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AACN Advanced Critical Care


Volume 21, Number 1, pp.5-14
2010, AACN

Drug
Update

Earnest Alexander, PharmD, FCCM, and


Gregory M. Susla, PharmD, FCCM
Department Editors

Management of Hypertensive Emergencies:


A Drug Therapy Perspective for Nurses
Amanda J. Hays, PharmD
Thaddus D. Wilkerson, PharmD

ccording to the Joint National Committee on Detection, Evaluation, and


A
Treatment of High Blood Pressure, patients with a systolic blood pressure
(SBP) of more than 180 mm Hg or a diastolic blood pressure (DBP) of more
than 120 mm Hg have a hypertensive crisis.1 The bedside nurse should have a
clear understanding as to the variety of definitions used to describe hypertensive
crises and how to properly manage the disease states with both pharmaceutical
and nursing care. Two-thirds of patients with an acute elevation in blood pressure levels do not demonstrate acute end-organ damage and are diagnosed with
hypertensive urgency. These patients can be treated with oral therapy to reduce
their blood pressure over days. Hypertensive emergency, in contrast, accounts
for the remaining one-third of patients who present with acute elevations in
blood pressure levels and will require intravenous medication for the treatment
of life-threatening acute end-organ failure.1
Patients with hypertensive crisis (also referred to as hypertensive emergency)
have evidence of acute end-organ damage that can manifest as encephalopathy,
ischemic or hemorrhagic strokes, acute aortic dissection, acute coronary
syndromes, heart failure, pulmonary edema or respiratory failure, acute renal
failure, hemolytic anemia, or pregnancy-related conditions such as hemolysis,
elevated liver enzyme levels, and low platelet count (HELLP) syndrome or
preeclampsia and eclampsia. The presence of acute end-organ damage, not the
blood pressure reading alone, should be the guiding factor in distinguishing
whether the patient is having a hypertensive urgency or emergency, hence
guiding therapeutic choices.
The diagnosis of hypertension is common, affecting 1 of 3 people or approximately 73 million Americans.2 Despite the high prevalence of hypertension,
only 1% of all patients will experience a hypertensive emergency annually. This
1% of patients accounts for approximately 25% of all emergency department
visits; in the United States, up to 14% of these visits lead to subsequent hospitalization.3 As medication adherence decreases, the incidence of hypertensive
urgencies and emergencies increases. With prompt diagnosis and proper treatment, the 1-year survival rate is 90%.4
In this review, we focus on key points for administration and monitoring of
medications currently available to treat hypertensive emergency, evaluate the
goals of pharmaceutical therapy, and explain the role of disease states in choosing a pharmaceutical agent.
Amanda J. Hays is Pharmacy Quality Improvement Manager, Alaska Native Medical Center, 4315 Diplomacy Dr, Anchorage, AK 99508 (ajhays@anthc.org).
Thaddus D. Wilkerson is Clinical Pharmacist, Critical Care, Alaska Native Medical Center, Anchorage,
Alaska.

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Patient Monitoring
Patients with a hypertensive emergency should
be admitted to an intensive care unit (ICU) with
close monitoring of all vital organs by skilled
nursing staff. Intra-arterial blood pressure monitoring may be justified in those patients on
ultrashort-acting medications or those who
appear to have highly labile blood pressure levels. Intra-arterial monitoring, however, may be
difficult to accomplish when needing to transport patients to various locations in the hospital.5 Initial examination should include blood
pressure (using an appropriately sized blood
pressure cuff) and pulse readings in both arms
to ascertain differences between limbs and
ensure consistent assessment of response to
treatment.6 The bedside nurse also plays a vital
role in the ongoing evaluation of neurologic and
volume status. Mental status changes may be an
early sign of complications from overcorrection
of blood pressure.7 As a result of pressure natriuresis, a precipitous reduction in blood pressure
may occur requiring the administration of
normal saline to correct intravascular volume.6

disease states as represented in Table 1. The


patients medical history such as prior existence of hypertension, allergies, other diseases,
or medication usage may lead prescribers to
alter preferred therapy. Ultimately, the clinical
examination of the patient, severity of endorgan damage, and availability of various
pharmaceuticals will dictate the agent and the
route of administration chosen to treat hypertensive emergencies.6,10 Knowing and understanding the detailed mechanism of action and
pharmacokinetics of the medication used as
well as the patients comorbidities can help the
critical care nurse predict patient response.
Goals of Therapy
Most patients with hypertensive emergency do
not require more than a 10% to 15% reduction
in DBP in the first 30 to 60 minutes.1,11 In
patients with ascending aortic aneurysms or
dissections, this reduction should occur in 5 to
10 minutes, targeting an SBP of less than 120
mm Hg and mean arterial pressure of less than
80 mm Hg.11 Patients with acute ischemic
stroke may require only a 15% to 25% reduction in mean arterial blood pressure within the
first 24 hours.12 Rapid reductions in blood pressure levels slow the progression of end-organ
damage and must be balanced with the risks of
rapid overcorrection such as cerebral, renal,
and/or cardiovascular hypoperfusion and associated consequences.

