R e v i e w P a p e r

Blood Pressure Control in Acute

Cerebrovascular Disease
William B. Owens, MD
Acute cerebrovascular diseases (ischemic stroke,
intracerebral hemorrhage, and subarachnoid
hemorrhage) affect 780,000 Americans each year.
Physicians who care for patients with these
conditions must be able to recognize when acute
hypertension requires treatment and should
understand the principles of cerebral
autoregulation and perfusion. Physicians should
also be familiar with the various pharmacologic
agents used in the treatment of cerebrovascular
emergencies. Acute ischemic stroke frequently
presents with hypertension, but the systemic
blood pressure should not be treated unless the
systolic pressure exceeds 220 mm Hg or the
diastolic pressure exceeds 120 mm Hg. Overly
aggressive treatment of hypertension can
compromise collateral perfusion of the ischemic
penumbra. Hypertension associated with
intracerebral hemorrhage can be treated more
aggressively to minimize hematoma expansion
during the rst 3 to 6 hours of illness.
Subarachnoid hemorrhage is usually due to
aneurysmal rupture; systolic blood pressure
should be kept <150 mm Hg to prevent
rerupture of the aneurysm. Nicardipine and
labetalol are recommended for rapidly treating
hypertension during cerebrovascular emergencies.
Sodium nitroprusside is not recommended due to
its adverse effects on cerebral autoregulation and
intracranial pressure. Hypoperfusion of the
injured brain should be avoided at all costs.
J Clin Hypertens (Greenwich). 2011;13:205211.

2010 Wiley Periodicals, Inc.

T
he differential diagnosis of acute cerebrovas-
cular disease is quite broad, encompassing
thrombosis, dissection, vasculitis, and occlusion
of the brains arterial and venous systems. The
cerebrovascular diseases most commonly seen in
the acute care setting are ischemic stroke, intra-
cerebral hemorrhage, and subarachnoid hemor-
rhage. Together, these 3 conditions represent
approximately 780,000 cases annually in the
United States. A total of 600,000 of these cases
will be new; 87% will be ischemic strokes, 10%
will be intracerebral hemorrhages, and 3% will
be subarachnoid hemorrhages.
1
Risk factors for
cerebrovascular disease are similar to those for
coronary artery disease and include smoking,
hyperlipidemia, heavy alcohol consumption, and
diabetes mellitus. The primary risk factor for
cerebrovascular disease, however, is systemic
arterial hypertension.
2
Hypertension is also a
prominent presenting feature with all 3 types of
cerebrovascular emergencies. It behooves the phy-
sician, therefore, to understand the pathophysio-
logic rationale for managing blood pressure (BP)
in patients with acute neurologic deterioration.
This is especially important for patients present-
ing to an emergency department (ED) in a hospi-
tal that is not a stroke center or does not
have expert consultation services immediately
From the Division of Pulmonary and Critical Care
Medicine, University of South Carolina School of
Medicine, Columbia, SC
Address for correspondence:
William B. Owens, MD, Division of Pulmonary and
Critical Care Medicine, University of South Carolina
School of Medicine, 8 Medical Park Road, Suite 410,
Columbia, SC 29203
E-mail: wowens@uscmed.sc.edu
Manuscript received July 19, 2010; accepted August 26,
2010
doi: 10.1111/j.1751-7176.2010.00394.x
VOL. 13 NO. 3 MARCH 2011 THE JOURNAL OF CLINICAL HYPERTENSION 205
available. In that case, the physician must stabilize
the patient and appropriately manage the BP while
arranging transfer to an appropriate facility.
DISCUSSION
Principles of BP Management (Table I)
The two most important principles in the treatment
of any patient with acute cerebrovascular disease
are to avoid hypoxemia and hypoperfusion. Most
patients who arrive in the ED with cerebrovascular
emergencies are hypertensive and physicians focus
on lowering the systemic arterial pressure. However,
an overly aggressive reduction in BP can result in
worsening cerebral ischemia. At minimum, the sys-
tolic BP (SBP) should be kept above 90 mm Hg.
3
Cerebral perfusion pressure (CPP) is dened as the
difference between the mean arterial pressure (MAP)
and the intracranial pressure (ICP). Normal cerebral
blood ow is approximately 50 mL 100 g brain
tissue per minute and remains constant, despite uc-
tuations in systemic BP, via cerebral autoregulation.
