•
Section Four Vascular System
Chapter 82   Hypertension
Richard O. Gray
■  PERSPECTIVE
For most of the 20th century, elevated blood pressure (BP)
readings were thought to be associated with, but not causing,
morbidity and mortality. Not until large population-based
studies in the 1960s, such as the Framingham study, did physi-
cians begin to focus on hypertension as a treatable risk factor
for stroke, myocardial infarction (MI), peripheral vascular
disease, congestive heart failure, and renal disease. Medical
management of hypertension has reduced stroke mortality by
50% on an age-adjusted basis and has probably contributed to
the decline in mortality from coronary artery disease. As a
matter of public health, however, much remains to be done in
the treatment of hypertension. Although approximately 75%
of patients with chronically elevated BP are aware of their
disease, as few as one half to one fourth of these patients are
adequately treated and most surveillance data suggest this is
not improving.1-3 Although hypertension may be epidemic, it
rarely represents an emergency condition for the individual
patient. In the absence of acute end-organ damage, it is rarely,
if ever, necessary to lower a patient’s BP acutely in the emer-
gency department.
Hypertension is frequently encountered in the emergency
department (ED), where many factors can cause elevated BP.
Patients may measure their own blood pressure in a retail
pharmacy and present to the ED concerned that a symptom
they are experiencing is caused by the blood pressure eleva-
tion. Anxiety and pain often cause transient hypertension, but
evaluation of the patient for evidence of acute end-organ is­­
chemia is important. Most patients, even those with an exac-
erbation of chronically elevated BP, show a substantial decrease
in pressure without intervention during a short observation
period in the ED.4-6 Even if the patient’s BP does remain ele-
vated, urgent treatment is rarely beneficial or indicated, unless
there is evidence of end-organ damage. Patient education and
appropriate referral for long-term management should be
provided.7
■  PRINCIPLES OF DISEASE
Definition and Determination   pressure determinations in an ambulatory care setting.
of Hypertension
The Joint National Committee on Prevention, Evaluation, and
Treatment of High Blood Pressure in its seventh report has
dramatically changed how it classifies hypertension. In adults,
1076
a sustained systolic pressure less than 120 mm Hg and a dia-
stolic pressure less than 80 mm Hg are considered normal. If
the systolic pressure is between 120 and 139 mm Hg or if the
diastolic pressure is between 80 and 89 mm Hg, the term pre-
hypertension is applied, reflecting that the lifetime incidence of
hypertension in these individuals is twice that of individuals
in the “normal” range.2 The patient with a sustained systolic
pressure of 140 mm Hg or higher or a diastolic pressure higher
than 90 mm Hg is considered to be hypertensive. If hyperten-
sion, as defined by these arbitrary values, is not controlled, the
patient is at great risk for long-term morbidity and mortality.2,8
The diastolic pressure is the primary determinant of future
cardiovascular risk and is the most prevalent form of hyperten-
sion in patients younger than 50 years. In the two thirds of
adults older than 65 years who have hypertension, systolic
hypertension is more common and represents their greatest
cardiovascular risk. Even isolated systolic hypertension in
elderly patients is a significant risk factor for cardiovascular
disease, especially when combined with other risk factors. In
older patients, an elevated pulse pressure (determined by
subtracting diastolic from systolic pressure) is an equally
significant risk factor for stroke and MI.9-11
Proper technique is required to obtain accurate BP readings.
In patients with large extremities, a standard-size cuff may give
a falsely elevated BP. A larger cuff should be used. With rapid
deflation, inertia causes a gap between the actual pressure in
the cuff and the measured pressure on the gauge. The systolic
pressure should be recorded when the first tapping sound is
heard as the cuff is deflated. Although several endpoints have
been used to define diastolic pressure, the most widely accepted
is the total disappearance of sound. In patients who do not have
complete disappearance of these sounds, the point of distinct
muffling should be recorded as the diastolic pressure.
A single elevated BP does not necessarily mean that the
patient has hypertension. This is especially true in children.12
BP measurement should be repeated after the patient is in a
reclining position for at least 10 minutes and should be checked
in both arms. If the second reading is also elevated or close to
the hypertensive range, the patient should be advised of the
potential for hypertension and referred for repeated blood
Pathophysiology
Hypertension is not a single disease but, rather, the result of
a number of disease processes. By far the most common cate-

gory is essential hypertension. No specific cause of essential
hypertension has been identified, although heredity, age, race,
obesity, and the amount of dietary sodium may contribute to
elevated BP.12 Prehypertension has been intensely studied
because patients who later become hypertensive may provide
clues about the physiologic changes that eventually produce a
fixed elevation of BP. Two major theories exist: (1) hyperten-
sion results from alterations in the contractile properties of
smooth muscle in arterial walls, and (2) alterations of arterial
smooth muscle are a response to chronically elevated BP
resulting from a primary failure of normal autoregulatory
mechanisms. Research has focused on the role of calcium ions
in vascular smooth muscle. Vascular tone depends on a trans-
membranous supply of calcium ions, and calcium antagonists
suppress virtually all vasoconstrictive responses of vascular
smooth muscles, including the peripheral resistance vessels.
Most patients with established hypertension have elevated
peripheral arterial resistance and normal cardiac output. The
findings are similar in the majority of prehypertensive indi-
viduals, many of whom have decreased plasma volume and
elevated heart rate. This tachycardia seems to be caused not
by an increased sympathetic tone but by a decreased parasym-
pathetic tone. Autoregulatory mechanisms are blunted, and
pharmacologic autonomic blockade has minimal effect on
BP.
Other patients with hypertension have a very different cir-
culatory status with an elevated cardiac output and hyper­
kinetic circulation. The increase in cardiac output results
from an increase in both heart rate and stroke volume. There
appears to be a large sympathetic component with an increase
in both cardiac beta-adrenergic and alpha-adrenergic tone.
Autonomic blockade returns the BP readings to normal.
Renin, Angiotensin, and Aldosterone
The role of renin and angiotensin as a cause of essential hyper-
tension is not clear. Renin is an enzyme produced by the
kidney that splits off angiotensin I from a plasma globulin
precursor.13 Angiotensin I is converted by an enzyme in the
lung to produce angiotensin II. Angiotensin II is a potent
vasoconstrictor and also stimulates aldosterone production in
the adrenal gland. Figure 82-1 depicts the renin-angiotensin-
aldosterone axis. Patients with hypertension may be divided
into clinical groups according to renin levels. Determining the
renin-sodium profile, which is the plasma renin activity mea-
sured against the 24-hour urine sodium content, is especially
useful in making this distinction.
In normal individuals, angiotensin effects depend on sodium
levels. Inhibition of angiotensin-converting enzyme (ACE)
has some effect on BP in normotensive individuals with normal
total body sodium but greatly reduces BP in those with sodium
depletion. When ACE inhibitors are administered to patients
with hypertension, their acute effect on BP is closely related
to the plasma renin activity. With chronic administration,
however, the effect of ACE inhibitors on BP no longer corre-
lates with pretreatment plasma renin activity.14 Elevated
renin and angiotensin levels are responsible for the hyper­
tension seen in ischemic renal disease, and angiotensin is
a major contributor to maintaining the progressive rise of BP
in accelerated hypertension. In the latter condition, renin
and angiotensin levels are increased because of areas of renal
ischemia secondary to arteriolar necrosis. ACE inhibitors or
angiotensin blockers are clearly the drugs of choice in hyper-
tensive patients with diabetes or decreased left ventricular
function or both.
