PDL_pages3_20Final_R.

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A Supplement to

Hypertensive Crises in the

Critical Care Setting:
Current Perspectives and Practice Challenges

Highlights of a Symposium

Faculty
Paul E. Marik, MD, MB, BCh, FCCP, Chair
Thomas Jefferson University
Philadelphia, Penn.
Stephan A. Mayer, MD
Columbia University College of Physicians and Surgeons
New York-Presbyterian Hospital
Columbia University Medical Center
Neurological Institute
New York, N.Y.
Joseph Varon, MD, FCCP
The University of Texas Health Science Center
Houston, Tex.
The University of Texas Medical Branch
Galveston, Tex.

Topic Highlights
Introduction
Management Principles for
Hypertensive Crisis
Management of Acute Hypertension
in Patients With Stroke
AHA/ASA Guideline Updates on
Treating Hypertension in Patients
With Stroke
Perioperative Hypertension

Sponsored by the American College of Chest Physicians (ACCP)

The American College of Chest Physicians (ACCP) is accredited by
the Accreditation Council for Continuing Medical Education to
provide continuing medical education for physicians.
This Product Fulfills the ACCP Learning Category II: Self-Directed.
Supported by an educational grant from PDL BioPharma, Inc.
PDL_pages3_20Final_R.qxd 3/20/2008 11:26 PM Page 2

Hypertensive Crises in the

Critical Care Setting:
Current Perspectives and Practice Challenges

Topic Highlights
Introduction 4
This supplement is based on proceedings of a sympo- Hypertensive Crises
sium held on October 24, 2007, in Chicago, Ill. Prevalence
This supplement was produced by the medical educa- Pathophysiology
tion department of Elsevier Society News Group, a di-
vision of Elsevier/International Medical News Group. Management Principles for Hypertensive Crisis 5
Neither the editor of CHEST Physician, the Editorial
Advisory Board, the American College of Chest Physi-
Initial Management of Blood Pressure
cians, nor the reporting staff contributed to its content. Choices of Pharmacologic Treatment
The opinions expressed in this supplement are those of
the faculty and do not necessarily reflect the views of Management of Acute Hypertension in
the American College of Surgeons, the supporter, or of
the Publisher. Patients With Stroke 7
Copyright 2008 by the American College of Chest
Physicians, Elsevier/International Medical News Group
AHA/ASA Guideline Updates on Treating
and its Licensors. No part of this publication may be re- Hypertension in Patients With Stroke 8
produced or transmitted in any form, by any means, with- BP Management in Patients With Intracerebral Hemorrhage
out prior written permission of the Publisher. Elsevier Inc.
will not assume responsibility for damages, loss, or claims
Intracranial Pressure Management
of any kind arising from or related to the information con- Intracranial Pressure Monitoring
tained in this publication, including any claims related BP Management in Patients With Acute Ischemic Stroke
to the products, drugs, or services mentioned herein.
Disclaimer Perioperative Hypertension 10
The American College of Chest Physicians (ACCP) Pathophysiology of Acute Postoperative Hypertension
and its officers, regents, executive committee members, Preoperative Treatment of Hypertension
members, related entities, employees, representatives
and other agents (collectively, ACCP Parties) are not
responsible in any capacity for, do not warrant and ex-
Summary 12
pressly disclaim all liability for, any content whatsoev-
er in any ACCP publication and the use or reliance on References 13
any such content. By way of example, without limit-
ing the foregoing, this disclaimer of liability applies to CME Post-Test: See Page 3 for instructions
the accuracy, completeness, effectiveness, quality, ap-
pearance, ideas, or products, as the case may be, of or
resulting from any statements, references, articles, po- FACULTY
sitions, claimed diagnosis, claimed possible treatments,
services, or advertising, express or implied, contained
in any ACCP publication. Furthermore, the content Paul E. Marik, MD, MB, BCh, FCCP, Chair
should not be considered medical advice and is not in- Professor of Medicine
tended to replace consultation with a qualified med-
ical professional. Under no circumstances, including Director of Pulmonary and Critical Care Medicine
negligence, shall any of the ACCP Parties be liable for Thomas Jefferson University
any DIRECT, INDIRECT, INCIDENTAL, SPECIAL Philadelphia, Penn.
or CONSEQUENTIAL DAMAGES, or LOST PROF-
ITS that result from any of the foregoing, regardless of Stephan A. Mayer, MD
legal theory and whether or not claimant was advised Associate Professor of Clinical Neurology and Neurosurgery
of the possibility of such damages.
Columbia University College of Physicians and Surgeons
Director, Neuro-Intensive Care Unit
New York-Presbyterian Hospital
Columbia University Medical Center
Neurological Institute
New York, N.Y.
Joseph Varon, MD, FCCP
Clinical Professor of Medicine
Professor, Acute and Continuing Care
The University of Texas Health Science Center
Houston, Tex.
Clinical Professor of Medicine
The University of Texas Medical Branch
www.esng-meded.com Galveston, Tex.
PDL_pages3_20Final_R.qxd 3/20/2008 11:27 PM
PARTICIPANTS WILL READ
THIS MONOGRAPH AND THEN
PARTICIPATE IN AN ONLINE
EVALUATION FORM.
Target Audience
This activity is designed for cardiolo-
gists, cardiothoracic surgeons, critical
care physicians, fellows-in-training, gen-
eral practitioners, advanced practice
nurses, registered nurses, and physician
assistants involved in the care of patients
with hypertensive emergencies.
Needs Assessment
Hypertensive emergencies are life-threat-
ening conditions that require immediate
blood pressure (BP) reduction to prevent
or arrest progressive end-organ damage.
With the use of titratable intravenous an-
tihypertensive agents, the intensive care
unit remains the most appropriate clin-
ical setting to achieve BP control. This
activity will review hypertensive emer-
gencies, which include a spectrum of
clinical syndromes, and will focus on
specific drugs and therapeutic strategies
available in the intensive care unit.
Learning Objectives
Identify pharmacotherapeutic
agents for the treatment of hyper-
tensive crises.
List strategies for the treatment of
acute hypertension in subarach-
noid, intracerebral, and ischemic
stroke, as recommended in cur-
rent evidence-based guidelines.
Review controversies related to
perioperative BP control in pa-
tients undergoing cardiac surgery.
Characterize clinical challenges to
obtaining target BP goals in hy-
pertensive emergencies, such as
eclampsia and sympathetic crisis.
