Hypertensive Encephalopathy
Recognition and Management
C. Venkata S. Ram, MD
Hypertensive encephalopathy is a dramatic syndrome char-
acterized by severe elevation of blood pressure, headache,
visual disturbances, altered mental status, and convulsions.
Although the syndrome is uncommon, to recognize and treat it
promptly is important or the condition may prove to be fatal.
Hypertensive encephalopathy should be distinguished from
other cerebral complications of severe hypertension by obtain-
ing careful history and performing thorough physical examina-
tion. The only definitive criterion for the diagnosis of this
syndrome is its prompt response to therapy. If the patient's
condition does not improve with hypotensive therapy, the physi-
cian should immediately search for alternate diagnoses. Potent
drugs are available for prompt reduction of blood pressure.
There are few medical emergencies in which the objective
response to therapy is so strikingly apparent as in hypertensive
encephalopathy.
(Arch Intern Med 138:1851-1853, 1978)
XJypertensive encephalopathy is a medical emergency
caused by abrupt and severe elevation of blood pres¬
sure. The present uncommon occurrence of this syndrome
reflects overall improved management of hypertension. It
is important to recognize hypertensive encephalopathy
because prompt reduction of blood pressure results in
amelioration of the syndrome, which is otherwise poten¬
tially fatal. Hypertensive encephalopathy was described
approximately 50 years ago.1 The widespread availability,
in recent years, of potent antihypertensive agents has
made the management of hypertensive encephalopathy
much easier. Hypertensive encephalopathy occurs during
the course of severe elevation of arterial blood pressure and
is not limited to any specific type of hypertension,
Accepted for publication May 17, 1978.
From the Department of Internal Medicine, University of Texas South-
western Medical School, Dallas.
Reprint requests to the Department of Internal Medicine, University of
Texas Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX
75235 (Dr Ram).
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although the syndrome tends to occur more commonly as a
complication in acute glomerulonephritis, toxemia of preg¬
nancy, and renal artery stenosis. In hypertensive encepha¬
lopathy, it is not only the absolute level, but also the rate at
which elevation of blood pressure occurs, that determine
the development of symptoms, since investigators have
demonstrated that rapid elevation of blood pressure in
previously normotensive subjects can derange the cerebral
blood flow.2
PATHOGENESIS
Normal cerebral blood flow (CBF) remains relatively
constant in a wide range of variations in systemic blood
pressure and is estimated to be 50 ml/min/100 g of brain.3-4
This remarkable constancy of CBF is accomplished by the
process of cerebral "auto-regulation"; by this process, with
severe elevation of blood pressure, cerebral arterioles
constrict to maintain adequate cerebral perfusion. In
hypertensive encephalopathy, derangement of cerebral
auto-regulation occurs (Figure). Originally, Oppenheimer
and Fishberg1 proposed that there is exaggerated spasm of
cerebral blood vessels in this condition, and this concept of
"over-regulation" was subsequently supported by Byrom's
classical work/' Recently, another concept, the so-called
breakthrough theory,2•" has been suggested as the mecha¬
nism for hypertensive encephalopathy. According to this
theory, severe elevation of blood pressure leads to decom¬
pensation or breakthrough of cerebral blood flow with a
consequent increase in CBF that results in cerebral edema.
These conflicting opinions are only of theoretical interest,
since in any event, prompt reduction of blood pressure is
mandatory in the management of hypertensive encepha¬
lopathy.
CLINICAL FEATURES
Headache, usually severe and generalized, is the most
common complaint. Visual complaints that range from
blurring of vision to transient blindness7 are quite
common. Nausea and vomiting (of projectile nature) are
initial complaints in many patients. Convulsions, focal or
 generalized, occur in some patients, especially children.8
Sometimes myoclonic twitches may be observed, but they
are more likely to occur in uremic encephalopathy rather
