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 Encephalopathy, Hypertensive
 

Encephalopathy, Hypertensive

INTRODUCTION

Background: Hypertension affects more than 60 million Americans. With adequate control, less than 1% will experience a hypertensive crisis. Hypertensive crisis is classified as hypertensive emergency or hypertensive urgency. Acute or ongoing vital target organ damage, such as the brain, kidney, or heart damage, 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 a hypertensive urgency and requires reduction in blood pressure within 24-48 hours. There is a continuum between the clinical syndrome of hypertensive urgency and emergency; hence, their distinction may not always be clear and precise.

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 was associated with group 3 Keith-Wagener-Barker retinopathy, which is characterized by retinal hemorrhages and exudates on funduscopic examination. Malignant hypertension was 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 (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 goes beyond the individualís 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:

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: Frequency of hypertensive encephalopathy corresponds to the occurrence of hypertension in the general population. Hypertension is more prevalent in African Americans, exceeding the frequency in other ethnic minority groups. Incidence of hypertensive encephalopathy is lowest in Caucasians.

Sex: Hypertension is more prevalent in men than in women.

Age: Hypertensive encephalopathy mostly occurs in middle-aged individuals who have a longstanding history of hypertension.

CLINICAL

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.

Physical: A thorough and complete neurologic and funduscopic exam is essential in evaluation of patient.

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

DIFFERENTIALS

Eclampsia
Encephalopathy, Dialysis
Encephalopathy, Hepatic
Encephalopathy, Uremic
Head Trauma
Pheochromocytoma
Subarachnoid Hemorrhage
Subdural Hematoma


Other Problems to be Considered:

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

WORKUP

Lab Studies:

Imaging Studies:

Other Tests:

TREATMENT

Medical Care: In patients without hypertension, cerebral autoregulation preserves a relatively constant cerebral blood flow at a range of mean arterial blood pressures between 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.

Pharmacologic agents selected for use in hypertensive encephalopathy should have few or no CNS side effects. Avoid agents such as clonidine, reserpine, and methyldopa. Although the clinical impact has not been determined, diazoxide is avoided because of impact of decreased cerebral blood flow. If neurological deterioration worsens with therapy, reconsider extent of blood pressure lowering or consider alternate diagnoses.
Nitroprusside is frequently considered first-line therapy due to rapid onset and short duration of action. 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 nitroglycerin poses a theoretical risk of intracranial shunting of blood. Thus, an increasing number of authorities are considering labetalol the preferred agent. Labetalol provides a steady consistent drop in BP without compromising cerebral blood flow. Due to non-selective beta blocking properties, it should be avoided in severe reactive airways disease and cardiogenic shock. Trimethaphan camsylate is used to reduce the shearing force in the presence of aortic dissection. Hydralazine has a limited role due to reflex tachycardia and should not be used with suspected coronary artery disease.