Faculty Disclosure
The ACCP remains strongly committed
to providing the best available evidence-
based clinical information to partici-
pants of this educational activity and re-
quires an open disclosure of any potential
conflict of interest identified by our fac-
ulty members. It is not the intent of the
ACCP to eliminate all situations of po-
Page 3
tential conflict of interest, but rather to
enable those who are working with the
ACCP to recognize situations that may
be subject to question by others. All dis-
closed conflicts of interest are reviewed
by the educational activity course direc-
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ACCP educational standards pertaining
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Through our review process, all ACCP
CME activities are ensured of indepen-
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presentations of information. Disclosure
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available during all educational activi-
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The following faculty members of the
Hypertensive Crises in the Critical Care
Setting: Current Perspectives and Prac-
tice Challenges enduring product have
disclosed to the ACCP that a relationship
does exist with the respective compa-
ny/organization as it relates to their pre-
sentation of material and should be
communicated to the participants of this
educational activity:
Paul E. Marik, MD, MB, BCh, FCCP:
Speaker bureau: PDL Pharmacia and
ESP Pharmacia. Stephan A. Mayer,
MD: Consultant fee, speaker bureau,
advisory committee: PDL Biopharma
and The Medicines Company. Joseph
Varon, MD, FCCP: Grant monies: The
Medicines Company-Velocity Trial; con-
sultant fee: The Medicines Company;
speaker bureau: PDL BioPharma; advi-
sory committee: The Medicines Compa-
ny and PDL BioPharma.
The ACCP requires that faculty mem-
bers also disclose any information with-
in their presentation(s) that is considered
investigational or products/procedures/
techniques that are defined as research
and not yet approved for any purpose.
Joseph Varon, MD, FCCP: The use of
clevidipine for the hypertensive crisis.
The Velocity Trial.
CME INSTRUCTIONS
The American College of Chest
Physicians designates this education-
al activity for a maximum of 2 AMA
PRA Category 1 Credit(s)TM. Physicians
should only claim credit commensu-
rate with the extent of their partici-
pation in the activity.
Anyone who attended the Hyper-
tensive Crises in the Critical Care Set-
ting: Current Perspectives and Prac-
tice Challenges session at CHEST
2007 when this content was present-
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1) Go to www.chestnet.org and
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Release Date: April 2008
Expiration Date: April 30, 2009
PDL_pages3_20Final_R.qxd 3/20/2008 11:27 PM
Hypertensive Crises in the Critical Care Setting:
Current Perspectives and Practice Challenges
Introduction
M ore than 40 million adults in the
United States have uncontrolled
1
hypertension. Although chronic hyper-
tension is an established risk factor for
cardiovascular, cerebrovascular, and renal
disease, acute elevations in blood pressure
(BP) can also result in acute end-organ
damage with significant morbidity.2
Hypertensive Crisis
The 1993 report of the Joint National
Committee (JNC) on the Prevention,
Detection, Evaluation, and Treatment of
High Blood Pressure defined hyper-
tensive crisis as a systolic BP >179
mm Hg or a diastolic BP >109 mm Hg.3
Acute BP elevation in the presence of
acute end-organ damage is considered a
hypertensive emergency. Clinical pre-
sentations of a hypertensive emergency
related to particular end-organ dysfunc-
tion include acute aortic dissection, acute
myocardial infarction, acute coronary
syndrome, renal failure, and eclampsia.
In contrast, hypertensive urgency de-
fines acute or chronic BP elevation that
does not involve end-organ damage.
These distinctions make management
of these two types of hypertensive crises
considerably different.2
Prevalence
Approximately one out of 100 patients
with essential hypertension will experi-
ence a hypertensive crisis at some point
in his or her life. These episodes already
complicate more than 27% of all acute
medical problems in patients presenting
to emergency departments (EDs).4 A
European study evaluated the prevalence
of hypertensive emergencies and urgen-
cies in an ED over a 1-year period.5 The
mean age of patients presenting with hy-
pertensive crisis was 64 years, and their
average BP was 210/128 mm Hg. Age
and diastolic BP were higher in hyper-
tensive emergencies than in urgencies.
Hypertensive crises (76% urgencies,
24% emergencies) represented more than
25% of all medical urgencies/emergen-
cies in this study. Chest pain, dyspnea,
4 Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 4
and neurologic deficits were the most fre-
quent signs of hypertensive emergencies;
headache, epistaxis, and faintness were
bleeding, and hypertensive encepha-
lopathy.7
Abnormalities of autoregulation have
most frequently seen in urgent cases. important implications for the treatment
Types of end-organ damage associated of hypertensive crises. A normotensive
with hypertensive emergencies included patient would be more likely to develop
cerebral infarction (24%), acute pul- end-organ damage at a lower BP than a
monary edema (23%), and hypertensive chronically hypertensive patient. Lower-
encephalopathy (16%).5 The high preva- ing BP into the normal range in a poor-
lence of hypertensive crisis found in this ly controlled, chronically hypertensive
study is probably similar to that in the patient may actually accelerate end-
United States and emphasizes a need for organ damage. In chronically hyperten-
appropriate diagnosis and management. sive patients, the lower limit of autoreg-
ulation is raised to a MAP of 100 to 120
Pathophysiology mm Hg and the upper limit to 150 to
The precise pathophysiology leading to 160 mm Hg. Hypoperfusion occurs at
the development of a hypertensive crisis the lower limit of the autoregulatory
is unknown. However, an abrupt increase curve, whereas hyperperfusion occurs at
in systemic vascular resistance is be- the upper limit.2,6 Autoregulation is
lieved to be the im- impaired in patients
mediate cause. The Approximately one with cerebrovascular
subsequent increase out of 100 patients disease and resembles
in BP generates me- that seen in chroni-
chanical stress and with essential cally hypertensive
endothelial injury, hypertension will patients. The average
leading to increased lower limit of au-
permeability, activa- experience a toregulation is about
tion of the coag- hypertensive crisis 20% to 25% below
ulation cascade, de- the resting MAP,
at some point in
position of fibrin and requiring a cautious
platelets, and a his or her life. 20% reduction of
breakdown of normal MAP in patients
autoregulatory function.2 Autoregula- having a hypertensive emergency. In
tionthe inherent ability of arteries to addition to abnormality or failure of
maintain a relatively constant blood flow autoregulation, the renin-angiotensin
by dilating or constricting in response to system is often activated during hyper-
changing perfusion pressuresis critical tensive crisis, leading to further vaso-
to maintain blood flow to vital organs. constriction, rise in BP, pressure natri-
For example, cerebral blood flow (CBF) uresis, hypovolemia, and production of
is maintained in normotensive subjects proinflammatory cytokines such as
with mean arterial pressures (MAP) as interleukin.2 The resulting ischemia
low as 60 mm Hg and as high as 150 prompts further release of vasoactive
mm Hg. When MAP exceeds approxi- substances, perpetuating a vicious cycle
mately 150 mm Hg, however, cerebral that can culminate in end-organ hypo-
vessels can no longer constrict effective- perfusion, ischemia, and dysfunction that
ly against this high perfusion pressure manifest as a hypertensive emergency.2
and autoregulation fails.6,7 Increased The therapeutic goal in the treatment of
blood flow may leave brain tissue patients with hypertensive crisis is to
unprotected against the harmful effects break the cycle of rising BP, vascular
of BP changes, such as disruption of injury, hypovolemia, and further elevation
the blood-brain barrier, cerebral edema, of BP.
PDL_pages3_20Final_R.qxd 3/20/2008 11:27 PM Page 5
Management Principles for Hypertensive Crisis
D istinguishing hypertensive urgen-
cies from emergencies is important
in formulating an effective therapeutic
excessive correction of BP should be
avoided to reduce the risk of hypoper-
fusion and further injury. Continuous
plan. Patients with hypertensive urgency infusion of a short-acting, titratable an-
should have their BP reduced within 24 tihypertensive agent tailored to the spe-
to 48 hours; patients with a hypertensive cific type of emergency is the standard
emergency should have their BP lowered of care. Because of unpredictable phar-
immediately, although not to normal macodynamics, sublingual and intra-
levels.2 Most patients seen in the ED or muscular formulations of antihyperten-
admitted to the hospital with an elevat- sive drugs should not be used. Most
ed BP are chronically hypertensive, patients with severe hypertension on
with a rightward shift of the initial evaluation will not evince end-
pressure/flow (cerebral and renal) au- organ damage and may thus be consid-
toregulation curve (Figure 1).8 Addi- ered hypertensive urgencies. An overly
tionally, most patients with severe hy- rapid reduction of BP in patients with
pertension (diastolic BP >110 mm Hg) hypertensive urgency may also be asso-
in this circumstance do not have acute ciated with significant morbidity be-
end-organ damage. Although rapid an- cause of the rightward shift in the pres-
tihypertensive therapy in this setting sure/flow autoregulatory curve. Rapid
may result in significant morbidity, true correction of severely elevated BP below
hypertensive emergencies require a rapid the autoregulatory range of cerebral,
and controlled lowering of BP.2 Thus, the coronary, and renal vascular beds can re-
potential harm from overzealous lower- sult in a marked reduction in perfusion
ing of BP is simultaneously present with that can cause ischemia and infarction.
the need for careful and structured BP re- Although the BP of patients experi-
duction. encing hypertensive urgency must be
reduced in a slow and controlled fash-
Initial Management of BP ion to prevent organ hypoperfusion,
Patients having a hypertensive emer- patients with hypertensive urgency usu-
gency require a reduction in BP with- ally do not require prolonged hospital-
in minutes to a few hours, a course of ization and can be safely treated with
action usually undertaken in a fully oral antihypertensive drugs and close
staffed and equipped intensive care unit follow-up in the outpatient setting.2,6
(ICU). Since impaired or absent au-
toregulation occurs in patients with a Choice of Pharmacologic
hypertensive emergency and end-organ Treatment
damage is already present, a rapid and Several rapidly acting intravenous (IV)
Figure 1. Impaired Autoregulation Mean Arterial
Pressure (MAP) Versus Cerebral Blood Flow (CBF)
Versus Ischemia 8
CBF ml/100gm/min
edema
hemorrhage normotensive
50
ischemia 20 chronic hypertensive
infarction 10 penumbra
50 100 150 200 250
MAP (mm Hg)
Adapted with permission from Varon J and Marik PE.
Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
agents, such as labetalol, nicardipine,
fenoldopam, esmolol, and nitroprusside,
are available for treating patients with
hypertensive emergency (Table 1 on
page 6). Clevidipine is an investiga-
tional antihypertensive drug that is not
yet clinically available. To prevent pre-
cipitous falls in BP that can cause sig-
nificant morbidity or mortality, rapidly
acting IV agents should not be used
without sufficient monitoring capabili-
ty. The antihypertensive agent of choice
largely depends on presence and type of
end-organ damage. The immediate goal
of treatment is to reduce diastolic BP by
10% to 15%, or to approximately 110
mm Hg, over a period of 30 to 60 min-
utes. In patients with aortic dissection,
BP should be reduced more rapidly
(within 5 to 10 minutes) to a systolic BP
<120 mm Hg and a MAP <80 mm
Hg.2 When BP stabilizes following ad-
ministration of IV agents and the dan-
ger of further end-organ damage is re-
moved, oral antihypertensive therapy
can be initiated as IV agents are slowly
titrated down.
An important consideration prior to
initiating IV therapy is to assess the pa-
tients volume status. As a result of
pressure natriuresis, patients with hy-
pertensive emergencies may be volume
depleted, and restoration of intravas-
cular volume with IV saline solution
will help restore organ perfusion and
prevent a precipitous fall in BP when
antihypertensive regimens are initiat-
ed.2 Administering a diuretic agent in
addition to an antihypertensive agent
to lower BP should be avoided (unless
specifically indicated for volume over-
load) because of likely volume deple-
tion and the risk of a precipitous drop
in BP.2
Labetalol
Labetalol is a competitive blocker of
both 1- and -adrenergic receptors,
with an approximate 3:1 effect on -re-
ceptors compared with 1-receptors
when given IV. Because of its -block-
ing effects, labetalol either maintains or
slightly reduces heart rate. Unlike pure
-blocking agents that decrease cardiac
output, labetalol maintains cardiac out-
5
PDL_pages3_20Final_R.qxd 3/20/2008 11:27 PM
put in addition to having favorable
effects on coronary blood flow and resis-
tance.9 Labetalol also reduces systemic
vascular resistance without reducing to-
tal peripheral blood flow. The 1-block-
ing activity of labetalol, which interferes
with vasoconstriction of preglomerular
resistance vessels, may be one reason
why the drug has a minimal effect on re-
nal function. The rapid onset of action of
IV labetalol (ie, within 5 minutes) and
its duration of action of 3 to 6 hours
make it appropriate for use in hyperten-
sive emergencies.6
Esmolol
Esmolol is an ultrashort-acting, cardio-
selective -blocking agent. The onset of
action of esmolol occurs within 60 sec-
onds, and its duration of action is 10 to
20 minutes. Esmolol is commonly used
in patients with coronary artery disease
or poor cerebral compliance prior to a
strong nociceptive stimulus, such as in-
tubation or extubation. Esmolol is also
approved for the treatment of supraven-
tricular tachycardias and is used to low-
er BP postoperatively. Esmolol is rapid-
ly hydrolyzed by a red blood cell esterase
and is not dependent on hepatic or renal
metabolism.10 Given as either a bolus or
an IV infusion, esmolol is very useful for
critically ill patients in acute settings
such as hypertensive emergency. Its rapid
onset, short duration of action, and easy
reversibility distinguish it from other -
blockers.2,6,8
Fenoldopam
Fenoldopam mediates peripheral va-
sodilation by acting on peripheral
dopamine-1 receptors. The onset of
action of fenoldopam occurs within 5
minutes, with a maximal response
achieved within 15 minutes; the dura-
tion of action of fenoldopam is 30 to 60
minutes. Fenoldopam is potentially
nephroprotective and improves creati-
nine clearance, urine flow rates, and
sodium excretion in severely hyperten-
sive patients with both normal and
impaired renal function. Fenoldopam
is rapidly and extensively metabolized
by the liver, but without activation of
cytochrome P-450 enzymes. Because
it contains sodium metabisulfite,
fenoldopam should be used with caution
in patients with an allergy to sulfites.2,6
6 Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 6
Table 1. Dosages and Adverse Effects of Commonly
Used Intravenous Agents for Hypertensive Emergency
Agent Dosage
Labetalol 20-mg initial bolus, 20- to
80-mg repeat boluses or start
infusion at 2 mg/min;
maximum 24-hour dose of
300 mg
Esmolol 500-g/kg loading dose over
1 minute; infusion at 25 to
50 g/kg/min, increased by
25 g/kg/min q10-20 min to
a maximum of 300 g/kg/min
Fenoldopam 0.1-g/kg/min initial dose,
increase at 0.05- to
0.1-g/kg/min increments to
a maximum of 1.6 g/kg/min
Nicardipine 5 mg/h, increase at 2.5-mg/h
increments q5min to a
maximum of 15 mg/h
Nitroprusside 0.5 g/kg/min; increase to
maximum of 2 g/kg/min to
avoid toxicity
Nicardipine
Calcium channel blockers (CCBs) are
particularly useful in hypertensive crises.