Medication Administration
It is important to differentiate between patients
with hypertensive urgency versus those with
hypertensive emergency because the treatment
will vary. Oral therapy should be used in patients
with hypertensive urgency, with a goal of obtaining a gradual lowering of blood pressure levels
by 20% over 24 to 48 hours.8 If intravenous therapy is given to patients with hypertensive urgency
who do not exhibit signs of organ dysfunction,
the rapid reduction in blood pressure may result
in ischemia and infarction to organs that had
become dependent on the increased blood flow.
Medications used to treat hypertensive emergencies should be available in intravenous formulations with a fast onset and short duration of
action; such properties permit appropriate medication titration to manage blood pressure and
rapid reversal of drug activity if overcorrection
occurs. Although onset may be instantaneous,
intramuscular or sublingual therapies should be
avoided because they lack the ability to be
titrated and may lead to unpredictable precipitous drops in blood pressure levels.9

Medication Review
Drugs meeting ideal characteristics for the management of hypertensive emergency include
labetalol, esmolol, nicardipine, and fenoldopam.
A recently approved medication, clevidipine, has
the potential to be a preferred medication for
certain patient populations on the basis of
emerging clinical investigations. Other agents
such as sodium nitroprusside, nitroglycerin, and
hydralazine, although historically utilized, are
best reserved for specific situations or, as is the
case with phentolamine, limited to a single
disease state only. Information related to dose,
titration, adverse effects, and contraindications
for the medications reviewed is given in Table 2.
-Blockers
Esmolol (Brevibloc)

Disease StateFocused
Therapy
Patient comorbid conditions will influence
medication selection. Preferred agents exist to
treat hypertensive emergencies in particular

Esmolol is a cardioselective -adrenergic


blocker without peripheral 1-blocking activity and therefore no vasodilatory effects. It
was approved by the US Food and Drug
6

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Table 1: Recommended Antihypertensive Agents for Patients With Selected Comorbid


Conditions
Recommended Agent(s)
Condition
(Listed in Order of Preference)
Acute aortic dissection Labetalol
Nicardipine
esmolol

Considerations
Combination of a -blocker and a vasodilator is
recommended; nicardipine and
fenoldopam are less toxic and equally
effective alternatives to nitroprusside

Fenoldopam
esmolol
Nitroprusside
esmolol
Acute ischemic
stroke/intracerebral
bleed

Rapid reductions in blood pressure levels can


have negative outcomes including further
ischemic injury or death; nitroprusside
may increase intracranial pressure; avoid
longer-acting agents

Nicardipine
Labetalol
Fenoldopam

Acute myocardial
infarction

Labetalol

Acute postoperative
hypertension

Clevidipine

Esmolol

Plus
nitroglycerin
Most acute postoperative hypertension is
commonly seen in cardiothoracic,
vascular, head/neck, and neurologic
surgeries; manage pain and anxiety

Esmolol
Nicardipine
Labetalol

Acute pulmonary
edema/diastolic
dysfunction

Esmolol
Metoprolol

Plus
nitroglycerin
loop diuretic

Labetolol
Verapamil
Acute pulmonary
edema/systolic
dysfunction

Nicardipine
Fenoldopam

Plus
nitroglycerin
loop diuretic

Nitroprusside
Acute renal failure/
microangiopathic
hemolytic anemia

Fenoldopam

Hypertensive
encephalopathy

Labetalol

Nicardipine

Nicardipine
Fenoldopam

Preeclampsia,
eclampsia

Sympathetic crisis/
drug overdose

Nicardipine

Magnesium sulfate via continuous infusion is


used for the prevention of seizures; nitroprusside and angiotensin-converting enzyme
inhibitors are contraindicated in pregnancy

Verapamil

Avoid -blockers including labetalol

Labetalol
Hydralazine

Plus
magnesium
sulfate

Diltiazem
Nicardipine
benzodiazepine
Phentolamine

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Table 2: Dosage, Onset and Duration of Action, Adverse Effects, and Considerations for
Commonly Used Antihypertensive Medications
Onset of
Action