The role of hyperaldosteronism in essential hypertension is
debatable.15,16 Primary hyperaldosteronism may affect 8 to 32%
1077
Liver
Chapter 82 / Hypertension
Kidney Angiotensinogen
↓ Blood volume
↓ Renal blood flow Renin
↓ Sodium delivery
to the distal tubule
↑ Sympathetic
innervation
Angiotensin I
Angiotensin
converting
enzyme
Angiotensin II
Sodium retention
Potassium and Aldosterone secretion
hydrogen excretion
Figure 82-1.  The renin-angiotensin-aldosterone axis. Solid lines represent
stimulation, and dashed lines imply negative feedback mechanisms.
of patients, depending on the population of patients screened,
and it should be investigated in patients with refractory hyper-
tension.17 Hyperaldosteronism may occur with an isolated
adrenal aldosteronoma, bilateral microscopic multinodular
adrenal hyperplasia, macroscopic adrenal hyperplasia, a genetic
form called glucocorticoid remediable hyperaldosteronism, or
even adrenal carcinoma. Spontaneous hypokalemia in a patient
with hypertension should suggest primary hyperaldosteron-
ism, but this is not invariably present. Catecholamine levels
may also be abnormal. Primary hyperaldosteronism is usually
investigated by a comparison of the ratio of plasma aldosterone
concentration to plasma renin activity and confirmed by a
failure to inhibit aldosterone levels in the urine or plasma with
sodium loading.18
Renal Disease
Although essential hypertension is the most common form of
hypertension, early identification of secondary hypertension is
important because it may lead to cure or at least to a specific
and much easier treatment regimen. Of these other causes,
renal disease is the most prevalent. All types of renal disease
are associated with hypertension, although a direct relation-
ship can be demonstrated only in cases of unilateral renal
disease, in which the removal of the affected kidney cures the
hypertension. This is clear in unilateral renal arteriostenosis.
Renovascular hypertension results from the overproduction of
renin secondary to reduced blood flow through the stenotic
renal artery. The increased levels of renin lead to activation of
the angiotensin pathway and resultant hypertension. If the
renin level in the affected kidney is more than 50% higher
than the level in the normal kidney, a complete or partial cure
of the hypertension can be anticipated with surgery.
Another vascular lesion associated with arterial stenosis and
hypertension is fibromuscular dysplasia of the renal arteries.19,20
This disease is predominant in young white women, and flank
bruits are often present. The various types affect different
areas of the renal arteries. The result is progressive hyperten-
sion. Neither pharmacologic therapy nor surgical revision
offers a cure, but both treatments slow the disease process and
help preserve functional renal mass.
 1078
Primary renal disease can produce hypertension, but the
exact mechanism is unknown. Up to 70% of patients with
chronic pyelonephritis have elevated BP. Local ischemia
PART III  ■  Medicine and Surgery / Section Four • Vascular System
within the kidney is suspected as the cause of hypertension.
Some authors suggest local microvascular renal disease as the
final common pathway underlying essential hypertension.17
Hypertension in patients with nonspecific glomerulonephritis
may result from arteriolar lesions producing ischemia at the
level of the individual nephron. With the exception of renin-
secreting renal tumors, the exact cause of hypertension associ-
ated with the various nephropathies is unknown.
Arterial Disease
Abnormalities of the large arteries can also produce hyperten-
sion. Although uncommon, coarctation of the aorta is an impor-
tant cause of secondary hypertension, and early surgical
intervention can greatly improve the patient’s prognosis.21 The
triad of upper extremity hypertension, a systolic murmur best
heard over the back, and delayed femoral pulses should alert
the examiner to the diagnosis of coarctation. Hypertension
appears to result from the combined effects of mechanical
obstruction and activation of the renin-angiotensin system.22
Early diagnosis of coarctation is important because surgical
repair results in a consistent and sustained lowering of BP. In
adults, renal artery stenosis is an important cause of acceler-
ated onset of significant hypertension, and renal artery ultra-
sonography or angiography is advisable (on an ambulatory
basis) for patients with this type of onset of disease.
Loss of elasticity in the larger arteries associated with the
aging process produces systolic hypertension as well as eleva-
tions in pulse pressure. Arteriosclerosis from the deposition of
collagen and smooth muscle hypertrophy plays a major role in
the age-dependent stiffness of the central vasculature. Previ-
ously, elevated systolic pressure was not considered significant
and frequently was not treated. The current literature strongly
suggests that isolated systolic hypertension is associated with
an increased risk of stroke, heart disease, and renal failure and
should be treated. The cause of reduced elasticity in the arter-
ies associated with isolated systolic hypertension has not been
fully determined. Endothelial dysfunction that develops over
time with both aging and hypertension may play a critical role
in this process. Other factors that decrease central vascular
compliance include high dietary salt intake, tobacco use, ele-
vated homocysteine levels, and diabetes.
Glucocorticoids
Excessive glucocorticoids are associated with hypertension,
and the most common cause is iatrogenic steroid therapy.
Endogenous overproduction is rare and results from excessive
adrenocorticotropic hormone (ACTH) production by a pitu-
itary tumor, ectopic ACTH production by a nonpituitary
tumor, or glucocorticoid production by tumors of the adrenal
cortex. These patients show other signs and symptoms of
excessive glucocorticoids, including centripetal fat distribu-
tion, striae, easy bruising, muscular weakness, and poor healing.
The hypertension associated with hyperadrenalism is usually
not severe and can be controlled by treating the underlying
disease process.
Thyroid and Parathyroid Disease
Both hyper- and hypothyroidism are associated with elevations
in BP. In thyroid storm, patients are usually hypertensive and
tachycardic, and beta-blockade is a mainstay of the acute man-
agement. Patients with hypothyroidism also present with
hypertension as well as the other characteristic findings. Treat-
ment of the hypothyroidism usually results in correction of the
hypertensive state. Hypertension with hypercalcemia suggests
hyperparathyroidism, which is another rare secondary cause of
hypertension.
Sleep Apnea
Both obstructive and central forms of sleep apnea are associ-
ated with hypertension. Apnea itself is associated with a sig-
nificant increase in BP. Approximately 50% of patients with
sleep apnea have daytime hypertension, but many have
other risk factors for hypertension, such as obesity or alcohol
consumption. Studies suggest that treatment of nocturnal
hypoventilation may improve daytime BPs.23,24
Pheochromocytoma
Pheochromocytomas are responsible for less than 1% of cases
of hypertension. More than 90% of these patients are curable
with early diagnosis. Pheochromocytomas produce catechol-
amines and arise from cells of the sympathetic nervous system.
The most common site is the adrenal medulla. Patients with
neurofibromatosis (von Recklinghausen’s disease) have an
increased incidence of pheochromocytoma. Pheochromocy-
toma, medullary carcinoma of the thyroid, and parathyroid
adenomas form the triad of multiple endocrine neoplasia
(adenomatosis), type 2.
The characteristic feature of pheochromocytoma is parox-
ysms of hypertension associated with palpitations, tachycardia,
malaise, apprehension, and sweating. Many patients have a
persistently elevated BP interspersed with episodes of greater
hypertension that occur sporadically and vary greatly in sever-
ity, frequency, and duration. These episodes may be related
to physical and emotional stress, eating, position, or even mic-
turition. A prodrome of apprehension and nonspecific abdomi-
nal pain progressing to headache, palpitations, and angina may
be seen. Because of the episodic nature of this syndrome, the
patient is often dismissed with a diagnosis of hyperventilation
syndrome or anxiety. An excessively elevated BP associated
with these symptoms is enough to suggest a pheochromocy-
toma. Patients may also display increased BP when treated
with beta-blocking agents (beta-blockers).
