AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

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

INTRODUCTION

Section 2 of 10  

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

Background

Hypertension affects more than 60 million Americans. With adequate control, fewer than 1% of patients experience a hypertensive crisis. Hypertensive crisis is classified as hypertensive emergency or hypertensive urgency. Acute or ongoing vital target organ damage, such as damage to the brain, kidney, or heart, in the setting of severe hypertension is considered a hypertensive emergency. It requires a prompt reduction in blood pressure within minutes or hours. The absence of target organ damage in the presence of severe elevation of blood pressure with diastolic blood pressure frequently greater than 120 mm Hg is considered hypertensive urgency, and it requires reduction in blood pressure within 24-48 hours. A continuum exists between the clinical syndrome of hypertensive urgency and emergency; hence, their distinction may not always be clear and precise.¹

In 1928, Oppenheimer and Fishberg introduced the term hypertensive encephalopathy to describe the encephalopathic findings associated with the accelerated malignant phase of hypertension. The terms accelerated and malignant were used to describe the retinal findings associated with hypertension. Accelerated hypertension is associated with group 3 Keith-Wagener-Barker retinopathy, which is characterized by retinal hemorrhages and exudates on funduscopic examination. Malignant hypertension is associated with group 4 Keith-Wagener-Barker retinopathy, which is characterized by the presence of papilledema, heralding the neurologic impairment from an elevated intracranial pressure.

Hypertensive encephalopathy describes the transient migratory neurologic symptoms associated with the malignant hypertensive state in hypertensive emergency. The clinical symptoms usually are reversible with prompt initiation of therapy. In the evaluation of an encephalopathic patient, exclude systemic disorders and various cerebrovascular events that may present with a similar constellation of clinical findings.

Pathophysiology

The clinical manifestations of hypertensive encephalopathy are due to increased cerebral perfusion from the loss of blood-brain barrier integrity, resulting in exudation of fluid into the brain. In normotensive individuals, an increase in systemic blood pressure over a certain range (ie, 60-125 mm Hg) induces cerebral arteriolar vasoconstriction, thereby preserving a constant cerebral blood flow and an intact blood-brain barrier.

In chronically hypertensive individuals, the cerebral autoregulatory range gradually is shifted to higher pressures as an adaptation to chronic elevation of systemic blood pressure. This cerebral autoregulatory response is overwhelmed during a hypertensive emergency in which the acute rise in systemic blood pressure exceeds the individual's cerebral autoregulatory range, resulting in hydrostatic leakage across the capillaries within the central nervous system. With persistent elevation of the systemic blood pressure, arteriolar damage and necrosis occur. The progression of vascular pathology leads to generalized vasodilatation, cerebral edema, and papilledema, which clinically manifest as neurologic deficits and altered mentation in hypertensive encephalopathy.

Frequency

United States

Of the 60 million Americans with hypertension, fewer than 1% of patients develop a hypertensive emergency.

Mortality/Morbidity

The morbidity and mortality associated with hypertensive encephalopathy are related to the degree of target organ damage. Without treatment, the 6-month mortality rate for hypertensive emergencies is 50%, and the 1-year mortality rate approaches 90%.

Race

The frequency of hypertensive encephalopathy corresponds to the occurrence of hypertension in the general population. Hypertension is more prevalent in black people, exceeding the frequency in other ethnic minority groups. The incidence of hypertensive encephalopathy is lowest in white people.

Sex

Hypertension is more prevalent in men than in women.

Age

Hypertensive encephalopathy mostly occurs in middle-aged individuals who have a long-standing history of hypertension.

CLINICAL

Section 3 of 10  

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

History

Most patients have a history of hypertension. Of those without a prior history of hypertension, place emphasis on past medical history, medication list, and medication compliance. Actively seek drug-induced causes.

• Patients usually have vague neurologic symptoms and may present with symptoms of headache, confusion, visual disturbances, seizures, nausea, and vomiting. Headaches are usually anterior and constant in nature. The onset of symptoms usually occurs over 24-48 hours, with neurologic progression over 24-48 hours.
• Patients also may present with symptoms resulting from other end organ damage. Examples of these symptoms include the following:
• • Cardiovascular symptoms of aortic dissection, congestive heart failure, angina, palpitations, irregular heart beat, and dyspnea
  • Renal hematuria and acute renal failure

Physical

A thorough and complete neurologic and funduscopic examination is essential in evaluation of patients.

