SYMPOSIUM ON CEREBROVASCULAR
INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENTDISEASES
Emerging Medical and Surgical Management Strategies
in the Evaluation and Treatment of Intracerebral Hemorrhage
EDWARD M. MANNO, MD; JOHN L. D. ATKINSON, MD; JIMMY R. FULGHAM, MD;
AND EELCO F. M. WIJDICKS, MD
Intracerebral hemorrhage (ICH) accounts for approximately 10%
of all strokes and causes high morbidity and mortality. Rupture of
the small perforating vessels of the cerebral arteries is caused by
chronic hypertension, which induces pathologic changes in the
small vessels and accounts for most cases of ICH; however,
amyloid angiopathy and other secondary causes are being seen
more frequently with the increasing age of the population. Recent
computed tomographic studies have revealed that ICH is a dy-
namic process with up to one third of initial hemorrhages expanding
within the first several hours of ictus. Secondary injury is believed to
result from the development of cerebral edema and the release of
specific neurotoxins associated with the breakdown products of
hemoglobin. Treatment is primarily supportive. Surgical evacuation
is the treatment of choice for patients with neurologic deterioration
from infratentorial hematomas. Randomized trials comparing surgi-
cal evacuation to medical management have shown no benefit of
surgical removal of supratentorial hemorrhages. New strategies
focusing on early hemostasis, improved critical care management,
and less invasive surgical techniques for clot evacuation are prom-
ising to decrease secondary neurologic injury. We review the patho-
physiology of ICH, its medical management, and new treatment
strategies for improving patient outcome.
Mayo Clin Proc. 2005;80(3):420-433
CBF = cerebral blood flow; CPP = cerebral perfusion pressure; CSF =
cerebrospinal fluid; CT = computed tomography; FFP = fresh frozen
plasma; GCS = Glasgow Coma Scale; ICH = intracerebral hemorrhage;
ICP = intracranial pressure; IV = intravenous; IVH = intraventricular
hemorrhage; MAP = mean arterial pressure; SAH = subarachnoid hemor-
rhage; STICH = Surgical Trial in Intracerebral Haemorrhage
I ntracerebral hemorrhage (ICH) is a common devastating
neurologic event that causes high morbidity and mortal-
ity with profound economic implications. Unlike the de-
clining mortality with subarachnoid hemorrhage (SAH)
due to improvements in surgical and critical care tech-
niques, the morbidity and mortality of ICH have remained
relatively unchanged throughout the past several decades.
Recent advances in our understanding of the pathophysiol-
ogy involved in the development and progression of ICH
have suggested a considerable amount of neurologic dam-
age after the initial ICH event. New medical strategies and
surgical techniques have been developed to prevent or treat
From the Department of Neurology (E.M.M., J.R.F., E.F.M.W.) and Department
of Neurologic Surgery (J.L.D.A.), Mayo Clinic College of Medicine, Rochester,
Minn.
Individual reprints of this article are not available. The entire Symposium on
Cerebrovascular Diseases will be available for purchase as a bound booklet
from the Proceedings Editorial Office at a later date.
2005 Mayo Foundation for Medical Education and Research
420 Mayo Clin Proc. March 2005;80(3):420-433
secondary complications. We review our current under-
standing of these mechanisms and treatment options.
DEFINITION AND EPIDEMIOLOGY
Intracerebral hemorrhage is bleeding that occurs directly
into the brain parenchyma. It is differentiated from intra-
ventricular hemorrhage (IVH) and SAH, which involve
bleeding into the brains ventricular system and subarach-
noid space, respectively. Often, ICH is classified as pri-
mary (unrelated to congential or acquired lesions), second-
ary (directly related to congenital or acquired conditions),
and/or spontaneous (not secondary to trauma or surgery).
Intracerebral hemorrhage is common, with an estimated
prevalence of 37,000 cases per year in the United States.1 It
is twice as prevalent as SAH2 and accounts for approxi-
mately 10% of all strokes. The prevalence of ICH is ex-
pected to increase as the population ages and the racial
demographics change in the United States.3
Incidence rates vary on the basis of age, race, and demo-
graphics. The most recent population-based studies using
computed tomographic (CT) verification estimate that the
overall incidence of ICH is between 12 and 15 cases per
100,000 population.4 There is a slight male predominance.1
The incidence of ICH increases exponentially with increas-
ing age, with rates doubling every 10 years after age 35
years.2 The overall mean age for patients with ICH is 61
years.5 Incidence rates are estimated to be twice as high in
African American, Hispanic, and Japanese populations.6-9
The reason for the large discrepancy among populations is
unclear but probably is accounted for by differences in
education, poor control of hypertension, and lack of health
care availability.6 Alcohol consumption and low serum
cholesterol levels have been theorized to account for some
differences in the Japanese population.7,8 Hispanics may
have an increased rate of cavernous angiomas.9
The economic burden of ICH is substantial. Estimated
lifetime costs, including patient care and lost productivity,
are $125,000 per person per year with an aggregate cost of
$6 billion per year in the United States. In comparison,
estimated lifetime costs are $5.6 billion per year for SAH
and $29.0 billion per year for ischemic stroke.10-12
Morbidity and mortality associated with ICH are dis-
mal, with 30-day mortality ranging between 30% and 40%
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 INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT

in hospital-based studies13,14 to as high as 52% in commu- TABLE 1. Causes of Spontaneous Intracerebral Hemorrhage*
nity-based studies.15,16 The annual mortality rate after 30- Primary Secondary
day survival was 8% per year for 5 years in 1 community- Hypertension Vascular malformations
based study with almost half of all later deaths attributed to Cerebral amyloid angiopathy Arteriovenous malformations
complications of the original hemorrhage (myocardial in- Anticoagulant/fibrinolytic use Dural arteriovenous fistulas
Antiplatelet use Cavernous malformations
farction, sudden death, extracranial hemorrhage, pneumo- Drug use Aneurysms
nia, etc).17 Only 21% to 38% of patients with ICH were Amphetamines Saccular
independent at 6 months.15 Cocaine Mycotic
Phenylpropanolamine Fusiform
Other illicit drugs Tumors
Other bleeding diathesis Primary brain tumors
CAUSES Secondary metastasis
Hemorrhagic transformation of a
Some of the many causes of ICH are listed in approximate cerebral infarction
descending order in Table 1. Intracerebral hemorrhage sec- Venous infarction with hemorrhage
ondary to pathologic changes initiated by chronic hyper- secondary to cerebral venous
thrombosis
tension is responsible for approximately 75% of all cases of Moyamoya disease
primary ICH.18 More recent clinical and pathologic series
*Primary hemorrhage unrelated to underlying congenital or acquired
have reported a lower percentage.19 Cerebral amyloid angi- brain lesions or abnormalities. See text for details.
opathy, the next most common cause of primary ICH, is
distinct from systemic amyloidosis and leads to the infiltra-
tion of amyloid protein into the media and adventitia of the Secondary hemorrhages into brain areas after ischemic
cortical arterioles of the brain. Its prevalence increases with stroke or due to cerebral venous thrombosis can occur and
age; more than 60% of autopsy samples from patients older reflect bleeding into compromised brain. Small areas of
than 90 years exhibit some degree of amyloid deposition. microhemorrhage can coalesce in a delayed fashion after
Cerebral amyloid angiopathy is estimated to account for severe head trauma. This occurs commonly at gray and
more than 20% of all ICH in patients older than 70 years.20 white matter interfaces and usually reflects substantial
Underlying vascular abnormalities such as arterio- pathologic damage.
venous malformations, cerebral aneurysms, or cavernous
angiomas are an important cause of secondary ICH. The
RISK FACTORS
exact frequency of their occurrence is difficult to establish
but may approximate 5% of all ICH. Vascular abnormali- The most notable and modifiable risk factor for ICH is the
ties occur primarily in younger populations, accounting for presence of hypertension.26 Hypertension, detected in most
approximately 38% of ICH in patients younger than 45 patients with ICH, is the basis for the term hypertensive
years.21 Bleeding directly into primary or metastatic brain hemorrhage. Risk of ICH appears to be related to the
tumors is another cause of secondary ICH but accounts for severity and the duration of hypertension. The exact quan-
less than 10% of all ICH.22 tification of risk is difficult to ascertain, but a response
A growing source of secondary ICH, anticoagulant or curve similar to the pack-year concept with smoking prob-
fibrinolytic use accounts for approximately 10% of all ably exists.4 Thus, short-term severe hypertension may
ICH. Long-term anticoagulant use increases the risk of have the same risk and effect as mild hypertension sus-
ICH 10-fold.22,23 The National Institute of Neurological tained for a longer period. Control of hypertension notably
Disorders and Stroke (NINDS) trial rated the overall risk of decreases the risk of ICH, although this effect appears to
ICH after tissue plasminogen activator use for ischemic have plateaued in the 1980s.19
stroke to be 6.4%.24 A recent reanalysis of these data cited Several case-control studies have implicated heavy al-
several risk factors for ICH: age older than 70 years, serum cohol intake as a risk factor for ICH.27-31 This effect may be
glucose level greater than 300 mg/dL, National Institutes of mediated partially by hypertension, although studies con-
Health stroke score higher than 20, and early ischemic trolling for hypertension have supported an independent
changes detected on CT.25 effect of alcohol.29,30 The reason for this may relate to
Sudden severe elevation in blood pressure is another impaired coagulation or platelet function or an increase in
source of ICH seen commonly in malignant hypertension but cardiac arrhythmias leading to increased cardioembolic
rarely after carotid endarterectomy. Intracranial hemorrhage hemorrhagic infarctions.31
due to cocaine, amphetamine, or phenylpropanolamine use The Multiple Risk Factor Intervention Trial32 and a re-
may be secondary to sudden elevation in blood pressure, mul- cent case-control study33 reported that cholesterol levels
tifocal cerebral vessel spasm, or drug-induced vasculitis.22 lower than 160 mg/dL imparted a 3-fold increased risk of

Mayo Clin Proc. March 2005;80(3):420-433 www.mayoclinicproceedings.com 421

INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT

FIGURE 1. Anatomical location and computed tomographic images of the common sites of
intracerebral hemorrhage attributed to chronic hypertension. Pathologic changes to the
perforating vessels of the cerebral arteries lead to rupture and hemorrhage into deep white
matter (A), basal ganglia (B), thalamus (C), pons (D), and cerebellum (E). See text for
details. Center image from N Engl J Med,3 with permission. Copyright 2001 Massachusetts
Medical Society. All rights reserved.

ICH in hypertensive middle-aged men. However, this find-
ing was not verified by other cohort studies.34,35 Similarly,
cardiac studies evaluating reductase inhibitors observed no
increase in ICH, although these studies were not designed
to study this effect.36,37 The effect of low cholesterol levels
on ICH requires further confirmation.38
A higher incidence of a point mutation in the gene
involved in the formation of factor XIII, responsible for
fibrin cross-linking, has been reported in patients with
ICH.39 Other reported risk factors include aspirin use,
epistaxis, and smoking.40,41 Also, there may be some sea-
sonal variation in the incidence of ICH, with a greater
occurrence of ICH reported in the colder months.42
PATHOPHYSIOLOGY
Intracranial hemorrhage secondary to hypertension occurs
in areas of the brain that are perfused by the perforating
arteries that arise directly from the large basal cerebral
arteries (Figure 1). These perforating arteries are directly
exposed to the effects of hypertension because they lack the
protection normally afforded by a preceding gradual de-
crease in vessel caliber.43 Chronic hypertension induces a
series of pathologic changes that lead to segmental con-
striction of these vessels. This process was labeled
lipohyalinosis by Fisher.44
Lipohyalinosis represents 2 pathologic processes that
include atherosclerosis of the larger (100-500 m) perfo-
rating arteries and arteriolosclerosis of the smaller (<100
m) perforating vessels. Atherosclerosis occurs most com-
monly at the branch points of vessels and is characterized
by subintimal fibroblast proliferation accompanied by
deposition of lipid-filled macrophages. Arteriolosclerosis
involves the replacement of smooth muscle cells in the
tunica media with collagen.43 These processes result in the
development of noncompliant, narrowed vessels that are
susceptible to both sudden closure (lacunar infarction) or
rupture (ICH). The mechanism of actual hemorrhage is
presumably due to rupture of these fragile vessels, but this
has been difficult to prove pathologically. Cerebral micro-
aneurysms, described by Charcot and Bouchard45 and fur-
ther delineated by Fisher,46 are described in only a small
number of patients. Hemorrhagic expansion of fibrin or
bleeding globules of tissue have been described but are
believed to be limited to ICH secondary to sudden eleva-
tions in blood pressure.43
A substantial amount of tissue damage occurs after an
initial hemorrhage. Traditionally, ICH was believed to
cause secondary damage by the local mass effect of an
expanding hematoma. However, animal models have failed
to reveal a local pressure effect of an introduced non-
hemorrhagic focal mass.47 It is now believed that the initial

