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Hemorrhagic Stroke

 Author: David S Liebeskind, MD; Chief Editor: Rick Kulkarni, MD
http://emedicine.medscape.com/article/1916662-overview#showall
Practice Essentials
In hemorrhagic stroke, bleeding occurs directly into the brain parenchyma. The usual mechanism
is thought to be leakage from small intracerebral arteries damaged by chronic hypertension. The
terms intracerebral hemorrhage and hemorrhagic stroke are used interchangeably in this article
and are regarded as separate entities from hemorrhagic transformation of ischemic stroke.
Essential update: Intensive BP reduction may greatly suppress hematoma growth in
intracerebral hemorrhage even after antithrombotic therapy
A new study suggests that in patients with intracerebral hemorrhage, intensive blood pressure
(BP) reduction early in their treatment lessens the absolute growth of hematomas, with the effect
being especially pronounced in patients who have undergone prior antithrombotic therapy. These
results were drawn from a combined analysis of INTERACT (Intensive Blood Pressure
Reduction in Acute Cerebral Hemorrhage Trial) 1 and 2.
[1]

The study involved 1310 patients who had undergone repeat 24-hour computed tomography
(CT) scans, including 665 who received intensive BP reduction therapy (target BP < 140 mm Hg
systolic) and 645 controls (target BP < 180 mm Hg systolic). A total of 235 patients in the
intensive reduction and control groups had received antithrombotic medication prior to
intracerebral hemorrhage.
[1]

The investigators found that, in patients who had not had prior antithrombotic therapy,
hematoma volume increased 1.1 mL on repeat CT scan in those who underwent intensive BP
reduction, compared with 2.4 mL in controls. In patients who had previously taken
antithrombotics, however, the difference between the intensive-reduction and control groups was
much greater, with the increase in hematoma volume being 3.4 mL in the intensive-reduction
patients and 8.1 mL in the controls.
[1]

Signs and symptoms
Patients with intracerebral bleeds are more likely than those with ischemic stroke to have
headache, altered mental status, seizures, nausea and vomiting, and/or marked hypertension.
Even so, none of these findings reliably distinguishes between hemorrhagic and ischemic stroke.
Focal neurologic deficits
The type of deficit depends on the area of brain involved. If the dominant (usually the left)
hemisphere is involved, a syndrome consisting of the following may result:
 Right hemiparesis
 Right hemisensory loss
 Left gaze preference
 Right visual field cut
 Aphasia
 Neglect (atypical)
If the nondominant (usually the right) hemisphere is involved, a syndrome consisting of the
following may result:
 Left hemiparesis
 Left hemisensory loss
 Right gaze preference
 Left visual field cut
See Clinical Presentation for more detail.
Diagnosis
Laboratory tests should include a complete blood count (CBC), a metabolic panel, and—
particularly in patients taking anticoagulants—coagulation studies (ie, prothrombin time or
international normalized ratio [INR] and an activated partial thromboplastin time).
[2]

Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be
obtained on an emergent basis. Brain imaging aids diagnosing hemorrhage, and it may identify
complications such as intraventricular hemorrhage, brain edema, or hydrocephalus. Either
noncontrast computed tomography (NCCT) scanning or magnetic resonance imaging (MRI) is
the modality of choice.
See Workup for more detail.
Management
The treatment and management of patients with acute intracerebral hemorrhage depends on the
cause and severity of the bleeding. Basic life support, as well as control of bleeding, seizures,
blood pressure (BP), and intracranial pressure, are critical. Medications used in the treatment of
acute stroke include the following:
 Anticonvulsants - To prevent seizure recurrence
 Antihypertensive agents - To reduce BP and other risk factors of heart disease
 Osmotic diuretics - To decrease intracranial pressure in the subarachnoid space
A potential treatment for hemorrhagic stroke is surgical evacuation of the hematoma. However,
the role of surgical treatment for supratentorial intracranial hemorrhage remains controversial.
Outcomes in published studies are conflicting.
Endovascular therapy using coil embolization, as an alternative to surgical clipping, has been
increasingly employed with great success, although controversy still exists over which treatment
is ultimately superior.
See Treatment and Medication for more detail.
Image library
Axial noncontrast computed tomography scan of the brain of a 60-year-old
man with a history of acute onset of left-sided weakness. Two areas of intracerebral hemorrhage are
seen in the right lentiform nucleus, with surrounding edema and effacement of the adjacent cortical
sulci and right sylvian fissure. Mass effect is present upon the frontal horn of the right lateral ventricle,
with intraventricular extension of the hemorrhage.
Background
The terms intracerebral hemorrhage and hemorrhagic stroke are used interchangeably in this
article and are regarded as separate entities from hemorrhagic transformation of ischemic stroke.
Hemorrhagic stroke is less common than ischemic stroke (ie, stroke caused by thrombosis or
embolism); epidemiologic studies indicate that only 8-18% of strokes are hemorrhagic.
[3]
However, hemorrhagic stroke is associated with higher mortality rates than is ischemic stroke.
(See Epidemiology.)
[4]

Patients with hemorrhagic stroke present with focal neurologic deficits similar to those of
ischemic stroke but tend to be more ill than are patients with ischemic stroke. However, though
patients with intracerebral bleeds are more likely to have headache, altered mental status,
seizures, nausea and vomiting, and/or marked hypertension, none of these findings reliably
distinguishes between hemorrhagic and ischemic stroke. (See Presentation.)
[5]

Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be
obtained on an emergent basis (see the image below). Brain imaging aids in excluding ischemic
stroke, and it may identify complications of hemorrhagic stroke such as intraventricular
hemorrhage, brain edema, and hydrocephalus. Either noncontrast computed tomography (NCCT)
scanning or magnetic resonance imaging (MRI) is the modality of choice. For more information,
see Ischemic Stroke in Emergency Medicine. (See Workup.)
Axial noncontrast computed tomography scan of the brain of a 60-year-old
man with a history of acute onset of left-sided weakness. Two areas of intracerebral hemorrhage are
seen in the right lentiform nucleus, with surrounding edema and effacement of the adjacent cortical
sulci and right sylvian fissure. Mass effect is present upon the frontal horn of the right lateral ventricle,
with intraventricular extension of the hemorrhage.
The treatment of patients with acute stroke depends on the cause and severity of the bleeding.
Basic life support, as well as control of bleeding, seizures, blood pressure (BP), and intracranial
pressure, are critical. Surgical evacuation of the hematoma is a potential therapeutic option, but it
remains controversial. (See Treatment.)
For patient education information, see the Stroke Health Center, as well as Stroke.
Anatomy
Knowledge of cerebrovascular arterial anatomy and the brain regions supplied by the arteries is
useful in determining which vessels are involved in acute stroke. Atypical patterns that do not
conform to a vascular distribution may indicate another diagnosis, such as venous infarction.
The cerebral hemispheres are supplied by 3 paired major arteries: the anterior, middle, and
posterior cerebral arteries. The anterior and middle cerebral arteries are responsible for the
anterior circulation and arise from the supraclinoid internal carotid arteries. The posterior
cerebral arteries arise from the basilar artery and form the posterior circulation, which also
supplies the thalami, brainstem, and cerebellum. The angiograms in the images below
demonstrate some portions of the circulation involved in hemorrhagic strokes.
Frontal view of a cerebral angiogram with selective injection of the left internal
carotid artery illustrates the anterior circulation. The anterior cerebral artery consists of the A1 segment
proximal to the anterior communicating artery with the A2 segment distal to it. The middle cerebral
artery can be divided into 4 segments: the M1 (horizontal segment) extends to the limen insulae and
gives off lateral lenticulostriate branches, the M2 (insular segment), M3 (opercular branches), and M4
(distal cortical branches on the lateral hemispheric convexities).
Lateral view of a cerebral angiogram illustrates the branches of the anterior cerebral artery (ACA) and
sylvian triangle. The pericallosal artery has been described as arising distal to the anterior
communicating artery or distal to the origin of the callosomarginal branch of the ACA. The segmental
anatomy of the ACA has been described as follows: (1) the A1 segment extends from the internal carotid
artery (ICA) bifurcation to the anterior communicating artery, (2) A2 extends to the junction of the
rostrum and genu of the corpus callosum, (3) A3 extends into the bend of the genu of the corpus
callosum, and (4) A4 and A5 extend posteriorly above the callosal body and superior portion of the
splenium. The sylvian triangle overlies the opercular branches of the middle cerebral artery, with the
apex representing the sylvian point. Frontal projection from a right
vertebral artery angiogram illustrates the posterior circulation. The vertebral arteries join to form the
basilar artery. The posterior inferior cerebellar arteries (PICA) arise from the distal vertebral arteries.
The anterior inferior cerebellar arteries (AICA) arise from the proximal basilar artery. The superior
cerebellar arteries (SCA) arise distally from the basilar artery before its bifurcation into the posterior
cerebral arteries.
Pathophysiology
In intracerebral hemorrhage, bleeding occurs directly into the brain parenchyma. The usual
mechanism is thought to be leakage from small intracerebral arteries damaged by chronic
hypertension. Other mechanisms include bleeding diatheses, iatrogenic anticoagulation, cerebral
amyloidosis, and cocaine abuse.
Intracerebral hemorrhage has a predilection for certain sites in the brain, including the thalamus,
putamen, cerebellum, and brainstem. In addition to the area of the brain injured by the
hemorrhage, the surrounding brain can be damaged by pressure produced by the mass effect of
the hematoma. A general increase in intracranial pressure may occur.
Subarachnoid hemorrhage
The pathologic effects of subarachnoid hemorrhage (SAH) on the brain are multifocal. SAH
results in elevated intracranial pressure and impairs cerebral autoregulation. These effects can
occur in combination with acute vasoconstriction, microvascular platelet aggregation, and loss of
microvascular perfusion, resulting in profound reduction in blood flow and cerebral ischemia.
[6]
See the images below.
Noncontrast computed tomography (CT) scanning was performed
emergently in a 71-year-old man who presented with acute onset of severe headache and underwent
rapid neurologic deterioration requiring intubation. The noncontrast CT scan (left image) demonstrates
diffuse, high-density subarachnoid hemorrhage in the basilar cisterns and both Sylvian fissures. There is
diffuse loss of gray-white differentiation. The fluid-attenuated inversion-recovery (FLAIR) image (right)
demonstrates high signal throughout the cortical sulci and in the basilar cisterns, as well as in the
dependent portions of the ventricles. FLAIR is highly sensitive to acute subarachnoid hemorrhage; the
suppression of high cerebrospinal fluid signal aids in making subarachnoid hemorrhage more
conspicuous than do conventional magnetic resonance imaging sequences.
Computed tomographic angiography examination and subsequent
cerebral angiography were performed in 71-year-old man who presented with acute onset of severe
headache and underwent rapid neurologic deterioration. Multiple aneurysms were identified, including
a 9-mm aneurysm at the junction of the anterior cerebral and posterior communicating arteries seen on
this lateral view of an internal carotid artery injection. Balloon-assisted coil embolization was
performed. Lateral view of a selective injection of the left internal
carotid artery demonstrates a microcatheter passing distal to the aneurysm neck. This lateral view from
an angiogram performed during balloon-assisted coil embolization demonstrates significantly
diminished filling of the aneurysm.
Etiology
The etiologies of stroke are varied, but they can be broadly categorized into ischemic or
hemorrhagic. Approximately 80-87% of strokes are from ischemic infarction caused by
thrombotic or embolic cerebrovascular occlusion. Intracerebral hemorrhages account for most of
the remainder of strokes, with a smaller number resulting from aneurysmal subarachnoid
hemorrhage.
[7, 8, 9, 10]

In 20-40% of patients with ischemic infarction, hemorrhagic transformation may occur within 1
week after ictus.
[11, 12]

Differentiating between the different types of stroke is an essential part of the initial workup of
patients with stroke, as the subsequent management of each disorder will be vastly different.
Risk factors
The risk of hemorrhagic stroke is increased with the following factors:
 Advanced age
 Hypertension (up to 60% of cases)
 Previous history of stroke
 Alcohol abuse
 Use of illicit drugs (eg, cocaine, other sympathomimetic drugs)
Causes of hemorrhagic stroke include the following
[10, 11, 13, 14, 15]
:
 Hypertension
 Cerebral amyloidosis
 Coagulopathies
 Anticoagulant therapy
 Thrombolytic therapy for acute myocardial infarction (MI) or acute ischemic stroke (can cause
iatrogenic hemorrhagic transformation)
 Arteriovenous malformation (AVM), aneurysms, and other vascular malformations (venous and
cavernous angiomas)
 Vasculitis
 Intracranial neoplasm
Amyloidosis
Cerebral amyloidosis affects people who are elderly and may cause up to 10% of intracerebral
hemorrhages. Rarely, cerebral amyloid angiopathy can be caused by mutations in the amyloid
precursor protein and is inherited in an autosomal dominant fashion.
Coagulopathies
Coagulopathies may be acquired or inherited. Liver disease can result in a bleeding diathesis.
Inherited disorders of coagulation such as factor VII, VIII, IX, X, and XIII deficiency can
predispose to excessive bleeding, and intracranial hemorrhage has been seen in all of these
disorders.
Anticoagulant therapy
Anticoagulant therapy is especially likely to increase hemorrhage risk in patients who metabolize
warfarin inefficiently. Warfarin metabolism is influenced by polymorphism in the CYP2C9
genes. Three known variants have been described. CYP2C9*1 is the normal variant and is
associated with typical response to dosage of warfarin. Variations *2 and *3 are relatively
common polymorphisms that reduce the efficiency of warfarin metabolism.
[16]

Atrioventricular malformations
Numerous genetic causes may predispose to AVMs in the brain, although AVMs are generally
sporadic. Polymorphisms in the IL6 gene increase susceptibility to a number of disorders,
including AVM. Hereditary hemorrhagic telangiectasia (HHT), previously known as Osler-
Weber-Rendu syndrome, is an autosomal dominant disorder that causes dysplasia of the
vasculature. HHT is caused by mutations in ENG, ACVRL1, or SMAD4 genes. Mutations in
SMAD4 are also associated with juvenile polyposis, so this must be considered when obtaining
the patient’s history.
HHT is most frequently diagnosed when patients present with telangiectasias on the skin and
mucosa or with chronic epistaxis from AVMs in the nasal mucosa. Additionally, HHT can result
in AVMs in any organ system or vascular bed. AVM in the gastrointestinal tract, lungs, and
brain are the most worrisome, and their detection is the mainstay of surveillance for this disease.
Hypertension
The most common etiology of primary hemorrhagic stroke (intracerebral hemorrhage) is
hypertension. At least two thirds of patients with primary intraparenchymal hemorrhage are
reported to have preexisting or newly diagnosed hypertension. Hypertensive small-vessel disease
results from tiny lipohyalinotic aneurysms that subsequently rupture and result in
intraparenchymal hemorrhage. Typical locations include the basal ganglia, thalami, cerebellum,
and pons.
Aneurysms and subarachnoid hemorrhage
The most common cause of atraumatic hemorrhage into the subarachnoid space is rupture of an
intracranial aneurysm. Aneurysms are focal dilatations of arteries, with the most frequently
encountered intracranial type being the berry (saccular) aneurysm. Aneurysms may less
commonly be related to altered hemodynamics associated with AVMs, collagen vascular disease,
polycystic kidney disease, septic emboli, and neoplasms.
Nonaneurysmal perimesencephalic subarachnoid hemorrhage may also be seen. This
phenomenon is thought to arise from capillary or venous rupture. It has a less severe clinical
course and, in general, a better prognosis.
Berry aneurysms are most often isolated lesions whose formation results from a combination of
hemodynamic stresses and acquired or congenital weakness in the vessel wall. Saccular
aneurysms typically occur at vascular bifurcations, with more than 90% occurring in the anterior
circulation. Common sites include the following:
 The junction of the anterior communicating arteries and anterior cerebral arteries—most
commonly, the middle cerebral artery (MCA) bifurcation
 The supraclinoid internal carotid artery at the origin of the posterior communicating artery
 The bifurcation of the internal carotid artery (ICA)
Genetic causes of aneurysms
Intracranial aneurysms may result from genetic disorders. Although rare, several families have
been described that have a predisposition—inherited in an autosomal dominant fashion—to
intracranial berry aneurysms. A number of genes, all categorized as ANIB genes, are associated
with this predisposition. Presently, ANIB1 through ANIB11 are known.
Autosomal dominant polycystic kidney disease (ADPKD) is another cause of intracranial
aneurysm. Families with ADPKD tend to show phenotypic similarity with regard to intracranial
hemorrhage or asymptomatic berry aneurysms.
[17]

Loeys-Dietz syndrome (LDS) consists of craniofacial abnormalities, craniosynostosis, marked
arterial tortuosity, and aneurysms and is inherited in an autosomal dominant manner. Although
intracranial aneurysms occur in LDS of all types, saccular intracranial aneurysms are a
prominent feature of LDS type IC, which is caused by mutations in the SMAD3 gene.
[18]

Ehlers-Danlos syndrome is a group of inherited disorders of the connective tissue that feature
hyperextensibility of the joints and changes to the skin, including poor wound healing, fragility,
and hyperextensibility. However, Ehlers-Danlos vascular type (type IV) also is known to cause
spontaneous rupture of hollow viscera and large arteries, including arteries in the intracranial
circulation.
Patients with Ehlers-Danlos syndrome may also have mild facial findings, including lobeless
ears, a thin upper lip, and a thin, sharp nose. The distal fingers may appear prematurely aged
(acrogeria). In the absence of a suggestive family history, it is difficult to separate Ehlers-Danlos
vascular type from other forms of Ehlers-Danlos. Ehlers-Danlos vascular type is caused by
mutations in the COL3A1 gene; it is inherited in an autosomal dominant manner.
See Genetic and Inflammatory Mechanisms in Stroke, as well as Blood Dyscrasias and Stroke.
Information on metabolic diseases and stroke can be found in the following articles:
 Methylmalonic Acidemia
 Homocystinuria/Homocysteinemia
 Fabry Disease
 MELAS – Mitochondrial Encephalomyopathy, Lactic Acidosis, Strokelike Episodes
 Hyperglycemia/Hypoglycemia
Hemorrhagic transformation of ischemic stroke
Hemorrhagic transformation represents the conversion of a bland infarction into an area of
hemorrhage. Proposed mechanisms for hemorrhagic transformation include reperfusion of
ischemically injured tissue, either from recanalization of an occluded vessel or from collateral
blood supply to the ischemic territory or disruption of the blood-brain barrier. With disruption of
the blood-brain barrier, red blood cells extravasate from the weakened capillary bed, producing
petechial hemorrhage or frank intraparenchymal hematoma.
[10, 11, 19]
(For more information, see
Reperfusion Injury in Stroke.)
Hemorrhagic transformation of an ischemic infarct occurs within 2-14 days postictus, usually
within the first week. It is more commonly seen following cardioembolic strokes and is more
likely with larger infarct size.
[10, 12, 20]
Hemorrhagic transformation is also more likely following
administration of tissue plasminogen activator (tPA) in patients whose noncontrast computed
tomography (CT) scans demonstrate areas of hypodensity.
[21, 22, 19]
See the image below.
Noncontrast computed tomography scan (left) obtained in a 75-year-
old man who was admitted for stroke demonstrates a large right middle cerebral artery distribution
infarction with linear areas of developing hemorrhage. These become more confluent on day 2 of
hospitalization (middle image), with increased mass effect and midline shift. There is massive
hemorrhagic transformation by day 6 (right), with increased leftward midline shift and subfalcine
herniation. Obstructive hydrocephalus is also noted, with dilatation of the lateral ventricles, likely due to
compression of the foramen of Monroe. Intraventricular hemorrhage is also noted layering in the left
occipital horn. