American Journal of Therapeutics 14, 135139 (2007)

Management of Hypertensive Crises

Carlos Feldstein, MD*

Hypertensive emergencies are life-threatening conditions because their course is complicated with
acute target organ damage. They can present with neurological, renal, cardiovascular, microangiopathic hemolytic anemia, and obstetric complications. After diagnosis, they require the
immediate reduction of blood pressure (in ,1 hour) with intravenous drugs such as sodium
nitroprusside, administered in an intensive care unit. These patients present with a mean arterial
pressure .140 mm Hg and grade III to IV retinopathy. Only occasionally do they have hypertensive
encephalopathy, reflecting cerebral hyperperfusion, loss of autoregulation, and disruption of the
blood-brain barrier. In hypertensive emergencies, blood pressure should be reduced about 10%
during the first hour and another 15% gradually over the next 2 to 3 hours to prevent cerebral
hypoperfusion. The exception to this management strategy is aortic dissection, for which the target is
systolic blood pressure ,120 mm Hg after 20 minutes. Oral antihypertensive therapy can usually be
instituted after 6 to 12 hours of parenteral therapy. Hypertensive urgencies are severe elevations of
blood pressure without evidence of acute and progressive dysfunction of target organs. They
demand adequate control of blood pressure within 24 hours to several days with use of orally
administered agents. The purpose of this review is to provide a rational approach to hypertensive
crisis management.
Keywords: hypertensive crisis, hypertensive emergencies, management

INTRODUCTION
The majority of cases of severe hypertension characterized by diastolic blood pressure (BP) .120 mm Hg
or systolic BP .180 mm Hg can be controlled with
drugs given orally. However, in some patients hypertension is life-threatening because there is evidence of
rapid failure of vital organs; these patients require
immediate reduction of BP, usually in ,1 hour, by
means of intravenous drugs.18 These conditions,
called hypertensive emergencies, can occur at any
age, and their more frequent causes are listed in Table 1.
Although hypertensive emergencies have become
less common, it is estimated that about 1% of hypertensive patients will develop a hypertensive crisis.1,2
It has been estimated that hypertensive emergencies
Hypertension Program, Hospital de Clinicas Jose de San Martn,
Buenos Aires University and Instituto Universitario de Ciencias
de la Salud, Buenos Aires, Argentina.
*Address for correspondence: Av Rivadavia 4243, 6P, Buenos Aires
(1205), Argentina. E-mail: carlfel@yahoo.com
10752765 2007 Lippincott Williams & Wilkins

account for .25% of all patients visits to the

medical section of an emergency department, with
hypertensive emergencies detected in one-third of
these cases.3
Most patients presenting with hypertensive emergency have had previously inadequately controlled
or unknown chronic hypertension, although the
disorder can present in previously normotensive
individuals, particularly when associated with preeclampsia or acute glomerulonephritis.47 Hypertensive emergencies also may develop in the course of
secondary hypertension, particularly that associated
with renovascular disease, pheochromocytoma, and
(less frequently) primary aldosteronism. Critically
elevated BP without evidence of acute and progressive dysfunction of target organs is called hypertensive urgency.18 Such patients require adequate
control of BP within 24 hours to several days by means
of orally administered agents in a closely monitored
outpatient setting.
The purpose of this review is to describe a rational
approach toward and appropriate therapy for hypertensive crises.

136

Feldstein

Table 1. Causes of hypertensive emergencies.

Uncontrolled essential hypertension
Cerebrovascular conditions
Hypertensive encephalopathy
Ischemic stroke
Intracerebral hemorrhage
Eclampsia, pre-eclampsia
Renal Diseases
Acute glomerulonephritis
Renovascular hypertension
Renal crises from systemic sclerosis
Post-renal transplantation
Renal malformation
Endocrine Diseases
Pheochromocytoma
Cushing syndrome
Primary aldosteronism
Aortic dissection
Aortic coarctation
Drug-induced hypertension
Cocaine
Amphetamine
SSRI
MAOI in combination with certain foods or drugs
Rebound hypertension
Abrupt withdrawal of clonidine, ACEI, or b-blockers
Postoperative hypertension
Burns
Head injuries and CNS trauma
Autonomic hyperactivity (Guillain-Barre syndrome)
Vasculitis
SSRI, selective serotonin reuptake inhibitors; ACEI, angiotensinconverting enzyme inhibitors; MAOI, monoamine oxidase
inhibitors; CNS, central nervous system.