Duration
of Action

12 mg/h initial rate,


46 mg/h usual
maintenance
(maximum dose 21
mg/h)

24 min

515 min

Enalaprilat

1.25 mg over 5 min every


46 h, titrate by 1.25 mg
increments every 1224
h intervals (maximum
dose 5 mg every 6 h)

15 min,
1224 h
peak
effect up
to 4 h

Esmolol

500 mcg/kg loading dose


immediate 1030 min Thrombophlebitis, Contraindicated in
extravasation
over 1 min, infusion at
pregnancy, sinus
to 60 s
resulting in
2550 mcg/kg/min,
bradycardia,
necrosis and
titrated by 25
uncompensated
sloughing,
mcg/kg/min every 1020
heart failure, AV
nausea,
min (maximum dose
block greater
flushing,
300 mcg/kg/min)
than first degree;
diaphoresis,
caution with
dizziness,
COPD, asthma;
somnolence,
avoid use with
bradycardia
diltiazem/verapamil; incompatible
with sodium
bicarbonate

Fenoldopam

0.10.3 mcg/kg/min initial 5 min,


dose, titrated by
peak
0.050.1 mcg/kg/min
effect at
every 15 min (maximum
15 min
dose 1.6 mcg/kg/min)

Drug

Dose

Clevidipine

Adverse Effects
Insomnia,
headache,
nausea,
vomiting

Contraindications
and Considerations
Phospholipid
vehicle;
contraindicated
in soybean, soy,
egg allergic
patients; change
solution q 4 h

Headache,
Contraindicated in
dizziness,
pregnancy;
hypotension
caution with
in high renin
severe aortic
states, cough,
stenosis,
hyperkalemia
ischemic heart
disease,
hypertrophic
cardiomyopathy,
unstented renal
artery stenosis,
and preexisting
renal
insufficiency;
variable and
unpredictable
response

3060 min Nausea,


headache,
flushing,
dizziness,
hypokalemia,
phlebitis,
tachycardia

Monitor serum
potassium every
6 h during
infusion; may
abruptly stop or
quickly taper
infusion because
there is no
rebound
hypertension

(continues)

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Table 2: Dosage, Onset and Duration of Action, Adverse Effects, and Considerations for
Commonly Used Antihypertensive Medications (Continued )
Onset of
Action

Duration
of Action

Dose

Hydralazine

1020 mg IV/IM; may


515 min
repeat every 46 h
(maximum dose 40 mg)

112 h

Reflex
tachycardia,
orthostasis,
lupus-like
syndrome,
fluid and
sodium
retention,
increased
intracranial
pressure,
flushing,
headache,
fever

Labetalol

25 min,
20 mg initial bolus,
peak
2080 mg repeat
effect at
boluses every 10 min
515
(maximum dose 300 mg
min
total in 24 h) or infusion
0.52 mg/min titrated by
0.5 mg/min every 15
min (maximum rate
6 mg/min)

218 h

Orthostatic
Caution with COPD,
hypotension,
systolic heart
dizziness,
failure, severe
fatigue,
bradycardia, or
nausea,
AV block greater
vomiting,
than first degree;
paresthesias,
safe in
scalp tingling,
pregnancy;
bronchospasm
prolonged action
with extended
infusions;
gradual taper
required

Nicardipine

5 mg/h, titrated by
2.5 mg/h every 15 min
(maximum dose
15 mg/h)

46 h

Headache,
dizziness,
flushing,
nausea,
peripheral
edema, reflex
tachycardia,
prolonged
hypotension,
infusion site
reactions

Contraindicated in
advanced aortic
stenosis, acute
myocardial
infarction;
caution with
portal
hypertension,
hypertrophic
cardiomyopathy,
hepatic/renal
impairment; safe
in pregnancy

Nitroglycerin

Weight based: 0.250.5 mcg/ 15 min


kg/min, titrated by 0.25
mcg/kg/min every 35
min (maximum dose of
1 mcg/kg/min); nonweight based: 5 mcg/
min, titrated by 5
mcg/min every 510
min (maximum dose
100 mcg/min)

510 min

Headache,
dizziness,
reflex
tachycardia

Contraindicated in
cerebral
hemorrhage and
closed-angle
glaucoma;
patients develop
tolerance

515 min

Adverse Effects

Contraindications
and Considerations

Drug

Delayed and
unpredictable
blood
pressurelowering
effects; safe in
pregnancy

(continues)