Traditional CCBsverapamil and dilti-
azemact primarily on the cardiovas-
cular system to depress cardiac contrac-
tility and affect nodal conduction. Their
primary use does not include systemic
vasodilation.11 However, nicardipine and
a new CCB, clevidipine, are potent sys-
temic vasodilators. Both also minimally
depress left ventricular function and
rarely induce conduction abnormali-
ties.12,13 For cardiovascular patients in
hypertensive crisis, nicardipine and cle-
vidipine are particularly appropriate
treatment choices.
Nicardipine is a highly vascular-se-
lective CCB, having strong cerebral and
coronary vasodilatory activity. The on-
set of action of IV nicardipine is from
5 to 15 minutes, with a duration of ac-
tion of 4 to 6 hours. Nicardipine de-
creases afterload by reducing total pe-
ripheral resistance without reducing
cardiac output and has little or no neg-
ative inotropic effect on the heart. Like
esmolol, nicardipine is approved for use
in the treatment of perioperative
Adverse Effects
Hypotension, dizziness,
nausea/vomiting,
paresthesias, scalp
tingling, bronchospasm
Nausea, flushing,
first-degree heart block,
infusion-site pain
Nausea, headache,
flushing
Headache, dizziness,
flushing, nausea,
edema, tachycardia
Thiocyanate and cyanide
toxicity, headache,
nausea/vomiting, muscle
spasm, flushing
hypertension. The feasibility and safety
of IV nicardipine for treating acute hy-
pertension in patients with intracerebral
hemorrhage (ICH) within 24 hours of
symptom onset was recently evaluated.
The trials primary outcome was the tol-
erability of treatment, as assessed by
achieving and maintaining a goal MAP
<130 mm Hg (consistent with Ameri-
can Heart Association [AHA] guide-
lines) for 24 hours after initiation of the
nicardipine infusion. The primary out-
come of tolerability was reached in 25 of
the 29 patients in the trial (86%). Steady,
effective BP reduction occurred in pa-
tients with ICH treated with IV
nicardipine within 24 hours of symptom
onset.14 Treated patients were able to
maintain a MAP <130 mm Hg, below
the 2007 AHA/American Stroke Asso-
ciation (ASA) threshold for treatment of
elevated BP in patients with ICH.14
Neurologic deterioration was observed in
4 of 29 patients in the trial, and
hematoma enlargement was observed in
5 patients. Nicardipine also has been
shown to reduce both cardiac and cere-
bral ischemia and to increase both stroke
volume and coronary blood flow, with a
PDL_pages3_20Final_R.qxd 3/20/2008 11:28 PM
favorable effect on myocardial oxygen
balance.2,15 These effects make nicardi-
pine particularly useful in patients with
hypertensive crisis who also have coro-
nary artery disease or systolic heart fail-
ure.
Clevidipine
Clevidipine is a third-generation CCB
with ultrashort-acting vasodilator ac-
tivity. It reduces BP by a direct and se-
lective effect on arterioles, thereby re-
ducing afterload without affecting
cardiac filling pressures or causing reflex
tachycardia. Clevidipine is being evalu-
ated as a potential treatment for hyper-
tensive emergencies.2,16 In one open-la-
bel, single-arm study, patients with
persistent systolic BP >180 mm Hg or
diastolic BP >115 mm Hg were treat-
ed with clevidipine in the ED. Most pa-
tients in the study (81%) had evidence
of end-organ injury, including renal
Management of Acute Hypertension
in Patients With Stroke
A pproximately 700,000 people ex-
perience a new or recurrent stroke
1
each year in the United States. Of all
strokes, 87% are ischemic, with ICH
and subarachnoid hemorrhage account-
ing for the remainder. ICH is the dead-
liest and most disabling form of stroke
(the estimated 30-day mortality rate is
30% to 50%)21,22 and produces the
most extreme hypertension that physi-
cians are likely to encounter in clinical
practice. When considered separately
from other cardiovascular diseases,
stroke ranks third among all causes of
death, exceeded only by heart disease
and cancer.1
Chronically hypertensive patients are
particularly prone to ICH, and acute hy-
pertension is common in these patients.
Management of arterial BP in the setting
of acute stroke is based on available clin-
ical and experimental evidence and pe-
riodically updated practice guidelines
published by the AHA/ASA. Optimal
management, however, remains contro-
versial. Reductions in BP carry a risk of
producing further ischemic brain dam-
age in patients with ischemic stroke and
Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 7
and/or coronary artery disease. Mean
systolic BP rapidly decreased during
the titration period, with a median time
of 9.5 minutes to achieving a 15% re-
duction. At 18 hours, BP was reduced
by 55 mm Hg (27%) from baseline.17
Similar to esmolol, clevidipine is rapid-
ly metabolized by red blood cell es-
terases, and its metabolism is not af-
fected by renal or hepatic function.