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hemorrhage dissects along the white matter tissue planes of
the brain, encircling islands of intact neural tissue. Neuro-
logic deterioration after this point often is attributed to the
development of cerebral edema,48 which appears within
hours secondary to clot retraction with extrusion of plasma
proteins into the underlying white matter. Later, delayed
thrombin formation may contribute directly to neural toxic-
ity or indirectly through damage to the blood-brain barrier
with subsequent worsening of vasogenic edema. Peak
edema occurs 3 to 7 days after the hemorrhage and corre-
lates with lysis of red blood cells. Both hemoglobin and its
degradation products have been implicated in direct and
indirect neural toxicity.48,49 The importance of the develop-
ment of cerebral edema in ICH has been supported by
retrospective evidence suggesting that patients with a
larger amount of cerebral edema relative to the initial hem-
orrhage volume have worse clinical outcomes.50
The role of ischemia in the pathophysiology of ICH is
unclear. Numerous cerebral blood flow (CBF) studies have
described an area of decreased perfusion surrounding a
cerebral hemorrhage,51-53 suggesting that large areas of
brain surrounding ICH may be at risk of ischemia. Glu-
tamate and other excitotoxins have been reported in cases
of ICH.54,55 Similarly, DNA markers of cell damage and
apoptosis have been noted in perihematomal tissue.56,57
However, recent positron emission tomographic data have
caused researchers to question the role of ischemia in
ICH.58 Zazulia et al58 reported a normal oxygen extraction
ratio in the perihematomal region, suggesting that this re-
gion is not ischemic and that the decreased perfusion oc-
curs in response to decreased cerebral metabolism.
CLINICAL PRESENTATION
The clinical presentation of ICH depends on the size, loca-
tion, and presence of intraventricular extension of the hem-
orrhage. Headache of variable intensity always occurs and
may be accompanied by nausea and vomiting, focal signs,
and progressive neurologic deficits. The deficits may not
follow a typical infarction distribution pattern seen in pa-
tients with large artery strokes.4 Seizures occur in approxi-
mately 10% of all patients with ICH and in almost one half
of patients with lobar hemorrhage.20,59 Almost all seizures
occur at onset of bleeding or within the first 24 hours of
ictus and are not predictive of the development of delayed
epilepsy.60
Patients with large hemorrhages present in stupor or
coma. This may be secondary to elevated intracranial pres-
sure (ICP) leading to decreased cerebral perfusion or due to
direct infiltration or distortion of diencephalic or brainstem
structures.3 Patients with blood extending into the ventricu-
lar system often experience a reduced level of alertness
Mayo Clin Proc. March 2005;80(3):420-433
INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT
because of ventricular ependymal irritation or the develop-
ment of hydrocephalus.
Clinically, putaminal hemorrhages present with con-
tralateral motor deficits, gaze paresis, aphasia, or hemi-
neglect. Thalamic hemorrhages also present with contralat-
eral sensory loss. Pupillary and oculomotor abnormalities
may coexist if the thalamic hemorrhage extends into the
rostral brainstem. It is important to recognize cerebellar
hemorrhages, which present with nausea, vomiting, ataxia,
nystagmus, decreased level of consciousness, and ipsilat-
eral gaze palsies or facial paralysis. Pontine hemorrhages
are not subtle, presenting with coma, pinpoint pupils, dis-
turbed respiratory patterns, autonomic instability, quad-
riplegia, and gaze paralysis. Almost all pontine hemor-
rhages are fatal. Lobar hemorrhages present according to
the location of the hemorrhage.3,20,60,61
DIAGNOSIS
The diagnostic study of choice in ICH is noncontrasted
head CT. Clinical criteria alone are insufficient for diagno-
sis.1 Head CT provides a substantial amount of informa-
tion, including the size and location of the hemorrhage and
the presence of intraventricular, subarachnoid, or subdural
blood. It clearly differentiates ICH from nonhemorrhagic
cerebral infarctions and may reveal an underlying struc-
tural abnormality. Hemoglobin appears bright on noncon-
trasted head CT but in extremely rare instances such as se-
vere anemia may become isodense.1,60
Magnetic resonance imaging is sensitive for detecting
ICH; it is useful for dating hemorrhages and for identifying
small vascular lesions that may be missed with conven-
tional CT. Magnetic resonance imaging is limited in early
detection of ICH by the time required to obtain imaging
and by the limited ability to monitor a patient while in the
scanner.1,60,61
The location of a hemorrhage may provide information
about the underlying etiology. Hemorrhages that originate
in the deep subcortical structures (putamen, caudate, thala-
mus), pons, cerebellum, or periventricular deep white mat-
ter (Figure 1), particularly in patients with a history of
hypertension, result from rupture of the deep perforating
arteries. Single or multiple hemorrhages in elderly persons
that extend to the cortical surface are most likely attribut-
able to amyloid angiopathy. A system has been proposed
and supported by neuropathologic studies for the diagnosis
of ICH related to cerebral amyloid angiopathy.62,63
The role of cerebral angiography in ICH has been ad-
dressed by 2 studies. Zhu et al64 reported low yield from
cerebral angiography in identifying an underlying lesion in
patients older than 45 years who had a history of hyperten-
sion and had hemorrhages in deep subcortical structures.
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INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT
FIGURE 2. Expansion of an initial intracerebral hemorrhage. An 82-
year-old man with a history of hypertension and cigarette smoking
presented to the emergency department immediately after developing
a severe headache and right-sided hemiparesis. The initial computed
tomogram (left) revealed an intracerebral hemorrhage into the left
basal ganglia. Approximately 3 hours after ictus, the patient abruptly
deteriorated neurologically into a coma. Emergent computed tomo-
gram (right) revealed a large increase in size of the initial hemorrhage
with extension into the ventricular system.
However, Halpin et al65 reported finding an underlying
lesion in 84% of patients (32/38) that appeared to have
some structural abnormality detected on previous neuro-
imaging. Findings on CT that should prompt cerebral an-
giography include the presence of subarachnoid or intra-
ventricular blood, an abnormal calcification or prominent
draining vein, or blood that extends to the perisylvian or
interhemispheric fissure (Figure 2).65 Current recommen-
dations are to consider angiography for young patients
with no clear source of hemorrhage who may be surgical
candidates. Angiography is not required for older patients
with hemorrhages in locations typically associated with
hypertension.1
A complete laboratory evaluation, including a complete