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Table 2: Dosage, Onset and Duration of Action, Adverse Effects, and Considerations for
Commonly Used Antihypertensive Medications (Continued )
Onset of
Action

Duration
of Action

Adverse Effects

Contraindications
and Considerations

Drug

Dose

Nitroprusside

0.30.5 mcg/kg/min,
titrated in increments
of 0.5 mcg/kg/min up to
maximum dose of
2 mcg/kg/min to avoid
toxicity

Seconds to 110 min


2 min

Phentolamine

15 mg bolus, repeated
every 515 min to a
maximum of 15 mg per
dose

Immediate 1530 min Flushing,


Contraindicated in
tachydyrenal
srhythmia,
impairment,
dizziness,
coronary or
nausea,
cerebral
vomiting,
arteriosclerosis
angina, miosis,
nasal
congestion

Thiocyanate and Avoid in aortic


cyanide
stenosis or
toxicity,
coarctation;
headache,
caution with
nausea,
acute myocardial
vomiting,
infarction,
muscle spasm,
hepatic/renal
flushing,
impairment;
rebound
monitor for
hypertension,
metabolic
coronary steal
acidosis
syndrome

Abbreviations: AV, arterioventricular; COPD, chronic obstructive pulmonary disease.

Administration for perioperative hypertensive emergencies and has been considered by


some to be ideal for use in critically ill
patients and especially useful in patients with
increased cardiac output, heart rate, and
blood pressure.9 Esmolol may be administered intravenously by bolus dosing followed
by a continuous infusion.13 When used as
monotherapy, as many as one-third of
patients will require higher doses to control
postoperative hypertension.13 In hypertensive
emergencies, a second agent may also be
required to achieve adequate blood pressure
lowering, specifically in patients with aortic
aneurysm or dissection for whom esmolol is
the preferred medication.6 Bradycardia and
excessive hypotension can be managed by
slowing or discontinuing the infusion. Intraarterial blood pressure monitoring is recommended for administration. Elimination is not
dependent upon hepatic or renal function.

blood flow. In addition, it does not cause a


reflex increase in systolic volume.10,14,15 It is
considered a preferred therapy in the treatment of renal hypertensive patients because
elevated renin levels are reduced by the administration of labetalol.13 Despite the decreased
sensitivity to the chronotropic effects of
-blockade with age, labetalol appears to have
an increased myocardial sensitivity to the negative inotropic effects and may also be the
agent of choice in elderly persons.13 The use of
labetalol for the treatment of hypertension
urgencies and emergencies related to pregnancy is considered safe and effective.16,17
Labetalol may be given by intravenous bolus or via continuous infusion until the goal
blood pressure is achieved. In limited clinical
scenarios such as aortic dissection, doses up to
6 mg/min have been used. Patients with
hepatic impairment may have an increased
responsiveness and thus require lower doses or
closer monitoring.
Abrupt withdrawal of labetalol may cause
acute tachycardia, rebound hypertension, and
ischemia; therefore, it should be gradually
tapered, especially in patients with coronary
artery disease.13 Intra-arterial blood pressure

Labetalol (Trandate)
Labetalol is a combined 1- and nonselective
-adrenergic receptor blocker that reduces
afterload while maintaining cardiac output and
does not reduce cerebral, coronary, or renal
10

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monitoring is not required.10 An oral dosage


form is available; however, dosing differences
exist because the ratios of -blockade to
-blockade differ depending on the route of
administration: 1:3 (oral) and 1:7 (intravenous).

light exposure, intra-arterial monitoring


requirements, cerebral blood flow reductions,
increases in ICP, and possible detrimental
effects in patients with coronary artery disease.6
Abrupt cessation of the agent results in a rapid
rise in blood pressure levels.
Prolonged administration, especially in
patients with renal impairment, leads to an
increased risk of developing fatal cyanide or
thiocyanate toxicity. Toxicity can be recognized by disorientation, hypoxia, encephalopathy, muscle twitching, hyperreflexia, nausea,
vomiting, tinnitus, cardiac arrest, coma, and
irreversible neurologic deficits. Unfortunately,
signs and symptoms of toxicity can manifest
too late for appropriate treatment, and cyanide/
thiocyanate levels are insensitive and not
widely available.
Monitoring should include acid-base balance for metabolic acidosis related to cyanide
toxicity, venous oxygen concentration, and
signs of extravasation because it can lead to
local tissue necrosis. Rates as low as 4 mcg/kg/
min for as few as 2 to 3 hours lead to toxicity.
It is not recommended to use the maximum
dose for more than 10 minutes.

Vasodilators
Fenoldopam (Corlopam)

Fenoldopam is a peripheral vasodilator with


a unique mechanism of action. Vasodilation
is mediated by peripheral dopamine-1 receptors with high selectivity for proximal and
distal tubules of the kidney causing renal
artery vasodilation, inhibition of sodium
reabsorption, natriuresis, and diuresis. Fenoldopam should be considered a preferred
agent in patients with renal impairment and
has been safely used in patients with liver disease or heart failure.18 It is contraindicated in
patients with glaucoma and has not been
studied in patients with increased intracranial
pressure (ICP).
Fenoldopam is administered via continuous
infusion. High-doserelated tachycardia may
occur and will increase myocardial oxygen
demand in patients with angina. Fenoldopam is
as effective as nitroprusside for the treatment of
hypertensive emergencies, and because of its
effects on the kidneys, improves creatinine clearance, urine flow rates, and sodium excretion.19
Rebound hypertension with abrupt discontinuation or tapering of the infusion is uncommon.10

Nitroglycerin (Tridil)
The clinical utility of nitroglycerin as monotherapy for treatment is limited because of the
development of tolerance and adverse effects.
When administered as a continuous infusion
for blood pressure control, nitroglycerin causes
pronounced venous dilation and results in
decreased preload, cardiac output, and oxygen
demands while increasing coronary blood
flow and suppressing coronary vasospasms.
This agent has utility for acute coronary syndromes, pulmonary edema, and postcoronary
artery bypass surgery but is not ideal for
hypertensive emergencies because of the lack
of arteriolar vasodilation.6 Nitroglycerin can
cause pronounced hypotension and reflex tachycardia exacerbated by volume depletion. Tolerance will develop with continuous infusions of
24 to 48 hours.

Sodium nitroprusside (Nipride)


As an arterial and venous vasodilator, sodium
nitroprusside is highly effective for the treatment of most hypertensive emergencies and
has historically been considered a first-line
agent.6,10 Nitroprusside should be avoided in
patients with aortic stenosis or coarctation
and used cautiously in patients with acute
myocardial infarction because of the potential
for coronary steal syndrome. Because of the
potential for life-threatening toxicities and the
availability of newer pharmacologic agents
that have a safer medication adverse effect
profile, nitroprusside should be limited for use
when other agents are unavailable.
Given as a continuous infusion, sodium
nitroprusside has a rapid onset, is easily titratable, and demonstrates reduction of both preload and afterload. Although nitroprusside
has some ideal characteristics for this indication, there are limitations associated with the
agent: short drug stability, degradation from

Hydralazine (Apresoline)
Hydralazine is a direct arterial vasodilator that
reduces afterload. It has a fairly limited role
in the treatment of hypertensive emergencies.
Clinical trials have demonstrated that minimal
drug crosses into placental circulation; therefore, hydralazine should be preferred for use in
the treatment of eclampsia or preeclampsia.
11

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Hydralazine has a latent onset of action and


prolonged blood pressurelowering effect. It
may exacerbate ICP in patients with a preexisting increased ICP. Reflex tachycardia may
require concomitant -blocker administration
for select at-risk patients, including those with
coronary artery disease or aortic dissection.
Patients should be monitored closely during and
following infusion for orthostasis and precipitous reductions in blood pressure levels. Because
of the potential for delayed and unpredictable
drops in blood pressure levels, it can be difficult
to titrate and is not recommended for the general treatment of hypertensive emergency.6

tion is an oil-in-water emulsion containing


200 mg/mL of lipid, careful aseptic technique
should be utilized to minimize infection risks
and the solution should be used within 4 hours.
The emulsion provides 2 kcal/mL of energy
and should be included in the patients total
daily energy replacement. Ultimately, the medication offers a new option for rapid reduction
in blood pressure levels in patients needing
short-term intravenous therapy.
Nicardipine (Cardene)
Nicardipine is a second-generation dihydropyridine calcium channel blocker that is selective
for arterial vascular smooth muscle with
strong cerebral and coronary vasodilatory
activity. Nicardipine does not affect cardiac
conduction and has no antiarrhythmic effects.13
It is beneficial for patients with coronary artery
disease and systolic heart failure because it
increases stroke volume and improves myocardial oxygen balance and coronary blood
flow.6,10 It is as effective as nitroprusside in
patients with severe postoperative hypertension and in patients presenting to the emergency department with hypertensive emergency
and acute pulmonary edema. Nicardipine
has been studied in pregnancy and is safe and
effective.17 In the 2007 guidelines for early
management of adult ischemic stroke,
nicardipine is recommended for patients with
severe hypertension defined as SBP of more
than 230 mm Hg or DBP of more than 121 mm
Hg, likely based on the evidence showing
reduction in cerebral ischemia.12
Nursing concerns with the administration of
nicardipine include solution incompatabilities,
light sensitivity, limited 24-hour stability, and
significant drug-drug interactions requiring
pharmacist screening. Avoid infusion in small
peripheral veins; administration through central catheters is preferred. An oral formulation
is available. Although relatively easy to titrate,
hypotension may be prolonged if it occurs.

