AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
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• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

A hypertensive emergency is a condition in which elevated blood pressure results in target organ damage. The systems primarily involved include the central nervous system, the cardiovascular system, and the kidneys. Malignant hypertension and accelerated hypertension are both hypertensive emergencies, with similar outcomes and therapies. In order to diagnose malignant hypertension, papilledema must be present. Accelerated hypertension is defined as a recent significant increase over baseline blood pressure that is associated with target organ damage. This is usually vascular damage on funduscopic examination, such as flame-shaped hemorrhages or soft exudates, but without papilledema.

Hypertensive urgency must be distinguished from emergency. Urgency is defined as severely elevated blood pressure (ie, systolic >220 mm Hg or diastolic >120 mm Hg) with no evidence of target organ damage.

Hypertensive emergencies require immediate therapy to decrease blood pressure within minutes to hours. In contrast, no evidence suggests a benefit from rapidly reducing blood pressure in patients with hypertensive urgency. In fact, such aggressive therapy may harm the patient, resulting in cardiac, renal, or cerebral hypoperfusion. This article discusses hypertensive emergency, but therapy for hypertensive urgency is discussed briefly.

Pathophysiology

The pathogenesis of malignant hypertension is not fully understood. The characteristic vascular lesion is fibrinoid necrosis of arterioles and small arteries, which causes the clinical manifestations of end-organ damage. Red blood cells are damaged as they flow through vessels obstructed by fibrin deposition, resulting in microangiopathic hemolytic anemia.

Another pathologic process is the dilatation of cerebral arteries following a breakthrough of the normal autoregulation of cerebral blood flow. Under normal conditions, cerebral blood flow is kept constant by cerebral vasoconstriction in response to increases in blood pressure. In patients without hypertension, flow is kept constant over a mean pressure of 60-120 mm Hg. In patients with hypertension, flow is constant over a mean pressure of 110-180 mm Hg because of arteriolar thickening. When blood pressure is raised above the upper limit of autoregulation, arterioles dilate. This results in hyperperfusion and cerebral edema, which cause the clinical manifestations of hypertensive encephalopathy.

Why some patients with severe hypertension develop end-organ damage while others do not is unclear.

Frequency

United States

Up to 1% of patients with essential hypertension develop malignant hypertension. The average age at diagnosis is 40 years, and men are affected more often than women. People who smoke cigarettes, black people, and patients with secondary hypertension are at higher risk than the general population.

Mortality/Morbidity

Prior to effective therapy, life expectancy was less than 2 years, with most deaths resulting from stroke, renal failure, or heart failure. The survival rate at 1 year was less than 25% and at 5 years was less than 1%. With current therapy, including dialysis, the survival rate at 1 year is greater than 90% and at 5 years is 80%. The most common cause of death is cardiac, with stroke and renal failure also common. Gastrointestinal symptoms are nausea and vomiting. Diffuse arteriolar damage can result in microangiopathic hemolytic anemia.

• The heart's initial response to systemic hypertension is to develop concentric left ventricular hypertrophy. Eventually, the left ventricle becomes dilatated. This is reflected on physical examination by a fourth heart sound initially, followed by the typical changes of dilated cardiomyopathy. In the earliest stages, electrocardiogram (ECG) and echocardiogram reveal left atrial enlargement and left ventricular hypertrophy. The cardiac presentation of malignant hypertension is angina and/or myocardial infarction or congestive heart failure.
• The funduscopic changes are flame-shaped retinal hemorrhages, soft exudates, and papilledema. Neurological presentations are occipital headaches, cerebral infarct, cerebral hemorrhage, or hypertensive encephalopathy. Hypertensive encephalopathy is a symptom complex of severe hypertension, headache, vomiting, visual disturbance, mental status changes, seizure, and retinopathy with papilledema. Focal signs and symptoms are uncommon and may indicate another process, such as cerebral infarct or hemorrhage.
• Renal disease presents as proteinuria, microscopic hematuria, red blood cell casts, and azotemic oliguric renal failure. Diffuse intrarenal ischemia results in increased levels of plasma renin, angiotensin II, and aldosterone, with resulting hypovolemia and hypokalemia. Sodium depletion is common and may be severe.

Race

Black people are at higher risk of developing hypertensive emergencies than the general population.

Sex

Men are affected more often than women.

Age

The average age at diagnosis is 40 years, but a wide range of ages is observed.

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The history should screen for symptoms of malignant hypertension, focusing on the cardiac, renal, and central nervous systems. Underlying medical disorders should be reviewed, including the possibility of eclampsia. The patient's medications and other drugs should be thoroughly reviewed.

