32 
Hypertensive Crises
SERGIO L. ZANOTTI-CAVAZZONI
CHAPTER OUTLINE
Introduction and Terminology
Pathophysiology
Approach to Management
Should the Blood Pressure Be Lowered Acutely?
How Much Should the Blood Pressure Be Lowered?
Which Medication Should Be Used to Lower the Blood
Pressure?
Specific Clinical Considerations
Hypertensive Encephalopathy
Hypertensive Crisis in Cerebrovascular Accidents
Acute Aortic Dissection
Hypertensive Crises in Pregnancy
Postoperative Hypertension
Catecholamine-Associated Hypertensive Crisis
Conclusions
Introduction and Terminology
Hypertension is a common clinical disorder and one of the most
common preventable contributors to disease and death. Estimates
indicate that almost 30% of the U.S. adult population has elevated
blood pressure.1 Furthermore, one-third of these patients are unaware
of their diagnosis, and of those who are diagnosed and treated,
only 34% have adequate control of their blood pressure.2 Severe
elevations in blood pressure, hypertensive crises, occur in about
1% of patients with chronic hypertension.1 Most patients with
significantly elevated blood pressure (systolic pressure ≥180 mm Hg
and/or diastolic pressure ≥120 mm Hg) do not have evidence of
acute end-organ damage or symptoms. However, a small subset
can experience significant acute end-organ damage and these
patients require immediate treatment to prevent irreversible organ
dysfunction.
The report of the Eighth Joint National Committee on Evidence-
Based Guidelines for the Management of High Blood Pressure in
Adults defines hypertension as a systolic pressure of 140 mm Hg
or higher and/or a diastolic pressure of 90 mm Hg or higher.3 The
Eighth Joint National Committee on Evidence-Based Guidelines
for the Management of High Blood Pressure in Adults also provides
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targets and guidelines for long-term treatment of patients with
hypertension based on age and comorbid conditions such as diabetes
mellitus and chronic renal disease. The terms malignant hypertension
and accelerated hypertension are no longer used. Hypertensive crises
are defined as severe elevations in blood pressure. Although some
experts suggest reference blood pressure values (systolic pressure
≥180 mm Hg and/or diastolic pressure ≥120 mm Hg), it is prefer-
able to evaluate acute elevations of blood pressure within the context
of each individual patient and the effects of a given blood pressure
on organ function in that patient. For example, an acute raise in
diastolic blood pressure to a value of 100 mm Hg can cause sig-
nificant damage in a previously normotensive individual, whereas
a diastolic pressure of 130 mm Hg may be tolerated in a patient
with a history of uncontrolled hypertension. As we will see, these
patients will require different therapeutic approaches.
A hypertensive emergency is a severe elevation in blood pressure
associated with the presence of acute end-organ damage. Hyper-
tensive emergencies require immediate control of blood pressure,
within 1 to 2 hours to prevent further organ damage. This usually
requires the use of intravenous (IV) medications and invasive
monitoring (arterial line) in a high-dependency unit such as the
intensive care unit (ICU). The principal systems susceptible to
acute end-organ damage from severe elevations in blood pressure
include the central nervous, cardiovascular, and renal systems (Fig.
32.1). Several clinical situations are associated with hypertensive
emergencies (Box 32.1). The absolute level of blood pressure and
the time course of this elevation determine the development of a
hypertensive emergency. However, acute end-organ damage can
occur at different blood pressure values in different patients.
Therefore it is more useful to define hypertensive emergencies with
the presence of acute end-organ damage as opposed to specified
numbers of systolic or diastolic blood pressure. True hypertensive
emergencies are uncommon. Based on large claims databases it is
estimated as one to two cases per million per year. Based on ret-
rospective studies it is estimated that hypertensive emergencies
constitute less than 1% of all visits to an adult emergency depart-
ment for one year.4 In addition to initiating immediate therapeutic
interventions, patients with a hypertensive emergency may require
further diagnostic evaluation to determine the cause of their elevated
blood pressure. Depending on the population studied, 20% to
50% of patients presenting with a hypertensive emergency have
a secondary cause of hypertension identified.5
Severe elevations of blood pressure in the absence of acute-end
organ damage do not constitute a hypertensive emergency and
occur far more frequently. In these clinical situations blood pressure
543
 544 Pa rt 2 Critical Care Cardiovascular Disease
• Fig. 32.1  
• BOX 32.1  Hypertensive Emergencies
Hypertensive encephalopathy
Cerebrovascular accident
Acute aortic dissection
Acute left ventricular failure
Acute myocardial infarction
Acute renal failure
Preeclampsia/eclampsia
Catecholamine excess states
Postoperative hypertension
can be lowered more gradually, over 24 to 48 hours. This usually
can be accomplished with oral medications and does not require
invasive hemodynamic monitoring in an ICU. These elevations
of blood pressure can be associated with chronic stable organ
dysfunction, such as stable angina, chronic renal insufficiency, or
previous cerebrovascular accident, without evidence of acute end-
organ damage.
Pathophysiology
The underlying pathophysiology of hypertensive crises is still not
fully understood. The transition of mild hypertension or normoten-
sion to a hypertensive crisis is usually caused by an event that
leads to an abrupt increase in blood pressure. Situations associated
with this event may include cessation of hypertensive medications
with potential rebound effects, consumption of illicit drugs, and
severe pain, as well as several clinical syndromes. Blood pressure
(BP) is determined by the product of cardiac output (CO) and
systemic vascular resistance (SVR): BP = CO × SVR. In most
hypertensive crises, the initial rise in blood pressure is secondary to
increased systemic vascular resistance. The rise in systemic vascular
resistance is believed to be caused by humoral vasoconstrictors.6
With the increase in blood pressure, mechanical stress on the
arteriolar wall leads to endothelial damage and fibrinoid necrosis
of the arterioles.6,7 Vascular damage leads to loss of autoregulatory
mechanisms, ischemia, and acute end-organ damage, which prompts
further release of vasoconstrictors and initiates a vicious cycle
(Fig. 32.2).6,7
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Hypertensive encephalopathy
Stroke
Retinal hemorrhages
Papilledema
Myocardial ischemia
Acute heart failure
Dissecting aortic aneurysm
Hematuria
Red blood cell casts
Renal failure
End-organ failure in hypertensive emergency.
