The term hypertensive encephalopathy was introduced in 1928 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, as follows:
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 neurologic impairment from an elevated intracranial pressure (ICP)
With adequate control of hypertension, less than 1% of patients experience a hypertensive crisis. A hypertensive crisis is classified as either a hypertensive emergency or a hypertensive urgency,[1] as follows:
Acute or ongoing vital target organ damage (eg, damage to the brain, kidney, or heart) in the setting of severe hypertension is considered a hypertensive emergency; a prompt reduction in blood pressure is required within minutes or hours
The absence of target organ damage in the presence of a severe elevation in blood pressure (with diastolic blood pressure frequently exceeding 120 mm Hg) is considered a hypertensive urgency; a reduction in blood pressure is required within 24-48 hours
A continuum exists between the clinical syndromes of hypertensive urgency and emergency; hence, the distinction between the 2 syndromes may not always be clear and precise in practice.[2]
Hypertensive encephalopathy refers to the transient migratory neurologic symptoms that are associated with the malignant hypertensive state in a hypertensive emergency. The clinical symptoms are usually reversible with prompt initiation of therapy. In the evaluation of an encephalopathic patient, it is vital to exclude systemic disorders and various cerebrovascular events that may present with a similar constellation of clinical findings.
The clinical manifestations of hypertensive encephalopathy are due to increased cerebral perfusion from the loss of blood-brain barrier integrity, which results 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 (CBF) and an intact blood-brain barrier.
In chronically hypertensive individuals, the cerebral autoregulatory range is gradually shifted to higher pressures as an adaptation to the chronic elevation of systemic blood pressure.[3] This adaptive 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 (CNS). Brain MRI scans have shown a pattern of typically posterior (occipital greater than frontal) brain edema that is reversible. This usually is termed reversible posterior leukoencephalopathy or posterior reversible encephalopathy syndrome (PRES).[4]
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 are clinically manifested as neurologic deficits and altered mentation in hypertensive encephalopathy.
The most common cause of hypertensive encephalopathy is abrupt blood pressure elevation in a chronically hypertensive patient. Other conditions that can predispose a patient to elevated blood pressure and cause the same clinical situation include the following:
Chronic renal parenchymal disease
Acute glomerulonephritis
Renovascular hypertension
Withdrawal from hypertensive agents (eg, clonidine)
Of the 60 million Americans with hypertension, less than 1% develop a hypertensive emergency. The morbidity and mortality associated with hypertensive encephalopathy are related to the degree of target-organ damage. Without treatment, the 6-month mortality for hypertensive emergencies is 50%, and the 1-year mortality approaches 90%.
Hypertensive encephalopathy mostly occurs in middle-aged individuals who have a long-standing history of hypertension. Hypertension in general is more prevalent in men than in women. The frequency of hypertensive encephalopathy in various ethnic groups corresponds to the frequency 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.
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 strongly emphasize the need for medical compliance. Explain 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.
Most patients with hypertensive encephalopathy have a history of hypertension. In patients who do not have a prior history of hypertension, place emphasis on the past medical history, the medication list, and medication compliance. Actively seek drug-induced causes, for example, sympathomimetic agents and illicit drugs such as cocaine.[5]
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.[6] Examples of these symptoms include the following:
Cardiovascular symptoms of aortic dissection, congestive heart failure, angina, palpitations, irregular heartbeat, or dyspnea
A thorough and complete neurologic and ophthalmoscopic (funduscopic) examination is essential in the evaluation of patients. On ophthalmoscopy, grade IV retinal changes are associated with hypertensive encephalopathy,[7] including papilledema, hemorrhage, exudates, and cotton-wool spots (see the images below). Although papilledema is usually considered a more severe finding, it actually does not confer worse survival than hemorrhages and exudates alone.[8]
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Papilledema. Note the swelling of the optic disc, with blurred margins.
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Hypertensive retinopathy. Note the flame-shaped hemorrhages, soft exudates, and early disc blurring.
Neurologic examination reveals transient and migratory neurologic nonfocal deficits ranging from nystagmus to weakness and an altered mental status ranging from confusion to coma.
In addition, include a careful vascular examination to evaluate for vasculopathy; radiologic examinations might not acutely identify ischemic stroke.