The diagnosis is confirmed with elevated urinary levels of
catecholamines, metanephrines, and vanillylmandelic acid,25
usually to more than twice the normal levels. Treatment con-
sists of alpha-blockade to control hypertension and subsequent
beta-blockade for the control of cardiac dysrhythmias. After
the hypertension is adequately controlled, the tumor should
be surgically removed.
Other Causes
Eating foods that contain large amounts of tyramine can cause
episodic hypertension (Box 82-1). Tyramine causes release of
norepinephrine stored in nerve endings. This response is nor-
mally transient; tyramine is rapidly destroyed by monoamine
oxidase. Problems arise if a patient is being treated with a
monoamine oxidase inhibitor (MAOI), which protects tyra-
mine from destruction. Relatively small amounts of tyramine
can cause severe and prolonged hypertension. A number of
therapeutic agents can also induce a hypertensive crisis in
patients taking MAOIs. These include meperidine, the
amphetamines, ephedrine, reserpine, guanethidine, and
tricyclic antidepressants. The hypertension can be controlled
by using an alpha-blocking agent (alpha-blocker) such as
phentolamine.
 1079
Foods and Drugs Causing Hypertensive Crisis in BOX 82-2 Conditions Defining Hypertensive Crisis
BOX 82-1 Patients Taking Monoamine Oxidase Inhibitors

Chapter 82 / Hypertension
Accelerated or Malignant Hypertension
Foods* Hypertensive encephalopathy
Natural or aged cheeses Microangiopathic hemolytic anemia
Pickled herring Acute renal failure
Chicken liver Aortic Dissection
Coffee in large amounts
Chocolate Eclampsia/Preeclampsia
Broad beans Severe Hypertension in the Setting of:
Beer, wine Myocardial ischemia
Snails Left ventricular failure
Yeast Uncontrolled hemorrhage
Citrus fruits Systemic reperfusion therapy for stroke or myocardial
Cream infarction
Drugs Postoperative state
Sympathomimetic amines (e.g., amphetamines)
Methyldopa
Dopamine
Tryptophan there is evidence of acute dysfunction in the cardiovascular,
Reserpine neurologic, or renal organ system (Box 82-2). These conditions
Guanethidine are true medical emergencies and mandate early reduction
Tricyclic antidepressants of BP, preferably within 1 hour of identification of the
condition.2,29,30
*All contain significant amounts of tyramine except for broad beans, In the past, the range of hypertensive emergencies included
which contain dopamine.
patients who presented with any emergent condition associ-
ated with a marked elevation of BP. The elevated BP in these
Excess catecholamine effect can result from the acute with- patients is often a physiologic response to an acute condition,
drawal of clonidine or beta-blocker therapy.26 Clonidine acts and aggressive treatment for hypertension may actually increase
centrally as an alpha-adrenoreceptor agonist. The sudden morbidity and mortality. This is especially true for patients
withdrawal of this agent may result in catecholamine excess with acute intracranial events.31
and severe hypertension 16 to 48 hours later. Many of the
symptoms associated with clonidine withdrawal are similar to Hypertensive Encephalopathy
those of pheochromocytoma, including anxiety, tremor, palpi-
tations, and severe headache. Urinary catecholamine levels are Throughout the normal range of BP, cerebral blood flow is
markedly elevated. Treatment consists of restarting clonidine maintained by fluctuations in the vascular tone of the cerebral
therapy or using alpha-blockers. This characteristic limits resistance vessels known as autoregulation. Hypertensive
clonidine’s usefulness as an antihypertensive agent in non- encephalopathy is an uncommon syndrome resulting from an
compliant patients. abrupt, sustained rise in BP that exceeds the limits of cerebral
Alcoholism or alcohol withdrawal may precipitate hyperten- autoregulation of the small resistance arteries in the brain.
sion. Use of nonsteroidal anti-inflammatory agents, including Above a mean arterial pressure (MAP) of approximately
the selective cyclooxygenase-2 inhibitors, may inhibit the 160 mm Hg, autoregulation may be unable to control cerebral
antihypertensive effects of diuretics and drugs that work on blood flow, resulting in vasospasm, ischemia, increased vascu-
the renin-angiotensin system.27,28 lar permeability, punctate hemorrhages, and brain edema.
Immediate reduction of BP by 30 to 40% reverses the vaso-
Emergency Department Presentation spasm. Excessive reduction of BP must be avoided to prevent
increasing cerebral ischemia. In normal humans, autoregula-
Hypertension is seen in the ED in the following four general tion operates above an MAP of approximately 60 mm Hg. In
ways: patients with uncontrolled hypertension, however, the level of
autoregulation is elevated, cerebral ischemia may occur at a
1. “Hypertensive emergency” or “hypertensive crisis” with much higher MAP, and BP reduction should generally not
acute end-organ ischemia take the MAP below 100 mm Hg.
2. “Hypertensive urgency,” a historical term of no clinical Hypertensive encephalopathy is (1) acute in onset and (2)
value related to arbitrarily elevated BP with nonspecific reversible. Patients present with severe headaches, vomiting,
symptoms. These patients probably are best referred to drowsiness, and confusion. Seizures, blindness, focal neuro-
simply as having poorly controlled or inadequately con- logic deficits, or coma may occur. Papilledema is usually
trolled hypertension. present, along with significant hypertensive retinopathy. Dif-
3. Mild hypertension without end-organ ischemia ferential diagnosis includes strokes and intracranial hemor-
4. Transient hypertension related to anxiety or the primary rhage (ICH), meningoencephalitis, brain tumors, and metabolic
complaint coma. Careful neurologic examination often differentiates
between a space-occupying lesion and hypertensive encepha-
■  CLINICAL PRESENTATION OF lopathy because focal deficits from hypertensive encephalopa-
thy usually do not follow a singular anatomic pattern. They
HYPERTENSIVE EMERGENCIES
may occur on opposite sides of the body or may have multiple
A small number of hypertensive patients present with a true areas of involvement. Computed tomography is usually normal,
hypertensive emergency. BP is usually markedly elevated and and the electroencephalogram shows only nonspecific abnor-
 1080
malities. The cerebrospinal fluid is clear, with an increased
opening pressure and normal or increased protein.
Hypertensive encephalopathy is a true medical emergency;
PART III  ■  Medicine and Surgery / Section Four • Vascular System
untreated patients develop increasing coma, and death may
ensue within a few hours. Rapid, controlled reduction of BP
is essential with a careful reduction of the MAP by 25% or to
a diastolic pressure of 100 to 110 mm Hg over 1 hour. The
standard treatment regimen in the United States has long been
intravenous (IV) nitroprusside, but labetalol is now widely
used, and other agents, such as fenoldopam, nicardipine, and
enalaprilat, have also proven effective. Clevidipine is a newer
ultra-short-acting calcium channel blocker under investigation
for the management of hypertensive emergencies.32 Use of an
oral or nontitratable agent may result in excessive reduction of
BP and irreversible cerebral ischemia. Nifedipine was widely
used in the past for rapid mitigation of hypertension, particu-
larly in the context of heart failure, but it has largely fallen out
of favor because of numerous serious adverse effects related
to uncontrolled hypotension and sympathetic release.30,33
All patients with hypertensive encephalopathy should be
hospitalized, and establishment of an arterial line for BP moni-
toring is desirable.