• In a recent review, the most common presentations of hypertensive emergencies at an emergency department were chest pain (27%), dyspnea (22%), and neurologic deficit (21%).
• The primary cardiac symptoms are angina, myocardial infarction, and pulmonary edema. Orthostatic symptoms may be prominent.
• Neurologic presentations are occipital headache, cerebral infarction or hemorrhage, visual disturbance, or hypertensive encephalopathy (a symptom complex of severe hypertension, headache, vomiting, visual disturbance, mental status changes, seizure, and retinopathy with papilledema).
• Medications or drugs that may cause a hypertensive emergency include cocaine, monoamine oxidase inhibitors (MAOIs), and oral contraceptives; the withdrawal of beta-blockers, alpha-stimulants (such as clonidine), or alcohol also may cause hypertensive emergency.
• Renal disease may present as oliguria or any of the typical features of renal failure.
• Gastrointestinal symptoms are nausea and vomiting.

Physical

The initial evaluation begins with a thorough physical examination. Once again, the focus is on the cardiovascular and central nervous systems and on the retinal examination.

• Cardiovascular system
• • Blood pressure must be checked in both arms to screen for aortic dissection or coarctation. If coarctation is suspected, blood pressure also should be measured in the legs.
  • Screen for carotid or renal bruits.
  • Palpate the precordium, looking for sustained left ventricular lift.
  • Auscultate for a third or fourth heart sound or murmurs.
  • Volume status must be assessed, with orthostatic vital signs, examination of jugular veins, assessment of liver size, and investigation for peripheral edema and pulmonary rales.
• Central nervous system
• • A complete neurologic examination is needed to screen for localizing signs.
  • Focal neurologic signs might not be attributable to encephalopathy. Focal signs mandate screening for cerebral hemorrhage, infarct, or the presence of a mass.
• Retinal examination: A funduscopic examination may reveal flame-shaped retinal hemorrhages, soft exudates, or papilledema.

Causes

The pathogenesis is not fully understood. Up to 1% of patients with essential hypertension develop malignant hypertension, and the reason some patients develop malignant hypertension while others do not is unknown. Other causes include any form of secondary hypertension; complications of pregnancy; use of cocaine, MAOIs, or oral contraceptives; and the withdrawal of alcohol, beta-blockers, or alpha-stimulants. Renal artery stenosis, pheochromocytoma (most pheochromocytomas can be localized using CT scan of the adrenals), aortic coarctation, and hyperaldosteronism are secondary causes of hypertension. Both hyperthyroidism and hypothyroidism can cause hypertension.

DIFFERENTIALS

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• Multimedia
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Other Problems to be Considered

Renal failure (any cause)
Stroke
Subarachnoid hemorrhage
Intracranial mass
Head injury
Epilepsy or postictal state
Connective-tissue disease (especially lupus with cerebral vasculitis)
Drug overdose or withdrawal
Cocaine or amphetamine ingestion
Acute anxiety

WORKUP

Section 5 of 11  

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Lab Studies

• Initial laboratory studies include a complete blood count and electrolytes, including calcium, BUN, creatinine, glucose, coagulation profile, and urinalysis.
• Other laboratory studies are indicated only as directed by the initial workup. This may include cardiac enzymes, urinary catecholamines, thyroid-stimulating hormone (TSH), and 24-hour urine collection for vanillylmandelic acid (VMA) and catecholamines.
• Renal function should be evaluated through a urinalysis, complete chemistry profile, and complete blood count. Expected findings include elevated BUN and creatinine, hyperphosphatemia, hyperkalemia or hypokalemia, glucose abnormalities, acidosis, hypernatremia, and evidence of microangiopathic hemolytic anemia. Urinalysis may reveal proteinuria, microscopic hematuria, and RBC or hyaline casts.
• In patients with hyperaldosteronism (a secondary cause of hypertension), aldosterone promotes renal potassium wasting, resulting in low serum potassium.

Imaging Studies

• Routine screening consists of a chest radiograph. The chest radiograph is useful for assessment of cardiac enlargement, pulmonary edema, or involvement of other thoracic structures, such as rib notching with aortic coarctation or a widened mediastinum with aortic dissection.
• Other tests, such as head CT scan, transesophageal echocardiogram, and renal angiography, are indicated only as directed by the initial workup.

Other Tests

• An ECG is an essential part of the evaluation. The ECG is necessary to screen for ischemia, infarct, or evidence of electrolyte abnormalities or drug overdose.

Procedures

• No procedures are performed routinely for the evaluation of malignant hypertension.

TREATMENT

Section 6 of 11  

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Medical Care

Patients with malignant hypertension usually are admitted to an intensive care unit for continuous cardiac monitoring and frequent assessment of neurologic status and urine output. An intravenous line is started for fluids and medications. Patients typically have altered blood pressure autoregulation, and overzealous reduction of blood pressure to reference range levels may result in organ hypoperfusion. The initial goal of therapy is to reduce the mean arterial pressure by approximately 25% over the first 24-48 hours. An intra-arterial line is helpful for continuous titration of blood pressure. Sodium and volume depletion may be severe, and volume expansion with isotonic sodium chloride solution must be considered.

Hypertensive urgencies do not mandate admission to a hospital. The goal of therapy is to reduce blood pressure within 24 hours, which can be achieved as an outpatient.

Consultations

• In patients with stroke, cardiac compromise, or renal failure, appropriate consultation should be considered.
• In institutions with specialists in hypertension, prompt consultation may improve the overall control of blood pressure.

Diet

Initially, patients treated for malignant hypertension are instructed to fast until stable. Once stable, all patients should obtain good long-term care of their hypertension, including a diet that is low in salt. If indicated, the patient should follow a diet that can induce weight loss.

Activity

Activity is limited to bedrest until the patient is stable. Patients should be able to resume normal activity as outpatients once their blood pressure has been controlled.

MEDICATION

Section 7 of 11  

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No trials exist comparing the efficacy of various agents in the treatment of malignant hypertension. Drugs are chosen based on their rapidity of action, ease of use, special situations, and convention.

Once the diagnosis of hypertensive emergency is made, the most commonly used intravenous (IV) drug is nitroprusside. An alternative for patients with renal insufficiency is IV fenoldopam. Labetalol is another common alternative, providing easy transition from IV to oral (PO) dosing. Beta-blockade can be accomplished intravenously with esmolol or metoprolol. Also available parenterally are diltiazem, verapamil, and enalapril. Hydralazine is reserved for use in pregnant patients, while phentolamine is the drug of choice for a pheochromocytoma crisis.

Drug Category: Vasodilators

Reduce systemic vascular resistance (SVR), decreasing afterload and improving cardiac output.

Drug Category: Calcium channel blockers

These agents cause vascular smooth muscle to relax, which in turn leads to vasodilation and a corresponding drop in blood pressure.

Drug Category: Beta-adrenergic blockers

Inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.

Drug Category: Alpha-adrenergic blockers

At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of the alpha-receptor blockers.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Patients with hypertensive emergencies should be admitted to the hospital for close hemodynamic monitoring and administration of IV antihypertensive medications.
• Secondary causes of hypertension should be investigated.
• Oral medications should be initiated as soon as possible in order to ease transition to an outpatient setting.

Further Outpatient Care

• The best way to prevent further episodes of hypertensive emergencies is to ensure that the patient has close outpatient follow-up for hypertension treatment. This can usually be accomplished by a general medicine or family practice physician, but referral to a hypertension specialist should also be considered for patients who require complex drug therapy or additional secondary workup.

Complications

• Overzealous reduction of blood pressure can result in organ hypoperfusion.
• In a hypovolemic patient, enalapril has an unpredictable response with a possible uncontrolled drop in blood pressure.
• Target organ damage can be missed without a thorough evaluation.

Prognosis

• Prior to effective therapy, life expectancy was less than 2 years, with most deaths resulting from stroke, renal failure, or heart failure. The survival rate at 1 year was less than 25% and at 5 years was less than 1%.
• With current therapy, including dialysis, the survival rate at 1 year is greater than 90% and at 5 years is 80%. The most common cause of death is cardiac, with stroke and renal failure also common.

Patient Education

• Patients must be taught an appropriate diet for long-term management.
• Upon discharge, patients should know the signs and symptoms that should prompt immediate notification of a physician.
• Upon discharge, patients should know the proper dosing and side effects of their medications.
• For excellent patient education resources, visit eMedicine's Diabetes Center. Also, see eMedicine's patient education article High Blood Pressure.

MISCELLANEOUS

Section 9 of 11  

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• Clinical
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• Follow-up
• Miscellaneous
• Multimedia
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Medical/Legal Pitfalls

• Reducing blood pressure too rapidly can result in patient harm.
• Properly diagnosing hypertensive emergency and urgency is essential to proper triage and treatment.
• All patients should be carefully assessed for secondary causes of hypertension.
• Upon discharge, patients should have close follow-up care. They should know the signs and symptoms that necessitate immediate notification of a physician.

MULTIMEDIA

Section 10 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Malignant hypertension. Hypertensive retinopathy. Note the flame-shaped hemorrhages, soft exudates, and early disc blurring.
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Media type:  Photo

Media file 2:  Malignant hypertension. Papilledema. Note swelling of the optic disc with blurred margins.
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Media type:  Photo

REFERENCES

Section 11 of 11

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• Differentials
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• References

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Article Last Updated: Oct 10, 2006