Clinical evaluation
Medical history should include previous treatments
(antihypertensive agents and compliance), illicit drug
use (cocaine and others), cardiovascular manifestations
(heart failure, angina, aortic disection), and neurologic
symptoms (headache, blurred vision, changes in mental
status, nausea, vomiting, weakness, and renal symptoms
such as hematuria and oliguria). Information about other
medical conditions such as thyroid disease, Cushing
syndrome, systemic lupus, systemic sclerosis, abdominal
pain, and dyspnea and the date of most recent menstruation should be ascertained. Physical examination
must be directed toward the cardiovascular and neurological systems. BP must be measured in both arms to
detect any significant differences. Other tests include
peripheral pulse exploration for absence or delay (which
would suggest aortic dissection), fundoscopy (searching
for soft exudates, hemorrhages, and papilledema), cardiac
and lung auscultation (S3, rales), assessment of mental
American Journal of Therapeutics (2007) 14(2)

status, and examination for focal or lateralizing neurologic signs that are infrequent in hypertensive encephalopathy and usually suggest some other cerebrovascular
disease (hemorrhage, embolism, or atherosclerotic thrombosis). Laboratory studies and electrocardiography
should be performed immediately after presentation
and may provide crucial clues to underlying conditions.
Imaging should be performed for presumptive diagnosis
of the primary cause of the hypertensive crisis.
Management of hypertensive crisis
The distinctions between hypertensive emergencies
and urgencies are often ambiguous. It appears to be
better to institute immediate antihypertensive treatment for all patients, with the agent and route of
administration chosen on the basis of clinical criteria
and available resources.8
The first consideration in BP management in the
setting of a life-threatening condition is that BP level is
not the most critical factor in determining the existence
of a hypertensive emergency. Prehospital treatment
may include furosemide when there is clear evidence of
volume expansion, as in heart failure or acute nephritis.
On the other hand, the use of loop diuretics may
worsen hypertension that is secondary to increased
renin production by causing further volume contraction. Nitrates and oxygen administration may be used
in conditions where they are indicated. In hypertensive
emergencies, sublingual or oral nifedipine is absolutely
contraindicated because it produces a nonpredictable
reduction of BP, accompanied by heart and brain ischemia. Clonidine is also contraindicated because it is
a strong sedative and causes hypertensive rebound
when it is withdrawn.
After hospital admission the hypertensive emergency should be managed with one of the parenteral
drugs listed in Table 2, according to etiology. The main
objective is to reverse end-organ damage, which is
accomplished by reducing mean arterial pressure by
up to 25% over minutes to a few hours. Once the
patients condition has stabilized, an oral medication
can be substituted and the physician should discuss
long-term follow-up plans.
The following are the drugs of choice in the
treatment of hypertensive emergencies.
Sodium nitroprusside is a first-choice agent for the
majority of hypertensive emergencies.10,11 This agent is
a potent arterial and venous vasodilator with a very
rapid onset of action (within seconds of beginning an
infusion) and a very short duration of effect; it is easily
titratable. It is administered as an intravenous infusion,
with intra-arterial line BP monitoring. Nitroprusside
reduces preload, afterload, and myocardial oxygen requirements. Because it is light-sensitive, the containers

Hypertensive Crisis

137

Table 2. Agents for management of hypertensive crises.

Drug

Dose

Onset of action

Sodium nitroprusside

0.2510 mg/kg/min as IV infusion;

maximal dose for 10 minutes only
5100 mg/min as IV infusion
0.10.3 mg/kg/min as IV infusion
515 mg/hr as IV infusion
1020 mg as IV bolus
or intramuscularly; repeat
every 46 hours
(maximum dose: 40 mg)

Seconds to 2 minutes
after beginning of infusion
25 minutes
515 minutes
15 minutes
1020 minutes

Nitroglycerin
Fenoldopam
Nicardipine
Hydralazine

Duration of action
13 minutes
510 minutes
30 minutes to 4 hours
15120 minutes
38 hours

IV, intravenous.

and tubings must be light-resistant. Sodium nitroprusside doses can be carefully adjusted for a controlled
reduction of BP. Its main indications are hypertensive
crises complicated with hypertensive encephalopathy,
heart failure, aortic dissection, and adrenergic crisis.
The most important adverse effect of sodium nitroprusside include intoxication with thiocyanate (a
metabolite of nitroprusside), which can occur when
this agent is administered for more than 48 to 72 hours,
particularly in patients with renal or liver dysfunction.
Thiocyanate intoxication presents with nausea, vomiting, tinnitus, muscle cramps, hyperreflexia, disorientation, and psychosis.12 Treatment of thiocyanate
toxicity includes administration of hydroxycobalamin
and sodium thiosulfate infusions, and in chronic renal
failure dialysis may be indicated. Nitroprusside in high
doses may increase intracranial pressure, which could
limit its usefulness in patients with central nervous
system complications. Extravasation can cause local
tissue necrosis.
Nitroglycerin is a powerful venodilatator that reduces
preload, increases coronary blood flow through collateral coronary vessels dilation, suppresses coronary
vasospasm, and decreases cardiac oxygen demands.
Higher doses are required to produce arteriolar vasodilatation. Nitroglycerin is the best agent in hypertensive crises that are complicated with ischemic heart
disease and after coronary bypass.10,12 Tolerance to
nitroglycerine develops if it is administered continuously for 24 to 48 hours. Glass containers must be used
because polyvinyl chloride containers and tubing may
absorb it in an unpredictable manner. This agent is
contraindicated for cerebral hemorrhage, because it
may increase intracranial pressure, and for closedangle glaucoma.
Nicardipine is a dihydropyridine calcium antagonist
with intermediate onset and duration of effect and a
prolonged half-life, which has been used for the control

of perioperative hypertension in cardiac surgery

patients. Nicardipine also reduces cerebral ischemia.
Its adverse effects include reflex tachycardia, headache,
nausea, and vomiting. This agent potentiates curare
effects and has interaction with inhalant anesthetics.
Nicardipine contraindications are heart block, acute
myocardial infarction, and renal failure.2,7
Fenoldopam is a selective agonist of dopaminergic-1
receptors, which produces arterial vasodilatation and
increased renal blood flow and natriuresis that is
beneficial in patients with renal failure.13 This agent
has a rapid onset of action and ease of BP titration.
Fenoldopam must be administered as an intravenous
infusion and not as a bolus; the increments must not
exceed 0.1 mg/kg/min at 20-minute intervals, and the
highest dose should not exceed 1.7 mg/kg/min. It does
not cause rebound hypertension, and therefore it can be
withdrawn by tapering off or stopping its administration abruptly. The efficacy of fenoldopam is similar to
that of nitroprusside, but it has the advantage of not
requiring a line for intra-arterial BP monitoring.
However, it is expensive and not readily available in
some places. Its main indications are severe hypertension with renal failure and acute heart failure.
Fenoldopam is contraindicated for glaucoma. Side
effects include headache, flushing, dizziness, tachycardia or bradycardia, hypokalemia, and local phlebitis.
Labetalol is a nonselective b- and a1-blocker (in the
ratio of 37:1) with a rapid onset of action, sustained
effect, and low toxicity.12,14 It reduces peripheral
vascular resistance without a reflex increase in systolic
volume. Labetalol administration does not require
intra-arterial BP monitoring. Its main indications are
hypertensive encephalopathy and adrenergic crisis.
This agent is contraindicated for heart failure, heart
block, and chronic obstructive pulmonary disease.
Esmolol is an ultrarapid, short-acting b-1 selective
adrenergic blocker with no intrinsic sympathomimetic
American Journal of Therapeutics (2007) 14(2)

138

Feldstein

activity; it has been approved by the U.S. Food and

Drug Administration only for perioperative hypertensive emergencies. Esmolol administration requires a
line for intra-arterial BP monitoring. Adverse reactions
include thrombophlebitis and extravasation of this
agent, resulting in local necrosis. It is contraindicated
for cocaine toxicity when used alone and in heart failure, chronic obstructive pulmonary disease/asthma, and
atrioventricular block.
Hydralazine is a direct arterial vasodilator. It also has
the property of improving uterine blood flow. The
adverse effects include significant reflex sympathetic
stimulation, sodium and water retention, flushing,
headache, and increase of intracranial pressure. It is
indicated only for pre-eclampsia and eclampsia
and is contraindicated for patients with coronary
atherosclerosis.1,2,49
Phentolamine is a competitive, nonselective a-blocker
and is the drug of choice only for adrenergic crisis
(drug-induced or secondary to pheocromocytoma).
After administration of an intravenous bolus injection
of 5 to 10 mg, BP decreases within several minutes.68

cerebrovascular resistance fails to respond to changes

in cerebral perfusion pressure. When BP is suddenly
reduced in these conditions, cerebral blood flow may be
strongly decreased and neurologic deficits may worsen.
There is consensus that BP must not be reduced
in ischemic stroke patients unless they are candidates
for thrombolytics.16 When thrombolytic treatment
is planned for ischemic stroke, the BP must be
#180/105 mm Hg. If the BP is .220/120 it would
be acceptable to gradually reduce the BP in 24 to
48 hours. When diastolic BP is .140 mm Hg, sodium
nitroprusside should be administered in order to
decrease diastolic BP 10% to 15% in 12 to 24 hours.
There is no evidence that hypertension increases the
risk of intracerebral hemorrhage or of a new hemorrhage. Vasospasm and reduction of brain perfusion are
common in areas adjacent to an intracerebral hematoma. Furthermore, in ischemic stroke the sudden
reduction of mean arterial pressure may aggravate
brain ischemia. In some cases, hypertension may be
a secondary phenomenon and BP may spontaneously
decrease in a few hours.

Management of specific conditions

Heart failure

In general, BP should be reduced about 10% during the

first hour and another 15% gradually over the next 2 to
3 hours. The exception is aortic dissection, for which
the target is systolic BP ,120 mm Hg after 20 minutes.
In the elderly, use of lower doses of drugs is recommended, and the BP should not be reduced as much
as in younger patients. Because many patients with
hypertensive crisis are volume-depleted as a result of
pressure-induced natriuresis, the use of loop-diuretics
should be avoided initially unless there is clear
evidence of volume overload. Because of the same reason, potent vasodilators such as nitroprusside should
be avoided because it may cause a sudden decrease in
BP below a safe target level. Oral antihypertensive
therapy can usually be instituted after 6 to 12 hours of
parenteral therapy.15

When the patient has pulmonary edema, nitroglycerin

or nitroprusside is the drug of choice, and the target is
to reduce BP to normal or near-normal levels.

Hypertensive encephalopathy
The main goal of treatment is to decrease mean arterial
pressure by 20% or diastolic BP to 100 to 110 mm Hg in
the first hour. In general, the drug of choice is sodium
nitroprusside. Nevertheless, sometimes it may reduce
cerebral blood flow in areas with a fixed arterial
narrowing and thus lead to cerebral steal phenomenon
and focal ischemia. It has been proposed that labetalol or
nicardipine may be a better choice, because these drugs
are less likely to decrease cerebral blood flow. Lack of
improvement in neurologic symptoms suggests a stroke.
Cerebral blood flow autoregulation is disrupted in the
setting of acute brain ischemia. This results when
American Journal of Therapeutics (2007) 14(2)

Coronary insufficiency
Nitroglycerin is the drug of choice and should be
rapidly titrated to the desired effect. One alternative
to the intravenous route is to administer 1.25 mg of
isosorbide dinitrate aerosol upon arrival.17 If BP does
not decrease with use of nitroglycerin, then nitroprusside should be added to the regimen. Nevertheless, the
adverse reactions of nitroprusside may include baroreflex activation, causing tachycardia, and coronary
steal phenomenon, with worsening of ischemia in
areas with fixed coronary stenosis. Other agents that
can be used when there is no concomitant heart failure
are b-blockers.
Aortic dissection
In this condition, systolic BP must be reduced to 100 to
120 mm Hg as soon as possible, by means of a
combined treatment with sodium nitroprusside and
a b-blocker (esmolol appears to be more useful
than propranolol). b-blockade must be established
first, before starting the nitroprusside infusion. An
alternative agent is labetalol, which may be used as the
only treatment because it has both b- and a-blocking
effects. Heart rate must be maintained between 60 and
80 beats/minute.