Dihydropyridine Calcium
Channel Blockers
Clevidipine (Cleviprex)

Clevidipine is the newest antihypertensive


agent available in the United States. It is a
third-generation dihydropyridine calcium
channel blocker that causes arteriole vasodilatation, decreases afterload, and increases
stroke volume and cardiac output without
affecting cardiac filling pressures or heart
rate.20,21 Clevidipine has demonstrated safety
and efficacy in cardiac surgery patients
and in patients presenting to the emergency
department and ICU with underlying
severe hypertension, heart failure, or renal
dysfunction.22,23
A linear relationship exists between SBP
lowering and clevidipine dosing. This relationship has been demonstrated to lead to precise
and titratable blood pressure control
when compared with nitroprusside and
nitroglycerin.20,23 Clevidipine infusions are
titrated by doubling the rate every 90 seconds
until close to goal blood pressure, at which
time additional dose adjustments may occur at
5- to 10-minute intervals. Limited short-term
experience with doses up to 32 mg/h has been
reported; data beyond 72-hour duration of use
are minimal.13
Elimination of clevidipine is linked to rapid
metabolism by red blood cell esterases and not
through hepatic or renal pathways. Data suggest that clevidipine protects against arterial
ischemia and may improve splanchnic blood
flow and renal function.20,21 Clevidipine is available as a premixed formulation in a phospholipid vehicle that is contraindicated in patients
who have allergies to soybeans, soy-related
products, eggs, or egg products because of the
risk of allergic reactions. Because the medica-

-Blocker
Phentolamine (Regitine)

Phentolamine not only lowers blood pressure


levels by solely blocking -adrenergic activity
but also has positive inotropic and chronotropic effects on the heart. It has a very limited
role in the treatment of hypertensive emergencies and is reserved for catecholamine-induced
situations such as pheochromocytoma or certain medication-related toxicities (eg, cocaine,
12

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methamphetamine, phencyclidine, or monoamine


oxidase inhibitors and tyramine).6 Prolonged
exposure or continuous infusion may cause
tachydysrhythmias or angina. Therefore, once
the initial hypertensive episode is controlled,
the patient should be transitioned to phenoxybenzamine, an oral -blocker.

rate adjustments can facilitate achievement of


goal blood pressure. After obtaining the initial
goal reduction in blood pressure levels, the
patient should be transitioned to oral therapy.
The critical care nurse plays a vital role in
the care of the patient with hypertensive emergency. Understanding the goals of therapy,
choice of pharmaceutical agent, considerations for administration and monitoring, and
preferred agents based on disease states is
critical in optimizing care.

Angiotensin-Converting
Enzyme Inhibitors
Enalaprilat (Vasotec)

Enalaprilat is an intravenous angiotensinconverting enzyme inhibitor that is the active


metabolite of oral enalapril. Enalaprilat is
administered via direct intravenous bolus or
via slow infusion.13 Enalaprilat differs from the
other agents in that it has a relatively longer
onset and duration of action with delayed
peak effects. Interpatient variability in plasma
renin activity, especially in the setting of
volume depletion, can lead to unpredictable
responses.6 The pharmacokinetic parameters
exhibited by enalaprilat limit the ability for
rapid titration of blood pressure, therefore
lessening its role in hypertensive emergencies.6