Clevidipine is currently under investi-
gation in the United States and is not
approved by the US Food and Drug Ad-
ministration for any indication at this
time (February 2008).2,16
Nitroprusside
Nitroprusside is a very potent antihy-
pertensive agent, with an onset of action
that occurs within seconds and a dura-
tion of action of 1 to 2 minutes.2 The ef-
fect of nitroprusside on cardiac output is
variableusually decreasing output in
ICH. For example, management of BP in
patients during acute ischemic stroke
(AIS) is complicated by the need to
maintain brain perfusion. Lowering BP
in the acute setting may avoid the dele-
terious effects of high BP but may also
lead to cerebral hypoperfusion and wors-
ening of the AIS. Autoregulation failure
and uncontrolled hypertension can ag-
gravate tissue injury, worsen brain ede-
ma, and increase ICP.23-27 For a success-
ful outcome in stroke patients with acute
hypertension, the clinician must deli-
cately balance treating the hypertension
while avoiding the potential conse-
quences. A very narrow range of BP be-
comes the therapeutic target: if BP falls
too low, the patient is placed at higher
risk for ischemia; if BP is raised too high,
brain edema can spread and ICP can rise
even higher.
Stroke is not a single entity, and nu-
merous pathophysiologic processes can
result in similar end-organ damage.
Microcirculatory abnormalities are like-
ly involved, and formation of micro-
scopic thrombi responsible for impairing
microcirculation in the cerebral arterioles
patients without congestive heart failure,
but increasing output in patients with a
low output state.6 As an arterial and ve-
nous vasodilator, nitroprusside decreas-
es CBF while increasing intracranial
pressure (ICP),2,18,19 effects that are par-
ticularly unwanted in patients having a
hypertensive crisis. A significant reduc-
tion in regional blood flow (ie, coronary
steal) can occur in patients with coro-
nary artery disease who are treated with
nitroprusside.2 Elimination of nitro-
prusside, which contains 44% cyanide by
weight, requires adequate liver and renal
function. Documented cyanide toxicity
has resulted in cardiac arrest, coma, en-
cephalopathy, convulsions, and irre-
versible focal neurologic abnormali-
ties.2,20 Special monitoring and storage
requirements further limit the utility of
this drug for the treatment of hyperten-
sive crises.
and capillaries is a complex phenome-
non.28 ICH is more common in patients
with extensive small vessel disease,23,29,30
which may be attributable to microa-
neurysms of the arterioles. Cerebral au-
toregulation also is maintained at the
level of the arterioles, constricting with
an increase in BP, dilating with a de-
crease in BP, and normally operating be-
tween 50 and 150 mm Hg. However,
failure of autoregulation must be as-
sumed in neurocritical care patients. In
otherwise healthy hypertensive patients,
the absolute level of CBF is the same as
that of normal people without hyper-
tension. CBF autoregulation, however,
with its characteristic shift toward high-
er pressure in patients with chronic hy-
pertension, impairs tolerance to hy-
potension.6,31 Patients with chronic
hypertension have an increased risk of is-
chemic injury with a sudden decrease in
the cerebral perfusion pressure (CPP)
below the lower limit of autoregula-
tion.8,31
7
PDL_pages3_20Final_R.qxd 3/20/2008 11:28 PM
AHA/ASA Guideline Updates on Treating
Hypertension in Patients With Stroke
T he AHA and the ASA Stroke Coun-
cil published revised guidelines in
2007 for the detection and treatment of
ICH and AIS.24,32 The guidelines offer
recommendations on BP management
for patients with each type of stroke, and
the new guidelines for ICH treatment
address management of increased ICP in
these patients.
BP Management in Patients
With ICH
In primary ICH, the risk of acute hem-
orrhagic expansion with uncontrolled
BP elevation must be balanced with the
theoretical risk of inducing cerebral is-
chemia in the edematous region sur-
rounding the hemorrhage if BP is low-
ered too aggressively. For primary ICH,
the guideline writers found little
prospective evidence to revise the exist-
Figure 2. American Heart Association/American
Stroke Association 2007 Guidelines for Treating
Elevated Blood Pressure (BP) in Spontaneous
Intracerebral Hemorrhage 32
Systolic BP 180 mm Hg
or
MAP 130 mm Hg
Evidence or suspicion
of elevated ICP?
Yes No
Consider
 Monitoring ICP
 Reduction of BP using
intermittent or continuous
IV medications to keep
CPP 60-80 mm Hg
MAP=mean arterial pressure; ICP=intracranial pressure; IV=intravenous;
CPP=cerebral perfusion pressure.
8 Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 8
ing BP threshold. The previous (1999)
AHA/ASA recommendation was to
maintain systolic BP
180 mm Hg
and/or MAP <130 mm Hg.23 The 2007
guidelines suggest that if systolic BP is
>200 mm Hg or MAP is >150 mm Hg
in a patient with ICH, continuous IV an-
tihypertensive therapy should be con-
sidered, with monitoring performed
every 5 minutes (Figure 2).32 A target
BP of 160/90 mm Hg is recommended.
BP can be monitored adequately with an
automated cuff, and continuous moni-
toring of MAP should be considered for
patients who require continuous IV in-
fusion of antihypertensive medications
and for those whose neurologic status is
deteriorating.32
It is unknown if more aggressive BP
control immediately after the onset of
ICH can decrease bleeding without com-
Systolic BP 200 mm Hg
or
MAP 150 mm Hg
Consider
 Reduction of BP with
continuous IV infusion
 Monitoring BP every 5 minutes
Consider
 Modest BP reduction (eg,
MAP 110 mm Hg or target BP
160/190 mm Hg) using
intermittent or continuous IV
medications
 Reexamining patient every 15
minutes
promising the perfusion of the brain sur-
rounding the ICH, but this approach is
being actively investigated. The Antihy-
pertensive Treatment in Acute Cerebral
Hemorrhage (ATACH) pilot study, be-
gun in 2005, is investigating the control
of BP in patients with ICH. In addition,
the phase III, randomized, international
Intensive Blood Pressure Reduction in
Acute Cerebral Hemorrhage (INTER-
ACT) study will determine whether low-
ering BP levels after the start of ICH will
reduce the risk of a patient dying or in-
curring a long-term disability.32 Results
of these two studies should provide a
more reliable, evidence-based rationale for
BP control in patients with ICH.
ICP Management
The exact frequency of increased ICP in
patients with ICH is unknown, and
many patients with smaller bleeds will
likely not have an elevated ICP. For pa-
tients with ICH who do have clinical ev-
idence of increased ICP, the AHA/ASA
guidelines recommend taking conserva-
tive measures initially followed by addi-
tional interventions as necessary. A bal-
anced approach is suggested32:
Head-of-bed elevation: Elevating
the head of the bed to 30 improves
jugular venous outflow and lowers
ICP. In hypovolemic patients, ele-
vating the head of the bed may be
associated with a fall in BP and an
overall fall in CPP; therefore, care
must be taken to exclude hypo-
volemia before this intervention.
