INVITED REVIEW ARTICLE
Hypertensive Crisis
Maria Alexandra Rodriguez, MD, Siva K. Kumar, MD, and Matthew De Caro, MD
Abstract: Hypertension is a common chronic medical condition affecting
over 65 million Americans. Uncontrolled hypertension can progress to a
hypertensive crisis defined as a systolic blood pressure ⬎180 mm Hg or a
diastolic blood pressure ⬎120 mm Hg. Hypertensive crisis can be further
classified as a hypertensive urgency or hypertensive emergency depending
on end-organ involvement including cardiac, renal, and neurologic injury.
The prompt recognition of a hypertensive emergency with the appropriate
diagnostic tests and triage will lead to the adequate reduction of blood
pressure, ameliorating the incidence of fatal outcomes. Severely hypertensive
patients with acute end-organ damage (hypertensive emergencies) warrant
admission to an intensive care unit for immediate reduction of blood pressure
with a short-acting titratable intravenous antihypertensive medication. Hy-
pertensive urgencies (severe hypertension with no or minimal end-organ
damage) may in general be treated with oral antihypertensives as an outpa-
tient. Rapid and short-lived intravenous medications commonly used are
labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside, and cle-
vidipine. Medications such as hydralazine, immediate release nifedipine, and
nitroglycerin should be avoided. Sodium nitroprusside should be used with
caution because of its toxicity. The risk factors and prognosticators of a
hypertensive crisis are still under recognized. Physicians should perform
complete evaluations in patients who present with a hypertensive crisis to
effectively reverse, intervene, and correct the underlying trigger, as well as
improve long-term outcomes after the episode.
Key Words: hypertension, hypertensive crisis, hypertensive emergency,
hypertensive urgency
(Cardiology in Review 2010;18: 102–107)
S ystemic hypertension (HTN) is a common medical condition
affecting over 1 billion people worldwide, and more than 65
million Americans. It is a risk factor for premature cardiovascular,
renal, and cerebrovascular disease, and is responsible for up to 7
million deaths a year. Hypertension is defined as a systolic blood
pressure (SBP) ⬎140 mm Hg or diastolic blood pressure (DBP) ⬎
90 mm Hg in patients with known HTN or otherwise measured on
2 or more settings. Approximately 30% of the United States popu-
lation age ⱖ18 have some form of HTN, making it one of the most
common chronic medical conditions.1,2 The 2 principal categories of
high blood pressure (BP) are essential (or primary) HTN and
secondary HTN. Essential HTN has a more widespread presentation
with an idiopathic source. This disease process occurs more com-
monly in patients with a variety of risk factors including black race,
family history of HTN,3 dyslipidemia, alcohol intake, obesity, and
personality traits, such as a hostile attitude.4 In contrast, secondary
HTN accounts for 5% to 10% of hypertensive patients and is
regularly caused by an underlying and frequently correctable etiol-
From the Department of Medicine, Cardiology Division, Jefferson Medical
College/Thomas Jefferson University Hospital, Philadelphia, PA.
Correspondence: Maria Alexandra Rodriguez, MD, Department of Medicine,
Division of Cardiology, Thomas Jefferson University Hospital, Jefferson
Heart Institute, 925 Chestnut St, Mezzanine, Philadelphia, PA 19107. E-mail:
maria.a.rodriguez@jeffersonhospital.org.
Copyright © 2010 by Lippincott Williams & Wilkins
ISSN: 1061-5377/10/1802-0102
DOI: 10.1097/CRD.0b013e3181c307b7
102 | www.cardiologyinreview.com
ogy, including primary renal disease, renovascular disease, and
endocrine disorders such as a pheochromocytoma, Cushing syn-
drome or primary aldosteronism.
It is estimated that 1% to 2% of the HTN population will present
with an acute and severe elevation in BP termed “hypertensive crisis.”5
A hypertensive crisis is often described as a SBP ⬎180 mm Hg or a
DBP ⬎120 mm Hg, with or without end-organ damage. It is further
characterized as a hypertensive urgency or hypertensive emergency.