• Funduscopic examination: Grade IV retinal changes are associated with hypertensive encephalopathy, including papilledema, hemorrhage, exudates, and cotton-wool spots.
• Neurologic examination reveals transient and migratory neurological nonfocal deficits ranging from nystagmus to weakness and an altered mental status ranging from confusion to coma.
• Include careful vascular examination to evaluate for vasculopathy because radiologic examinations might not acutely identify ischemic stroke.
• Other target organ damage that may be found includes the following:
• • Cardiovascular - S₃, elevated neck veins, peripheral edema, murmurs, abdominal pulsations, and diminished pulses
  • Renal - Acute renal failure, pulmonary edema, and peripheral edema
  • Pulmonary - Pulmonary edema, rales, and wheezes

Causes

The most common cause of hypertensive encephalopathy is abrupt blood pressure elevation in the chronically hypertensive patient. Other conditions predisposing a patient to elevated blood pressure can cause the same clinical situation.

• Chronic renal parenchymal disease
• Acute glomerulonephritis
• Renovascular hypertension
• Withdrawal from hypertensive agents (eg, clonidine)
• Encephalitis, meningitis
• Pheochromocytoma
• Sympathomimetic agents (eg, cocaine, amphetamines, phencyclidine [PCP], lysergic acid diethylamide [LSD])
• Eclampsia and preeclampsia
• Head trauma
• Collagen vascular disease
• Autonomic hyperactivity
• Vasculitis
• Ingestion of tyramine-containing foods or tricyclic antidepressants in combination with monoamine oxidase inhibitors (MAOIs)

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Acute CNS event
Acute thrombotic stroke
Cerebral embolus
CNS mass lesions
Encephalitis
Intracranial hemorrhage
Renal failure

WORKUP

Section 5 of 10  

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

Lab Studies

• Hypertensive encephalopathy is a diagnosis of exclusion; evaluate other etiologies as indicated clinically in the workup. Evaluation includes determining the extent of hypertensive damage and excluding intracranial processes. Laboratory and radiologic studies should not take the place of a careful history and physical examination, which includes a complete neurological and funduscopic examination.
• • CBC count: Obtain a CBC count to determine whether microangiopathic hemolytic anemia is present.
  • Urinalysis, BUN, and creatinine: With hypertensive nephropathy, an elevated creatinine with hematuria and casts may be present.
  • Cardiac enzymes: Exclude myocardial ischemia with cardiac enzymes.
  • Urine toxicology screen: This study is important in excluding drug-induced hypertensive encephalopathy.

Imaging Studies

• Consider a head CT scan to evaluate the presence of stroke, hemorrhage, or intracranial masses.
• Obtain chest radiographs to evaluate for possible complications of hypertensive encephalopathy, including aspiration due to altered mentation. Chest radiographs can also be used to evaluate for other conditions, eg, acute pulmonary edema and aortic dissection.

Other Tests

Perform electrocardiogram to evaluate for the presence of cardiac ischemia.

TREATMENT

Section 6 of 10  

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

Medical Care

In patients without hypertension, cerebral autoregulation preserves a relatively constant cerebral blood flow at a range of mean arterial blood pressures of 60-90 mm Hg. In chronically hypertensive patients, autoregulation is altered and shifted upward to maintain a relatively constant cerebral blood flow at a higher mean arterial blood pressure range.

• When initiating therapy, the baseline blood pressure must be considered to avoid excessive blood pressure lowering and prevent cerebral ischemia. Lowering the mean arterial pressure by 25% and the diastolic blood pressure to 100-110 mm Hg usually is a safe maneuver because of the pressure autoregulatory cerebral blood flow range.
• Acute monitoring in an intensive care unit with arterial blood pressure monitoring is required for adequate titration of pharmacologic agents and monitoring of end organ function.

MEDICATION

Section 7 of 10  

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

Pharmacologic agents selected for use in hypertensive encephalopathy should have few or no CNS adverse effects. Avoid agents such as clonidine, reserpine, and methyldopa. Although the clinical impact has not been determined, diazoxide is avoided because of the impact of decreased cerebral blood flow. If neurological deterioration worsens with therapy, reconsider the extent of blood pressure lowering or consider alternate diagnoses.