Malignant Hypertension
Malignant (accelerated) hypertension is severe hypertension
associated with evidence of acute and progressive damage to
end organs. This syndrome can occur at any time in the clinical
course of hypertension. The diastolic BP is usually greater
than 130 mm Hg. Readings below this level are seldom associ-
ated with either malignant hypertension or hypertensive
encephalopathy, although rarely either can occur with diastolic
pressures as low as 110 mm Hg. The vast majority of patients
with diastolic pressures higher than 130 mm Hg do not develop
either of these clinical syndromes. Malignant hypertension
affects only 1% of the hypertensive population.30
The pathologic process begins when a rapid, sustained rise
in BP overwhelms the high-pressure autoregulatory mecha-
nism, causing the small arterioles to dilate. As these vessels
dilate, pressure in the proximal capillary beds increases, and
fluid leaks into the tissues. The arterioles may rupture and
leak plasma and blood, resulting in fibrin deposition into their
walls. This combination of necrosis of myofibrils in smooth
muscle cells, leaking of plasma, and fibrin deposition in the
walls of arterioles is fibrinoid necrosis and is responsible for end-
organ damage. These changes within the small arterioles are
directly visible in the retina as linear hemorrhages dissecting
along nerve fibers. The disruption of the arteriolar wall causes
obstruction of the vessel and ischemia downstream. In the
retina, this produces a cotton-wool spot that consists of swollen,
ischemic axons. The aggregation of materials within the isch-
emic axons produces a nuclear-like structure termed the cytoid
body. Hard exudates, which consist of lipid deposits located
deep in the retina, are also a common finding. These fine,
punctate, shiny lesions can be distinguished from cotton-wool
spots, which are larger and have blurred edges and a more
diffuse appearance.
Patients with malignant hypertension appear ill and often
present with complaints of severe headache, blurred vision,
dyspnea, and chest pain or with symptoms of uremia. If
untreated, it may result in acute renal failure, severe cardiac
decompensation, MI, hypertensive cerebral hemorrhage, or
hypertensive encephalopathy.
The diagnosis of malignant hypertension cannot be made
on the basis of BP readings alone. In addition to elevated BP,
these patients must have evidence of acute end-organ damage
as a result of the hypertension. The physical examination may
reveal an enlarged left ventricle and rales at the lung bases.
Marked retinal findings are often present, including linear
hemorrhages and cotton-wool patches. Acute elevation of
blood urea nitrogen and serum creatinine or the presence of
hematuria indicates involvement of the kidneys. Rarely, the
blood smear reveals red cell fragments, and fibrin degradation
products are elevated, giving a clinical picture compatible with
microangiopathic hemolytic anemia. Left ventricular hypertro-
phy and strain are usually seen on the electrocardiogram
(ECG). The chest radiograph may reveal cardiomegaly and
evidence of congestive heart failure.
Malignant hypertension is treated in a manner similar to that
for hypertensive encephalopathy by the judicious lowering of
MAP by 25% of pretreatment levels over the initial minutes
to hours and then toward a target of 160/100 over 2 to 6 hours,
avoiding excessive decreases in pressure that may precipitate
renal, cerebral, or coronary ischemia.2,29,30
All patients with malignant hypertension should be hospi-
talized, and invasive BP monitoring may be preferable. An
easily titratable agent, such as labetalol, nitroprusside, or
fenoldopam, is used, with the goal of avoiding any episodes of
hypotension.
Stroke Syndromes
Hypertension is often associated with stroke syndromes.34 In
most of these patients, elevated BP is the physiologic response
to the stroke and is not the immediate cause. Approximately
85% of strokes are nonhemorrhagic, and most patients who
have embolic or thrombotic strokes without an associated
hemorrhage do not sustain substantially elevated BP. These
patients have mild to moderate hypertension that has little
effect on the clinical course and may portend a better progno-
sis.35 In patients with long-standing hypertension, rapid reduc-
tion of BP may further reduce cerebral blood flow and cause
increased ischemia.
Except in cases of stroke caused by aortic dissection, anti-
hypertensive therapy is not indicated and may be harmful.
Some have recommended careful antihypertensive treatment
for patients with persistent, extreme elevations of BP after a
stroke (e.g., diastolic pressure >140 or MAP >130 mm Hg), but
data do not support this approach.36 The best current advice
is to limit reductions in BP for acute stroke patients to circum-
stances in which the BP elevation is causing injury to another
end organ, for example, myocardial ischemia. In these cases,
BP should be lowered cautiously to mitigate the effects on the
other end organ, but the ischemic neurologic deficit must not
increase. When fibrinolytic therapy is administered, significant
elevations of BP greatly increase the risk of secondary ICH,
and patients with persistent pressures higher than
185/110 mm Hg should not receive thrombolytic therapy until
their blood pressure is controlled.36,37
Patients with ICH often have a profound, reactive elevation
of BP. In most patients with ICH, hypertension is secondary
to the increased intracranial pressure (ICP) and to irritation of
the autonomic nervous system. This type of hypertension
often disappears rapidly and has little effect on clinical
outcome. Deterioration in most patients with ICH results from
hemorrhagic enlargement or edema. Data to support the phar-
macologic lowering of BP in patients with ICH are lacking.34
Persistent hypertension is associated with a poorer functional
outcome after ICH, and traditionally many centers treat hyper-
tension after ICH. Because cerebral perfusion pressure (CPP)
depends on systemic pressure, this practice may not be benefi-
cial. Although no conclusive evidence indicates that treating
hypertension in the acute period after ICH is beneficial,
modest reductions in BP (e.g., 20% reduction in MAP) have

not been clearly associated with a worse outcome and may be
advisable after discussion with the vascular neurosurgery
consultant.
If BP reduction is pursued in these patients, labetalol is the
agent of choice. Labetalol and other adrenergic blockers shift
cerebral autoregulation to lower pressures in patients with
intracranial mass lesions. This shift preserves cerebral blood
flow at lower pressures. Adrenergic blockers also preserve reac-
tivity to carbon dioxide partial pressure (Pco2).34 Nicardipine
also has been used successfully to treat hypertension in the
setting of acute intracerebral hemorrhage.38 ACE inhibitors
also shift autoregulation but have not been extensively studied
in patients with ICH or elevated ICP. Vasodilators such as
nitroprusside increase ICP, impair cerebrovascular reactivity
to changes in Pco2, and exacerbate any decrease in CPP for a
given level of BP reduction.
Pulmonary Edema
Most patients with congestive heart failure have some degree
of increased peripheral vascular resistance (PVR) and resultant
hypertension; this is a normal response. The degree of BP
elevation is moderate and does not represent a medical emer-
gency. When poorly controlled, however, long-standing hyper-
tension produces myocardial hypertrophy, which continues
until the hypertrophy can no longer overcome the increased
PVR; then the left ventricle begins to fail and dilates.
In most patients with this combination, the hypertension
results from increased PVR caused by elevated catecholamines
associated with the stress of pulmonary edema. With standard
treatment of pulmonary edema, including morphine, nitrates,
oxygen, ACE inhibitors, and furosemide, catecholamine levels
decrease and BP returns rapidly toward normal. In a small
number of patients, pulmonary edema results from an abrupt,
severe elevation of BP that precipitates acute left ventricular
failure. The BP must be lowered to reverse this process. Nitro-
glycerin is usually the first drug used, but if it does not ade-
quately reduce BP, nitroprusside should be the next choice.
Nitroprusside does not cause sodium retention; it improves
cardiac function, especially in the failing heart, and can be
carefully titrated and rapidly reversed. ACE inhibition has also
been used successfully as an adjunct in the acute treatment of
pulmonary edema.39,40 Although pressure often decreases sig-
nificantly with treatment of congestive heart failure, stroke
syndromes can occur as a consequence of hypotension occur-
ring during the treatment of acute pulmonary edema.41
Cardiac Ischemia
Hypertension and angina are often found together. If severe
hypertension is present with concurrent angina, immediate
lowering of BP is indicated to prevent myocardial damage. In
most of these patients, nitroglycerin and an IV beta-blocker,
such as metoprolol, are the agents of choice. ACE inhibitors
may be a useful adjunct and have also been shown to reduce
mortality in patients with MI. Calcium channel blockers may
be a useful alternative for patients unable to tolerate beta-
adrenergic blockade because of bronchospasm. Nitroprusside
may induce a reflex tachycardia and must be used with caution
in patients with cardiac ischemia. With systemic fibrinolytic
therapy, aggressive BP control is required due to the risk of
ICH.37
Renal Failure
The most important cardiovascular complication of chronic
renal failure (CRF) is hypertension.42,43 Uncontrolled hyper-
1081
tension accelerates the development of cardiovascular prob-
lems, which are the most common cause of death in both
dialysis and transplant patients. Hypertension also causes
Chapter 82 / Hypertension
further damage to diseased kidneys. Hypertension may appear
at any time during the course of CRF and occurs in more than
80% of patients with advanced renal failure. Glomerular
disease is associated with a higher incidence of hypertension
than is tubulointerstitial disease. In the absence of hyperten-
sion, CRF worsens more slowly; if hypertension is present but
controlled, the progression of CRF can be delayed. Patients
with renal failure secondary to malignant hypertension often
demonstrate a transient worsening of renal function during
their initial treatment period. After this initial period, renal
function improves.
The primary cause of hypertension for patients with CRF
is an actual or relative increase in extracellular volume second-
ary to sodium retention, as well as activation of the renin-
angiotensin system in diseased kidneys. Glomerular disease is
associated with greater sodium retention than is tubulointer-
stitial disease. Diuretics to improve fluid balance and ACE
inhibitors, angiotensin receptor blockers, or calcium channel
blockers should be the first-line agents to control hypertension
in patients with renal failure.44 Patients with CRF are fre-
quently seen in the ED. If their BP is significantly elevated,
the managing physician should be notified and the antihyper-
tensive regimen adjusted.
Severe elevation of BP may lead to acute renal failure or
may exacerbate CRF. Immediate reduction of BP is required.
Fenoldopam is the drug of choice, although the IV calcium
channel blocker nicardipine and nitroprusside are reasonable
alternatives.30
Pregnancy
Hypertension is one of the most common complications of
pregnancy, occurring in 5 to 10% of all pregnancies (see Chap-
ters 176 and 177). Antihypertensive agents may be needed but
in most patients can be delayed until hospital admission. The
exceptions are those women with severe preeclampsia or
eclampsia, both of which represent hypertensive emergencies
and can occur without an extreme elevation of BP. Any acute
elevation of the diastolic BP higher than 100 mm Hg in the
pregnant patient represents a true hypertensive emergency.
The treatment of hypertensive emergencies of pregnancy
should include reduction of BP, prevention and control of
seizures, and early obstetric consultation. Although it may
cause tachycardia and hypotension, the classic antihyperten-
sive agent of choice in preeclampsia has been IV hydralazine,
but this is falling out of favor due to its relative unpredictable
dose-response curve.30,45 Alternative antihypertensives include
labetalol and nicardipine. Nitroprusside is relatively contrain-
dicated because of the potential for accumulation of cyanide
in utero. Because of this potential complication, nitroprusside
should be reserved for those patients in whom other agents
have failed. Oral nifedipine has also been used in this setting,
although, as in other conditions, overshoot hypotension has
been observed.46 Preeclampsia and eclampsia are true hyper-
tensive emergencies and are discussed in Chapter 176.
Aortic Dissection
Aortic dissection is associated with a history of hypertension
(see Chapter 83). Medical therapy consists of reducing BP to
limit the extent of the dissection. The goals of medical therapy
are to lower BP to a systolic level of 100 to 120 mm Hg and to
reduce the ejection force of the heart. Classically, a beta-
blocker such as esmolol is given to control reflex tachycardia,
 1082
whereas a vasodilator (nitroprusside, fenoldopam, or nicardip-
Table 82-1 Summary
ine) is used to reduce BP. Single drug management using the of Drugs of Choice in the Treatment
combined alpha/beta-blocker labetalol is commonly used and of Hypertensive Emergencies
PART III  ■  Medicine and Surgery / Section Four • Vascular System

successful.29,30
ALTERNATIVE
OR SECOND-
■  MANAGEMENT OF EMERGENCY DRUG(S) OF CHOICE LINE DRUGS
HYPERTENSIVE EMERGENCIES
Accelerated Nitroprusside, Labetalol or
Vasodilators hypertension, fenoldopam nicardipine
hypertensive
Fenoldopam encephalopathy
Fenoldopam (Corlopam) is a peripheral dopamine-1 receptor Intracranial Labetalol Nitroprusside,
agonist approved for the treatment of hypertensive emergen- hemorrhage nicardipine
cies. Dopamine-1 receptors are located postsynaptically in the Acute pulmonary Nitroglycerin, Fenoldopam,
systemic and renal vasculature and mediate systemic, renal, edema nitroprusside ACE inhibitor
and mesenteric vasodilation as well as natriuresis. In contrast Cardiac ischemia Nitroglycerin, Nitroprusside,
to treatment with nitroprusside, fenoldopam therapy improves beta-blockers labetalol
renal function acutely in patients with malignant hyperten- Aortic dissection Nitroprusside + Labetalol
sion.47 Fenoldopam does not cross the blood-brain barrier, has beta-blockers
a rapid onset of action, and has an elimination half-life of Adrenergic crises Phentolamine, Labetalol
9 minutes.48-50 Reflex tachycardia, flushing, and headache nitroprusside +
may be observed, but hypotension occurs less often than with beta-blockers
nitroprusside therapy. Eclampsia, Labetalol Nicardipine,
The initial dose of fenoldopam is 0.1 µg/kg/min, and the preeclampsia hydralazine
dose is titrated in 0.1 µg/kg/min increments every 15 minutes ACE, angiotensin-converting enzyme.
until the desired effect is seen. The maximum recommended
dose is 1.6 µg/kg/min. Fenoldopam represents a reasonable
alternative to nitroprusside in the treatment of hypertensive angina, but a coronary steal phenomenon may occur.30 The
emergencies without the concerns of light sensitivity and cardiac response depends on the state of myocardial function.
cyanide or thiocyanate toxicity and also with fewer hypoten- Because of the reduction of preload by venous dilation, the
sive episodes. Fenoldopam has been used in trials without cardiac output often improves if congestive heart failure or
invasive BP monitoring.48 borderline myocardial function is present. Because nitroprus-
side is a cerebral vasodilator, it may increase ICP secondary to
Nicardipine increased cerebral blood flow. Nitroprusside is metabolized to
thiocyanate and is excreted slowly by the kidneys. Cyanide is
Nicardipine (Cardene) is a parenteral dihydropyridine calcium an intermediate metabolite, and its metabolism requires func-
channel blocker that has become very popular in the treatment tioning liver, kidneys, and adequate bioavailability of thiosul-
of postoperative hypertension. Nicardipine is titratable, has fate. In the presence of renal failure or during prolonged
less negative inotropic effect, and induces less tachycardia nitroprusside therapy, the thiocyanate concentration may
than does nifedipine. Nicardipine acts predominantly as a reach toxic levels of 10 mg/dL, and a clinical picture of weak-
vasodilator, but as with other calcium channel blockers, caution ness, hypoxia, nausea, tinnitus, muscle spasm, disorientation,
must be used when it is administered to patients with left and psychosis may develop. The prolonged use of nitroprus-
ventricular failure. Nicardipine is administered as an infusion side may produce hypothyroidism by inhibition of iodine
beginning at 5 mg/hr, increasing the infusion rate every 15 transport, and methemoglobinemia has occurred.
minutes until the desired reduction of BP has been achieved, Nitroprusside must be used as an IV solution. As capaci-
to a maximum dose of 15 mg/hr. Onset of action is 5 to 15 tance vessels dilate, the patient must be kept recumbent to
minutes and duration of action 4 to 6 hours. As with labetalol, prevent profound orthostatic hypotension. Because of nitro-
an oral form may facilitate the transition from acute to chronic prusside’s short half-life, stopping the infusion returns the BP
therapy. to pretreatment levels within 1 to 10 minutes. The amount of
Nicardipine is heavily metabolized in the liver, and caution BP reduction is dose related. Elderly patients and those receiv-
must be used in patients with cirrhosis. Nicardipine decreases ing antihypertensive medications are more sensitive to nitro-
the glomerular filtration rate in patients with compromised prusside’s effects. In all patients, the starting dose should be
renal function, a trait shared by nitroprusside. As with the 0.25 to 1.0 µg/kg body weight per minute. The average dose
other vasodilators, headache, flushing, and tachycardia are the required for the control of hypertension is 3.0 µg/kg/min.
most common adverse reactions seen with nicardipine. Nicar- Dosages greater than 800 µg/min are seldom required and
dipine has been best studied in pregnant patients and in the should not be used for long periods because of the accumula-
settings of postoperative and malignant hypertension, in which tion of cyanide and thiocyanate. Patients treated with nitro-
it appears to be a less toxic alternative to nitroprusside.2,30,51 prusside should be admitted to the intensive care unit for close
monitoring of BP, preferably by an intra-arterial line. The drug
Sodium Nitroprusside should be diluted and given by an automatic infusion device.
Nitroprusside is unstable in ultraviolet light, and the IV bag
Nitroprusside (Nipride and Nitropress) is a powerful vasodila- should be wrapped in opaque material. Only fresh solutions of
tor with a direct effect on the smooth muscle of both resistance nitroprusside less than 4 hours old should be used.
and capacitance vessels. Nitroprusside has historically been All types of hypertension respond to nitroprusside, although
the agent of choice for most hypertensive emergencies (Table certain patients may not have an adequate response. Side
82-1). Its rate of onset is extremely rapid, and its duration of effects are directly related to excessive vasodilation and resul-
action is very short. Nitroprusside does not usually worsen tant hypotension and can be avoided by careful monitoring of

BP and regulation of infusion rate. Extreme caution must be
taken to avoid the extravasation of nitroprusside because local
necrosis can be severe. Nitroprusside has not been proved to
be safe during pregnancy and should be avoided because of
the potential effect of thiocyanate on fetal thyroid tissue, the
risk of cyanide poisoning to the fetus, and the possibility of
fetal methemoglobinemia.
Nitroglycerin
Nitroglycerin is a vasodilating agent that acts predominantly
on the venous system, decreasing left ventricular end-diastolic
pressure. At normal doses, nitroglycerin has little effect on
arterial vascular tone and reduces BP by reducing preload and
cardiac output. These effects may be undesirable in patients
with impaired cerebral and renal perfusion. Nitroglycerin use
should be limited to patients with cardiac ischemia or pulmo-
nary edema. Nitroglycerin may be administered either sublin-
gually or intravenously. Care must be taken in patients with
right ventricular dysfunction to avoid hypotension, which may
exacerbate cardiac ischemia.
Hydralazine
Hydralazine (Apresoline) is a direct arteriolar vasodilator that
was widely used in the past for the hypertensive emergencies
of pregnancy. Recent studies, however, have shown that nicar­
dipine and labetalol are superior agents in this setting, and
hydralazine should not be considered first-line therapy for
acute treatment of hypertensive emergencies in the ED.52 The
usual starting dose of hydralazine is 5 mg IV, with repeated
doses of 5 to 10 mg every 20 minutes as needed to keep the
diastolic pressure below 110 mm Hg. Typically, a latent period
of 5 to 15 minutes is followed by a progressive and at times
precipitous fall in BP lasting for up to 12 hours.27 Hydralazine
is also associated with significant reflex tachycardia, which
may provoke angina in patients with coronary artery disease.
Other common side effects are flushing, nausea, and headache.
Chronic use is associated with a lupus-like syndrome that
usually resolves with discontinuation of the medication.
Beta-Blockers
Labetalol
Labetalol (Trandate and Normodyne) is a selective alpha1-
blocker and nonselective beta-blocker with a ratio of alpha/
beta-blockade between 1 : 3 and 1 : 7. It can be given orally or
IV. Labetalol lowers BP by blockade of the alpha1-receptors
in vascular smooth muscle and the cardiac beta-receptors.
Because of the simultaneous beta-receptor blockade, the usual
reflex tachycardia associated with vasodilators does not occur.
Labetalol does not cause the significant drop in cardiac output
associated with other beta-blockers. Although oral labetalol is
less likely to produce orthostatic hypotension, IV use is marked
by profound orthostatic changes. After IV labetalol, the patient
should be kept in the supine position for several hours. Labet-
alol does not affect cerebral blood flow or renal function.34,53
With IV labetalol, BP generally decreases within 5 to 10
minutes, with maximum effect in 30 minutes.
The initial dose of labetalol is 20 mg infused over 2 minutes.
The BP should be rechecked every 5 minutes, and if only
minimal change occurs, an additional dose is given every 10
minutes in increments of 20, 40, or 80 mg to a total of
300 mg of labetalol, depending on BP response. A preferable
approach may be to give the initial loading dose and then an
infusion at 1 or 2 mg/min, which can be titrated upward.54,55
1083
When given in this manner, labetalol appears to be a safe
agent, with minimal adverse reactions. Because labetalol is a
beta-blocker, it is contraindicated in patients with congestive
Chapter 82 / Hypertension
heart failure, heart block, and asthma. Labetalol also appears
to be contraindicated for treatment of hypertension secondary
to pheochromocytoma because it may result in paradoxical
hypertension.
Labetalol therapy cannot be as closely controlled or as
quickly reversed as nitroprusside or fenoldopam therapy.
However, use of labetalol may not require admission to an
intensive care unit. Labetalol does not appear to exacerbate
coronary artery disease or cause uncontrolled drops in BP.
The transition to oral therapy is smooth. After initial control
of BP with IV labetalol, oral labetalol should be started when
diastolic pressure rises 10 mm Hg. Labetalol is an excellent
alternative to nitroprusside when constant BP monitoring is
not feasible. Labetalol is superior as a single agent in patients
who have aortic dissection or cardiac ischemia with intact left
ventricular function.
Esmolol
Esmolol (Brevibloc) is an ultra-short-acting, selective beta1-
blocker without intrinsic sympathomimetic activity. It typi-
cally has little effect on BP in normal individuals but may be
very useful to control the reflex tachycardia seen with vasodi-
lating agents such as nitroprusside. Esmolol is initiated with a
loading dose of 500 µg/kg over 1 minute, followed by an infu-
sion of 50 to 100 µg/kg/min. Maximal effect occurs in 5 minutes.
If necessary, another bolus of 500 µg/kg is given, and the drip
is increased by 50 µg/kg/min. This cycle may be repeated
every 5 minutes until the desired heart rate response is seen,
up to a maximum dose of 300 µg/kg/min. Because the elimina-
tion half-life of esmolol is 9 minutes, any effect resolves within
30 minutes of discontinuing the infusion, with substantial
recovery from beta-blockade in 10 to 20 minutes. Contraindi-
cations are similar to those with labetalol, including cocaine
overdose, pheochromocytoma, congestive heart failure, heart
block, and reactive airway disease. Esmolol also causes tissue
necrosis when extravasated into the soft tissue and may cause
thrombophlebitis when infused into small veins.
Alpha-Blockers
Phentolamine (Regitine) is an alpha-blocking agent used for
catecholamine-induced hypertensive crises (e.g., pheochro-
mocytoma, MAOI crisis, and cocaine overdose). Phentolamine
is usually given IV in 1- to 5-mg boluses, although it may
be given as an infusion at a rate of 5 to 10 µg/kg/min.51,53
The effect is immediate and may last up to 15 minutes.
Reflex tachycardia may be seen. After BP is under control,
oral phenoxybenzamine, a long-acting alpha-blocker, may be
used.
Enalaprilat and Enalapril
Enalaprilat (Vasotec) is a parenteral active metabolite of the
ACE inhibitor enalapril. This drug has been studied in limited
numbers of patients with true hypertensive emergencies.
Hypotension is rare with the use of enalaprilat, but caution
should be used in patients who may be volume depleted. The
acute dose is 0.625 to 5 mg administered as a single bolus.
Peak effects generally occur in 15 minutes but may be delayed
for hours. The response is not dose related, and one study
showed an average drop in MAP of 35% at all doses and a 60%
response rate.56 Although no adverse effects were seen in this
study, which excluded patients older than 80 years and with
 1084
known renovascular disease, such a significant drop in MAP
might exceed the limits of vascular autoregulation in some
patients. In fact, azotemia has been reported among older
PART III  ■  Medicine and Surgery / Section Four • Vascular System
patients in studies of ACE inhibition after MI.57
Adverse effects seen with ACE inhibitors such as enalaprilat
include idiopathic angioedema, cough, and renal failure. Renal
failure has been classically described in patients with bilateral
renovascular disease. ACE inhibitors are considered toxic in
the first trimester of pregnancy.
■  CLINICAL PRESENTATION AND
MANAGEMENT OF POORLY   sion in the ED, unless the patient has known (i.e., previously
CONTROLLED HYPERTENSION
Elevated BP without evidence of progressive end-organ
involvement does not require urgent treatment in the ED.2
Historically, these patients, on the basis of arbitrarily defined
BP elevations and the ill-conceived term “hypertensive
urgency,” were inappropriately treated with antihypertensive
agents in the ED with little regard for the chronicity of the
condition, potential adverse effects of acutely lowering their
BP, or transition to a stable, oral, outpatient regimen for long-
term control. It is unnecessary to lower BP acutely in the ED
for these patients, and this practice may actually cause
increased risk of adverse effects.7,58 These patients are best
managed with a long-term, ambulatory regimen, monitored
and adjusted by their primary care provider.
Patients with elevated BP who are asymptomatic or have
nonspecific symptoms require a thorough history and physical
examination, paying special attention to the cardiovascular,
funduscopic, and neurologic systems and findings. Depending
on the presentation, laboratory testing may be helpful, includ-
ing a urinalysis and electrolyte panel to evaluate renal func-
tion. In patients without any history of renal disease, a normal
urinalysis obviates the need for blood tests of renal function.59
A chest radiograph and ECG are obtained to evaluate patients
with chest pain or symptoms of cardiac dysfunction. If initial
evaluation fails to show any acute end-organ damage and myo-
cardial ischemic symptoms are not present, the patient may be
Table 82-2 Recommendations for Ambulatory Blood Pressure Therapy*
BLOOD PRESSURE SYSTOLIC BLOOD DIASTOLIC BLOOD
CLASSIFICATION PRESSURE (MM HG) PRESSURE (MM HG)
Normal <120 and <80
Prehypertension 120–139 or 80–89
Stage 1 140–159 or 90–99
hypertension
Stage 2 ≥160 or ≥100
hypertension
*Treatment determined by highest blood pressure category.
†
Treat patients with chronic kidney disease or diabetes to blood pressure goal of <130/80 mm Hg.
‡
Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker.
Modified from the Seventh Report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure. JNC7 complete report.
Hypertension 42:1206, 2003.
referred for outpatient evaluation within 7 days. Unfortunately,
the evaluation for end-organ ischemia and referral for subse-
quent care occurs in a minority of patients with elevated blood
pressures in most EDs.60-62
In some patients, it is evident that ongoing chronic pharma-
cologic therapy is indicated. In the ambulatory setting, the
decision to initiate pharmacologic therapy for well-documented
hypertension must be based on the degree of hypertension
(Tables 82-2 and 82-3). These recommendations are not
without controversy.2,63-65 It is rarely advisable to initiate
or substantially modify the outpatient treatment of hyperten-
diagnosed and treated) hypertension, and treatment is restarted
or modified in close consultation with the primary care pro-
vider. Large population-based studies comparing different
classes of antihypertensive agents have established the thia-
zide diuretics, such as hydrochlorothiazide at 25 to 50 mg
once a day, as the first-line agent of choice in the absence of
compelling indications for other classes of antihyperten-
sives.2,66-68 These agents are inexpensive, well tolerated, and
easy to take. Other more expensive agents have failed to show
better efficacy in preventing the cardiovascular complications
of hypertension.
Beta-blockers or calcium channel blockers are substituted
or added as indicated.2,9,66-70 Common starting doses of generic
beta-blockers include atenolol 25 to 50 mg or metoprolol 50 mg
once or twice daily. For patients with other health problems,
specific classes of drugs have been shown to be particularly
beneficial; the comorbid conditions should guide antihyper-
tensive therapy. For patients with intact left ventricular func-
tion and a history of MI, a beta-blocker is the agent of choice.