Cerebrospinal fluid drainage: When
an intraventricular catheter is used
to monitor ICP, cerebrospinal fluid
drainage is an effective method for
lowering ICP. This can be accom-
plished by intermittent drainage
for short periods in response to sud-
den elevations in ICP.
Analgesia and sedation: In unstable
patients who are intubated, IV se-
dation is needed for maintenance of
ventilation and control of airways,
as well as for other procedures. Se-
dation should be titrated to mini-
mize pain and increases in ICP, yet
PDL_pages3_20Final_R.qxd 3/20/2008 11:28 PM Page 9

should not hinder evaluation of the

patients clinical status. This is usu- Figure 3. Autoregulatory Failure Detected With
ally accomplished with IV propofol Brain Tissue Oxygen Analysis 33
or midazolam for sedation and fen-
tanyl, remifentanil, or alfentanil for
analgesia and antitussive effect.
Neuromuscular blockade: Muscle
activity may further raise ICP by in-
creasing intrathoracic pressure and
obstructing cerebral venous out-
flow. If the patient is not responsive
to analgesia and sedation alone,
neuromuscular blockade may be
considered. However, the prophy-
lactic use of neuromuscular block-
ade in patients without proven in-
tracranial hypertension has not been
shown to improve outcomes.
Osmotic therapy: The most com-
monly used agent is mannitol, an
intravascular osmotic agent that
can draw fluid from both edematous
and nonedematous brain tissue. In
addition, mannitol increases car-
diac preload and CPP, thus de-
creasing ICP through cerebral au-
toregulation. The use of hypertonic Real-time relationship of the physiologic parametersbrain oxygen tension (PBrO2),
saline solutions (a continuous 3% cerebral perfusion pressure (CPP), and intracranial pressure (ICP)over 2 hours in a patient
with intracerebral hemorrhage complicated by intracranial hypertension. Note the striking parallel
sodium chloride acetate infusion at relationship between PBrO2 and CPP, indicative of autoregulatory failure.
1 mL/kg/hour or 23.4% via a cen- Adapted with permission from Wartenberg KE et al.
tral line at 0.5 to 2.0 mL/kg) has
been shown to reduce ICP in a va-
riety of conditions, even in cases re- ICP Monitoring Although not addressed in the new
fractory to treatment with hyper- ICP monitoring is routine in the man- AHA/ASA guidelines, brain tissue oxy-
ventilation and mannitol. agement of neurocritical patients. For gen monitoring is another variable to
Hyperventilation: Hyperventilation monitoring ICP in patients with ICH, consider in the management of patients
is one of the most effective methods the new guidelines point out that the with ICH. Using a LICOX (Integra
for rapidly reducing ICP, with a de- information provided by standard com- Lifesciences Corporation, Plainsboro,
sired target of PCO2 of 28 to 32 puted tomography or magnetic reso- New Jersey) monitor, brain tissue oxy-
mm Hg. Despite its effectiveness in nance imaging is static, and frequent gen levels can be plotted as a function
lowering ICP, early aggressive hy- imaging studies in patients with ICH of CPP (Figure 3).33 Because brain tis-
perventilation to PCO2 levels 26 are impractical. ICP monitoring, via a sue hypoxia is linked to poor outcomes
mm Hg has fallen out of favor, pri- ventricular drain or parenchymal ICP (a normal value is approximately 40
marily because it tends to cause ex- probe inserted via a bolt to detect dy- mm Hg), CPP targets based on mea-
cessive vasoconstriction and reduc- namic changes, is used primarily in co- surements provided by the monitor can
tions in CBF. matose patients with a high suspicion be refined and adjusted, particularly in
Barbiturate coma: Barbiturates in of elevated ICP based on the presence of patients with impaired or absent au-
high doses are effective in lowering intracranial mass effect on brain imag- toregulation.34
refractory intracranial hypertension, ing.32 The new 2007 ICH guidelines
but are ineffective or potentially now emphasize the importance of ICP BP Management in Patients
harmful as a first-line or prophy- monitoring in this subset of patients, With AIS
lactic treatment in patients with because it allows calculation of the cere- Because of a lack of unambiguous data,
brain injuries. High-dose barbitu- bral perfusion pressure (MAP - ICP= the appropriate treatment of arterial hy-
rate treatment acts by depressing CPP). For comatose patients with ICP pertension in patients with AIS remains
cerebral metabolic activity. This re- monitoring in place, vasoactive med- controversial. Although severe hyper-
sults in a reduction in CBF, which ications are ordered based on specific tension may be considered an indication
is coupled with metabolism, and a CPP targets (rather than systolic BP or for treatment, data that define precise
fall in ICP. MAP targets). levels of arterial hypertension requiring

Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges 9
PDL_pages3_20Final_R.qxd 3/20/2008 11:28 PM
emergency management are inconclusive
or conflicting. Theoretical reasons for
lowering BP include reducing the for-
mation of brain edema, lessening the risk
of hemorrhagic transformation of the
infarction, preventing further vascular
damage, and forestalling early recurrent
stroke. In addition, urgent antihyper-
tensive therapy may be needed to treat
patients with acute stroke who have oth-
er forms of acute end-organ damage such
as hypertensive encephalopathy, aortic
dissection, acute renal failure, acute pul-
monary edema, or acute myocardial in-
farction. Conversely, aggressive treat-
ment of BP may lead to worsening
neurologic status by reducing perfusion
pressure to ischemic areas of the
brain.24,25
The new guidelines on management of
AIS recommend a cautious approach to
the treatment of arterial hypertension. As
recommended in previous AHA/ASA
guidelines, the 2007 guidelines confirm
that patients who have other medical
Perioperative Hypertension
H ypertension is one of the most com-
mon chronic illnesses encountered
in the perioperative period, and the risk
of stroke is fairly substantial. Patients at
higher risk include the elderly, particu-
larly those with preexisting hyperten-
sion.36 Other patients already at risk for
vascular events are placed at elevated risk
also by invasive procedures. Preexisting
hypertension is, in fact, the most com-
mon medical reason for postponing
surgery37 and with some justification. A
case-control study that analyzed risk fac-
tors for postoperative cardiovascular
death found that patients with a preop-
erative history of hypertension were 4
times more likely to die of cardiovascu-
lar causes within 30 days of their surgi-
cal procedure than were nonhypertensive
patients.38 Conversely, delaying surgery
solely for the purpose of BP control may
be unnecessary, according to some re-
searchers, particularly in the case of mild
to moderate hypertension.39 One study
of 989 patients scheduled for surgery
with well-controlled hypertension ran-
domized patients with diastolic BP be-
10 Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 10
indications for aggressive treatment of
BP should be treated. The level of BP
that would mandate treatment is not
specified in the guidelines, but there is
a consensus that medications should be
withheld unless the systolic BP is >220
mm Hg or the diastolic BP is >120 mm
Hg. A new goal BPa reduction of ap-
proximately 15% to 25% during the
first 24 hours after onset of strokeis
now specified. No data were available to
guide selection of specific medications
for lowering BP in patients with AIS,
according to the new guidelines. How-
ever, based on a general consensus, la-
betalol or nicardipine is recommended to
accomplish the reduction in BP. If BP re-
mains uncontrolled, the guidelines cite
nitroprusside as a possible alternative
treatment.24
Because the maximal interval from
stroke onset until treatment with re-
combinant tissue plasminogen activator
(rtPA) is short, many AIS patients with
sustained hypertension above recom-
tween 110 and 130 mm Hg to undergo
surgery after receiving 10 mg of in-
tranasal nifedipine or to have their
surgery postponed. No statistically sig-
nificant difference in postoperative com-
plications was found.40
The incidence of perioperative hyper-
tension has been estimated to range from
3% to 75%, depending on the criteria
used to define it and on the individual
patient.41 Perioperative hypertension is
particularly common in the setting of
cardiovascular surgery. An accepted de-
finition of perioperative hypertension is
a single elevation more than 50% of the
preoperative value; postoperatively, a pa-
tient with a systolic BP 20% or more of
the preoperative value that persists
longer than 15 minutes is considered
hypertensive. Acute postoperative hy-
pertension (APH) has been defined as a
significant elevation in arterial BP dur-
ing the immediate postoperative period
that may lead to serious neurologic, car-
diovascular, or surgical-site complica-
tions. Such cases require intervention and
management.42,43
mended levels cannot be treated with IV
rtPA. Patients who are candidates for
rtPA should have their systolic BP low-
ered to 185 mm Hg and their diastolic
BP lowered to 110 mm Hg before lyt-
ic therapy is started. BP must be main-
tained below 180/105 mm Hg for at
least the first 24 hours after IV rtPA
treatment.24
Both myocardial ischemia and cardiac
arrhythmias are potential complications
of AIS. The most common arrhythmia
detected is atrial fibrillation, which may
be either a cause or a complication of the
stroke. In regard to monitoring patients
with AIS, the guidelines cite a general
consensus that patients should have car-
diac monitoring for at least the first 24
hours, and patients with any serious car-
diac arrhythmia should be treated. How-
ever, the utility of prophylactic medica-
tions to prevent cardiac arrhythmias
among patients with AIS is not
known.24,35
Pathophysiology of APH
The pathophysiologic mechanism un-
derlying APH varies with the surgical
procedure. The final common pathway
leading to hypertension, however, ap-
pears to be activation of the sympathe-
tic nervous system, as evidenced by
elevated plasma catecholamine concen-
trations. At the time of development,
plasma catecholamine concentrations are
significantly greater in patients with
postoperative hypertension than in nor-
motensive postoperative patients.42,43
The volume depletion that results from
pressure natriuresis may further simulate
the release of vasoconstricting substances
from the kidney.44 The primary hemo-
dynamic alteration observed in APH is
increased afterload (systemic vascular
resistance and BP, with or without tachy-
cardia); activation of the renin-an-
giotensin-aldosterone system may also
contribute to APH.42,45
The systemic vasodilatation associated
with anesthesia in hypertensive patients
with increased systemic vascular resis-
tance can have a profound effect on ar-
PDL_pages3_20Final_R.qxd 3/20/2008 11:29 PM
terial pressure. MAP has been identified
as an independent predictor of stroke and
all-cause mortality in both normotensive
and hypertensive patient populations.46
A 1999 analysis demonstrated that each
10-mm Hg increase in MAP was inde-
pendently associated with a 20% in-
crease in the risk of stroke and a 14%
increase in the risk of all-cause mortali-
ty.46 In the perioperative setting, patients
with hypertension may display increased
cardiovascular lability during anesthesia.
Researchers have demonstrated that in-
duction of anesthesia is associated with
a decrease in arterial pressure to a simi-
lar nadir in patients with or without hy-
pertension. However, because the hy-
pertensive patients studied generally had
a higher preinduction arterial pressure,
the absolute decrease in arterial pressure
in these patients was greater.47
Preoperative Treatment of
Hypertension
With the exception of angiotensin-con-
verting enzyme (ACE) inhibitors and
angiotensin II receptor blockers (which
should be discontinued 10 hours be-
fore surgery), patients with hypertension
should continue to receive all their an-
tihypertensive therapies preoperatively.
One randomized study found that 100%
of hypertensive patients undergoing vas-
cular surgery who were treated with an
ACE inhibitor up until the morning of
surgery experienced hypotension requir-
ing ephedrine when anesthetized. The
incidence of induction-induced hy-
potension was significantly less
(P<0.001) among patients whose ACE
inhibitor treatment had been previous-
ly discontinued.48 Discontinuation of
diuretic therapy can lead to hypokalemia,
which can result in the patient overre-
sponding to muscle relaxants as well as
prolonged apnea. Severe hypokalemia
can also lead to cardiac arrhythmias.49
CCBs may increase the incidence of post-
operative bleeding in patients undergo-
ing surgery because of inhibition of
platelet aggregation.50,51 However, the
multiple benefits of CCBs likely out-
weigh the risk of continuing treatment
perioperatively. -Blockers have been
found to reduce the intraoperative inci-
dence of myocardial ischemia in patients
with mild hypertension,52 and their
withdrawal may increase the risk of ac-
Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 11
celerated angina, myocardial infarction, elevation in the operative setting such as
and sudden death. Patients undergoing pain and anxiety should be treated be-
surgery who have or are at risk for coro- fore the administration of any antihy-
nary artery disease should maintain pe- pertensive therapy. Other causes of acute
rioperative -blockade.53,54 There are perioperative hypertension, such as hy-
less compelling data, however, support- pothermia with shivering, hypoxemia,
ing initiation of -blockade therapy for hypercarbia, or bladder distension, can
hypertensive patients undergoing sur- be reversed without having to resort to
gery. any antihypertensive treatment. When
treatment is required, a short-acting IV
Assessing Risk agent such as nicardipine, labetalol, or
Current American College of Cardiolo- esmolol is the agent of choice. The CCB
gy/AHA practice guidelines place un- nicardipine is particularly useful in the
controlled hypertension in the same operative setting. At bolus doses rang-
category as advanced age and an abnor- ing from 0.25 to 2.0 mg, nicardipine
mal electrocardiogram, as a minor rapidly decreased arterial pressure in
predictor of increased perioperative patients undergoing cardiac surgery.