This is maintained between a CPP of 50 mm Hg and
150 mm Hg.
3
When the CPP falls below 50 mm Hg,
cerebral blood owfalls in a linear fashion. Likewise,
when the CPP exceeds 150 mm Hg, arteriolar vaso-
constriction is exhausted and cerebral edema occurs.
Chronic hypertension shifts this curve to the right,
so cerebral autoregulation may be lost at a higher
CPP than in normal patients. Acute cerebrovascular
disruption, such as that seen with massive stroke,
intracerebral hemorrhage, or aneurysmal rupture,
severely impairs cerebral autoregulation. In these
cases, cerebral perfusion follows a linear relationship
with CPP (Figure).
Since most hospitals do not have the capability
to routinely place intracranial pressure monitors,
the treating physician must rely on the MAP and
their clinical examination of the patient to make
decisions regarding BP management. Rapid lower-
ing of the systemic BP has been associated with
neurologic deterioration in several smaller studies
and case series, although large randomized control
trials examining this are lacking.
4,5
In patients in
whom there is suspicion of cerebral hypoperfusion,
intravenous uid boluses, followed by vasopressor
therapy, are indicated to augment cerebral blood
ow.
Acute Ischemic Stroke
Acute ischemic stroke results in two types of neuro-
nal injury. The core, or central part of the infarc-
tion, consists of cellular necrosis and irreversibly
damaged brain tissue. Unfortunately, this area of
the brain is beyond salvage with current therapies.
The second type is the penumbra, which varies in
size and surrounds the core.
3
The penumbra repre-
sents ischemic, but not infarcted, neuronal tissue
and is the focus of most interventions for acute
stroke. This area is not usually evident on com-
puted tomography scanning but can be detected
using magnetic resonance imaging. The typical pat-
tern is one of mismatch between diffusion-weighted
images (which represent the infarcted core) and per-
fusion-weighted images (which represent ischemic,
but potentially viable, tissue).
6
The majority of patients who present to the ED
with acute stroke will be hypertensive,
7,8
but it is not
known whether this represents a natural compensa-
tory mechanism. It has been shown that without
treatment, the hypertension present at the time of
admission will decline over the next 24 hours and
this decline may continue for up to 7 days after
Table I. Recommendations for BP Control in Cerebrovascular Emergencies
Emergency Target BP Rationale
Hypotension,
regardless of cause
MAP 70 mm Hg
SBP 90 mm Hg
Cerebral perfusion depends on adequate systemic BP and should
be maintained at all costs!
Subarachnoid
hemorrhage
MAP 90110 mm Hg
SBP 120150 mm Hg
SBP spikes above 150 mm Hg, increase the risk of rerupture of
the aneurysm, which carries a 75% risk of mortality
Intracerebral
hemorrhage
MAP 100120 mm Hg
SBP 140160 mm Hg
Cerebral perfusion needs to be maintained, but BP should be
rapidly lowered to prevent expansion of the hematoma
Acute ischemic
stroke
Dont lower BP unless SBP
exceeds 220 mm Hg or DBP
exceeds 120 mm Hg, unless
thrombolytics have been given
After an ischemic stroke, a penumbra of viable, but threatened,
brain tissue exists around the infarcted area. This penumbra
depends on collateral circulation and adequate perfusion, and
dropping BP can lead to death of this tissue. So, while the
temptation to lower BP is there, RESIST!
Post-thrombolysis
for stroke
MAP 100130 mm Hg
SBP 140180 mm Hg
After tPA, the balance is between adequate perfusion of the
penumbra and the risk of hemorrhage with higher BPs
Abbreviations: BP, blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure; tPA, tissue plasminogen activator.
THE JOURNAL OF CLINICAL HYPERTENSION VOL. 13 NO. 3 MARCH 2011 206
the stroke.
7,8
The American Heart Association
American Stroke Association (AMA ASA) Scientic
Statement on the early treatment of stroke recom-
mends that arterial hypertension not be treated in the
acute phase unless the SBP exceeds 220 mm Hg,
the diastolic BP (DBP) exceeds 120 mm Hg, or if
there is evidence of other acute end-organ damage
due to hypertension, such as cardiac ischemia,
pulmonary edema, aortic dissection, or acute renal
failure.
9
Severe hypertension is considered a contraindica-
tion to the use of thrombolytics in acute ischemic
stroke
9
due to the increased risk of hemorrhagic
conversion. If thrombolytic therapy is given, the BP
should be more tightly controlled than if the patient
were treated conservatively. The SBP should be
treated if it exceeds 180 mm Hg, and the DBP
should be treated if it exceeds 105 mm Hg.
10,11
The role of induced hypertension in the treatment
of stroke for patients who are not eligible for throm-
bolytic therapy is still being investigated. Several
smaller studies, totaling 152 patients, have looked at
augmenting the MAP to improve cerebral blood ow
to the penumbra.
1217
Phenylephrine has been the
agent most commonly used, since it is a peripheral a-
agonist and there are few a
1
receptors in the cerebral
vasculature. This allows for systemic vasoconstric-
tion without impairing cerebral blood ow.
18
While
this treatment has theoretical promise and is
supported by these trials, it is not recommended as
routine therapy until larger studies assessing its ef-
cacy and safety have been performed.
9
Intracerebral Hemorrhage
Intracerebral hemorrhage (ICH) is dened as non-
traumatic bleeding into the parenchyma of the brain
or into the cerebral ventricles. The most common
sites for ICH are the basal ganglia, thalamus, cere-
bellum, and brainstem.
19
Hemorrhage occurs when
small penetrating arteries rupture. Pathologic studies
show that there is often medial and smooth muscle
degeneration of these vessels. In elderly patients, b-
amyloid deposition in smaller arteries leads to amy-
loid angiopathy; lobar ICH and recurrent bleeding
is seen in this condition.
19
Hypertension has been
identied as the biggest risk factor for ICH.
20
Formerly, it was believed that ICH was a mono-
phasic event and that the bleeding was complete by
the time the patient arrived to the hospital. Com-
puted tomography studies of patients with ICH
have shown that this is not true, and that there is
progression in the size of the hematoma for up to
6 hours following the initial hemorrhage.
21,22
Expansion of the volume of the hematoma may be
due in part to uncontrolled hypertension and a
localized coagulopathy related to consumption of
clotting factors.
23
Mortality from ICH is directly
correlated to hematoma volume and the Glasgow
Coma Score (GCS) at the time of admission.
Patients with a GCS of <9 and a hematoma
Figure. Cerebral autoregulation in normal and chronically hypertensive patients. Thick black line indicates normal
cerebral autoregulation; thick grey line, rightward shift of autoregulation due to chronic arterial hypertension; thin
line, impaired cerebral autoregulation due to acute ischemia. Reprinted with kind permission from Springer
Science+Business Media.
11
VOL. 13 NO. 3 MARCH 2011 THE JOURNAL OF CLINICAL HYPERTENSION 207
volume of >60 mL were found by Broderick and
colleagues to have a 30-day mortality of 90%,
while those with a hematoma volume of <30 mL
and a GCS of 9 or better had a 30-day mortality
of 17%.
24
Controlling hematoma expansion may
represent the best therapeutic option for the patient,
but whether persistent hypertension after ICH leads
to hematoma expansion is debatable and the ideal
target BP is not known. The vast majority of
patients with ICH will be hypertensive, and this
may in fact be a protective reex to maintain cere-
bral perfusion if there is brainstem compression
(the Cushing-Kocher response).
25
The Intensive Blood Pressure Reduction in Acute
Cerebral Hemorrhage (INTERACT) trial compared
standard BP control (180 mm Hg SBP) with intensive
control (140 mm Hg SBP) and found no difference in
90-day mortality or neurologic outcome. There was a
trend toward lower hematoma volume with the
intensive group, but this did not reach statistical sig-
nicance.
26
To date, this is the largest randomized
study examining the effect of BP control on ICH.
The National Institutes of Healthsponsored Antihy-
pertensive Therapy in Acute Cerebral Hemorrhage
(ATACH) study compared 3 tiers of BP regula-
tion, keeping the SBP between 170 mm Hg and
200 mm Hg (tier one), 140 mm Hg to 170 mm Hg
(tier two), and 110 mm Hg to 140 mm Hg (tier
three). This study showed that tighter BP control was
safe and feasible, but the small size (n=60) of ATACH
was not powered to detect a mortality benet or
reduction in size of hematoma expansion.
27
Together
with INTERACT, the results of the phase I ATACH
study should serve as a basis for future studies
designed to investigate the possibility of a mortality
benet with a reduction of systemic BP in ICH.
BP control in the management of ICH can be
more aggressive than with acute ischemic stroke,
mainly because of the lack of an ischemic penum-
bra with ICH.
25,28
The rim of the hematoma may
be vulnerable to impaired cerebral perfusion, how-
ever, and any BP reduction should be moderate.
29
Currently, the AHA ASA recommends modest
reduction of BP to a target of 160 90 mm Hg, with
a MAP of 110 mm Hg, if there is no suspicion of
intracranial hypertension.
30
If there is concern for
elevated intracranial pressure, early intracranial
pressure monitoring and therapy directed toward
maintaining a cerebral perfusion pressure of 60 mm
Hg to 80 mm Hg is recommended.
30
Subarachnoid Hemorrhage
Nontraumatic subarachnoid hemorrhage (SAH)
most commonly results from rupture of a large
artery aneurysm. Arteriovenous malformations and
perimesencephalic arterial rupture cause a minor-
ity of cases of SAH. The major risk factors are
hypertension, cigarette smoking, and heavy alcohol
consumption.
31
The mortality from SAH related to
aneurysmal rupture approaches 50%, and between
20% and 30% of survivors will have signicant
neurologic impairment.
32
Rebleeding of the ruptured aneurysm has an
incidence of 4% in the rst 24 hours after SAH.
The incidence falls to 1% each day thereafter until
the aneurysm is secured.
33
While a direct link
between hypertension following SAH and rebleed-
ing has not been established,
34
most neurosurgeons
and intensivists will treat elevated BP. Higher rates
of rebleeding have been observed when the SBP
exceeds 160 mm Hg,
35
so a target SBP of 120 mm
Hg to 150 mm Hg seems prudent. With SAH in
particular, attention should be paid to both the
MAP (and its relationship with cerebral perfusion)
and the SBP, since larger cerebral arteriesthe site
of most aneurysmswill be more sensitive to wide
uctuations in the pulse pressure.
Pharmacologic Therapy (Table II)
The ideal drug for managing BP in acute cerebro-
vascular emergencies would be rapidly titratable,
have a short half-life, and have a minimal number
of side effects. As with any treatment, the pharma-
cologic regimen prescribed for each patient must be
individualized, taking into account comorbid condi-
tions and the goal of therapy. Antihypertensives
most commonly used in cerebrovascular emergen-
cies include nicardipine, labetalol, and esmolol.
Vasopressors that are useful when BP augmen-
tation is desirable include phenylephrine and
norepinephrine.
Nicardipine. Nicardipine is a dihydropyridine-
derived calcium channel blocker that produces
peripheral arterial vasodilatation without affecting
cardiac conduction pathways.
36
This effect allows
for BP reduction without the risk of bradydysrhyth-
mias. It can be given intravenously with a usual
dose of 5 mg h to 15 mg h. Nicardipine has been
shown to reduce both cerebral and coronary ische-
mia in the setting of uncontrolled hypertension
37
and is considered a rst-line agent.
Labetalol. Labetalol blocks a-, b
1
-, and b
2
-adren-
ergic receptors. Due to the combined blockade of
both a- and b-receptors, cardiac output is main-
tained while the systemic BP is lowered.
37
Cerebral
blood ow is not compromised with labetalol,
THE JOURNAL OF CLINICAL HYPERTENSION VOL. 13 NO. 3 MARCH 2011 208
making it a desirable agent in the treatment of
uncontrolled hypertension during cerebrovascular
emergencies.
38
Bradycardia may occur and labetalol
is generally not given if the heart rate is <60 beats
per minute. Labetalol can be given intermittently in
20- to 40-mg intravenous boluses until BP targets
are achieved. Alternatively, a continuous infusion
starting at 0.5 mg min can be administered (with
or without a loading dose of 2040 mg) and
titrated to keep the BP in the desired range.
Esmolol. Esmolol is a selective antagonist of b
1
-
adrenergic receptors. Its duration of action is only
10 to 20 minutes, compared with 4 to 6 hours for
labetalol. This effect makes esmolol very attractive
for the treatment of hemodynamically unstable
patients.
39
In the event of signicant bradydysrhyth-
mias or hypotension, the drug can be stopped and
the effect will quickly disappear. A loading dose of
500 lg kg, followed by an infusion of 25 lg kg min
to 300 lg kg min, is the usual regimen.
Fenoldopam. Fenoldopam is a dopaminergic (DA1-
receptor) agonist. Its primary mechanism of action
is in the proximal and distal renal tubules.
37
It
lowers systemic BP while augmenting renal blood
ow, so it is an attractive agent for patients with
both a cerebrovascular emergency and accelerated
hypertensive nephropathy. Its effects on the cerebral
vasculature are not well-known, so it is not used as
commonly as other agents are. The dose is
0.1 lg kg min by continuous infusion, titrated
upward as necessary to achieve the target BP.
Phenylephrine. Phenylephrine is a selective a
1
-
adrenergic receptor agonist and can be used to aug-
ment BP in patients with hypotension and cerebral
hypoperfusion. The lack of b-receptor agonism
reduces the rate of tachydysrhythmias compared
with dopamine and norepinephrine. Since a
1
-recep-
tors are relatively rare in the cerebral vasculature,
phenylephrine infusion leads to peripheral vasocon-
striction without compromising cerebral perfu-
sion.
18
The usual starting dose is 40 lg min,
titrated upward as needed.
Norepinephrine. Like phenylephrine, norepineph-
rine is a potent a
1
-adrenergic receptor agonist;
however, it is also a b
1
-receptor agonist. This effect
can be useful in the setting of bradycardia due to
increased intracranial pressure (the Cushing reex)
or with myocardial systolic dysfunction. The start-
ing dose is 4 lg min, titrated upward to maintain
adequate cerebral perfusion.
Sodium Nitroprusside. Sodiumnitroprusside (SNP)
has long been considered a mainstay in the treat-
ment of hypertensive emergencies, but there is
Table II Pharmacologic Agents
Drug Dose Mechanism: Pros and Cons
Nicardipine 5- to 15-mg h
infusion
Calcium channel antagonist with no suppression of the atrioventricular
node; acts as a cerebral arterial vasodilator. Very titratable with few side
effects and preferred for most neurocritical care patients
Labetalol 20- to 40-mg
intravenous
bolus, or 0.5- to
2.0-mg min infusion
Combined a- and b-receptor antagonist; especially useful in hyperadrenergic
conditions (cocaine intoxication, subarachnoid hemorrhage). Can cause
bradycardia and bronchospasm.
Esmolol 500 lg kg intravenous
bolus, followed by a
25- to 300-lg kg min
infusion
Selective b
1
-receptor antagonist; has very short half-life. Effect of the drug is
lost 10 to 20 min after the infusion is stopped.
Fenoldopam 0.1- to 1.6-l kg min
infusion
DA1 receptor agonist; lowers systemic blood pressure while increasing renal
blood ow, so it can be useful when there is evidence of acute renal failure
Phenylephrine 40- to 200-lg min
infusion
a-Receptor agonist. Causes peripheral vasoconstriction while maintaining
cerebral perfusion. Tachyphylaxis is common.
Norepinephrine 4- to 30-lg min
infusion
a- and b
1
-receptor agonist. Predominant effect is peripheral
vasoconstriction, but it also has inotropic and chronotropic effects.
Tachydysrhythmias may occur with higher doses.
Sodium
nitroprusside
Doesnt matter Sodium nitroprusside dilates both arterioles and veins, which increases
cerebral edema and intracranial pressure. It also worsens cerebral
autoregulation and has no place in neurocritical care
VOL. 13 NO. 3 MARCH 2011 THE JOURNAL OF CLINICAL HYPERTENSION 209
evidence that SNP may be deleterious in patients
with cerebrovascular emergencies and uncontrolled
hypertension. SNP is a potent dilator of both arteri-
oles and veins, which can lead to increased cerebral
edema and intracranial pressure.
40
In addition,
renal or hepatic dysfunction can lead to impaired
metabolism and accumulation of toxic levels of
cyanide and thiocyanate.
11,37
Given the ready avail-
ability of safer alternatives, sodium nitroprusside
should not be used in the treatment of hypertension
associated with cerebrovascular disease.
CONCLUSIONS
Acute cerebrovascular diseases are common events,
and physicians should be comfortable with managing
BP derangements in these patients. Above all, the
treating physician should ensure that hypoxemia and
cerebral hypoperfusion are avoided, as this can result
in signicant secondary brain injury. When uncon-
trolled hypertension is present, the physician must
decide two things: one, what is the optimal BP for this
patient; and two, what is the best pharmacologic
agent to reach this goal. Prompt treatment, while
avoiding exacerbating cerebral ischemia, is an inte-
gral part of the care of patients with acute cerebrovas-
cular disease.
Disclosures: The author reports no nancial or proprietary
interests in any of the subject matter discussed in this manu-
script. No nancial support for this paper has been obtained.
REFERENCES
1 Rosamond W. Heart disease and stroke statistics 2008
update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee.
Circulation. 2008;117(4):e25e146.
2 Lewington S. Age-specic relevance of usual blood pres-
sure to vascular mortality: a meta-analysis of individual
data for one million adults in 61 prospective studies. Lan-
cet. 2002;360(9349):19031913.
3 Powers WJ. Acute hypertension after stroke: the scientic
basis for treatment decisions. Neurology. 1993;43:461
467.
4 Ahmed N, Na sman P, Wahlgren NG. Effect of intrave-
nous nimodipine on blood pressure and outcome after
acute stroke. Stroke. 2000;31(6):12501255.
5 Lavin P. Management of patients with hypertension in
acute stroke. Arch Intern Med. 1986;146(1):6668.
6 Fisher M, Albers GW. Applications of diffusion-perfusion
magnetic resonance imaging in acute ischemic stroke.
Neurology. 1999;52:17501756.
7 Wallace JD, Levy LL. Blood pressure after stroke. JAMA.
1981;246:21772180.
8 Britton M, Carlsson A, de Faire U. Blood pressure course
in patients with acute stroke and matched controls.
Stroke. 1986;17:861864.
9 Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines
for the early management of adults with ischemic stroke:
a guideline from the American Heart Association Ameri-
can Stroke Association Stroke Council, Clinical Cardiol-
ogy Council, Cardiovascular Radiology and Intervention
Council, and the Atherosclerotic Peripheral Vascular
Disease and Quality of Care Outcomes in Research Inter-
disciplinary Working Groups. Stroke. 2007;38(5):1655
1711.
10 Furlan A, Higashida R, Wechsler L, et al. Intra-arterial
prourokinase for acute ischemic stroke: the PROACT II
study: a randomized controlled trial. JAMA. 1999;282:
20032011.
11 Rose JC, Mayer SA. Optimizing blood pressure in neuro-
logic emergencies. Neurocrit Care. 2004;1(3):287299.
12 Rordorf G, Cramer SC, Erd JT, et al. Pharmacological
elevation of blood pressure in acute stroke. Clinical effects
and safety. Stroke. 1997;28:21332138.
13 Rordorf G, Koroshetz WJ, Ezzeddine MA, et al. A pilot
study of drug-induced hypertension for treatment of acute
stroke. Neurology. 2001;56:12101213.
14 Hillis AE, Barker PB, Beauchamp NJ, et al. Restoring
blood pressure reperfused Wernickes area and improved
language. Neurology. 2001;56:670672.
15 Hillis AE, Ulatowski JA, Barker PB, et al. A pilot random-
ized trial of induced blood pressure elevation: effects on
function and focal perfusion in acute and subacute stroke.
Cerebrovasc Dis. 2003;16:236246.
16 Koenig MA, Romergryko GG, de Grouchey M, et al.
Safety of induced hypertension therapy in patients with
acute ischemic stroke. Neurocrit Care. 2006;4:37.
17 Marzan AS, Hungerbu hler HJ, Studer A, et al. Feasibility
and safety of norepinephrine-induced arterial hypertension
in acute ischemic stroke. Neurology. 2004;62:11931195.
18 Stead LG, Bellolio F, Gilmore RM, et al. Pharmacologic
elevation of blood pressure for acute brain ischemia.
Neurocrit Care. 2008;8:259261.
19 Qureshi AI, Tuhrim S, Broderick JP, et al. Spontaneous
intracerebral hemorrhage. N Engl J Med. 2001;344:1450
1460.
20 Brott T, Thalinger K, Hertzberg V. Hypertension as a risk
factor for spontaneous intracerebral hemorrhage. Stroke.