than in hypertensive encephalopathy per se. Focal cere-
brovascular deficits, such as hemiparesis and aphasia, can
punctuate the course of hypertensive encephalopathy but
are usually transient. Sustained cerebrovascular deficits
should arouse the physician's suspicion as to possible other
diagnoses.
Hypertensive encephalopathy is also characterized by
alteration in mental status, ranging from slight disorienta¬
tion to ultimate coma if the condition progresses. On
examination, blood pressure is invariably elevated. Brady-
cardia, if present, might reflect increased intracranial
pressure. Most patients with hypertensive encephalopathy
are alert during the initial stages, but the sensorium is
bound to be clouded if the encephalopathic process is
uninterrupted. Mild (transient) neurological deficits,
including cranial nerve palsies, especially of the facial
nerve, may be noted.
Fundi usually reveal severe focal or generalized arterio-
lar spasm with exudates or hemorrhages; although papil-
ledema is present in most patients, the syndrome can occur
in the absence of papilledema.7 Brain scan and films of the
skull are almost always normal. Electroencephalographic
patterns in hypertensive encephalopathy are nonspecifical-
ly abnormal, and therefore, of no immediate help in the
diagnosis. Cerebrospinal fluid is usually clear and under
increased tension in most, but not all, cases; the protein
content is normal or elevated.
DIFFERENTIAL DIAGNOSIS
When a patient with severe headache, papilledema,
altered mental status, and severe hypertension is exam¬
ined, the most likely diagnosis is hypertensive encephalop¬
athy. The only definitive criterion, however, for confirm¬
ing the diagnosis is the prompt response of the patient's
condition to antihypertensive therapy.
Hypertensive encephalopathy must be distinguished
from other neurological manifestations of severe hyper-
Severe Elevation
tension, namely, cerebral infarction or hemorrhage, and
uremic encephalopathy. In 43 cases diagnosed as hyperten¬
sive encephalopathy, Ziegler et al9 found that in a majority
of the cases, there was evidence of cerebral infarction,
hemorrhage, or uremic encephalopathy. Therefore, meticu¬
lous evaluation of the patient should be carried out before
making the diagnosis of hypertensive encephalopathy. The
differential diagnosis of this disorder should include the
possibilities of an intracranial mass lesion, seizure disor¬
der, and meningitis—all of which may coexist with severe
hypertension. Finally, the potential of reflex elevation of
systemic blood pressure as a result of ischemia of brain
must be considered; there are certain intrinsic mechanisms
in the brain stem that, when rendered ischémie, reflexly
elevate the blood pressure as a protective phenomenon.10
MANAGEMENT
Parenteral hypotensive drugs produce prompt and
dramatic relief of symptoms of hypertensive encephalopa¬
thy. Once the diagnosis is apparent, the blood pressure
should be lowered to near normal levels. The preferred
drugs in the treatment of hypertensive encephalopathy
(Table) are discussed in this section. The patient should
ideally be observed and given medication in an intensive
care unit.
Sodium Nitroprusside
Sodium nitroprusside is a potent vasodilating agent that
reduces the blood pressure promptly and effectively. The drug
must be administered by continuous intravenous drip, and
constant blood pressure monitoring is mandatory. Sodium nitro¬
prusside (50 mg lyophilized powder) should be dissolved in 500 to
1,000 ml of 5% dextrose in water and administered intravenously
in the dosage range of 0.3 to 6.0 fig/kg body weight per minute.
Occasionally, higher doses are required to achieve the desired
blood pressure level.
Advantages of this drug include its potency, rapid onset and
offset of action, and relative safety. The drug, importantly, has no
direct effect on the CNS. Side effects with nitroprusside are
uncommon. One potential effect, however, is induction of hypoten¬
sion, which can be avoided by careful monitoring.
The potential of thiocyanate toxic reaction should be kept in
mind, however; nitroprusside is converted in the body to cyanide,
which, in turn, is rapidly converted by the liver to thiocyanate,
which is excreted by the kidney. Thiocyanate ions can accumulate

CerebralOver-Regulation
(Exaggerated Vasospasm)
\
Cerebral Under-Regulatlon
in renal failure and serum thiocyanate concentrations greater
than 12 mg/dl are considered toxic.11 Manifestations of thiocya¬
nate toxicity include nausea, vomiting, and confusion. Rare cases
of hypothyroidism caused by thiocyanate toxicity12 and methemo-
globinemia after nitroprusside therapy" have been reported.
(Breakthrough of Circulation)
The therapy of hypertensive encephalopathy with nitroprusside
is usually of short duration; and, therefore, the potential of

>k. Hypertensive
Encephalopathy
y thiocyanate toxicity does not preclude use of this drug.
Diazoxide
Diazoxide is a potent hypotensive agent that is closely related to
the thiazide group of drugs. It is a rapidly effective drug with a
Pathogenesls of hypertensive encephalopathy. hypotensive action that is due to a reduction in peripheral vascular

Drugs Used in the Treatment of Hypertensive Encephalopathy

Drug Dose Advantages Disadvantages
Sodium 0.3-6.0 /ig/kg/min, Predictably effective and safe; Close monitoring is essential; potential of thiocyanate
nitroprusside continuous Intravenous rapid onset of action; free of toxicity with prolonged administration, especially in
drip cardiac stimulation renal failure; possible ¡nactlvatlon of the drug If the
container Is exposed to light
Diazoxide 300 mg, or 5 mg/kg, rapid Rapid onset of action; sustained Reflex tachycardia; does not always produce a response;
Intravenous Injection effect If response occurs; ease nausea/vomiting; potential of overshoot In the blood
of administration pressure response; fluid retention
Trlmethaphan 3-5 mg/min, continuous Rapidly effective; free of cardiac Paralytic ileus; bladder atony; cycloplegia and mydriasis
camsylate Intravenous drip stimulation

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 resistance through direct relaxation of arterioles.14
Diazoxide is administered as a rapid intravenous bolus, 300 mg
or 5 mg/kg body weight; rapid administration is necessary to
overcome the protein binding of the drug. Blood pressure response
is seen within three to five minutes after the drug is given, and the
effect of a single dose may persist for six to 18 hours.15 If there is
no response to the first dose, a second injection can be given
within a half to one hour.
The advantage of diazoxide is that it can be given as a bolus
injection rather than as a continuous intravenous drip. However,
according to current recommendations, the drug needs to be given
as a standard dose, and the lack of a titratable dose may
potentially result in overshoot of blood pressure response in an
occasional patient.
Diazoxide causes reflex cardiac stimulation, and an angina-like
syndrome with its use has been reported.16 The inhibitory effect of
diazoxide on labor1' should be considered if the drug is used to
treat hypertensive encephalopathy complicating toxemia of preg¬
nancy. Fluid retention, accompanying diazoxide therapy, can be
counteracted by concomitant administration of a loop diuretic.
Hyperglycemia following the use of diazoxide is temporary and
does not ordinarily require specific therapy in persons who are not
diabetic.
Trimethaphan Camsylate
Trimethaphan camsylate is a rapidly effective hypotensive
agent with an action that is mediated by ganglionic blockade. The
drug is given as a continuous intravenous drip in the dosage of 3 to
5 mg/min, and this dosage should be adjusted depending on the
blood pressure response. The onset of action is within five to ten
minutes, and the effect may last for five to ten minutes following
cessation of therapy.
Since the drug has an orthostatic effect, its effectiveness can be
enhanced by elevating the head-end of the patient's bed. Because
of generalized ganglion blockade, prolonged administration of
trimethaphan (for more than one or two days) may result in
paralytic ileus, bladder atony, and mydriasis—thus warranting
discontinuance of therapy. Respiratory paralysis attributable to
trimethaphan has been reported.18
Other
Drugs and Therapy
Hydralazine hydrochloride, a direct vasodilating agent has been
successfully used in the treatment of hypertensive emergencies
for several years. Although effective in appropriate doses, its use
in hypertensive encephalopathy has now been largely supplanted
by the more potent drugs already discussed.
Clonidine hydrochloride, methyldopa, and reserpine should not
be used for the treatment of hypertensive encephalopathy because
of their delayed action and direct CNS effects.
Convulsions that occur during the course of hypertensive
encephalopathy are usually well controlled with reduction of blood
pressure itself, but occasionally, anticonvulsive therapy may be
required. Once the encephalopathy has fully resolved, appropriate
oral antihypertensive therapy must be begun.
COMMENT
Although it is sometimes difficult to distinguish hyper¬
tensive encephalopathy from other cerebral complications
of severe hypertension, the sine qua non of hypertensive
encephalopathy is its prompt response to hypotensive
therapy. The therapy of hypertensive encephalopathy does
not depend on the resolution of the controversy as to
whether cerebral circulatory over-regulation or under-
regulation is the underlying mechanism; rather, prompt
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reduction of blood pressure is essential. Presently, nitro¬
prusside and diazoxide are the drugs of choice, although
because of the smoother action of nitroprusside, it is pre¬
ferred in several institutions. Various untoward effects
make trimethaphan a less desirable treatment choice.
If the patient's neurologic syndrome does not improve
(or worsens) with therapy, alternate diagnoses should be
immediately sought. When the encephalopathic crisis has
fully resolved, suitable oral drug therapy must be begun.
The physician should also probe possible factor(s) for
precipitous elevation of blood pressure, such as reasons for
cessation of drug therapy, or possible onset and/or
progression of renal artery stenosis. There are few medical
emergencies in which objective response to therapy is so
readily apparent as in hypertensive encephalopathy.
Nonprpprietary Names and Trademarks of Drugs
Clonidinehydrochloride-Caiapres.
Diazoxide—Hyperstat.
Sodium nitroprusside-Mpride.
Trimethaphan camsylate—Arfonad.
References
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