Vasoconstrictors
SVR
BP
End-organ ischemia
Endothelial damage
Loss of autoregulation
• Fig. 32.2  Pathophysiology of hypertensive emergency. Increase in
humoral vasoconstrictors leads to increased systemic vascular resistance
(SVR), which raises blood pressure. As blood pressure (BP) increases,
endothelial damage results in loss of autoregulation and organ ischemia.
Organ ischemia increases release of vasoconstrictors, and a vicious circle
is initiated.
Approach to Management
Despite the abundance of evidence providing guidance and support
to the long-term benefits of treating chronic hypertension, there
is a paucity of high-level evidence to guide clinicians in the treatment
of hypertensive emergencies. However, a systematic approach with
consideration of underlying pathophysiology can help the clinician
to avoid common pitfalls in the clinical management of patients
with hypertensive crises. The most common pitfall in treating
patients with hypertensive crises involves treating numbers without
evaluating individual patients for acute end-organ damage. This
usually is associated with inappropriate use of IV drugs with the
potential for precipitous and harmful drops in blood pressure. A
methodical approach to patients with severe elevations in blood
pressure can help establish safe and effective treatment. To that
effect, the clinician should address three fundamental questions:
1. Should the blood pressure be lowered acutely?
2. How much should the blood pressure be lowered?
3. Which medication should be used to lower the blood
pressure?

Should the Blood Pressure Be Lowered Acutely?
To answer this question, the clinician must determine if there is
evidence of acute end-organ damage. In patients with hypertensive
emergencies (the presence of acute end-organ damage), the blood
pressure should be lowered acutely to a safe target to prevent
further end-organ damage. An organized approach in the evaluation
of the patient is necessary. A focused history should determine a
previous diagnosis of hypertension, medication history, use of illicit
drugs or over-the-counter agents with potential hypertensive effects,
and the presence of symptoms consistent with neurologic, visual,
cardiac, or renal dysfunction. Physical examination should confirm
vital signs. It is important to measure blood pressure adequately
and in both upper extremities. Pulses should also be checked in
all extremities, as inequalities in blood pressure or pulses can exist
with aortic dissection. In addition, a thorough neurologic and
cardiopulmonary examination should evaluate possible signs of
end-organ failure such as altered mentation, new focal neurologic
deficits, or cardiogenic pulmonary edema. A funduscopic examina-
tion of the eyes should be done to look for signs of acute papillary
edema or new retinal hemorrhages. A set of simple diagnostic tests
can complete the evaluation for acute end-organ damage. An
electrocardiogram (ECG) to rule out active ischemia and a chest
x-ray to assess for pulmonary edema or signs of aortic pathology
can help the clinician to evaluate the cardiopulmonary system.
Abnormalities in blood urea nitrogen, creatinine, and the urinalysis
(red blood cell casts) suggest renal involvement. Additional tests
may be indicated based on the individual characteristics of each
case. An algorithm to establish the presence of acute end-organ
damage at the bedside when evaluating patients is presented in
Fig. 32.3.
If there is evidence of acute end-organ damage based on the
clinical evaluation, the patient’s blood pressure should be lowered
acutely. However, if after a careful systematic clinical evaluation,
Does this patient have mental status change?
Yes
Does this patient have new focal findings?
Do the optic fundi show papilledema,
hemorrhages, or exudates?
No
Does the ECG show signs of Yes
cardiac ischemia?
Is there evidence of acute LV dysfunction?
No
Yes
Is the serum creatinine elevated?
Does the UA show red cells or red cell casts?
No
No need to lower blood pressure acutely
• Fig. 32.3  Evaluation algorithm for hypertensive emergency. Systematic
evaluation for possible acute end-organ damage can proceed according
to this scheme. If the answer to any of the questions is “Yes,” the patient
has a hypertensive emergency and blood pressure should be lowered
acutely. If the answer to all questions is “No,” the patient does not have
a hypertensive emergency and the blood pressure can be lowered gradu-
ally. ECG, Electrocardiogram; LV, left ventricular; UA, urinalysis.
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CHAPTER Hypertensive Crises 545
the examination and diagnostic tests do not show evidence of
acute end-organ damage, the blood pressure does not require
immediate reduction. It is important to emphasize that the presence
or absence of acute end-organ damage and not the numerical value
of the blood pressure should dictate the acuity with which blood
pressure reduction should be achieved.
How Much Should the Blood Pressure
Be Lowered?
Once the decision to lower a patient’s blood pressure acutely is
made, the next step should be to establish a safe therapeutic target
for the blood pressure reduction. The goals for treating hypertensive
emergencies are to lower blood pressure to a level that prevents
ongoing acute end-organ damage and at the same time to avoid
iatrogenic damage caused by precipitous falls in blood pressure
causing hypoperfusion to organs. Understanding the autoregulation
of blood pressure in normal states and in patients with chronic
hypertension is essential to achieve these goals.
Different organs can autoregulate and maintain a constant blood
flow through a range of mean arterial pressures (MAPs). Under
normal conditions cerebral autoregulation keeps blood flow constant
between MAPs of 60 to 150 mm Hg.8 When the MAP drops,
cerebral arteries dilate, and if the MAP rises, they constrict to
maintain a constant blood flow to the brain. Drops in the MAP
below the lower limit of autoregulation lead to hypoperfusion
resulting in brain ischemia. Rises in the MAP above the higher
limit of autoregulation lead to acute end-organ damage from
hypertension (hypertensive emergency). In the case of the brain,
this may result in hypertensive encephalopathy. With chronic
hypertension, compensatory functional and structural changes
occur in the vasculature.9,10 These changes will shift the autoregula-
tory curve to the right.11 The autoregulatory curve for cerebral
blood flow in healthy individuals and in patients with chronic
hypertension is shown in Fig. 32.4. Hence, patients with chronic
hypertension have a higher tolerance to elevated blood pressures,
H as their autoregulatory curve is shifted to the right. This explains
Y
P
why many patients present with severely elevated blood pressure
E and no evidence of acute end-organ damage. However, rapid
R reductions of blood pressure to “normal” levels can fall below the
T lower autoregulatory capacity of the circulation in a chronically
E hypertensive patient. This phenomenon explains the hypoperfusion
N
S of vital organs and the development of renal failure or cerebral
I
V
E
E
M
Cerebral blood flow
E
R
G
Normal
E
N
C Chronic
Y hypertension
60 120 180
Mean arterial pressure (mm Hg)
• Fig. 32.4  Autoregulation of cerebral blood flow. Cerebral blood flow
autoregulation curves are depicted for normotensive (solid purple line) and
chronic hypertensive (dashed blue line) states.