The distinction is based on the degree of BP elevation and the presence
or absence of target organ damage.6 Prompt recognition between a
hypertensive urgency and hypertensive emergency could dictate man-
agement and triage. Treatment in the emergency room for an uncom-
plicated hypertensive urgency or admission to the intensive care unit
with immediate BP reduction for a hypertensive emergency can prevent
adverse outcomes that may include myocardial infarction (MI), stroke,
renal failure, coma, and death.
This article reviews hypertensive crisis—its identification, asso-
ciated risk factors, pathophysiology, management, and treatment.
DEFINITION
The Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure, with the most
recent report in 2003,7 classifies 4 stages of BP: normal, prehyper-
tension, stage 1 HTN, and stage 2 HTN. Pre-HTN is defined as a
SBP of 120 to 139 mm Hg or a DBP of 80 to 89 mm Hg. Stage 1
is a SBP 140 to 159 or a DBP 90 to 99 mm Hg, while stage 2 is a
SBP ⱖ160 mm Hg or a DBP ⱖ100 mm Hg. Although not a category
in Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure, a SBP ⬎179 mm Hg or a
DBP ⬎109 mm Hg is termed “severe hypertension.” More signifi-
cant than the BP rise is the briskness of the increase and the degree
of target organ damage. The degree of BP elevation and length of
time HTN has been present will determine the overall outcome.7
In 1914, clinician Franz Volhard and pathologist Theodor Fahr,
who had completed extensive work on renovascular HTN, were the first
to coin the term “malignant HTN”; the radical changes in BP that we
recognize in the present day as a hypertensive urgency. They described
this occurrence as a condition where individuals with severe HTN had
parallel renal failure, retinopathy with papilledema, fibrinoid necrosis,
uremia, and accelerated death.8 In 1921, Keith and Wagener identified
similar patients who had papilledema and severe retinopathy with no
findings of renal insufficiency, concluding that to have malignant HTN,
symptoms could occur independently. They introduced the term “ac-
celerated HTN.”9 In 1928 Oppenheimer and Fishberg were the first to
describe a hypertensive encephalopathy associated with headaches,
convulsions, and central nervous system deficits in the setting of
accelerated HTN.10
Accelerated HTN is currently recognized as a severely elevated
BP with a SBP ⬎179 mm Hg or a DBP ⬎109 mm Hg associated with
ocular hemorrhages, exudates, and no papilledema (grade III Kimmel-
stiel-Wilson retinopathy).11 Malignant HTN may be used to define a
marked HTN consisting of ocular hemorrhages and exudates with
papilledema (grade IV Kimmelstiel-Wilson retinopathy).12 The term
malignant HTN previously relating to encephalopathy or nephropathy
is no longer used and has been removed from the National and
International Blood Pressure Control guidelines.
Cardiology in Review • Volume 18, Number 2, March/April 2010
Cardiology in Review • Volume 18, Number 2, March/April 2010
Medication noncompliance or the inadequate treatment of
stage 1 or stage 2 HTN may lead to the development of hypertensive
urgency, often defined as a SBP ⬎180 mm Hg or a DBP ⬎120 mm
Hg in the absence of or minimal target end organ damage.7 These
patients present with nonprogressive symptoms of headache, short-
ness of breath, epistaxis, or pedal edema.7 It is more desirable to
reduce their BP within hours of presentation.
Hypertensive emergency is severe HTN ⬎220/140 mm Hg and
a DBP ⬎120 to 130 mm Hg, which irrevocably causes end-organ
damage including but not limited to the cardiac, renal, and central
nervous systems. Although the absolute BP elevation is not a criterion
for diagnosis, a hypertensive emergency is most consistently seen with
a DBP ⱖ120 mm Hg,13 and accounts for 25% to 30% of all hyperten-
sive crises.14 Unlike hypertensive urgencies, with no end-organ dam-
age, hypertensive emergencies may lead to acute MI, hypertensive
encephalopathy, intracranial hemorrhage, dissecting aneurysm, acute
renal failure, and pulmonary edema because of left ventricular dysfunc-
tion. Organ injury is most common with a DBP ⬎130 mm Hg unless
the patient is a child or pregnant.15 In pregnant females a SBP ⬎169
mm Hg or DBP ⬎109 mm Hg is considered a hypertensive emergency
and should be treated promptly.16
EPIDEMIOLOGY
Hypertensive crisis affects 500,000 Americans or approxi-
mately 1% of hypertensive adults.17–19 Nearly 3.2% of patients
presenting to the emergency room have a hypertensive crisis; with
the decrease in incidence of HTN as a result of the advent of
medications, the incidence has reduced substantially. Even so, the
5-year survival rate among all patients who present with a hyper-
tensive crisis is 74%.20 Zampaglione et al evaluated the prevalence
of hypertensive crisis in an emergency department during 12
months, and the frequency of end-organ damage during the first 24
hours after presentation. They found that 76% of the hypertensive
crises were hypertensive urgencies and 24% were hypertensive
emergencies, representing more than one-fourth of all medical
urgencies-emergencies.21 Hypertensive crises were more prevalent
among patients with renal disease, including renal artery stenosis
and chronic kidney disease.