cardiovascular risk among patients un- Arterial pressure decreased in a dose-
dergoing noncardiac surgery.54 It is still dependent manner, without associated
unclear if postponing surgery in patients changes in heart rate or hemodynamic
with hypertension to achieve control of functioning.55 One study that compared
BP will reduce cardiac risk. The man- the efficacy of IV nicardipine with that
agement of patients with poorly con- of nitroprusside for patients with acute,
trolled BP in the perioperative setting severe hypertension found that both
should be based on the individual were effective for immediate control of
patients clinical presen-
tation (eg, baseline BP, The management of patients
concomitant disease) and
with poorly controlled BP in the
the assumed risks of the
surgery. Absent an emer- perioperative setting should be
gency, surgery should be based on the individual patients
deferred in patients with
acute end-organ hyper- clinical presentation (eg, baseline
tensive injury (eg, cardiac BP, concomitant disease) and the
failure, myocardial is-
chemia, acute renal dys-
assumed risks of the surgery.
function, papilledema/
encephalopathy). For high-risk patients BP but that there were significantly few-
(eg, previous stroke, active coronary er side effects (ie, hypotension, dizziness,
artery disease) with a systolic BP >180 nausea/vomiting) with nicardipine
mm Hg and/or a diastolic BP >110 mm treatment.56
Hg, surgery should be postponed until The investigational CCB clevidipine
BP is brought under control. For low- has been tested in the perioperative set-
risk patients with these same BP values, ting. In the phase III Efficacy Study of
a 10% to 20% reduction in BP Clevidipine Assessing Its Preoperative
achieved with an IV -blocker and a ben- Antihypertensive Effect in Cardiac
zodiazepine for anxiolysis prior to Surgery-1 (ESCAPE-1) trial, clevidipine
surgeryis advisable. For patients un- achieved a 92.5% rate of treatment
dergoing cardiac surgery, there is a con- success for patients with preoperative hy-
sensus that hypertension should be treat- pertension. (Treatment failure was de-
ed if BP is >140/90 mm Hg or MAP is fined as the premature and permanent
>105 mm Hg.42 discontinuation of clevidipine for any
reason or failure to decrease systolic BP
Intraoperative Control by 15% from baseline at any time
of BP within the 30-minute treatment peri-
When the decision is made to proceed od.)57 Among cardiac surgery patients
with surgery for a patient with hyper- with postoperative hypertension treated
tension, common contributors to BP in the ESCAPE-2 trial, a similar rate of
11
PDL_pages3_20Final_R.qxd 3/20/2008 11:29 PM
treatment success (91.8%) was reached.58
The Evaluation of Clevidipine in the Pe-
rioperative Treatment of Hypertension
Assessing Safety Events (ECLIPSE) tri-
al, one of the largest trials ever conduct-
ed in patients with acute hypertension
(N >1,500), compared clevidipine with
nitroglycerin, nitroprusside, or nicardip-
ine. Clevidipine maintained BP control
within a tighter range than did the com-
parator agents. The trial also demon-
strated a survival advantage for clev-
idipine compared with nitroprusside
Summary
A ppropriate and timely treatment of
patients in hypertensive crisis is es-
sential to avoid serious adverse outcomes.
Hypertensive crises are classified either
as urgencies or emergencies, and distin-
guishing the two conditions is necessary
for appropriate treatment. Hypertensive
urgencies are severe elevations of BP
without evidence of acute and progres-
sive dysfunction of organs. End-organ
damage is absent in hypertensive urgen-
cies, and adequate control of BP within
24 hours to several days, using orally
administered agents, is recommended
in such cases.
Carrying the potential for acute end-
organ damage, hypertensive emergencies
are life-threatening conditions that may
present with neurologic, renal, cardio-
vascular, or obstetric complications. In
hypertensive emergencies, diastolic BP
should generally be reduced by 10% to
15% (or to approximately 110 mm Hg)
during the first hour. Patients with hy-
pertensive crises are best treated in an
ICU with titratable, IV antihypertensive
agents. Several rapidly acting agents are
12 Hypertensive Crises in the Critical Care Setting: Current Perspectives and Practice Challenges
Page 12
(1.7% vs 4.7% fatalities, P=0.045). Oth-
er safety endpointsstroke, heart attack,
and kidney dysfunctionwere similar
for clevidipine and the other three anti-
hypertensive agents.57
Finally, patients in the perioperative
setting should be closely monitored for
clonidine withdrawal syndrome. Be-
cause clonidine is not available for par-
enteral administration, withdrawal is
most likely when oral intake is restrict-
ed in the perioperative period. Onset of
the syndromecharacterized by exces-
available, including labetalol, esmolol,
fenoldopam, nicardipine, and sodium
nitroprusside. Although nitroprusside is
commonly used to treat severe hyper-
tension, it is an extremely toxic drug that
should be used only in rare circum-
stances. To prevent a precipitous drop in
BP, volume status should always be de-
termined in the patient with hyperten-
sive crisis before initiating IV treatment.
When BP is stable, IV agents may be
slowly titrated down and replaced with
oral antihypertensive therapy.
Rapid shifts in blood volume and in-
creased activity of the sympathetic ner-
vous system that accompany surgery can
result in perioperative hypertension,
which increases vasoconstriction and vas-
cular resistance. The increased BP can
damage vessels, resulting in inflamma-
tion and leaking of fluid or blood into
tissues. Complications such as hemor-
rhagic stroke, ischemic stroke, en-
cephalopathy, myocardial ischemia or
infarction, heart arrhythmia, congestive
heart failure, and bleeding at the surgi-
cal site are potential consequences. When
sive sympathetic activity with rebound
hypertension, tachycardia, agitation, and
vomiting-can occur as early as 8 hours
after cessation of high-dose (ie, >1 mg/
day) clonidine therapy.59 The syndrome
can be worsened by the use of nonselec-
tive -blockers and may be reversed by
administering intramuscular clonidine
or treatment with methyldopa or la-
betalol. Converting the surgery patient
to the clonidine patch preoperatively is
recommended.
a surgical patient presents with uncon-
trolled preoperative hypertension, clini-
cians should be wary but not overly
alarmed. Precise management of arteri-
al pressure in the perioperative period,
using appropriate antihypertensive med-
ication, can improve clinical outcomes by
avoiding hypotensive episodes, ensur-
ing adequate end-organ perfusion, and
facilitating the transition to long-term
therapy for BP control.
Abnormalities of autoregulation dic-
tate that BP reductions in patients with
poorly controlled, chronic hypertension
are done with particular care. The po-
tential for harm from overzealous low-
ering of BP exists concurrently with the
need for careful and structured BP
reduction. Management of arterial BP
and increased ICP in the setting of
acute stroke should comply with new-
ly published practice guidelines from
AHA/ASA. In all cases, treatment of
hypertensive crisis or perioperative
hypertension should be tailored to the
clinical circumstances of the individual
patient.
PDL_pages3_20Final_R.qxd 3/20/2008 11:29 PM
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