On the basis of evidence of increased mortality, such patients
should not be treated with immediate-release dihydropyridine
calcium channel blockers.71 For patients with diabetes, ACE
inhibitors or angiotensin receptor blockers (ARBs) have ben-
efits with respect to the preservation of renal function beyond
that seen with BP control alone. In diabetic patients as well as
in those with a history of left ventricular failure, an ACE
inhibitor or an ARB should be the drug of choice. Elderly
INITIAL DRUG THERAPY
LIFESTYLE WITHOUT COMPELLING WITH COMPELLING
MODIFICATION INDICATION INDICATION
Encourage
Yes No antihypertensive Drug(s) for compelling
drug indicated indications†
Yes Thiazide-type diuretics Drug(s) for compelling
for most indications†
May consider ACEI, Other antihypertensive
ARB, BB, CCB, or drugs (diuretics,
combination ACEI, ARB, BB,
CCB) as needed
Yes Two-drug combination
for most‡ (usually
thiazide-type diuretic
and ACEI or ARB or
BB or CCB)
 1085
Table 82-3 Antihypertension Drugs*

Chapter 82 / Hypertension
USUAL DOSE RANGE, TOTAL COMMON SIDE EFFECTS AND
DRUG TRADE NAME MG/DAY AND INTERVAL COMMENTS

Diuretics (Common) Short-term: increases

Thiazides cholesterol and glucose
Chlorothiazide Diuril 125–500 qd levels; biochemical
Chlorthalidone Hygroton 12.5–50 qd abnormalities: decreases
Hydrochlorothiazide Hydrodiuril, Microzide, Esidrix 12.5–50 qd potassium, sodium, and
Polythiazide Renese 2–4 qd magnesium levels, increases
Indapamide Lozol 1.25–5 qd uric acid and calcium levels;
Metolazone Mykrox, Zaroxolyn 0.5–1 (b-tid), 2.5–5 qd rare: blood dyscrasias,
photosensitivity, pancreatitis,
Loop Diuretics hyponatremia
Bumetanide Bumex 0.5–4 b-tid
Furosemide Lasix 40–240 b-tid
Torsemide Demadex 3–100 q-bid
Potassium-Sparing Agents Hyperkalemia may occur
Amiloride hydrochloride Midamor 5–10 qd
Triamterene Dyrenium 25–100 qd
Aldosterone Receptor Blockers
Spironolactone Aldactone 25–100 qd
Eplerenone Inspra 50–100 q-bid
Adrenergic Inhibitors Postural hypotension
Central alpha-Agonists Sedation, dry mouth,
Reserpine 0.05–0.25 qd bradycardia, withdrawal
Clonidine hydrochloride Catapres 0.2–1.2 b-tid hypertension
Catapres-TTS 0.1–0.3 weekly
Guanabenz acetate Wytensin 4–8 bid
Guanfacine hydrochloride Tenex 0.5–2 qd
Methyldopa Aldomet 250–1000 bid
Alpha-Blockers Hepatitis and lupus-like
Doxazosin mesylate Cardura 1–16 qd syndrome
Prazosin hydrochloride Minipress 2–20 b-tid Postural hypotension
Terazosin hydrochloride Hytrin 1–20 qd
Beta-Blockers Bronchospasm, bradycardia,
Acebutolol1,2 Sectral 200–800 qd heart failure, may mask
Atenolol1 Tenormin 25–100 q-bid insulin-induced
Betaxolol1 Kerlone 5–20 qd hypoglycemia; less serious:
Bisoprolol fumarate1 Zebeta 2.5–10 qd impaired peripheral
Metoprolol tartrate1 Lopressor 50–300 bid circulation, insomnia, fatigue,
Metoprolol succinate1 Toprol-XL 50–300 qd decreased exercise tolerance,
Nadolol Corgard 40–320 qd hypertriglyceridemia (except
Nebivolol hydrochloride Bystolic 5–20 qd agents with intrinsic
Penbutolol sulfate2 Levatol 10–20 qd sympathomimetic activity)
Pindolol2 Visken 10–60 bid
Propranolol hydrochloride Inderal 40–480 bid
Inderal LA 40–480 qd
Timolol maleate Blocadren 20–60 bid
Combined alpha- and beta-Blockers Postural hypotension,
Carvedilol Coreg 12.5–50 bid bronchospasm
Labetalol hydrochloride Normodyne, Trandate 200–1200 bid
Direct Vasodilators Headaches, fluid retention,
Hydralazine hydrochloride Apresoline 50–300 bid tachycardia
Minoxidil Loniten 5–100 qd Lupus syndrome
Hirsutism
Calcium Antagonists Conduction defects, worsening
Nondihydropyridines of systolic dysfunction,
Diltiazem hydrochloride Cardizem SR 50–300 bid gingival hypertrophy
Cardizem CD, Dilacor XR, 5–100 qd
Tiazac
Verapamil hydrochloride Isoptin SR, Calan SR 90–480 bid Constipation
Verelan, Covera HS 120–480 qd
 1086
Table 82-3 Antihypertension Drugs—cont’d
USUAL DOSE RANGE, TOTAL COMMON SIDE EFFECTS AND
PART III  ■  Medicine and Surgery / Section Four • Vascular System

DRUG TRADE NAME MG/DAY AND INTERVAL COMMENTS

Calcium Antagonists Pedal edema, flushing,

Dihydropyridines headache, gingival
Amlodipine besylate Norvasc 2.5–10 qd hypertrophy
Felodipine Plendil 2.5–20 qd
Isradipine DynaCirc 5–20 bid
DynaCirc CR 5–20 qd
Nicardipine Cardene SR 60–90 bid
Nifedipine Procardia XL, Adalat CC 30–120 qd
Nisoldipine Sular 20–60 qd
ACE Inhibitors Common: cough; rare:
Benazepril hydrochloride Lotensin 5–40 q-bid angioedema, hyperkalemia,
Captopril (G) Capoten 25–150 b-tid rash, loss of taste, leukopenia
Enalapril maleate Vasotec 5–40 q-bid
Fosinopril sodium Monopril 10–40 q-bid
Lisinopril Prinivil, Zestril 5–40 qd
Moexipril Univasc 7.5–15 q-bid
Perindopril Aceon 4–8 q-bid
Quinapril hydrochloride Accupril 5–80 q-bid
Ramipril Altace 1.25–20 q-bid
Trandolapril Mavik 1–4 qd
Angiotensin II Receptor Blockers Angioedema (very rare),
Candesartan Atacand 8–32 qd hyperkalemia
Eprosartan Tevetan 400–800 q-bid
Losartan potassium Cozaar 25–100 q-bid
Valsartan Diovan 80–320 qd
lrbesartan Avapro 150–300 qd
Olmesartan Benicar 20–40 qd
Telmisartan Micardis 20–80 qd
Renin Inhibitors
Aliskiren Tekturna 150–300 qd Rare angioedema,
hyperkalemia (especially
with ACE inhibitor use),
hypotension, diarrhea, rash,
renal stones
*This list is of single agents only; multiple combination agents are also manufactured.
1
Beta1 selective
2
Intrinsic sympathomimetic activity; beta1 selective with no related vasodilation
ACE, angiotensin-converting enzyme.

patients with isolated systolic hypertension may benefit from
the addition of a long-acting calcium channel blocker when
diuretic monotherapy fails. Patients with prostatism or dyslip-
idemia may benefit from alpha-blocker therapy, although a
large prospective trial comparing the thiazide diuretic chlortha-
lidone with three other types of therapy showed an increased
incidence of congestive heart failure and stroke in the group
treated with the alpha-blocker doxazosin.72 Regardless of the
agent used, long-term reduction of BP to the target level
remains the most important endpoint for the prevention of
cerebrovascular, heart, and renal disease.
Mild or Transient Hypertension
A vast majority of the hypertension encountered in the ED is
either transient or mild. The most common causes of transient
hypertension are pain and anxiety. In these patients, end-
organ ischemia does not occur, and attention is focused on
treatment of the primary process. Patients with incidental
hypertension identified during a visit for another purpose
should simply be referred to their primary care physicians for
repeated measurement in a few days to a few weeks. Most
patients, even those with poorly treated chronic hypertension,
show an improvement in their BP with watchful waiting.4

KEY CONCEPTS
■ The presence or absence of acute target organ damage
determines whether a hypertensive emergency exists
and whether treatment of the BP elevation is indicated in
the ED.
■ All patients with persistent and marked elevations in BP
(e.g., diastolic BP >110 mm Hg or systolic BP
> 200 mm Hg) should be carefully evaluated for the
presence of acute end-organ ischemia.
■ The therapeutic goal for treatment of the majority of
hypertensive emergencies is careful reduction of the BP
The references for this chapter can be found online by accessing the
accompanying Expert Consult website.
1087
with a titratable agent. Mean arterial pressure should be
Chapter 82 / Hypertension
reduced by no more than 20 to 25% over minutes to
hours. The diastolic pressure generally should not fall
below 100 to 110 mm Hg. The exceptions to these rules
may be patients with hypertensive complications of
pregnancy, hypertensive emergencies of the pediatric
population, and patients with aortic dissection.
■ Patients without acute end-organ ischemia should not
receive antihypertensive agents in the ED, and they may
be safely referred for outpatient follow-up.