Like HTN, hypertensive crises are more prevalent in the
elderly and the non-Hispanic black population; yet men are affected
2 times more often than women.18,19 Severe HTN is seen more
frequently in noncompliant individuals, black men, persons of lower
socioeconomic status, and the elderly.18,22 A retrospective study of
symptomatic patients who presented to a Brazilian emergency room
with DBP ⬎120 mm Hg, found that hypertensive crises accounted
for 0.5% of emergency cases studied, and 1.7% of clinical emer-
gencies, with hypertensive urgencies being more common.23 The
proportion presenting with hypertensive crisis was lower than
the Zampaglione study because of the possibility of pseudocrisis in
the latter. There was a high prevalence of hypertensive pseudocrisis
(presenting emotionally charged, or in pain) when hypertensive
crisis was suspected. Patients with hypertensive emergencies were
older (59.6 ⫾ 14.8 vs. 49.9 ⫾ 18.6 years, P ⬍ 0.001) and had greater
DBP (129.1 ⫾ 12 vs. 126.6 ⫾ 14.4 mm Hg, P ⬍ 0.05) than those
with hypertensive urgencies. Cerebrovascular complications (39%
ischemic stroke and 17% hemorrhagic stroke) and acute pulmonary
edema (25%) were the most frequent target-organ lesions.23
ETIOLOGY
Acute and severe BP elevation can occur as a complication of
essential or secondary HTN, or it can happen idiopathically. The
most common cause for a hypertensive crisis is chronic HTN with
an acute exacerbation. One of the most common precipitants is
medication noncompliance; although in general 8% of hypertensive
© 2010 Lippincott Williams & Wilkins
Hypertensive Crisis
emergencies and 28% of hypertensive urgencies presenting to the
emergency room are unaware of having a diagnosis of HTN.22 Other
etiologies include withdrawal syndrome from centrally acting anti-
hypertensives; peripheral ␣-blockers, or ␤-blockers causing an in-
creased sympathetic flow. In previously normotensive individuals,
the use of drugs such as oral contraceptives, cocaine, phencyclidine,
monoamine oxidase inhibitors with tyramine or other agents such as
linezolid, nonsteroidal anti-inflammatory drugs, or amphetamines
puts them at jeopardy.24
Secondary causes of HTN can lead to a hypertensive crisis.
This includes renal parenchymal disease, renovascular disease, renal
infarction, pregnancy (preeclampsia), endocrine, and central nervous
system disorders. Systemic illnesses with renal involvement, such as
systemic lupus erythematosus, microangiopathic hemolytic anemia
(TTP/HUS), endocrine disorders such as Cushing disease, primary
aldosteronism, or a pheochromocytoma, and autonomic hyperactiv-
ity in spinal cord/head injuries, or cerebrovascular accident infarc-
tion/hemorrhage can precipitate a crisis.25 Many types of surgeries
in patients with a known history of HTN can be associated postop-
eratively with HTN crisis including cardiac surgery, major vascular
surgery, head and neck surgery and trauma. Postoperative HTN,
defined as a SBP ⱖ190 mm Hg and a DBP ⱖ100 mm Hg on 2
consecutive readings have been reported in 4% to 35% of patients at
least in part because of a high catecholamine state and increased
vascular resistance26,27 (Table 1).
In a retrospective cohort study on malignant HTN of a
multiethnic population in Amsterdam between 1993 and 2005,
racial differences were found in patients who developed hyper-
tensive crisis. The incidence of malignant HTN and renal dys-
function was higher in blacks compared with whites. The data
demonstrated that in blacks, as many as 40% of patients who
presented with hypertensive emergencies developed renal failure.
This may be due to ethnic disparities in BP control, noncompli-
ance, and insurance status.28
Other risk factors associated consist of less effective control of
SBP as an outpatient,29 the lack of a primary care physician and
medical insurance,30 black males, lack of resources, smoking, diabetes,
autumn season, and the morning hours between 6 AM and 12 PM.25
PATHOPHYSIOLOGY
The precise pathophysiology of a hypertensive crisis is not
well known. It is recognized that an individual is able to maintain
organ perfusion with varying degrees of BP by autoregulatory
mechanisms. Two general theories, the pressure hypothesis and the
humoral hypothesis, suggest that when a critical imbalance of
pressure and/or humoral factors occurs a series of pathologic events
lead to myointimal proliferation and fibrinoid necrosis.31
TABLE 1. Common Causes of a Hypertensive Crisis
Medication noncompliance
Antihypertensive drug withdrawal (ie, clonidine)
Renal parenchymal disease
Renovascular disease
Drugs (ie, cocaine, PCP)
Collagen vascular diseases (SLE)
Cushing disease
Pheochromocytomas
Preeclampsia and eclampsia
Postoperative state
PCP indicates phencyclidine; SLE, systemic lupus erythematosus.
www.cardiologyinreview.com | 103
Rodriguez et al
The renin-angiotensin system plays a central role in the
homeostasis of BP.32 A rise in plasma renin activity (PRA) stimu-
lates the production of angiotensin II, a vasoconstrictor that results
in increased vascular resistance and BP. In severe HTN there is
amplification of the renin-angiotensin system; a rise in levels of
renin and angiotensin II leading to high aldosterone secretion,
resulting in damage to the endothelium of blood vessels, as evi-
denced by fibrin thrombi in the vessels.33 It is proposed that high BP
leads to high vascular reactivity and critical levels of vasoactive
agents such as norepinephrine, angiotensin II, and vasopressin
leading to natriuresis, which brings about hypovolemia, triggering
even more elevation of the vasoconstrictive agents. This leads to
arteriolar fibroid necrosis which precipitates endothelial damage
followed by platelet deposition and release of thromboxane which
can result in a microangiopathic hemolytic anemia. It further results
in myointimal proliferation/damage with an endpoint of ischemia.
Ischemia releases further vasoconstrictive agents as mentioned
above, which propagates the cycle.33 Ultimately there is elevation of
asymmetric dimethylarginine, an endogenous nitric oxide synthase
inhibitor.34 Asymmetric dimethylarginine may play an important
role in the pathogenesis of preeclampsia.
Whereas increased vascular resistance is the mediator of
hypertensive crisis, both sodium overload and catecholamine excess
can lead to severe vasoconstriction. Conditions that primarily in-
volve increased sodium reabsorption in the kidney, such as primary
hyperaldosteronism and genetic disorders such as glucocorticoid
remediable aldosteronism (GRA), pseudohyperaldosteronsim (ie,
Liddle syndrome), and 11-hydroxylase deficiencies would be ex-
pected to suppress renin secretion and thus limit the concentration of
circulating angiotensin II. However, these sodium avid conditions
may ultimately result in severe vasoconstriction through the classic
Guytonian mechanism for autoregulation and thus manifest hyper-
tensive crisis.35,36
Blumenfield et al suggest a hypertensive crisis can be strati-
fied according to disorders that are caused by increased PRA levels
ⱖ0.65 ng/mL/h, designated as R type HTN corrected by antihyper-
tensives that suppress renin and angiotensin II, such as ACE inhib-
itors and ␤-blockers (R drugs), and sodium-volume dependent forms
of HTN in which PRA is not a factor (PRA ⬍0.65 ng/mL/h). The
latter are V type HTN, and respond to diuretics, aldosterone antag-
onists, calcium channel blockers, or ␣-adrenergic receptor blockers
(V drugs)37 (Table 2).
CLINICAL PRESENTATION AND ASSESSMENT
Performing an adequate assessment is of utmost importance
to determine whether a patient’s presentation is because of a hyper-
tensive emergency or hypertensive urgency. This will indicate the
appropriate treatment and its promptness. The symptoms will ulti-
mately depend on the organ affected. The differentiation can be
made from a thorough history, physical examination, and relevant
studies including laboratory work, an electrocardiogram, echocar-
diogram, and radiographs. A detailed history is essential; it is vital
to inquire about the onset, duration, and severity of HTN, prior
organ damage, associated symptoms, recreational drug and alcohol
use, a list of medications (antihypertensive regimen with dosing and
over-the-counter preparations), compliance with the antihyperten-
sive regimen, and time/dose of the most recent ingested treatment.
Similarly, any patient who presents with a hypertensive crisis should
be evaluated for secondary causes of HTN. A sudden rise in BP with
undiagnosed HTN or the presentation in a young patient (⬍25 years
of age) would suggest a secondary source. More important than the
degree of BP elevation is the rise in BP compared with baseline;
those who have become adapted to a BP of 200 mm Hg will
104 | www.cardiologyinreview.com
Cardiology in Review • Volume 18, Number 2, March/April 2010
TABLE 2. Hypertensive Crises According to the Plasma
Renin Level
Disorders with high renin
Malignant hypertension
Medium to high renin states
Unilateral renovascular hypertension
Renal vasculitis (scleroderma, lupus, polyarteritis)
Renal trauma
Renin secreting tumors
Adrenergic crises: pheochromocytoma, cocaine abuse, clonidine
Probable medium to high renin states (PRA ⱖ0.65 ng/mL/h)
Hypertensive encephalopathy
Hypertension with cerebral hemorrhage
Hypertension with (impending) stroke
Hypertension with pulmonary edema
Hypertension with acute myocardial infarction or unstable angina
Dissecting aortic aneurysm
Perioperative hypertension
Sodium-volume overload, low renin states: PRA ⬍0.65 ng/mL/h
Acute tubular necrosis
Acute glomerulonephritis
Urinary tract obstruction
Primary aldosteronism
Low renin essential hypertension
Preeclampsia/eclampsia
Adapted from Blumenfield et al.37
PRA indicates plasma renin activity.
manifest fewer symptoms than a patient whose normal BP is lower
than 130 mm Hg.
There may be signs and symptoms associated with a hyperten-
sive crisis, or its manifestation may be silent. Silent HTN crisis has been
found to be especially common in young black men. In general, there
is no precise BP rise for the presentation of a hypertensive emergency.
Instead, the specific symptoms imply the presence of end-organ dam-
age. These symptoms include chest pain (myocardial ischemia or MI),
back pain (aortic dissection), dyspnea (pulmonary edema or congestive
heart failure), neurologic symptoms, seizures, or altered consciousness
(hypertensive encephalopathy).38
The most widespread signs and symptoms at presentation for
hypertensive urgency are headache (22%), epistaxis (17%), faintness
(10%), psychomotor agitation (10%), chest pain (9%), and dyspnea
(9%).21 Other less common symptoms include arrhythmias and pares-
thesias. In contrast, most patients with hypertensive emergencies com-
plain of chest pain (27%), dyspnea (22%), and neurologic deficits
(21%) (Fig. 1). Associated end-organ damage includes cerebral infarc-
tion (24.5%), acute pulmonary edema (22.5%), hypertensive encepha-
lopathy (16.3%), and congestive heart failure (12.0%).21 Less often
patients present with intracranial hemorrhage, acute aortic dissection,
acute MI, acute kidney injury, and eclampsia.20
The physical examination should initially focus on proper BP
measurement in the bilateral upper limbs with an appropriately sized
BP cuff, to evaluate for aortic dissection. Pulses should be palpated
and compared in the upper, femoral, and lower extremities. BP
readings in the supine, sitting, and standing positions are required to
measure volume status. Carotid arteries and abdominal arteries
should be auscultated for bruits, suggesting a cerebrovascular event.
A comprehensive cardiovascular examination is of value. An ele-
vated jugular venous pressure, third heart sound, gallop, and/or
pulmonary rales are evidence of heart failure. A prominent/displaced
© 2010 Lippincott Williams & Wilkins
Cardiology in Review • Volume 18, Number 2, March/April 2010
FIGURE 1. Common signs and symptoms of a hypertensive
crisis on initial presentation (from Zampaglione et al).21
apical impulse or a harsh intrascapular murmur is suggestive of a
coarctation of the aorta. Other significant tests include a fundoscopic
examination for the presence of hemorrhages, papilledema, or exu-
dates (confirming a hypertensive emergency), and a thorough neu-
rologic examination to assess for stroke, somnolence, stupor, visual
loss, focal deficits, seizures, or coma. Signs of hypertensive enceph-
alopathy are seizure, nausea/vomiting, or renal manifestations such
as oliguria and azotemia.14 Occasionally, hypertensive crises pro-
duce a clinical picture consistent with microangiopathic hemolytic
anemia, because of direct endothelial damage. Determining whether
microangiopathic hemolytic uremia is the primary cause of the
hypertensive crisis (through renal ischemia) or a consequence of the
hypertensive crisis is often difficult clinically, and only obvious in
retrospect, after instituting treatment and lowering BP.
Single-organ involvement is observed in approximately 83% of
patients presenting with hypertensive emergencies. Two-organ involve-
ment is found in 14% of patients, and multiorgan involvement (⬎3
organ systems) is found in approximately 3% of patients.21
MANAGEMENT/TREATMENT
Laboratory work in the nonclinic setting should include a
serum chemistry panel to test for hypokalemia or hypomagnesemia,
which would predispose to arrhythmias, renal and hepatic function
tests, along with a complete blood count and peripheral smear to
check for hemolysis and microangiopathic anemia, urinalysis with
microscopic examination of the urinary sediment for proteinuria, red
blood cells, and/or cellular casts. An electrocardiogram to assess for
coronary ischemia or left ventricular hypertrophy should be com-
pleted. A chest radiograph for those who present with chest pain or
shortness of breath would be indicative of pulmonary edema or a
widened mediastinum. Imaging studies, such as a head CT or MRI
for abnormal neurologic examinations, mental status changes, or
headaches and a chest CT scan or transesophageal echocardiogram
to rule out aortic dissection should also be performed. Of some
usefulness are plasma aldosterone and renin levels.
Proper management of severe HTN is essential to prevent
target organ injury of the brain, heart, kidneys, and vascular system.
The treatment goal should aim at reducing BP according to the
presentation type.
Hypertensive urgency can be managed with an oral medical
regimen and gradual BP control over 12 to 24 to 48 hours; patients
should not have their BP rapidly lowered to their normal base-
© 2010 Lippincott Williams & Wilkins
Hypertensive Crisis
line.39,40 The goal is to reduce the BP to 160/100 mm Hg over hours
to days with low doses of short-acting oral antihypertensive medi-
cations. These include oral labetalol (␣- and ␤-adrenergic blocker)
or clonidine (central ␣-2 agonist).41,42 Captopril has also been
suggested as a first-line agent in the treatment of hypertensive
urgency, but it needs to be used with caution.43 Aggressive paren-
teral antihypertensives and high loading doses of oral medications
should be strictly avoided. This could cause hypoperfusion of the
major arterial beds of the brain, heart, and kidneys, leading to
cerebral ischemia, cerebral infarction, myocardial ischemia, and
blindness.44 – 46 Instead, the patient may be discharged home after
observation, with instructions to increase the dose of their existing
antihypertensive regimen, adding an additional antihypertensive
medication or reinstituting the medication if noncompliant. These
patients should subsequently be followed on an outpatient basis
within 24 to 48 hours of discharge. Only those who are at higher risk
for adverse outcomes, such as patients with diabetes, history of
stroke, or coronary artery disease, should be considered for inpatient
observation. Similarly, patients who present with medication non-
compliance are at risk for progressing to hypertensive emergency
(ie, developing end-organ damage) and benefit from an inpatient
observation.
Hypertensive emergencies require immediate admission to an
intensive care unit for prompt BP control with a parenteral, titratable
antihypertensive agent while continuously monitoring BP, neuro-
logic status, and urine output. BP should be efficiently reduced
within minutes to an hour, and not immediately to normal levels.
The goal is to correct the BP to no less than 20% to 25% in the first
hour and then if stable to 160/100 to 160/110 mm Hg within the next
2 to 6 hours.7 An alternative is to reduce DBP by 10% to 15% or to
approximately 110 mm Hg in 30 to 60 minutes;47 with a goal
reduction to normal within 24 to 48 hours. The aggressive lowering
of BP may aggravate hypoperfusion and worsen end-organ dam-
age.48 Specific therapies are targeted to the end-organ damage
present. The rapid-acting antihypertensives preferred in hyperten-
sive emergencies are labetalol, esmolol, fenoldopam, clevidipine,
nitroprusside, and nicardipine.47 In addition, some patients, partic-
ularly those with normal kidney function, may have some element of
volume depletion because of the preceding pressure natriuresis that
occurred in the setting of very high BPs. Thus, in the absence of
clinical signs of volume overload, some volume expansion with
intravenous saline solution will help to suppress renin secretion and
to prevent significant hypotension once the vasodilating medications
begin to act.48 In patients with aortic dissection, however, a rapid
reduction of SBP ⬍120 mm Hg and mean arterial pressure ⬍80 mm
Hg should be achieved within 5 to 10 minutes, initially with
␤-blockers, to decrease the pressure impulse (dP/dT).49
Various short-acting medications are available for hyperten-
sive emergencies. Enalaprilat is an ACE inhibitor that is not recom-
mended for use in hypertensive crisis because of its slow onset of 1
hour and long duration of action of approximately 6 hours.46
Moreover, renal failure is common in patients with hypertensive
crises, either as a trigger for, or as a result of the crisis50 and this
could be further exacerbated by the use of an ACE inhibitor.47 It can
be used cautiously in the later stages of therapy in patients with heart
failure in the setting of a hypertensive crisis.
Labetalol is a combined ␣1 adrenergic receptor blocker and
nonselective ␤-blocker with an elimination half-life of about 5.5 hours.
It maintains cardiac output and reduces total peripheral resistance with
conservation of cerebral, renal, and coronary flow.51 Hypertensive
encephalopathy patients may benefit from labetalol, and it is the
preferred choice for acute myocardial ischemia, aortic dissection, acute
ischemic stroke, and hypertensive encephalopathy. Esmolol, on the
other hand, is a very short-acting ␤-blocker that decreases heart rate,
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Rodriguez et al
myocardial contractility, and cardiac output.52 It can be used cautiously
in patients with an acute MI concomitantly with nitroglycerin.
Nicardipine is a dihydropyridine derivative calcium channel
blocker with cerebral and coronary vasodilatory activity. This drug
has therapeutic benefits in increasing stroke volume and coronary
blood flow, making it useful for patients with coronary artery
disease. It is also recommended for the treatment of acute ischemic
stroke when DBP and SBP are not at goal.53
Clevidipine is a new short-acting intravenous third-generation
dihydropyridine calcium-channel blocker, which is a selective arte-
rial vasodilator available for intraoperative and critical care set-
tings.54 –56 It is a safe and effective alternative in the acute manage-
ment of moderate-to-severe HTN.56 –58 Its potential advantages
consist of its short half-life, affording greater acute titratability.
Fenoldopam is a dopaminergic DA1 receptor agonist that is a
peripheral vasodilator and a diuretic.57 It has been found to be a
rapid-acting, well-tolerated, and highly effective intravenous sub-
stance for the treatment of severe HTN.58
Sodium nitroprusside is a potent arterial and venous dilator that
decreases preload and afterload. Potential drawbacks include its ability
to decrease cerebral perfusion while increasing intracranial pressure, the
development of coronary steal (increasing mortality if used in the
setting of acute MI),59 and cyanide toxicity. Its use has been limited
typically for patients with acute pulmonary edema and/or severe left
ventricular dysfunction, and in patients with aortic dissection.60 It
should be administered with care in the setting of renal insufficiency,
because of the higher risk of cyanide accumulation.