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10. Feldstein C. Management of hypertensive crisis. Am J
Ther. 2007;14:135139.
11. Marik PE, Varon J. Hypertensive crises. Chest. 2007;131:
19491962.
12. Adams HP, del Zoppo G, Brass L, et al. AHA/ASA guidelines for the early management of adults with ischemic
stroke. Stroke. 2007;38:16551711.
13. Lacy CF, Armstrong LL, Goldman MP, et al. Drug Information Handbook. 17th ed. Winnipeg, Manitoba, Canada:
Lexi-Comp Inc; 2008.
14. Pearce CJ, Wallin JD. Labetalol and other agents that
block both alpha- and beta-adrenergic receptors. Cleve
Clin J Med. 1994;61:5969.
15. Olsen KS, Svendsen LB, Larsen FS, et al. Effect of
labetalol on cerebral blood flow, oxygen metabolism, and
autoregulation in healthy humans. Br J Anaesth. 1995;
75:5154.
16. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy
and Lactation. 6th ed. Philadelphia, PA: Lippincot
Williams & Wilkins; 2002.
17. Elatrous S, Nouira S, Ouanes Besbes L, et al. Short-term
treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol. Intensive
Care Med. 2002;28:12811286.
18. Tumlin JA, Dunbar LM, Oparil S, et al. Fenoldopam, a
dopamine agonist, for hypertensive emergency: a multicenter randomized controlled trial. Fenoldopam Study
Group. Acad Emerg Med. 2000;7:653662.
19. Shusterman NH, Elliott WJ, White WB. Fenoldopam, but
not nitroprusside, improves renal function in severely
hypertensive patients with impaired renal function. Am
J Med. 1993;95:161168.
20. Norlander M, Sjoquist PO, Ericsson H, et al. Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine,

Medications to Avoid
Particular antihypertensive medications should
be avoided in hypertensive emergencies. Sublingual or oral nifedipine has the ability to
produce sudden, unpredictable, and severe
reductions in blood pressure levels and may
precipitate renal, cerebral, or cardiac ischemia
with a potential for fatal outcomes.10,11 The
ability to produce excessive sedation and significant rebound hypertension from abrupt
cessation contraindicates the use of clonidine
in the treatment of hypertensive emergencies.10
Loop diuretics can cause further volume contraction and actually worsen hypertension that
is caused by increased renin production and
should be avoided unless specifically indicated
for volume overload.10,11
Conclusion
Selection of intravenous therapy often occurs
in the operating or emergency department
prior to the patient being transferred to the
ICU. For the critical care nurse, it is crucial
that there exists baseline knowledge of the
medication prescribed. Careful observation of
patient response and toxicity to therapies will
optimize outcomes. Continuous infusions are
preferred over intravenous bolus doses for
most patients; appropriate administration and
13

NCI200078_Layout 1 1/22/10 2:59 PM Page 14

Drug Update

A AC N

an ultrashort-acting calcium antagonist for rapid blood


pressure control. Cardiovasc Drug Rev. 2004;22(3):227
250.
21. Deeks ED, Keating GM, Keam SJ. Clevidipine: a review
of its use in the management of acute hypertension. Am
J Cardiovasc Drugs. 2009;9(2):117134.
22. Pollack CV, Varon J, Garrison NA, Ebrahimi R, Dunbar L,
Peacock WF 4th. Clevidipine, an intravenous dihydropy-

ridine calcium channel blocker, is safe and effective for


the treatment of patients with acute severe hypertension. Ann Emerg Med. 2009;53(3):329338.
23. Aronson S, Dyke C, Stierer K, et al. The ECLIPSE trials:
comparative studies of clevidipine to nitroglycerin,
sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth
Analg. 2008;107(4):11101121.

14

NCI200091_Layout 1 1/19/10 8:05 PM Page 15

AACN

Advanced
Critical Care
Test writer: Denise Hayes, RN, MSN, CRNP
Contact hour: 1.0
Category: A, Synergy CERP A
Passing score: 9 correct (75%)

CE Test Instructions
To receive CE credit for this test (ID# ACC2111), mark your answers on the form below, complete the
enrollment information and submit it with the $10 processing fee (nonmembers only; payable in US
funds) to the American Association of Critical-Care Nurses (AACN). Answer forms must be postmarked
by March 1, 2012. Within 3 to 4 weeks of AACNs receiving your test form, you will receive an AACN
CE certificate.
The American Association of Critical-Care Nurses (AACN) is accredited as a provider of continuing nursing education by
the American Nurses Credentialing Centers Commission on Accreditation. AACN has been approved as a provider of continuing education in nursing by the State Boards of Nursing of Alabama (#ABNP0062), California (#01036), and Louisiana
(#ABN12). AACN programming meets the standards for most other states requiring mandatory continuing education credit
for relicensure.