Other target-organ damage that may be found includes the following:
Complications of hypertensive encephalopathy result in neurologic deficits from hemorrhage and strokes, which can progress to death. Complications of hypertension include the following:
Hypertensive encephalopathy is a diagnosis of exclusion; other potential causes of the symptoms must be evaluated in the workup as indicated by the clinical findings. Evaluation includes determining the extent of hypertensive damage and excluding intracranial processes. Laboratory and radiologic studies do not take the place of a careful history and physical examination (see Presentation).
Obtain a complete blood count (CBC) to determine whether microangiopathic hemolytic anemia is present. Perform a urinalysis, and measure blood urea nitrogen (BUN) and creatinine levels; with hypertensive nephropathy, an elevated creatinine with hematuria and casts may be present. Order cardiac enzyme studies to exclude myocardial ischemia. Perform a urine toxicology screen to help exclude drug-induced hypertensive encephalopathy.
Consider computed tomography (CT) or magnetic resonance imaging (MRI) of the head to look for indications 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, such as acute pulmonary edema and aortic dissection.
Perform electrocardiography (ECG) to evaluate for the presence of cardiac ischemia.
In patients without hypertension, cerebral autoregulation preserves a relatively constant cerebral blood flow (CBF) at a mean arterial pressure (MAP) range of 60-90 mm Hg. In chronically hypertensive patients, autoregulation is altered and shifted upward to maintain a relatively constant CBF at a higher MAP range.
When therapy is initiated, it is important to consider the baseline blood pressure in order to avoid excessive blood pressure reduction and prevent cerebral ischemia. It is usually safe to reduce MAP by 25% and to lower the diastolic blood pressure to 100-110 mm Hg.
Acute monitoring in an intensive care unit (ICU) with arterial blood pressure monitoring is required for adequate titration of pharmacologic agents and monitoring of end-organ function. Potential complications of medical therapy (eg, overzealous reduction in blood pressure and adverse effects or toxicity of pharmacologic therapy) must be watched for.
Deterioration of clinical status despite therapy warrants immediate and further investigation into other possible etiologies or reevaluation of therapy for worsening hypertensive encephalopathy.
Pharmacologic agents selected for use in hypertensive encephalopathy should have few or no adverse effects on the central nervous system (CNS). Avoid agents such as clonidine, reserpine, and methyldopa. Although the clinical impact of diazoxide has not been determined, this agent is avoided because of the impact of decreased CBF. An increasing number of authorities are considering labetalol, nicardipine, and esmolol as preferred initial agents.
Nicardipine is a second-generation dihydropyridine-derivative calcium channel blocker, which has high vascular selectivity and strong cerebral and coronary vasodilatory activity. It has been shown to increase stroke volume and coronary blood flow.[9]
Labetalol provides a steady consistent drop in blood pressure without compromising CBF. It is frequently used as initial therapy. Because of its nonselective beta-blocking properties, labetalol should be avoided in severe reactive airway disease and cardiogenic shock.
Nitroglycerin has been used to provide a rapid reduction in elevated 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 sodium and hydralazine pose a theoretical risk of intracranial shunting of blood. Accordingly, these agents should be avoided in patients suspected of having increased intracranial pressure (ICP), because the potential intracerebral shunting of blood can increase the ICP. Hydralazine has a limited role in this setting, owing to reflex tachycardia, and it should not be used in patients with suspected coronary artery disease (CAD). Diuretics should also not be used in these patients unless there is clear evidence of volume overload. This is due to pressure natriuresis that occurs and leaves these patients volume depleted. Volume repletion by itself can sometimes lower the blood pressure.[10]
If neurologic deterioration worsens with therapy, it is necessary to reconsider the extent of blood pressure reduction or to consider alternate diagnoses.
Acute inpatient ICU 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, evaluation the progression of a neurologic insult, watch for overzealous reduction of blood pressure, or assess a possible alternative cause 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 alternative therapy with agents that do not require close monitoring until a monitored situation becomes available.
Recommend lifestyle modifications, including weight reduction to decrease the patient’s body mass index (BMI) to less than 27, moderation of alcohol and sodium intake, increasing physical activity, and avoidance of tobacco products.
Discharge patients on antihypertensives that were effective in maintaining an adequate blood pressure range during hospitalization. Emphasize the importance of adhering to antihypertensive therapy and scheduling reassessment at regular intervals to modify failing regimens.
Because hypertension is a chronic problem, regularly reassessment is vital. 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 a more effective treatment plan, document prior hypertensive medication regimens that have failed.