Drug Category: Antihypertensive -- Prevent complications and reduce morbidity
Drug Name
Nitroprusside sodium (Nitropress) -- First-line medication for hypertensive encephalopathy. Decreases systemic vascular resistance via direct dilatation of arterioles and veins. May cause intracerebral shunting of blood, increasing ICP.
Adult Dose 0.5-1 mcg/kg/min IV infusion, titrate to desired BP
Pediatric Dose Not established
Contraindications Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis and atrial fibrillation or flutter
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Potential for cyanide toxicity occurs with prolonged infusion (>72 h) and high infusion rate (>3 mcg/kg/min); suspect hyperreflexia, worsening mental status, and toxicity in presence of metabolic acidosis; treatment for cyanide toxicity includes amyl nitrate, thiosulfate, and hydroxocobalamin; dialysis may be necessary for thiocyanate toxicity; hypoxia by inhibition of hypoxia-induced vasoconstriction in the pulmonary vasculature causing perfusion to nonventilated areas of the lung
Drug Name
Labetalol (Normodyne) -- Competitive and selective alpha1 blocker and nonselective beta-blocker with predominantly beta effects at low doses. Onset of action is 5 min with half-life of 5.5 h. Provides a steady consistent drop in BP without compromising cerebral blood flow.
Adult Dose 20 mg IV bolus, then 20-80 mg IV bolus q10min; not to exceed 300 mg
Alternatively: 2 mg/min IV infusion, titrate to desired BP; not to exceed 300 mg
Pediatric Dose Not established
Contraindications Documented hypersensitivity; cardiogenic shock, pulmonary edema, bradycardia, atrioventricular block, uncompensated congestive heart failure, reactive airway disease, and severe bradycardia
Interactions Labetalol decreases effect of diuretics and increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex tachycardia, resulting from nitroglycerin use, without interfering with hypotensive effects; cimetidine may increase labetalol blood levels; glutethimide may decrease labetalol effects by inducing microsomal enzymes
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in impaired hepatic function; discontinue therapy if there are signs of liver dysfunction; in elderly patients, a lower response rate and higher incidence of toxicity may be observed
Drug Name
Nitroglycerin (Nitro-Bid) -- Provides arteriolar dilation and venodilation. Used in emergencies involving myocardial ischemia due to the dilatatory effects of nitroglycerin on coronary arteries.
Adult Dose 5-300 mcg/min IV infusion, titrate to desired BP
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severe anemia, shock, postural hypotension, head trauma closed angle glaucoma, or cerebral hemorrhage
Interactions Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in coronary artery disease, and low systolic and diastolic blood pressure
Drug Name
Trimethaphan camsylate (Arfonad) -- A ganglionic blocking agent primarily used in aortic dissection. Reduces heart rate and left ventricular ejection rate, thus lowering shearing force.
Adult Dose 0.5-10 mg/min IV infusion, titrate to desired BP
Pediatric Dose Not established
Contraindications Documented hypersensitivity; anemia; cerebral vascular disease; coronary artery disease; glaucoma; hypovolemia; MI; respiratory insufficiency; shock
Interactions Coadministration with anesthetic agents may cause hypotension; trimethaphan may potentiate neuromuscular blocking action of nondepolarizing agents and succinylcholine
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Decreased cardiac output and peripheral vascular resistance may occur, causing orthostatic hypotension; ganglionic blockade causes dry mouth, visual changes, urinary retention, and ileus
Drug Name
Hydralazine (Hydrea) -- Direct arteriolar dilator. Limited role because of reflex tachycardia causing increased cardiac oxygen demand.
Adult Dose 5-20 mg IV bolus
0.5-1 mg/min IV infusion
Pediatric Dose Not established
Contraindications Documented hypersensitivity; mitral valve rheumatic heart disease
Interactions MAO inhibitors and Beta blockers may increase hydralazine toxicity; pharmacologic effects of hydralazine may be decreased by indomethacin
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Hydralazine has been implicated in myocardial infarction; caution in suspected coronary artery disease
Drug Name
Phentolamine (Regitine) -- Alpha1 and alpha2 adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on the alpha receptors.
Adult Dose 5-10 mg IV bolus
0.2-5 mg/min IV infusion
Pediatric Dose Not established
Contraindications Documented hypersensitivity; coronary or cerebral arteriosclerosis and renal impairment
Interactions Concurrent administration of epinephrine or ephedrine may decrease phentolamine effects; ethanol increases phentolamine toxicity
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in tachycardia, peptic ulcer, and gastritis; cerebrovascular occlusions and myocardial infarctions can occur following phentolamine administration
Drug Name
Nicardipine (Cardene) -- Calcium channel blocker. Potent, rapid onset of action, ease of titration, and lack of toxic metabolites. Effective but limited reported experience in hypertensive encephalopathy.
Adult Dose Loading: 5-15 mg/h IV
Maintenance: 3-5 mg/h IV
Pediatric Dose Not established
Contraindications Documented hypersensitivity; severe hypotension, cardiogenic shock, atrial fibrillation, CHF
Interactions H2 blockers may increase bioavailability of nicardipine; coadministration with propranolol or metoprolol may increase cardiac depressant effects on A-V conduction
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Adjust dose in hepatic and renal impairment; may increase frequency and duration of angina attacks

FOLLOW-UP

Further Inpatient Care:

Further Outpatient Care:

In/Out Patient Meds:

Deterrence/Prevention:

Complications:

Prognosis:

Patient Education:

MISCELLANEOUS

Medical/Legal Pitfalls:

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Constructed by Dr N.A. Nematallah Consultant in perioperative medicine and intensive therapy, Al Razi Orthopedic Hospital , State of Kuwait, email : razianesth@freeservers.com