CE Test Form
Test ID#: ACC2111
FORM EXPIRES
March 1, 2012
Fee: $10 (no fee for
members of AACN)

Management of Hypertensive Emergencies:


A Drug Therapy Perspective for Nurses
Mark your answers clearly in the appropriate box. There is only one correct
answer per question. You may photocopy this form.
A

1.

4.

7.

10.

2.

5.

8.

11.

3.

6.

9.

12.

Last name_________________________________ First name______________________ AACN Member #______________________


Address____________________________________________________________________________________________________
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Telephone____________________________________________ E-mail __________________________________________________
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Card #_____________________________________ Exp. Date _________
Signature____________________________________________________

Program Evaluation
Objective 1 was met
Objective 2 was met
Objective 3 was met
The content was appropriate
My expectations were met
This method of CE is effective
for this content

Yes

No

The level of difficulty of this test was:

easy medium difficult

To complete this program, it took me


____________ hours/minutes.

Mail To: AACN


101 Columbia
Aliso Viejo, CA 92656
15

Or fax to 949-362-2021
Or take test online at
www.aacn.org>Continuing Education

NCI200091_Layout 1 1/19/10 8:05 PM Page 16

CE Test Questions

Management of Hypertensive Emergencies: A Drug Therapy


Perspective for Nurses
Objectives:
Upon completion of this article, the reader will be able to:
1. Understand the goals of pharmaceutical therapy in hypertensive emergency.
2. Recognize that disease states play a role in choosing a pharmaceutical agent to treat hypertensive emergency.
3. Describe key points for currently available medications to treat hypertensive emergency.

1. According to the Joint National Committee on


Detection, Evaluation, and Treatment of High Blood
Pressure, patients with which blood pressure have a
hypertensive crisis?
a. Systolic blood pressure (SBP) greater than 150 mm Hg or
diastolic blood pressure (DBP) greater than 100 mm Hg
b. SBP greater than 160 mm Hg or DBP greater than 110 mm Hg
c. SBP greater than 170 mm Hg or DBP greater than 115 mm Hg
d. SBP greater than 180 mm Hg or DBP greater than 120 mm Hg

7. Which vasodilators mechanism of action is mediated


by peripheral dopamine-1 receptors with high
selectivity for proximal and distal renal tubules?
a. Sodium nitroprusside
b. Fenoldopam
c. Nitroglycerin
d. Hydralazine
8. What adverse drug effect is associated with metabolic
acidosis in a patient receiving sodium nitroprusside?
a. Bronchospasm
b. Coronary steal syndrome
c. Cyanide toxicity
d. Lupus-like syndrome

2. What is correct about hypertensive emergency?


a. Annually, 25% of all hypertensive patients will experience
a hypertensive emergency.
b. Patients have evidence of acute end-organ damage.
c. Patients can be treated with oral therapy.
d. Diagnosis is based on blood pressure readings alone.

9. Which drug is preferred to treat eclampsia or


preeclampsia?
a. Esmolol
b. Enalaprilat
c. Hydralazine
d. Nicardipine

3. What may be an early sign of complications from overcorrection of blood pressure?


a. Mental status changes
b. Elevated liver enzyme levels
c. Thrombocytopenia
d. Tachypnea

10. Clevidipine is contraindicated in patients with which


condition?
a. Soybean allergy
b. Aortic stenosis
c. Glaucoma
d. Acute myocardial infarction

4. What type of medications should be used to treat


hypertensive emergencies?
a. Drugs with a long duration of action
b. Sublingual therapies
c. Drugs with a slow onset of action
d. Intravenous formulations

11. Which drug should be avoided because of excessive


sedation and significant rebound hypertension from
abrupt cessation?
a. Nifedipine
b. Clonidine
c. Furosemide
d. Bumetanide

5. What is the goal of therapy for most patients with


hypertensive emergency?
a. Gradual lowering of blood pressure levels by 20% over 24
to 48 hours
b. A 15% to 25% reduction in mean arterial blood pressure
within the first 24 hours
c. A 10% to 15% reduction in DBP in 5 to 10 minutes
d. A 10% to 15% reduction in DBP in the first 30 to
60 minutes

12. Which drug is the preferred agent to treat hypertensive


emergencies in patients with acute aortic dissection?
a. Phentolamine
b. Sodium nitroprusside
c. Labetalol
d. Fenoldopam

6. Which statement is correct about labetalol?


a. Abrupt withdrawal may cause rebound hypertension.
b. It causes a reflex increase in systolic volume.
c. It is a cardioselective beta-adrenergic antagonist.
d. It reduces cerebral blood flow.

16

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