Pharmacologic agents selected for use in hypertensive encephalopathy should have few or no adverse effects on the central nervous system (CNS). Antihypertensive medications used in this setting include labetalol, nicardipine, esmolol, nitroprusside sodium, phentolamine, nitroglycerin, and hydralazine.
Clinical Context:
Labetalol is a competitive and selective alpha1 blocker and a nonselective beta-blocker that has predominantly beta effects at low doses. The onset of action is 5 minutes, and the half-life is 5.5 hours. Labetalol produces a steady, consistent drop in blood pressure without compromising cerebral blood flow (CBF).
Clinical Context:
Nicardipine is a calcium channel blocker that has a potent and rapid onset of action, is easy to titrate, and lacks toxic metabolites. It appears to be effective in hypertensive encephalopathy, but the reported experience is limited.
Clinical Context:
Esmolol is an ultrashort-acting agent that selectively blocks beta1 receptors but has little or no effect on beta2 receptor types. It is particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Esmolol has been shown to reduce episodes of chest pain and clinical cardiac events in comparison with placebo. It can be discontinued abruptly if necessary.
Esmolol is useful in patients at risk for experiencing complications from beta blockade, particularly those with reactive airway disease, mild-to-moderate left ventricular dysfunction, or peripheral vascular disease. Its short half-life (8 minutes) allows easy titration to the desired effect and quick discontinuance if necessary.
Clinical Context:
Nitroprusside sodium decreases systemic vascular resistance by causing direct dilatation of arterioles and veins. It should be avoided in patients suspected of having increased ICP. It may cause intracerebral shunting of blood, thereby increasing ICP.
Clinical Context:
Phentolamine is an alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing the hypertension that results from catecholamine effects on the alpha-receptors.
Clinical Context:
Nitroglycerin provides arteriolar dilation and venodilation. It is used in emergencies involving myocardial ischemia because of its dilatory effects on coronary arteries.
Clinical Context:
Hydralazine is a direct arteriolar dilator. It plays a limited role in this setting because of reflex tachycardia causing increased cardiac oxygen demand. It should be avoided in patients suspected of having increased ICP.
What is hypertensive encephalopathy?What is the pathophysiology of hypertensive encephalopathy?What causes hypertensive encephalopathy?Which patient groups are at highest risk for hypertensive encephalopathy?What is included in patient education about hypertensive encephalopathy?Which clinical history findings are characteristic of hypertensive encephalopathy?What is the role of neurologic and ophthalmoscopic (funduscopic) exam in the evaluation of hypertensive encephalopathy?Which physical findings are characteristic of hypertensive encephalopathy?What are possible complications of hypertensive encephalopathy?Which conditions should be included in the differential diagnosis of hypertensive encephalopathy?What are the differential diagnoses for Hypertensive Encephalopathy?What is the role of lab tests in the workup of hypertensive encephalopathy?What is the role of imaging studies in the workup of hypertensive encephalopathy?What is the focus of the initial treatment for hypertensive encephalopathy?What is included in ICU care of patients with hypertensive encephalopathy?Which medications are used in the treatment of hypertensive encephalopathy?What is included in acute monitoring of patients with hypertensive encephalopathy?How is hypertensive encephalopathy prevented?What is included in long-term monitoring and care following treatment for hypertensive encephalopathy?What is the goal of drug treatment for hypertensive encephalopathy?Which medications in the drug class Antihypertensive, Other are used in the treatment of Hypertensive Encephalopathy?
Irawan Susanto, MD, FACP, Clinical Professor of Medicine, Director of Pulmonary Consultation and Procedures, Divisions of Interventional Pulmonology and Critical Care, University of California, Los Angeles, David Geffen School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Helmi L Lutsep, MD, Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center
Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Consultant, Abbott Vascular, Inc. .
Additional Contributors
Najia Huda, MD, Assistant Professor, Wayne State University School of Medicine; Director of MICU, Division of Pulmonary and Critical Care, Detroit Receiving Hospital
Disclosure: Nothing to disclose.
Acknowledgements
Ryan C Chang, MD Consulting Staff, Department of Internal Medicine, Divisions of Pulmonary and Critical Care, Kaiser Permanente San Francisco
Ryan C Chang, MD is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society
Disclosure: Nothing to disclose.
Oleh Wasyl Hnatiuk, MD Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences
Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
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