Hypertensive Crisis

Adrenergic crises
The drug of choice is phentolamine, and another option
is the combination of sodium nitroprusside and a
b-blocker. It has to be taken into account that b-blockers
can exacerbate hypertension in patients with adrenergic crisis and thus should not be used until adequate
a-receptor blockade is achieved. Labetalol is relatively
contraindicated because it produces more b- than
a-blocking effects, allowing a paradoxical increase in
BP from the absence of opposition to the a effect of
catecholamines (or cocaine, amphetamines, or tyramine
in those receiving monoamine oxidase inhibitors).
Pre-eclampsia
This condition, either mild or severe, is managed best
with a policy of delivery at or beyond 37 or 34 weeks
gestation, respectively.19 Even though no single antihypertensive drug has been proven to be better than
another, intravenously administered hydralazine is
probably the initial agent of choice.20 The aim is to
decrease diastolic BP to 80 to 100 mm Hg. Severe preeclampsia should be treated with intravenous magnesium to prevent progression to eclampsia. It must be
emphasized that nitroprusside is relatively contraindicated in pregnancy.
Hypertensive emergencies in the perioperative setting
The drugs of choice are esmolol, nitroglycerin (after
coronary bypass surgery), nicardipine, nitroprusside,
and fenoldopam.

REFERENCES
1. Calhoun DA, Oparil S. Treatment of hypertensive crisis.
N Engl J Med. 1990;25;323:11771183.
2. Elliott WJ. Management of hypertension emergencies.
Curr Hypertens Rep. 2003;5:486492.
3. Zampaglione B, Pascale P, Marchisio M, et al. Hypertensive urgencies and emergencies: prevalence and clinical
presentation. Hypertension. 1996;27:144147.

139
4. Jackson RE. Hypertension in the emergency department.
Emerg Med Clin North Am. 1988;6:173196.
5. Vaughan CJ, Delanty N. Hypertensive emergencies.
Lancet. 2000;356:411417.
6. Vidt DG. Emergency room management of hypertensive
urgencies and emergencies. J Clin Hypertens. 2001;3:158164.
7. Tuncel M, Ram CV. Hypertensive emergencies: etiology
and management. Am J Cardiovasc Drugs. 2003;3:2131.
8. Kaplan NM, ed. Clinical Hypertension. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2002:339356.
9. Blumenfeld JD, Laragh JH. Management of hypertensive
crises: the scientific basis for treatment decisions. Am J
Hypertens. 2001;14:11541167.
10. Murphy C. Hypertensive emergencies. Emerg Med Clin
North Am. 1005;13:9731007.
11. Gifford RW Jr. Management of hypertensive crises.
JAMA. 1991;266:829835.
12. Varon J, Marik PE. The diagnosis and management of
hypertensive crises. Chest. 2000;118:214227.
13. Murphy MB, Murray C, Shorten GD. Fenoldopam:
a selective peripheral dopamine-receptor agonist for the
treatment of severe hypertension. N Engl J Med. 2001;345:
15481557.
14. Chamontin B, Amar J, Chollet F, et al. Acute blood
pressure elevations [in French]. Arch Mal Coeur Vaiss.
2000;93(11 Suppl):14411447.
15. Elliott WJ. Clinical features and management of selected
hypertensive emergencies. J Clin Hypertens. 2004;6:587592.
16. Klijn CJ, Hankey GJ. American Stroke Association and
European Stroke Initiative. Management of acute ischaemic stroke: new guidelines from the American Stroke
Association and European Stroke Initiative. Lancet Neurol.
2003;2:698701.
17. Rubio-Guerra AF, Vargas-Ayala G, Narvaez-Rivera JL,
et al. Comparison between isosorbide dinitrate in aerosol
and in tablets for the treatment of hypertensive emergencies. Angiology. 2001;52:131135.
18. Henry CS, Biedermann SA, Campbell MF, Guntupalli JS.
Spectrum of hypertensive emergencies in pregnancy. Crit
Care Clin. 2004;20:697712.
19. Gregg AR. Hypertension in pregnancy. Obstet Gynecol
Clin North Am. 2004;31:223241.
20. Duley L. Pre-eclampsia and the hypertensive disorders of
pregnancy. Br Med Bull. 2003;67:161176.

American Journal of Therapeutics (2007) 14(2)