blood cell count, serum electrolytes, and coagulation pro-
file, as well as chest radiography and electrocardiography,
is important to detect underlying infections, hemorrhages,
electrolyte disturbances, or myocardial ischemia that may
accompany ICH.
HEMATOMA EXPANSION
Traditionally, ICH was believed to be a monophasic event.
Subsequent neurologic deterioration was attributed to the
development of cerebral edema. It is now accepted that a
large percentage of patients will develop hemorrhagic ex-
pansion of their initial bleeding. Brott et al,66 in a prospec-
tive observational study of patients evaluated within the
first 3 hours after ictus, described ICH expansion in 26% of
patients within the first hour after hospital admission (Fig-
424 Mayo Clin Proc. March 2005;80(3):420-433
ure 2). Another 12% of patients experienced ICH volume
expansion within 20 hours after admission. Hematoma ex-
pansion after the first 24 hours is rare.67 The ICH volume
can increase by as much as 40% and is associated with
neurologic deterioration.67 Attempts to identify predictive
factors for hematoma expansion have been limited; how-
ever, 1 study suggested that poorly controlled diabetes
mellitus and systolic blood pressure greater than 200 mm
Hg on hospital admission were associated with hematoma
volume expansion.68
INITIAL EVALUATION AND TREATMENT
Initial evaluation begins with obtaining a thorough patient
history of proceeding or initiating events and a thorough
general physical and neurologic examination. Previous or
current drug use, hemorrhages, or known structural lesions
can provide important information about a potential source
of hemorrhage. Left ventricular hypertrophy on electrocar-
diography or an enlarged heart on chest radiography or
physical examination is helpful for identifying a patient
with chronic hypertension. The presence of amyloid angi-
opathy is suggested by a history of cortical hemorrhages.
The patients level of consciousness must be monitored
closely because neurologic deterioration can occur quickly
with hematoma expansion or with rupture into the ventricu-
lar system. Poor airway control or a Glasgow Coma Scale
(GCS) score of 8 or less should prompt consideration of
elective endotracheal intubation. A GCS score of 8 or less
is used to select patients for intubation on the basis of
retrospective analysis from the traumatic coma data bank
that discovered an increased rate of aspiration pneumonia
in comatose patients.69 More recent evidence suggests that
an adequate cough and clearance of secretions may be all
that is necessary to maintain airway patency.70 However,
episodic oxygen desaturation or other evidence of pre-
sumptive respiratory insufficiency should prompt immedi-
ate intubation.
Endotracheal intubation must be performed in a con-
trolled setting by an experienced physician. Patients with
large cerebral hemorrhages or obstructive hydrocephalus
are at increased risk of elevated ICP. Pharmacological
agents and intubation techniques should be used to ensure
rapid and smooth airway control along with medications
designed to block increases in ICP. Lidocaine (1.0-2.0 mg/
kg of body weight intravenously [IV]) is administered to
blunt a cough reflex that can increase ICP during intuba-
tion. Short-acting barbiturates (thiopental, 1.0-1.5 mg/kg of
body weight, or propofol, 10-20 mg in incremental doses)
can be used for induction.60 Etomidate (0.1-0.2 mg/kg of
body weight IV) minimally affects ICP and can be used for
intubation. Fasciculations can occur with use of etomidate
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and often are misinterpreted as seizures. Midazolam gener-
ally is avoided because of unfavorable effects on ICP60
during induction, although the clinical importance of this is
uncertain. Neuromuscular paralysis ideally should be
avoided and may be unnecessary in many instances. When
required for airway control, a short-acting nondepolarizing
agent such as atracurium besylate (0.3-0.4 mg/kg of body
weight IV) or vecuronium bromide (0.2-0.3 mg/kg of body
weight IV) is preferred. Paralysis should be discontinued as
quickly as possible to allow for monitoring of the neuro-
logic examination.60
Once the airway is secure, mechanical ventilation
should be set to ensure adequate oxygenation and ventila-
tion. If elevated ICP is suspected, an intermittent manda-
tory ventilation volume and rate should be set to attain a
PCO2 of 30 to 35 mm Hg.
Isotonic IV fluids should be initiated and adjusted to
correct for any electrolyte abnormalities. The goal is to
achieve euvolemia and to maintain adequate intravascular
volume to optimize cerebral perfusion.71 Hypervolemia
worsens cerebral edema and should be avoided.
Glucose-containing solutions also should be avoided
except in patients with symptomatic hypoglycemia. Hyper-
glycemia is detrimental to damaged brain and should be
corrected. However, this correction should occur slowly
because a rapid decrease in the serum glucose level de-
creases serum osmolality and may worsen cerebral
edema.72
Patients receiving anticoagulant medications have larger
hematomas and worse outcomes.73 Bleeding progresses
slowly over several hours in most of these patients, necessi-
tating immediate discontinuation and reversal of anticoagu-
lation.71,73 The effects of warfarin can be reversed with fresh
frozen plasma (FFP) and vitamin K, although the optimal
dose for reversing anticoagulation is unclear. Vitamin K
administered parenterally is the most rapid way to provide
long-term reversal of warfarin-induced anticoagulation.
Substantial improvement in anticoagulation reversal has
been shown within 4 hours with use of 2 mg of IV vita-
min K.74 Infusion of IV vitamin K imparts a small risk
of anaphylaxis and should be given slowly. Immediate
changes in coagulation require procoagulant factors usu-
ally administered as units of FFP. Full replacement of all
coagulant factors can be estimated by giving FFP at 15 mL/
kg of body weight. A 70-kg man requires approximately
8 U of FFP to reverse anticoagulation.75 However, rapid
administration of this volume can be problematic for pa-
tients with limited cardiac reserve or intracranial com-
pliance. Preliminary studies suggest that a prothrombin
complex or factor VII concentrate may be faster and more
effective in reversing anticoagulation while avoiding the
difficulties of volume overload.76-78 However, use is re-
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INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT
stricted by limited availability. Anticoagulation in pa-
tients receiving heparin should be reversed with protamine
sulfate.
Experience is limited in the treatment of ICH caused by
thrombolytic therapy. Red blood cells, fibrinogen, cryopre-
cipitate, FFP, and platelets have all been recommended.
The efficacy of aminocaproic acid taken as a 5-g loading
dose followed by a dosage of 1 g/h is unknown.71
Seizure activity increases CBF and ICP that can result in
neuronal injury and destabilization of a critically ill pa-
tient.1 Seizures should be treated immediately with IV
lorazepam followed by a loading dose of phenytoin or
fosphenytoin.
The role of prophylactic anticonvulsant use in ICH is
controversial. American Heart Association guidelines for
the management of ICH recommend prophylactic anticon-
vulsant therapy for 1 month, after which time therapy
should be discontinued in the absence of seizures.1 Because
most seizures occur at the time of ICH or shortly thereafter,
our practice has been to avoid routine anticonvulsant use in
ICH. Anticonvulsants are considered for patients with lo-
bar hemorrhages, known or suspected structural lesions, or
a history of seizures.
Short-term management of hypertension after ICH has
been an issue of considerable debate. Hypertension after
ICH is common and may persist for a few days before
returning to baseline. This may be attributed to headache,
high circulating levels of catecholamine, or withdrawal of
antihypertensive medications. Hypertension after ICH also
may be initiated by brainstem-mediated release of cat-
echolamines in response to increased ICP. Sympathetic
outflow can be substantial and has important management
implications.
Advocates of aggressive blood pressure control express
concerns of hematoma expansion and worsening cerebral
edema after ICH.78 Hypertension after ICH has been re-
ported as a poor prognostic indicator in some outcome
studies,79,80 and 1 observational study reported better out-
comes in patients with ICH whose blood pressure was
maintained below a mean arterial pressure (MAP) of 125
mm Hg.81 The only randomized trial comparing antihyper-
tensive treatment after ICH to placebo was performed in
the era before CT and has been criticized for significant
differences between treatment groups.82
Cerebral blood flow studies consistently have described
an area of decreased blood flow surrounding an intracere-
bral hematoma that is close to ischemic levels.51,83,84 Sudden
decreases in blood pressure can lead to extension of this
area with subsequent hematoma expansion or worsening
ischemia. Support for these concerns was provided by an
elevated lower limit of cerebral autoregulation shown in
patients with ICH.85 Similarly, increased cerebral oxygen
www.mayoclinicproceedings.com 425
INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT
extraction, suggestive of early ischemia, was shown by
jugular venous oxygen monitoring in patients with large
hematomas who had received aggressive blood pressure
treatment.86
Recent evidence suggests that modest control of blood
pressure after ICH is probably safe. Qureshi et al,87 using an
ICH dog model, found no difference in perihematomal
blood flow between the controls and animals treated with
labetalol. Powers et al88 randomized 14 patients with ICH
and MAP greater than 120 mm Hg to a control group or to a
15% reduction in blood pressure with use of labetalol or
nicardipine. Regional CBF measured at baseline and after
treatment using positron emission tomography revealed no
difference between groups. Larger decreases in blood pres-
sure have not been studied.
Several agents are effective for lowering blood pressure
in ICH. There are theoretical advantages to using -
blockers, nicardipine, labetalol, and angiotensin-convert-
ing enzyme inhibitors because they have little effect on ICP
and do not compromise CBF. Sodium nitroprusside and
nitrates are readily accessible and easily titratable but cause
cerebral venodilation, which can suddenly increase ICP;
although never proved detrimental in neurologic patients,
these agents generally are avoided in patients with elevated
ICP. Hydralazine can decrease CBF, but its effects are
negligible. Sublingual nifedipine may decrease blood pres-
sure precipitously and is usually not used for patients with
brain injuries. Hypertension after ICH may be self-limit-
ing; therefore, use of short-acting parenteral medications
for blood pressure control may be prudent. Delayed hy-
potension can occur with enteral use of antihypertensive
medications because enteral medications become effective
as ICH-induced hypertension begins to resolve.
MEDICAL MANAGEMENT OF ICH
Once the patient is stabilized initially, medical therapy
for ICH becomes supportive. Care is focused on neuro-
logic monitoring, treatment of elevated ICP or cerebral
ischemia, and prevention and treatment of secondary
medical complications.
Monitoring is accomplished through a series of neuro-
logic examinations, preferably performed in a neurologic
intensive care unit by experienced nurses, physicians, and
other medical personnel. When this level of specialization
is unavailable, standardized neurologic examinations in-
cluding the GCS should be used. Intracranial pressure
monitoring, which may be useful in selected patients,60 is
reserved generally for patients with large hemorrhages,
those with intraventricular extension of the original hemor-
rhage, and patients with a GCS score of 8 or less. Patients
who need to be sedated or pharmacologically restrained
compromise monitoring of the neurologic examination and
426 Mayo Clin Proc. March 2005;80(3):420-433
are candidates for ICP monitoring. Although not proved to
improve outcome in ICH,89,90 ICP monitoring may be use-
ful to measure the response to various stimuli and maneu-
vers commonly used in the intensive care unit (eg, changes
in head elevation, responses to fluid administration, and
ventilator settings).60
Monitoring of ICP is accomplished by use of ICP bolts
or ventriculostomies. The ICP bolt system uses a fiberoptic
wire placed directly on the surface of the brain to measure
changes in brain tension. The ICP bolts are less invasive
and pose less risk of infection compared with ventriculos-
tomies but are prone to drift and cannot be recalibrated
once placed.91 Ventriculostomies or external ventricular
drains are catheters placed through the brain into the ven-
tricles that allow direct measurement of cerebrospinal fluid
(CSF) pressure in the ventricular system. Cerebrospinal
fluid can be withdrawn from ventriculostomies, which can
help in the management of elevated ICP. Insertion presents
a small risk of hemorrhage, and infection rates increase
with prolonged use. Traditionally, ventriculostomies were
changed every 7 days92; however, more recent evidence
suggests that, with close monitoring for infection, they can
be used for longer periods.93 Common practice is to use
prophylactic antibiotics and to obtain routine scheduled
CSF Gram stains, white blood cell counts, and cultures for
evidence of infection.
The role of ventricular drainage of CSF to treat hydro-
cephalus in ICH is unclear. In acute hydrocephalus, early
placement of an external ventricular drain may be lifesav-
ing.94 However, once hydrocephalus is established, use of
external CSF drainage may be limited. One retrospective
series showed no benefit with CSF drainage; the authors
hypothesized that irreversible damage had occurred by the
time of external ventricular placement.95
Ventricular drains may be useful for the application of
thrombolytic agents to decrease the size of IVH. The vol-
ume of IVH proportionately affects mortality in ICH.96,97 A
preliminary study has suggested that use of intraventricular
thrombolysis within 72 hours of IVH can decrease intra-