 546 Pa rt 2 Critical Care Cardiovascular Disease

ischemia often seen when blood pressure is lowered too far or too
fast.12 Based on these principles, most experts would recommend
that for most hypertensive emergencies the goal should be to lower
MAP by 15% to 25% over a period of several minutes to hours,
depending on the clinical situation.13 Reduction of blood pressure
to normal levels may be warranted in special situations such as
those involving patients with aortic dissection or previously nor-
motensive patients with a postoperative hypertensive emergency.
Which Medication Should Be Used to Lower
the Blood Pressure?
The ideal medication to treat a hypertensive emergency should
have a rapid onset of action, high potency, immediate reversibility,
no tachyphylaxis, and minimal or no adverse effects. Although
there is no perfect medication, several agents with some of these
characteristics are summarized in Table 32.1. There are a limited
number of studies comparing agents in terms of clinical outcomes.
With no clear outcome data, the selection of an agent is based on
the clinical scenario, pharmacologic characteristics of the drug,
and availability. Parenteral agents that are useful in treating
hypertensive emergencies are further discussed (in alphabetical
order).
Clevidipine
Clevidipine is an ultra–short-acting dihydropyridine calcium channel
antagonist that is approved for IV use to treat severe hypertension.
Clevidipine has vasoselective properties with a rapid onset of action
and a very short half-life (<1 minute).14 Clevidipine is metabolized
by red blood cell esterases; therefore its use is not affected in
patients with renal and/or hepatic failure. Clevidipine reduces
blood pressure by a direct and selective effect on arterioles. It does
not produce reflex tachycardia, and its effect on reducing afterload
is often associated with increased cardiac output. Clevidipine is
administered intravenously as a continuous drip. The initial dose
is usually 1 to 2 mg/h with adjustments as needed to obtain the
desired response in blood pressure. The maintenance dose is usually
4 to 6 mg/h; however, higher doses may be required in certain
clinical situations. Small studies have compared clevidipine to
nitroprusside for the treatment of severe hypertension in anesthetized
patients undergoing surgery.15,16 These studies showed that clevi-
dipine had similar effects on blood pressure control with less effect
on cardiac filling and heart rate. Although clevidipine has not been
studied extensively in other clinical situations, its characteristics
make it an attractive option for the treatment of hypertensive
emergencies outside the operating room. In addition to its
intraoperative use it has received increased attention in neurologic
hypertensive emergencies.17,18 Clevidipine is not recommended in
patients with severe aortic stenosis (owing to the high risk of severe
hypotension) or in patients with disordered lipid metabolism
(because it is administered in a lipid-laden emulsion). Clevidipine’s
emulsion contains soy and eggs and it is contraindicated in patients
with documented allergies to these substances.
Esmolol
Esmolol is an ultra–short-acting cardioselective, β-adrenergic agent
that can be administered intravenously for the treatment of
hypertensive emergencies.19 Esmolol has a rapid onset of action

TABLE
32.1  Pharmacologic Agents Used in Treating Hypertensive Emergencies

Elimination Onset of Duration

Drug Dosing Half-Life Action of Effect Advantages Disadvantages
Clevidipine Initial dose 1–2 mg/h with Initial half-life 2–4 min 15 min Rapid action, titratable, Rapidly metabolized in
titration Maintenance 1 min not metabolized by pseudocholinesterase-
dose 4–6 mg/h liver or kidney deficient patients
Esmolol 200–500 µg/kg over 9 min 2 min 18–30 min Easily titratable; Use with caution in patients
1–4 min, then 50 µg/kg cardioselectivity with heart failure or asthma
per minute for 4 min,
and titer, then infuse
50–300 µg/kg per
minute
Fenoldopam Initial dose, 0.1 µg/kg per 5–10 min 5 min 30–60 min Induces both a diuresis Use with caution in patients
minute with titration and natriuresis with glaucoma
every 15 min, no bolus
Labetalol Bolus 20 mg, then 5 h 2–5 min 2–4 h No reflex tachycardia Use with caution is patients
20–80 mg every 10 min with asthma, heart failure,
for maximum dose or bradycardia
300 mg. Infuse at
0.52–2 mg/min
Nicardipine Initial dose, 5 mg/h to 40–60 min 10–20 min 1–4 h Minimal cardiodepressant Possible adverse effects
maximum of 15 mg/h effects; minimal dose include hypotension,
adjustments required headache, and flushing
Nitroprusside Initial dose, 0.25 µg/kg per 14 min Within seconds 3–4 min Immediate onset of effect Hypotension; coronary steal;
minute, maximum dose cyanide toxicity; light
8–10 µg/kg per minute sensitivity; requires frequent
monitoring

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(within 2 minutes), a short elimination half-life (approximately 9
minutes), and a rapid offset of action (within 15 to 30 minutes
after stopping infusion).20 Esmolol is rapidly metabolized by red
blood cells and is not dependent on renal or hepatic function.20
These properties enable easy titration of the drug and make it
attractive in situations of a hypertensive emergency associated with
intense adrenergic responses or tachycardia. This agent is available
for IV use, both as a bolus and as a continuous infusion. The usual
dose is 0.5 mg/kg as a loading dose, followed by a maintenance
infusion of 25 to 300 µg/kg per minute titrated to the patient’s
individual response.20 Esmolol has been found effective in controlling
postoperative hypertension and tachycardia in several clinical
studies.21–23 Esmolol has also been used successfully to treat
hypertensive emergencies under other various clinical situations.24,25
Esmolol seems to be more effective in situations when both blood
pressure and tachycardia are present and there are no problematic
issues with β-blockade (severe systolic cardiac dysfunction or
asthma). It is often used in conjunction with other agents to achieve
a better response.
Fenoldopam
Fenoldopam is a selective dopamine agonist that causes systemic
and renal vasodilation by stimulating dopamine-1 adrenergic
receptors.26,27 Fenoldopam is administered intravenously and has
a rapid onset of action (5 minutes) and a short duration of action
(30 to 60 minutes).27 It is rapidly metabolized by conjugation in
the liver to inactive metabolites that are excreted by the kidney.
The plasma elimination half-life is approximately 5 to 10 minutes.27
Fenoldopam is administered as a continuous infusion (without a
bolus dose), at an initial dose of 0.1 µg/kg per minute; this dose
is titrated by 0.05 to µg/kg per minute based on desired effect up
to a maximum dose of 1.6 g/kg per minute.26 The most common
adverse effects of the drug are related to its vasodilator properties
and include hypotension, headache, reflex tachycardia, and flush-
ing.26 Fenoldopam also increases intraocular pressure and should
be used with caution in patients with glaucoma.28 Fenoldopam
has been demonstrated to be safe and effective in postoperative
hypertension.29 Two clinical studies in severely hypertensive patients
found fenoldopam to be comparable in efficacy to sodium nitroprus-
side.30,31 Because of its effects on the renal vasculature and its
ability to increase urine output, fenoldopam has been proposed
as a renal protective drug.32 In the setting of a hypertensive
emergency, protective effects of fenoldopam on renal function
have not been confirmed. However, because it does not affect renal
function adversely and does not have increased toxicity in patients
with renal failure, it may be a useful alternative to sodium nitroprus-
side in patients with hypertensive emergency and renal failure.
Labetalol
Labetalol is a combined α- and β-adrenergic receptor blocker that
is approved for both oral and IV use in the treatment of hyperten-
sion. Labetalol lowers blood pressure by decreasing systemic vascular
resistance by α1-blockade and at the same time counteracts the
reflex tachycardia from vasodilation through its β-blocker effect.33,34
Labetalol reduces peripheral vascular resistance while maintaining
cerebral, renal, and coronary blood flow. Unlike other β-blockers,
labetalol does not reduce cardiac output. When administered
intravenously it has a rapid onset of action (2–5 minutes) with
peak hypotensive effect occurring within 5 to 10 minutes and
lasting 2 to 4 hours.35 The drug is primarily metabolized by the
liver and has a plasma elimination half-life of about 5 hours.33
Labetalol is usually administered intravenously at a loading dose
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CHAPTER Hypertensive Crises 547
of 20 mg, followed by incremental doses of 20 to 80 mg every 10
minutes until the target blood pressure is achieved or a maximal
dose of 300 mg has been reached. An alternative regimen is a
continuous infusion starting at 1 to 2 mg/min and titrated upward
to achieve a desired blood pressure endpoint. Adverse effects of
labetalol include orthostatic hypotension, bronchospasm (should
be avoided in asthma patients), heart failure, and significant
bradycardia (should be avoided in the presence of sinus bradycardia
or heart block greater than first degree). Labetalol has been shown
to be effective in a wide range of clinical situations associated with
hypertensive emergencies.33,34,36–39
Nicardipine
Nicardipine is a short-acting calcium channel antagonist that
produces selective arteriolar dilation. Nicardipine decreases systemic
vascular resistance, without producing reflex tachycardia while
maintaining or increasing cardiac output.40 IV nicardipine has a
rapid onset offset of action (the major effect lasts 10–15 minutes,
and the plasma elimination half-life is 40–60 minutes), making
it easily titratable when treating hypertensive emergencies.41,42 An
initial dose of 5 mg/h is recommended, increasing the infusion
rate by 2.5 mg/h every 5 to 15 minutes (to a maximum rate of
15 mg/h) until the desired hemodynamic response is achieved.
Once the target blood pressure is achieved, the infusion rate can
be reduced to 3 mg/h and adjusted to maintain the desired endpoint.
The drug is rapidly distributed throughout the body and is
metabolized by the liver into inactive metabolites. Nicardipine
should be avoided or used cautiously in patients with aortic stenosis,
in patients with cardiomyopathy receiving β-blockers, and in patients
with impaired hepatic function. Several studies have documented
the utility and safety of nicardipine in patients with hypertensive
emergencies. Randomized studies have demonstrated that nicar-
dipine has similar efficacy when compared to nitroprusside in the
management of postoperative hypertension.41,43
Nitroprusside
For many years sodium nitroprusside was the standard IV drug
administered for hypertensive emergencies. Because of its potential
side effects and the appearance of safer and easier to use alternatives
it has fallen in disfavor in the view of many experts. However, it
is still available and remains a viable alternative today in many
settings. Nitroprusside is a potent balanced arterial and venous
vasodilator that decreases both cardiac afterload and preload.
Nitroprusside has a rapid onset of action (2–3 minutes) and a
short serum half-life (1–2 minutes) and may be easily titrated.44
Because of its potent effects on blood pressure, use of nitroprusside
requires invasive hemodynamic monitoring (arterial line for continu-
ous blood pressure monitoring). Nitroprusside is typically begun
at 0.3 µg/kg per minute and increased by 0.2 to 1 µg/kg per
minute every 3 to 5 minutes as needed until a maximum of 8–
10 µg/kg per minute. Cyanide and thiocyanate are metabolites of
nitroprusside with potential toxic effects. Cyanide is released
nonenzymatically from nitroprusside. Cyanide is converted to
thiocyanate by the liver. Finally, the kidney excretes thiocyanate.
The total dose of nitroprusside and the presence of liver or renal
dysfunction increase the risk of toxicity. Cyanide toxicity can be
associated with lactic acidosis, mental status changes, and hypoten-
sion. Signs of thiocyanate toxicity include delirium, headaches,
nausea, abdominal pain, and muscular spasms.45 To reduce possible
toxicity, the duration of treatment with nitroprusside should be
limited and the maintenance rate of infusion should not exceed
2  µg/kg per minute. In patients requiring higher doses of
 548 Pa rt 2 Critical Care Cardiovascular Disease
nitroprusside, an infusion of thiosulfate is recommended to decrease
the risk of toxicity.46 Hydroxocobalamin has also been demonstrated
to prevent and treat possible cyanide toxicity associated with the
use of nitroprusside. Patients taking nitroprusside should be carefully
monitored with special attention focused on unexplained acidosis
or dropping serum bicarbonate concentrations. Despite these
concerns, nitroprusside has been used successfully in the treatment
of hypertensive emergencies for many years and with proper precau-
tions toxicity is seldom encountered.
Other Agents
Several other agents have been used to treat severely elevated blood
pressure. Many of them have been abandoned secondary to the
emergence of safer and more efficacious alternatives. However,
there are a few agents that despite some limitations compared to
the drugs previously discussed may be useful in particular situations.
Nitroglycerin directly interacts with nitrate receptors producing
predominantly venous dilation. Because of its favorable effects on
coronary perfusion and its ability to reduce preload, it is a drug
well suited for treating hypertensive emergencies associated with
myocardial ischemia or acute left ventricular failure.47 Several clinical
studies have shown the safety and efficacy of nitroglycerin for the
treatment of hypertension after cardiac surgery.48–50 Nitroglycerin
is administered as a continuous infusion. The starting dose is 5 µg/
min, and this dose can be titrated until a maximum of 200 µg/
min is reached.
Phentolamine is an α-adrenergic blocking agent that may be
used for the management of catecholamine-induced hypertensive
emergencies, such as pheocromocytoma.51 Phentolamine is admin-
istered intravenously in 1- to 5-mg boluses. The effects are immediate
and may last up to 15 minutes. This drug may cause arrhythmias
and angina. Once the blood pressure is controlled, a long-acting
α-adrenergic blocking agent such as oral phenoxybenzamine can
be started.
Enalaprilat is an angiotensin-converting enzyme inhibitor that
can be administered intravenously. Its onset of action is within 15
minutes and its duration of action is 12 to 24 hours.52,53 The usual
dose is of 1.25 mg IV every 6 hours, titrated by increments of
1.25 mg at 12- to 24-hour intervals to a maximum dose of 5 mg
every 6 hours.54 The degree of blood pressure reduction with
enalaprilat correlates directly with the pretreatment levels of
angiotensin II and plasma renin activity.55 Enalaprilat is especially
useful in hypertensive emergencies associated with scleroderma
crises.56
Hydralazine is a vasodilator that has been used in pregnancy-
related hypertensive crises for many years. However, it has
unpredictable effects on blood pressure and a long half-life.
Nicardipine and labetalol are better choices for treating pregnant
patients with hypertensive emergencies in the ICU.
Specific Clinical Considerations
Hypertensive Encephalopathy
When rises in MAP exceed the upper limits of the cerebral blood
flow, autoregulatory curve endothelial damage with extravasation
of plasma proteins can lead to cerebral edema.57 Hypertensive
encephalopathy, the clinical manifestation of this phenomenon,
is characterized by headache, visual disturbances, confusion, and
focal or generalized weakness. If untreated, hypertensive encepha-
lopathy can lead to coma and death.58 Magnetic resonance imaging
has demonstrated that the majority of the cases involve the cortical
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• BOX 32.2  Differential Diagnosis of Hypertensive
Encephalopathy
Ischemic stroke
Intracerebral hemorrhage
Subarachnoid hemorrhage
Subdural hematoma
Epidural hematoma
Central nervous vasculitis
Brain mass
Seizure disorder
Central nervous system infection
Drug toxicity
Withdrawal syndrome
regions of the brain.59 However, hypertensive encephalopathy with
brainstem involvement has also been described.60,61 The differential
diagnosis of hypertensive encephalopathy includes several neurologic
syndromes (Box 32.2). These should be quickly ruled out by imaging
of the brain and other pertinent diagnostic tests. Treatment should
be instituted immediately. The goal is to reduce the MAP by 15%
to 20% within the first 1 to 2 hours.62 The hallmark of hypertensive
encephalopathy is improvement of symptoms once the blood
pressure is controlled. Caution should be taken not to cause
worsening neurologic symptoms from hypoperfusion caused by
lowering the MAP. Drugs suitable for treating hypertensive
encephalopathy include nicardipine, labetalol, fenoldopam, and
nitroprusside.
Hypertensive Crisis in
Cerebrovascular Accidents
Hypertension is common after both ischemic and hemorrhagic
strokes. Extreme elevations in blood pressure have been associated
with poor outcomes after ischemic and hemorrhagic stroke.63,64
Significant elevations in blood pressure after strokes raise concerns
for the potential development of reinfarction, cerebral edema,
increased hemorrhage size, or hemorrhagic transformation of
ischemic lesions. However, after acute stroke the cerebral vasculature’s
ability to autoregulate blood flow is impaired.65 During this time,
flow to the brain is highly dependent on MAP. Even modest
reductions in blood pressure can compromise blood flow to the
brain during this period with the potential for increased secondary
neurologic damage. Optimal treatment of blood pressure during
stroke is still not a settled debate. Based on available evidence the
approach to the acute management of high blood pressure in the
setting of acute strokes differs for ischemic and hemorrhagic strokes.
In ischemic strokes, current guidelines recommend withholding
therapy for hypertension in the acute phase unless the patient will
receive thrombolysis, there is evidence of concomitant acute end-
organ damage, or excessive elevations in blood pressure are present
(arbitrarily selected as systolic blood pressure [SBP] >220 mm Hg
or diastolic blood pressure >120 mm Hg).66 Acute blood pressure
management for patients with ischemic stroke who are candidates
for reperfusion therapy is summarized in Box 32.3. For hemorrhagic
strokes, the concerns over lowering cerebral perfusion pressure
need to be balanced by potential hematoma growth with elevated
blood pressure. Two recent clinical trials randomly assigned patients
with acute spontaneous intracerebral hemorrhage to an SBP target
of <140 mm Hg or <180 mm Hg. The first study, INTERACT2
(Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage

• BOX 32.3  Guidelines for Treatment of Hypertension
in Ischemic Cerebrovascular Accidents in
Patients Who Are Candidates for Acute
Reperfusion Therapy
Patient otherwise eligible for acute reperfusion therapy except that BP is
>185/110 mm Hg:
Labetalol 10–20 mg IV over 1–2 min; may repeat ×1; or
Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5–15 min to desired
effect (maximum 15 mg/min)
If BP is not maintained at or below 185/110 mm Hg; do not administer rtPA
Management of BP during and after rtPA or another reperfusion therapy to
maintain BP at or below 180/105 mm Hg:
Monitor BP every 15 min for 2 h from initiation of rtPA therapy, then every
30 min for 6 h, and then every hour for 16 h
If systolic BP >180–230 mm Hg or diastolic BP >105–120 mm Hg:
Labetalol 10 mg IV followed by continuous IV infusion 208 mg/min; or
Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5–15 min to desired
effect (maximum 15 mg/min)
If BP not controlled or diastolic BP >140 mm Hg, consider IV sodium
nitroprusside
BP, Blood pressure; IV, intravenously; rtPA, recombinant tissue-type plasminogen activator.
Trial 2) suggested that acutely lowering the SBP to 140 mm Hg
or lower was safe and associated with nonsignificant benefits on
death and major disability.67 However, the results of ATACH-II
(Antihypertensive Treatment of Acute Cerebral Hemorrhage II)
cast doubts on the benefits of targeting an SBP of 140 mm Hg
or lower.68 Close examination of these trials reveals that the achieved
blood pressures in the first 24 hours were lower in ATACH-II
compared with INTERACT2. Both trials support the safety of
SBP lowering to 140 mm Hg. Current guidelines state that in
patients with intracerebral hemorrhage and SBP between 150 and
220 mm Hg who do not have contraindication to acute blood
pressure treatment, lowering of SBP to 140 mm Hg is safe and
can be effective for improving functional outcome.69 IV labetalol
or nicardipine are most commonly used as first-line therapies.
Acute Aortic Dissection
Aortic dissection is a life-threatening complication of hypertension
caused by a tear in the intima of the aorta. This tear is then
propagated by the aortic pulse wave. The aortic pulse wave (first
derivative of pressure measured over time [dP/dt]) is dependent
on myocardial contractility, heart rate, and blood pressure. The
presenting symptom is usually severe, sharp chest pain of abrupt
onset. Chest x-ray may be associated with a widened mediastinum.
The diagnosis is best made with contrast-enhanced computed
tomography or transesophageal echocardiography.70,71 Aortic dis-
sections are classified as type A (proximal to the left subclavian
artery, involving the ascending aorta) or type B (distal to the left
subclavian artery, involving the descending aorta).71 The goal of
treatment is rapid reduction of the pulsatile wave (dP/dt) and
aortic stress. Both MAP and cardiac output must be controlled to
achieve this goal and prevent further propagation of the dissection
in the aorta. In patients with aortic dissection, the MAP and heart
rate should be reduced to normal values as quickly as possible.
Combining a vasodilator (nitroprusside, nicardipine, fenoldopam)
with a β-blocker (esmolol, metoprolol) is recommended.72 All
patients with aortic dissection need emergent cardiovascular surgical
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CHAPTER Hypertensive Crises 549
evaluation. Type A dissections usually require emergent surgery
to prevent serious complications such as acute aortic insufficiency,
hemopericardium, and cardiac tamponade.73 Type B dissection is
often managed medically. Indications for surgery in type B dis-
sections include complications such as leak, rupture, and impaired
flow to vital organs (see Chapter 33).
Hypertensive Crises in Pregnancy
Hypertension is a common complication of pregnancy and is
responsible for 18% of maternal deaths in the United States.74
The spectrum of disease varies from mild increases in blood pressure
to severe pregnancy-related syndromes with hypertensive emergencies
such as preeclampsia and eclampsia.75 Hypertension in pregnancy
is defined as an SBP of 140 mm Hg or higher or diastolic pressure
90 mm Hg or higher. Preeclampsia is a pregnancy-specific condition
defined by new-onset hypertension, proteinuria (>300 mg/24 h)
and pathologic edema during gestation. Eclampsia is defined by
the development of seizures or coma in a pregnant patient with
preeclampsia. The challenge in pregnant patients with hypertensive
crises is to lower the blood pressure to prevent maternal end-organ
damage while minimizing acute changes in placental perfusion
that could negatively affect the well-being of the fetus. Treatment
of severe preeclampsia and eclampsia includes delivery of the fetus,
magnesium sulfate for the prevention and treatment of seizures,
and appropriate blood pressure control. The goal is to reduce the
diastolic blood pressure to 100 mm Hg or the MAP by 20%.
Historically, hydralazine has been preferred in pregnant patients
for its safety profile from a fetal perspective. However, data suggest
it may not be the most effective or safe agent for this patient
population.76 For pregnant patients in need of acute lowering of
blood pressure in the ICU, drugs such as labetalol and nicardipine
are probably better options.77,78 Nitroprusside is reserved for
refractory cases, as a last resort, and for short periods because of
concerns for potential fetal cyanide toxicity. Finally, angiotensin-
converting enzyme inhibitors such as enalaprilat are contraindicated
in the second and third trimesters because of the increase in fetal
and neonatal morbidity and mortality.
Postoperative Hypertension
Postoperative hypertension deserving of immediate IV treatment
consideration has been arbitrarily defined as an SBP greater than
190 mm Hg or a diastolic blood pressure greater than 100 mm
Hg on two consecutive readings after surgery. Previous history of
hypertension, high body mass index, age, and the grade of surgical
stress are recognized risk factors for developing postoperative
hypertension.79 Severe increases in arterial blood pressure in the
immediate postoperative period can result in serious complications,
such as heart failure, arrhythmia, myocardial ischemia, wound
hemorrhage, and cerebral hemorrhage.80 Considering the deleterious
effects of prolonged postoperative hypertension, many authors
have recommended aggressive treatment.80 The goal of treatment
is similar to other hypertensive emergencies: decrease blood pressure
to safe levels and at the same time avoid complications related to
hypotension. Although some clinicians believe that postoperative
hypertension should be treated aggressively based on the potential
for acute end-organ damage, others recommend evaluating for
possible causes of hypertension, such as pain, hypercarbia, hypox-
emia, and urinary retention, before initiating antihypertensive
drugs. As most patients in the postoperative period are unable to
take oral medications, even patients with no clear evidence of
 550 Pa rt 2 Critical Care Cardiovascular Disease
acute end-organ damage will receive IV medications. In patients
with a previous history of hypertension a reasonable goal is to
reduce MAP by 20%. In patients with no previous history of
hypertension, the goal is to reduce blood pressure to normal levels.
Clevidipine, nitroprusside, labetalol, and nicardipine have all been
extensively studied in cardiac, vascular, and neurosurgical settings.
Nitroglycerin is commonly used in postcoronary bypass surgery,
and fenoldopam has been proposed for clinical settings with
increased risk of renal ischemia.
Catecholamine-Associated Hypertensive Crisis
A hypertensive crisis related to excess catecholamines can result
from several causes. Consumption of sympathomimetic agents
(amphetamines, cocaine, phencyclidine, and certain diet pills),
decongestants (ephedrine, pseudoephedrine), and other agents
(atropine, alkaloids) can result in excessive catecholamine release
and hypertension. Withdrawal from β-blockers or α-blocking agents
can cause a rapid surge in catecholamines and hypertension. In
these cases, reinitiating of the particular drug may be sufficient to
treat the elevated blood pressure. Additional causes include
pheochromocytoma, autonomic dysfunction (i.e., Guillain-Barré
syndrome), and ingestion of tyramine in conjunction with mono-
amine oxidase inhibitor therapy. As a rule, in catecholamine-related
hypertension the use of β-blockers as initial therapy should be
avoided. Loss of β-adrenergically mediated vasodilation leaves
α-mediated vasoconstriction unopposed and may cause further
elevation in blood pressure. Pheochromocytoma is a rare tumor
that produces excess catecholamine and can cause severe hyperten-
sion. Symptoms commonly associated with pheochromocytoma
include headache, palpitations, diaphoresis, abdominal pain, anxiety,
Key Points
• Hypertension is a common clinical disorder in patients admitted
to the ICU. Severe elevations in blood pressure most often are
not associated with symptoms or evidence of acute end-organ
damage.
• A hypertensive emergency is a severe elevation in blood pressure
associated with the presence of acute end-organ damage.
Hypertensive emergencies require rapid reductions of blood
pressure to safe levels.
• The treatment of a hypertensive crisis is guided by (1) whether
the blood pressure should be lowered acutely, (2) how much
Selected References
Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering
in patients with acute intracerebral hemorrhage. N Engl J Med.
2013;386:2355–2365.
Ault MJ, Ellrodt AG. Pathophysiological events leading to the end-organ
effects of acute hypertension. Am J Emerg Med. 1985;3:10–15.
Hemphill JC 3rd, Greenberg SM, Anderson C, et al. Guidelines for the
management of spontaneous intracerebral hemorrhage: a guideline
for healthcare professionals from the American Heart Association/
American Stroke Association. Stroke. 2015;46:2032–2060.
James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for
the management of high blood pressure in adults: report from the
members appointed to the Eighth Joint National Committee (JNC
8). JAMA. 2014;311:507–520.
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Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2020. Elsevier Inc. Todos los derechos reservados.
and hypertension. Some patients may present with orthostatic
symptoms. For patients with a hypertensive emergency associated
with pheochromocytoma, the drug of choice is phentolamine.
Once blood pressure is controlled a β-blocker can be added to
control tachycardia. For less critical situations or after acute
hypertension is controlled, the oral agent phenoxybenzamine can
be used.
Conclusions
Hypertension is a common disease among patients admitted to
the ICU. Severe elevations in blood pressure most often are associ-
ated with no symptoms and no evidence of acute end-organ damage.
However, a subset of patient with severe elevations in blood pressure
will incur acute end-organ damage and require immediate treatment
to prevent ongoing and potentially irreversible organ damage. The
hallmark of a hypertensive emergency is the occurrence of acute
end-organ damage in the presence of elevated blood pressure. As
discussed previously, there are no specific blood pressure values to
define this clinical situation. Intensivists must be adept at quickly
and systematically evaluating patients with elevated blood pressures
for evidence of acute end-organ damage. When present, they should
act quickly to reduce blood pressure to safe levels. In the absence
of acute end-organ damage, intensivists should exercise caution
and not fall into the trap of treating numbers with the potential
risk of causing more harm to patients owing to abrupt drops in
blood pressure. True hypertensive emergencies require rapid reduc-
tions of blood pressure with IV drugs, close blood pressure monitor-
ing, and should occur in a high-acuity setting. Once the blood
pressure has been stabilized, it is important to initiate a transition
to an oral regimen for long-term control of blood pressure.
it should be lowered, and (3) what medication should
be used.
• The ideal medication to treat a hypertensive emergency would
have a rapid onset of action, high potency, immediate reversibility,
no risk of tachyphylaxis, and minimal or no adverse effects.
• Parenteral agents with specific indications in the treatment of
hypertensive crises include clevidipine, esmolol, fenoldopam,
labetalol, nicardipine, and nitroprusside.
Jauch EC, Saver JL, Adams HP, et al. Guidelines for the early management
of patients with acute ischemic stroke: a guideline for healthcare
professionals from the American Heart Association/American Stroke
Association. Stroke. 2013;44:870–947.
Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure
lowering in patients with acute cerebral hemorrhage. N Engl J Med.
2016;375:1033–1043.
Strandgaard S. Autoregulation of cerebral blood flow in hypertensive
patients. The modifying influence of prolonged antihypertensive
treatment on the tolerance to acute, drug-induced hypotension. Circula-
tion. 1976;53:720–727.
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Review Questions
1. Which of the following factors is most important in determining
if a patient has a hypertensive emergency?
a. Systolic blood pressure 200 mm Hg or higher
b. Diastolic blood pressure 110 mm Hg or higher
c. Mean arterial pressure ≥120 mm Hg or higher
d. Presence of acute end-organ damage
e. Presence of severe headache
Answer: d. Hypertensive emergencies are defined by the presence
of acute organ damage. Key organs that can be affected by an
acute elevation of blood pressure resulting in a hypertensive
emergency include the brain, heart, and kidneys. It is important
to understand that blood pressure numbers in isolation cannot
be used to diagnose a hypertensive emergency. Previously
normotensive patients may have acute organ damage at lower
blood pressures and, conversely, chronically hypertensive patients
may tolerate very elevated blood pressure without evidence of
acute organ damage.
2. Patients who are chronically hypertensive and poorly controlled
will usually exhibit changes in capacity to autoregulate cerebral
blood flow in relation to MAP (relationship between blood
flow and mean arterial pressure = autoregulation curve). Which
of the following statements is most correct with respect to the
autoregulation curve in a chronically hypertensive patient?
a. The curve changes to a linear relationship (i.e., changes in
flow are directly proportional to changes in MAP).
b. Changes in the autoregulation curve are important only if
the patient develops shock or severe hypotension.
c. The curve shifts to the right, which means that the patient
is more likely to suffer cerebral ischemia with rapid correc-
tion of blood pressure to “normal levels.”
d. The curve shifts to the left, which means patients are more
capable of tolerating high MAP without developing acute
organ damage.
Answer: c. Under normal conditions cerebral autoregulation
will keep cerebral blood flow between MAP of 60 and 150 mm
Hg. In chronically hypertensive patients this relationship is
changed so that the autoregulation curve shifts to the right.
This means that chronically hypertensive patients are better
prepared to tolerate higher MAPs without developing acute
organ damage or a hypertensive emergency. Conversely, owing
to this shift chronically hypertensive patients are much more
likely to develop ischemia/hypoperfusion with rapid correction
of blood pressure to normal levels. This concept is very important
and it informs our therapeutic conduct at the bedside. This is
why most experts recommend a target reduction of 15% to
25% of the MAP for most hypertensive emergencies.
3. Which of the following statements is most correct regarding
use of antihypertensive agents for the therapy of a hypertensive
crisis?
a. Intravenous therapy is mandatory for the therapy of hyper-
tensive urgencies.
b. The antihypertensive therapy should rapidly reduce the
patient’s blood pressure to the normotensive range.
c. A short-acting intravenous drug is the optimal agent for
lowering the patient’s blood pressure.
d. Nitroprusside alone is the therapeutic agent of choice for
lowering the blood pressure in an acute aortic dissection.
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CHAPTER Hypertensive Crises
550.e3
Answer: c. With a short-acting intravenous drug, the clinician
has the ultimate control on achieving a precise blood pressure
target. Oral therapy can be used to treat some hypertensive
urgencies such as postoperative hypertension with a functioning
gut. Reduction of the blood pressure to less than 90 mm Hg
systolic, or even by as little as 35% of the initial mean arterial
pressure, has been associated with major organ dysfunction,
coma, and death. In hypertensive crises the mean blood pressure
should be initially reduced by 15% to 20%. Nitroprusside,
when used to treat hypertension associated with a dissecting
aortic aneurysm, should be used in combination with an
intravenous β-blocker.
4. Which of the following factors is most important in determining
the need to immediately decrease the blood pressure in a patient
presenting with an ischemic stroke?
a. Presence of altered mental status
b. Extent of infarct on computed tomography scan
c. Systolic blood pressure 200 mm Hg or higher
d. Decision to use systemic thrombolytic
Answer: d. Management of hypertension in the setting of an
acute ischemic stroke is based on an understanding of changes
that occur in the capacity to autoregulate blood flow in the
injured brain. During an acute ischemic stroke the autoregulation
curve for cerebral blood flow in relation to MAP becomes linear.
In other words, perfusion becomes directly dependent on MAP
owing to loss of autoregulation. Normally the body will
compensate by increasing MAP to preserve flow to the areas
of the brain surrounding the infarct. Decreases in blood pressure
can cause secondary neurologic injury be expanding the infarct
size. Based on this concept, current recommendations are to
tolerate high blood pressures in the setting of an acute ischemic
stroke. The main factor to change this approach would be the
use of systemic thrombolytics. In patients receiving thrombolytics
the systolic blood pressure must be keep below 180 mm Hg
to decrease the risk of hemorrhage.
5. Which of the following is most correct concerning treatment
of hypertension associated with aortic dissection?
a. Blood pressure target with aortic dissection is a 25% reduc-
tion in mean arterial pressure.
b. Blood pressure lowering target with aortic dissection should
be achieved within first hour.
c. Combination of a β-blocker and a vasodilator is optimum
therapy.
d. Avoiding dropping blood pressure below the autoregulatory
range is paramount in the therapy of aortic dissection.
Answer: c. Rationale:
Reducing the shearing force characterizes the rate of change of
pressure with respect to time (or dP/dt, the aortic pulse wave
[first derivative of pressure measured over time]) to minimize
the impact of each cardiac cycle on dissection and is one of the
most important principles of therapy of elevated blood pressure
with aortic dissection. Blood pressure should be lowered to
normal and should be accomplished within 15 to 30 minutes,
even at the expense of going below the autoregulatory range
for blood pressure. Drug choices include nitroprusside plus
esmolol; fenoldolpam plus esmolol; nicardipine plus esmolol;
or intravenous labetalol.