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.
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 (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.
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.
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.
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 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.