ventricular hematoma size and improve 30-day mortality.98
Further work in this area is pending.
Patients with IVH or large amounts of intracerebral
blood are at high risk of developing elevated ICP and/or
cerebral edema with subsequent neurologic injury and
deterioration. Treatment is focused on controlling ICP
while maintaining adequate cerebral perfusion to avoid
secondary ischemic complications. Although the absolute
values necessary to ensure adequate cerebral perfusion
cannot be given, in general, attempts are made to maintain
ICP at 20 mm Hg or less and cerebral perfusion pressure
(CPP) at 70 mm Hg or greater (CPP is equal to MAP
minus ICP).
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Numerous methods are used to lower elevated ICP.
Hyperventilation is highly effective and can be used to
rapidly lower ICP. Hyperventilation induces cerebral vaso-
constriction with subsequent decreases in cerebral blood
volume and pressure. It is believed to be mediated by
changes in CSF hydrogen ion concentrations.99 However,
its effects are short-lived because the choroid plexus be-
gins to equilibrate hydrogen ion concentrations within a
few hours.100 Sustained hyperventilation may be deleteri-
ous to ischemic brain, although this has not been directly
tested in ICH.101 Traditionally, PCO2 is lowered incremen-
tally to approximately 25 to 30 mm Hg. Practically, hyper-
ventilation is used to gain immediate control of elevated
ICP, whereas other methods are initiated to improve ICP
control.
Mannitol is used commonly to treat elevated ICP. Man-
nitol is a metabolically inert and poorly permeant hexose
sugar used as an osmotic diuretic.102 It has several putative
mechanisms of action. Osmotic agents are widely believed
to exert their effect by inducing an osmotic gradient be-
tween brain and blood that leads to the extraction of water
from the cerebral extracellular space into the intravascular
compartment.103 Animal models of middle cerebral artery
strokes have shown reduced water content of both edema-
tous and normal brain with repeated use of mannitol.104
Despite these findings, the effects on cerebral water con-
tent with use of mannitol may be limited clinically. The
immediate effect of mannitol is mediated probably through
the hemodynamic and rheologic effects of a rapid infusion
of an osmotic agent. The increase in intravascular blood
volume initiated with a dose of mannitol is believed to
increase cardiac output and decrease serum viscosity,
which leads to a compensatory decrease in cerebral blood
volume and ICP.105
Mannitol is administered parenterally in doses of 0.25 to
1.0 g/kg of body weight. Peak effect is in approximately 20
to 30 minutes and may have duration of action for several
hours.106 The preferred treatment of sudden elevation in
ICP is administration of IV boluses of mannitol as needed.
Scheduled or repetitive doses of mannitol are avoided be-
cause of concerns that mannitol may leak into damaged
brain tissue and worsen cerebral edema and/or cerebral
tissue shifts.107 However, these concerns may be overstated
because multiple doses of mannitol infusions induced no
significant changes in horizontal or vertical displacement
of brain tissue in large middle cerebral artery strokes.108
Careful attention must be paid to replace fluid and electro-
lyte losses with mannitol use.
Other methods to help control ICP elevation include
mild sedation, aggressive treatment of fever, and changes
in head position to lower ICP and optimize CPP. Barbitu-
rates and induced hypothermia are reserved for ICP eleva-
Mayo Clin Proc. March 2005;80(3):420-433
INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT
tion recalcitrant to other treatment methods. Corticoste-
roids generally are not recommended for ICH on the basis
of a randomized study of patients given dexamethasone at
20 mg/d vs placebo. The study was terminated prematurely
because of findings of similar 21-day mortalities between
the groups and an increased rate of medical complications
in the treatment group.109 However, a subset of patients
could potentially benefit from use of corticosteroids. In this
study, a subset of patients with midsized hematomas
showed a trend for improvement during the first week of
treatment and deteriorated only after discontinuation of
corticosteroids.110
Prevention and treatment of medical complications are
crucial to the management of ICH. Patients with ICH are at
risk of stress-induced gastric ulcers and should be treated
with prophylactic H2 receptor antagonist or proton pump
inhibitors. Immobilized and critically ill patients are at risk
of deep venous thrombosis. Sequential compression de-
vices may be used in place of subcutaneous heparin if
continued bleeding is a consideration. Hyperthermia is del-
eterious to ischemic neurons. Therefore, all fevers should
be aggressively evaluated and treated. Pharmacological
and external methods to control fever have had limited
success.111 Intravascular cooling devices are being evalu-
ated currently to control fever in both hemorrhagic and
ischemic stroke.
Information is limited about how long anticoagulants
can be discontinued safely in patients at high risk of cere-
bral embolism after ICH.109,112 A Mayo retrospective study
found that the 30-day probability of ischemic stroke after
warfarin cessation was 2.9% and concluded that temporary
discontinuation of warfarin therapy for 7 to 14 days after
ICH is probably safe.112 Similarly, the exact time at which
anticoagulants can be restarted safely is unknown. One
study using a statistically based decision model suggested
that anticoagulants should not be restarted only in patients
with atrial fibrillation.109 However, most authors believe
that anticoagulants can be restarted safely 10 to 14 days
after ICH.113
SURGICAL TREATMENT OF ICH
The role for surgical evacuation of ICH is uncertain. De-
spite several controlled studies that have shown no benefit
with surgery,114-116 surgical removal of ICH is common.
The reasons for the use of surgery are that proper random-
ized trials with adequate size and power have not been
performed, and observational studies and anecdotal ex-
perience have suggested that surgery may benefit selected
patients.
In practice, surgery may be performed as a lifesaving
measure in patients with large hematomas or in young
patients with cortical hemorrhages and secondary neuro-
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INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT
logic deterioration. Patients with profound and prolonged
neurologic deficits (GCS score 4) are believed to have
little chance for functional recovery and are considered
poor surgical candidates.1 Deep hemorrhages rarely are
evacuated. Patients with small hemorrhages (10 cm3) or
minimal neurologic deficits are treated medically.
There is general consensus that urgent surgical removal
is necessary for infratentorial hematomas 3 cm or larger in
diameter or for smaller hematomas that are neurologically
deteriorating from brainstem compression. Remarkable re-
coveries from cerebellar hematomas are possible, but early
intervention is critical. Rabinstein et al117 reported that all
patients who had lost upper brainstem reflexes or had
shown extensor posturing died despite surgical interven-
tion. External ventricular drainage of CSF in cerebellar
hematomas must be performed judiciously to avoid the
potential complication of upward herniation.
The proper management of medium-sized hematomas is
debatable. In most cases, no benefit with surgery has been
reported for spontaneous supratentorial ICH.114-116 All these
studies114-117 have been criticized for inadequate sample
size, lack of adequate controls, and variable implementa-
tions and timing of intervention and surgical techniques.118
A meta-analysis of these trials reported an increased trend
toward death and dependency after surgery; however,
when studies were included only from the more modern
post-CT era, a trend for improvement with surgery was
found.119
The role of surgery in ICH is being reevaluated in light
of recent technological advances.118 The goal of surgery is
to decrease the size of the hematoma and subsequently
limit local increases in ICP and neurotoxic edema second-
ary to blood-degradation products. To that purpose, mini-
mally invasive techniques designed to decrease hematoma
size while limiting surgical trauma have been developed. In
1985, Niizuma et al120 reported a CT-guided technique of
hematoma aspiration and lysis using urokinase. In 1989, a
series of randomized patients reported by Auer et al121
showed a decrease in 6-month mortality in the surgical
group (42% vs 70%; P<.01) and an improved quality of life
in patients with small ICH. The benefit in this series was
suggested to be due to the minimally invasive approach,
although benefit appeared to be limited to lobar hemor-
rhages with larger intracranial hematoma volumes. Recent
studies have shown the safety and feasibility of CT-guided
thrombolysis and aspiration of intracranial hematomas.122-125
This led to a multicenter randomized controlled trial of
stereotactic treatment of ICH with plasminogen activator.
In this study, 71 patients were randomized to either medical
therapy or stereotactic placement of a catheter into the
hematoma with scheduled periodic instillation of uroki-
nase and clot aspiration. Hematoma volume was followed
428 Mayo Clin Proc. March 2005;80(3):420-433
by serial CT imaging. In this study, there was a modest
reduction in hematoma volume with instillation of uroki-
nase and aspiration of clot; however, there was no differ-
ence in mortality. The authors speculated that a larger
reduction in hematoma volume may be required to im-
prove mortality.125
It is unknown whether emergent early open surgery
provides any benefit over a more delayed approach of
stereotactic catheter placement and instillation of uroki-
nase for hematoma evacuation. Two pilot studies that
successfully randomized patients to surgical or medical
treatments within 12 hours of hemorrhage showed the
feasibility of early surgical evacuation.126,127 Both studies
suggested a benefit with early surgery (<12 hours) but
were limited by small numbers. A recent surgical evalua-
tion of ultra-early evacuation of ICH (<3 hours) was
stopped after interim analysis because of an increased rate
of rebleeding.128
Because of the continued uncertainty and variation in
clinical practice, a new prospective randomized controlled
trial is under way and near completion. The international
Surgical Trial in Intracerebral Haemorrhage (STICH) com-
pares early surgical evacuation to conservative treatment.
Patients are randomized to an uncertainty principle based
on whether the surgeon is uncertain about the best possible
treatment. Patients who are included have hemorrhage vol-
umes between 20 and 80 mL and present with a GCS score
of 5 to 15.129 The trial was completed recently and showed
no benefit with surgical intervention.130
PREDICTORS OF OUTCOME
Numerous clinical series using logistic regression models
to define predictors of outcome in ICH have been under-
taken.79,80,96,131-136 The most consistent predictors across
studies are the size of the hemorrhage, GCS score at pre-
sentation, and the presence and volume of IVH. The most
powerful individual predictor appears to be the volume of
ICH measured on initial CT.133 This is estimated by using
the equation for calculating the volume of an ellipsoid
obtained by measuring the length, width, and depth of the
hematoma and then dividing by 2. A comatose patient with
an ICH volume greater than 60 cm3 has a 30-day mortality
of 91%.133
Other inconsistent predictors of poor outcome have in-
cluded advanced age, hydrocephalus, deep location of ICH,
and elevated blood pressure on hospital admission. In-
creased cerebral edema relative to the initial hemorrhage
size may be a marker for increased secondary neurologic
injury and has been reported as an adverse prognostic
sign.49 Not surprisingly, patients who require mechanical
ventilation have worse clinical outcomes.137
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Finally, Becker et al138 have found that withdrawal of
care orders initiated by physicians may introduce bias
regarding which prognostic factors are identified.
FUTURE DIRECTIONS
It is hoped that an improved understanding of the patho-
physiological changes that result in hematoma expan-
sion, the development of cerebral edema, and the identity
of hemoglobin degradation neurotoxins will lead to more
focused pharmacological treatments. A preliminary trial
of aminocaproic acid was unsuccessful for preventing
rebleeding in ICH139; however, Mayer140 has suggested
there may be a role for ultra-early hemostatic therapy
with recombinant factor VIIa to prevent further hematoma
expansion.
Further distillation of prognostic factors in ICH will
help identify subgroups of patients who may be enrolled in
future clinical trials. Best medical management has yet to
be defined and may include future treatments of blood
pressure and hypothermia, tight glucose control, and se-
lected use of glucocorticoids. Results from the STICH have
provided important information about the utility of surgical
evacuation of ICH but do not address questions about the
timing, approach, and technique of other procedures. Lysis
and removal of IVH associated with ICH needs to be
addressed in controlled randomized studies.
Progress in the field of neurorehabilitation may promote
recovery after ICH. Transplanted neural human stem cells
have been shown to improve functional recovery in an
animal model of ICH.141
CONCLUSIONS
Intracerebral hemorrhage will continue to be an important
problem as the population ages in the United States. Treat-
ment is limited currently and is primarily supportive. De-
spite historically poor outcomes in ICH, there is consider-
able hope that the identification of factors involved in
neurologic morbidity, early hemostasis, and removal of
intracerebral hematomas will improve the short-term treat-
ment of ICH. Algorithms for treatment and therapeutic
options are provided in Figures 3 and 4.
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INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT

Medical management

Obtain patient history; perform baseline laboratory

evaluation, emergent head CT, neurologic assessment

GCS score 8, or progressive Coagulopathy is present Seizures occur or MAP >130 mm Hg

neurologic deterioration, cortical hemorrhage
or respiratory insufficiency

Intubate patient; set ventilator
to initially maintain Pco2 at
30-35 mm Hg
Correct with fresh frozen
plasma, 15 mL/kg of body
weight, and vitamin K, 2 mg IV
Consider phenytoin load of
10-15 mg/kg of body weight
Consider treatment to decrease
by 15% with use of labetalol,
10-20 mg IV daily over 15 min,*
or hydralazine, 10-20 mg IV
every 15 min as needed,* or
nicardipine infusion, 5-15 mg/h*

Supportive care for stabilized patient

Neurologic assessments every 1-2 hours
IV fluids-normal saline with electrolyte replacement
at maintenance rates
Acetaminophen, cooling blankets to maintain
temperature below 37.5C
Sequential compression devices
Prophylaxis for gastric ulcers

Patient has GCS score 8 or neurologic deterioration

Place ICP monitor

Treat ICP >20 mm Hg
Hyperventilation
Mannitol, 0.25-1.0 g/kg of body weight as needed

FIGURE 3. Algorithm for the initial medical evaluation and treatment of intracerebral hemorrhage. Specific management decisions are based on
the presence of particular findings on computed tomography (CT) or the neurologic assessment of the patient. The best treatment (surgical vs
medical) for supratentorial hematoma volumes of 20 to 80 mL is unknown. See text for details. GCS = Glasgow Coma Scale; ICP = intracranial
pressure; IV = intravenous; MAP = mean arterial pressure.
*Doses per Mayo Clinic protocol. See reference 1 for guidelines.
See text for details.

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 INTRACEREBRAL HEMORRHAGE EVALUATION AND TREATMENT

Surgical management

Obtain patient history; perform baseline laboratory

evaluation, emergent head CT, neurologic assessment

Hydrocephalus is present on CT or Cerebellar hemorrhage >3 cm in Large accessible cortical hematoma

secondary neurologic deterioration diameter or hemorrhage of any size or secondary neurologic deterioration
due to intraventricular blood with neurologic deterioration in young patient

Place external ventricular drain Surgical evacuation Consider surgical evacuation

Supportive care for stabilized patient

Neurologic assessments every 1-2 hours
IV fluids-normal saline with electrolyte replacement
at maintenance rates
Acetaminophen, cooling blankets to maintain
temperature below 37.5C
Sequential compression devices
Prophylaxis for gastric ulcers

Patient has GCS score 8 or neurologic deterioration

Place ICP monitor

Treat ICP >20 mm Hg*
Hyperventilation
Mannitol, 0.25-1.0 g/kg of body weight as needed

FIGURE 4. Algorithm for the initial surgical evaluation and treatment of intracerebral hemorrhage. Specific management decisions are based on
the presence of particular findings on computed tomography (CT) or the neurologic assessment of the patient. Options are given for possible
surgical evacuation of hemorrhage. The best treatment (surgical vs medical) for supratentorial hematoma volumes of 20 to 80 mL is unknown.
See text for details. GCS = Glasgow Coma Scale; ICP = intracranial pressure; IV = intravenous.
*See text for details.

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