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 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:
In the US: Of the 60 million Americans with hypertension,
less than 1% will 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: 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.
Patients usually have vague neurologic complaints and may present with
symptoms of headache, confusion, visual disturbances, seizures, nausea, and
vomiting. Headaches are usually anterior and constant in nature. Onset of
symptoms usually occurs over 24-48 hours, with neurologic progression over
24-48 hours.
Patients also may present with complaints resulting from other end organ
damage. Examples of these complaints might 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
exam is essential in evaluation of patient.
Funduscopic exam: Grade IV retinal changes are associated with
hypertensive encephalopathy papilledema, hemorrhage, exudates, and cotton-wool
spots.
Neurologic exam 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 exam to evaluate for vasculopathy, as radiologic
exams might not acutely identify ischemic stroke.
Other target organ damage that may be found includes the
following:
Renal - Acute renal failure, pulmonary edema, and peripheral
edema
Pulmonary - Pulmonary edema, rales, and wheezes
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.
Chronic renal parenchymal disease
Acute glomerulonephritis
Renovascular hypertension
Withdrawal from hypertensive agents (eg, clonidine)
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, which includes a complete neurological and
funduscopic exam.
CBC for presence of microangiopathic hemolytic anemia
Urinalysis, BUN, and creatinine: With hypertensive nephropathy, an
elevated creatinine with hematuria and casts may be present.
Exclude myocardial ischemia with cardiac enzymes
Urine toxicology screen is important in excluding drug-induced
hypertensive encephalopathy.
Imaging Studies:
Consider head CT scan to evaluate the presence of stroke, hemorrhage, or
intracranial masses.
Perform chest x-ray (CXR) to evaluate for possible complications of
hypertensive encephalopathy, including aspiration due to altered mentation.
CXR can also evaluate for other insults, eg, acute pulmonary edema and aortic
dissection.
Other Tests:
Perform electrocardiogram to evaluate for presence of cardiac
ischemia.
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.
When initiating therapy, the baseline blood pressure must be taken in
context to avoid excessive blood pressure lowering and prevent cerebral
ischemia. Lowering the mean arterial pressure by 25% and 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.
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.
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.
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:
Acute in-patient 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 clinical
presentation.
Quickly and effectively treat severe hypertension to deter the 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 since 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:
Lifestyle modifications, including weight reduction to decrease BMI to
less than 27, moderation of alcohol and sodium intake, increasing physical
activity, and avoidance of tobacco
Adherence to antihypertensive therapy and interval reassessment to modify
failing regimen
Patient education and interval regular follow-up visits
Inform patient on effects of uncontrolled hypertension.
Educate patient on medication adherence and compliance.
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 to dietitian to reduce risk of vascular and hypertensive
disease.
Encourage lifestyle modifications, including smoking cessation, increasing
exercise, moderation of alcohol, and avoidance of tobacco.
Enforce need for medical compliance. Educate patient on complications of
persistent hypertension. Inform patient on signs of acute target organ damage,
including visual changes, persistent headaches, and neurological
changes.
MISCELLANEOUS
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, side effects or toxicity of pharmacological
therapy).
Constructed
by Dr N.A. Nematallah Consultant in perioperative medicine and intensive
therapy, Al Razi Orthopedic Hospital ,
State of Kuwait, email : razianesth@freeservers.com