Immediate release nifedipine, nitroglycerin, and hydralazine
should not be considered first-line drugs in the management of
hypertensive emergencies because of toxicity and side effects.61 The
use of short-acting nifedipine (either oral or sublingual) is no longer
considered appropriate or safe because of a rapid unpredictable fall
in BP, which may precipitate cerebral, renal, and cardiac ischemic
events.62,63 Nitroglycerin is a venodilator that reduces preload and
cardiac output. It is often used in conjunction with other antihyperten-
sive agents, primarily in acute MI and pulmonary edema. Hydralazine
is a direct-acting arteriolar vasodilator with a half-life of approximately
10 hours.64 It is commonly used in pregnant women because of its
ability to increase uterine perfusion (ACE inhibitors are teratogenic and
contraindicated). Other options in this patient population include labe-
talol, nicardipine, methyldopa, nifedipine, and prazosin. Studies have
shown that all these drugs lower BP in the intravenous or oral form,
with no evidence that any one is better than the other65 (Table 3).
PROGNOSIS
There are few data regarding the outcomes of a hypertensive
crisis. In a study of 315 patients with malignant HTN, 40% were alive
after 33 months. The most common causes of death were renal failure
(39.7%), stroke (23.8%), MI (11.1%), and heart failure (10.3%).20
Furthermore, studies of patients presenting to the emergency
room with a hypertensive crisis have demonstrated that most do not
receive the appropriate evaluation, medical regimen, and discharge
instructions proposed by the current guidelines. Two studies of
patients presenting to the emergency room with a hypertensive crisis
found that serum chemistry was only obtained in 70% to 73% of
patients, electrocardiogram in 53% to 70% of patients, chest x-ray in
24% to 46% of patients, and urinalysis in 43% to 44% of patients.
Two-thirds of the total number of patients evaluated did not have a
funduscopic examination in the emergency room, and only 19%
discharged had modification of their antihypertensive regimen.
Overall, only 6% obtained the tests recommended by the guidelines,
and 10% had no tests performed.66,67
The known duration of HTN and procuring the serum urea
level at presentation have been found to be the main predictors of
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Cardiology in Review • Volume 18, Number 2, March/April 2010
TABLE 3. Parenteral Agents Used in the Management of
Various Hypertensive Crises
Primary Condition Therapy
Acute aortic dissection Labetalol or nicardipine ⫹ esmolol,
nitroprusside ⫹ esmolol
Hypertensive encephalopathy Labetalol, nicardipine, fenoldopam,
clevidipine
Acute myocardial ischemia Nitroglycerin ⫾ esmolol, fenoldopam,
labetalol
Congestive heart failure Enalaprilat, loop diuretic
Eclampsia Hydralazine, nicardipine, labetalol
Pheochromocytoma Phentolamine, labetalol
Acute pulmonary edema Sodium nitroprusside, nicardipine,
fenoldopam, loop diuretic,
nitroglycerin
Acute ischemic stroke/ Nicardipine, fenoldopam, labetalol,
intracerebral bleed clevidipine
Acute renal failure/MAHA Nicardipine, fenoldopam
Adapted from Varon et al.47
MAHA indicates microangiopathic hemolytic anemia.
survival in hypertensive crisis, with poorer outcomes for black
patients.21 The 1-year mortality rate is 79% for patients with
untreated hypertensive emergencies,68 and 5-year survival rate
among all patients who present with hypertensive crisis is 74%.20
At times, cardiac enzymes are tested and found to be elevated.
With little to no evaluation of underlying coronary artery disease, it
becomes difficult to stratify patients for purposes of treatment and
diagnosis. It is difficult to discern whether troponin elevation is a
result of subendocardial ischemia because of extreme left ventricular
wall stress from the increase in afterload versus coronary artery
disease and unstable plaque that triggers a catecholamine surge with
resultant severe HTN.
Physicians should perform complete evaluations in patients who
present with a hypertensive crisis to effectively reverse the crisis,
intervene and correct the underlying trigger, to improve long-term
outcomes after the episode. Efforts to reduce the incidence of hyper-
tensive crisis should continue. For those unfortunate patients who do
present with hypertensive crisis, strategies to risk-stratify, educate, and
improve outcome after these events should be optimized.
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