1986;17:10781083.
21 Brott T, Broderick J, Kothari R, et al. Early hemorrhage
growth in patients with intracerebral hemorrhage. Stroke.
1997;28:15.
22 Kazui S, Naritomi H, Yamamoto H, et al. Enlargement of
spontaneous intracerebral hemorrhage: incidence and time
course. Stroke. 1996;27:17831787.
23 Olson JD. Mechanisms of homeostasis: effect on intrace-
rebral hemorrhage. Stroke. 1993;24:I109I114.
24 Broderick JP, Brott TG, Duldner JE, et al. Volume of
intracerebral hemorrhage: a powerful and easy-to-use pre-
dictor of 30-day mortality. Stroke. 1993;24:987993.
25 Qureshi AI, Wilson DA, Hanley DF, et al. Pharmacologic
reduction of mean arterial pressure does not adversely
affect regional cerebral blood ow and intracranial pres-
sure in experimental intracerebral hemorrhage. Crit Care
Med. 1999;27:965971.
26 Anderson CS, Huang Y, Wang JG, et al. Intensive blood
pressure reduction in acute cerebral haemorrhage trial
(INTERACT): a randomised pilot trial. Lancet Neurol.
2008;7(5):391399.
27 ATACH Investigators. Antihypertensive Treatment of
Acute Cerebral Hemorrhage (ATACH). Crit Care Med.
2010;38:637648.
28 Powers WJ, Zazulia AR, Videen TO, et al. Autoregulation
of cerebral blood ow surrounding acute (6 to 22 hours)
intracerebral hemorrhage. Neurology. 2001;57:1824.
29 Kidwell CS, Saver JL, Mattiello J, et al. Diffusion perfu-
sion MR evaluation of perihematomal injury in hyper-
acute intracerebral hemorrhage. Neurology. 2001;57:
16111617.
30 Broderick J, Connolly S, Feldmann E, et al. Guidelines for
the management of spontaneous intracerebral hemorrhage
in adults: 2007 update: a guideline from the American
THE JOURNAL OF CLINICAL HYPERTENSION VOL. 13 NO. 3 MARCH 2011 210
Heart Association American Stroke Association Stroke
Council, High Blood Pressure Research Council, and the
Quality of Care and Outcomes in Research Interdisciplin-
ary Working Group. Stroke. 2007;38:20012023.
31 Teunissen LL, Rinkel GJE, Algra A, et al. Risk factors for
subarachnoid hemorrhage a systematic review. Stroke.
1996;27:544549.
32 Ingall TJ, Whisnant JP, Wiebers DO, et al. Has there been
a decline in subarachnoid hemorrhage mortality? Stroke.
1989;20:718724.
33 Manno EM. Subarachnoid Hemorrhage. Neurol Clin N
Am. 2004;22:347366.
34 Ohkuma H, Tsurutani H, Suzuki S. Incidence and signi-
cance of early aneurysmal rebleeding before neurosurgical
or neurological management. Stroke. 2001;32:11761180.
35 Kassell NF, Torner JC, Haley EC Jr, et al. The Interna-
tional Cooperative Study on the timing of aneurysm
surgery. Part 1: overall management results. J Neurosurg.
1990;73:1836.
36 Wallin JD, Fletcher E, Ram CV, et al. Intravenous nicar-
dipine for the treatment of severe hypertension. A double-
blind, placebo-controlled multicenter trial. Arch Intern
Med. 1989;149:26622669.
37 Varon J, Marik PE. The diagnosis and management of
hypertensive crises. Chest. 2000;118:214227.
38 Olsen KS, Svendsen LB, Larsen FS, et al. Effect of labetalol
on cerebral blood ow, oxygen metabolism and autoregu-
lation in healthy humans. Br J Anaesth. 1995;75:5154.
39 Gray RJ. Managing critically ill patients with esmolol. An
ultra short-acting beta-adrenergic blocke. Chest. 1988;93:
398403.
40 Weiss MH, Spence J, Apuzzo ML, et al. Inuence of
nitroprusside on cerebral pressure autoregulation. Neuro-
surgery. 1979;4:5659.
VOL. 13 NO. 3 MARCH 2011 THE JOURNAL OF CLINICAL HYPERTENSION 211