-generation dihydropyridine calcium channel blocker. Although it has a longer duration of action, excess hypotension has not been seen in clinical trials comparing it with SNP.4 Nicardipine is used safely in such hypertensive emergencies as hypertensive encephalopathy, cerebral vascular accidents, and postoperatively.
Fenoldopam creates vasodilation by acting on peripheral dopamine type 1 receptors. It improves creatinine clearance and urine output, and is most useful in acute kidney injury.5 It is a well-tolerated and highly effective agent for use in most hypertensive crises, although is expensive and has limited hard outcome data.
Nitroglycerin is a potent venodilator that is used as an adjunct to other anti-hypertensives in the treatment of acute coronary syndromes and acute pulmonary edema.
Immediate-release nifedipine and clonidine are not recommended; they are long-acting and poorly titratable, with unpredictable hypotensive effects.
Hydralazine may be used in LV failure and in pregnancy.
Specific emergencies: Aortic dissection is the most rapidly fatal complication of severe HTN. Untreated, approximately 80% of patients with acute type-A dissections die within two weeks.6 In this specific setting, SBP should be decreased as rapidly as possible to <110 mm Hg in order to halt propagation of the dissection prior to surgery. Therapy should aim to reduce the shear stress on the aortic wall by decreasing both BP and heart rate. This can be accomplished with a combination of esmolol and SNP. Nicardipine and fenoldopam are effective alternatives to SNP. Labetalol is a good single-agent option, provided adequate heart rate suppression is achieved.
LV failure and acute pulmonary edema are associated with high systemic vascular resistance and activation of the Renin Angiotensin Aldosterone (RAAS) system. First-line therapy should consist of arterial vasodilators (e.g., SNP, nicardipine, fenoldopam) in combination with a loop diuretic. Nitroglycerin can be used as an adjunct to reduce LV preload.
In hypertensive encephalopathy, blood pressure exceeds the cerebral autoregulatory threshold, leading to breakthrough vasodilation and the development of cerebral edema. Characteristic symptoms include the insidious onset of headache, nausea, vomiting, and nonlocalizing neurologic signs (e.g., lethargy, confusion, seizures). It is important to exclude stroke, as treatment strategies differ. SNP is used widely in the treatment of hypertensive encephalopathy; it may increase ICP and should be used with caution. Nicardipine and labetalol are effective alternatives with favorable cerebral hemodynamic profiles.
Malignant HTN is characterized by neuroretinopathy: cotton wool spots, flame hemorrhages, and papilledema. Encephalopathy and other evidence of end-organ dysfunction might not be present, although renal disease is common. Preferred drugs are SNP and labetalol, although fenoldopam has been used successfully.