Labetalol provides a steady consistent drop in blood pressure without compromising cerebral blood flow. Labetalol is frequently used as initial therapy. Because of nonselective beta-blocking properties, it should be avoided in severe reactive airways disease and cardiogenic shock.

Nitroglycerin has been used to provide a rapid reduction in blood pressure complicating myocardial ischemia. The reduction in blood pressure may be severe and can cause further complications due to venodilatory effects in volume-contracted individuals. Nitroprusside and hydralazine pose a theoretical risk of intracranial shunting of blood. Thus, these agents should be avoided in patients suspected of having increased intracranial pressure (ICP) because they may cause intracerebral shunting of blood, which increases ICP. An increasing number of authorities are considering labetalol, nifedipine, and esomolol as the preferred initial agent.

Trimethaphan camsylate is used to reduce the shearing force in the presence of aortic dissection. Hydralazine has a limited role, owing to reflex tachycardia, and it should not be used in patients with suspected coronary artery disease.

Drug Category: Antihypertensive Agent

These agents are used to reduce blood pressure.

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

• Acute inpatient intensive care unit monitoring with arterial blood pressure monitoring is required for adequate titration of pharmacologic agents. Routinely perform neurologic reassessment to monitor signs of deterioration due to inadequate treatment, progression of neurologic insult, overzealous reduction in blood pressure, or alternate etiology of the clinical presentation.
• Quickly and effectively treat severe hypertension to avoid progression to coma and death. If invasive monitoring is not immediately available, initiate alternate therapy with agents that do not require close monitoring until a monitored situation becomes available.

Further Outpatient Care

• Regularly reassess hypertension because it is a chronic problem. Adequate control of hypertension is essential in preventing the progression of target organ disease.
• High blood pressure has been associated with a rapid rate of cognitive decline and an increased risk of cardiac and neurologic events.
• To guide the formulation of an effective treatment plan, document prior hypertensive medication regimes that have failed.

In/Out Patient Meds

• Discharge patients on antihypertensives that were effective in maintaining an adequate blood pressure range during hospitalization.

Deterrence/Prevention

• Recommend lifestyle modifications, including weight reduction to decrease body mass index (BMI) to less than 27, moderation of alcohol and sodium intake, increasing physical activity, and avoidance of tobacco products.
• Patients should adhere to antihypertensive therapy and schedule reassessment at regular intervals to modify failing regimens.

Complications

• Complications of hypertensive encephalopathy result in neurologic deficits from hemorrhage and strokes, which can progress to death.
• Complications of hypertension include the following
• • Coma
  • Death
  • Stroke
  • Nephropathy
  • Myocardial ischemia/infarction
  • Nephropathy
  • Retinopathy
  • Peripheral vascular disease

Prognosis

The morbidity and mortality associated with hypertensive encephalopathy are related to the degree of target organ damage. Without treatment, the 6-month mortality rate for hypertensive emergencies is 50%, and the 1-year mortality rate approaches 90%.

Patient Education

• Refer patients to a dietitian to reduce the risk of vascular and hypertensive disease.
• Encourage lifestyle modifications, including smoking cessation, increasing exercise, moderation of alcohol, and avoidance of tobacco.
• Educate patients about medication adherence and compliance and enforce the need for medical compliance. Educate patients regarding the effects of uncontrolled hypertension, including the complications of persistent hypertension. Inform patients about signs of acute target organ damage, including visual changes, persistent headaches, and neurological changes.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Hypertensive encephalopathy is a diagnosis of exclusion, and other potentially life-threatening etiologies must be considered in assessing a patient with neurologic deficits.
• Deterioration of clinical status despite therapy warrants immediate and further investigation into other possible etiologies or reevaluation of therapy for worsening hypertensive encephalopathy.
• Monitor complications of medical therapy (eg, overzealous reduction in blood pressure, adverse effects or toxicity of pharmacological therapy).

REFERENCES

Section 10 of 10

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

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15. Tsou TP, Yen ZS, Fang CC, et al. Hypertensive encephalopathy. J Emerg Med. Jul 2004;27(1):85-6. [Medline].
16. Tzourio C, Dufouil C, Ducimetiere P, Alperovitch A. Cognitive decline in individuals with high blood pressure: a longitudinal study in the elderly. EVA Study Group. Epidemiology of Vascular Aging. Neurology. Dec 10 1999;53(9):1948-52. [Medline].
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Article Last Updated: Jun 4, 2008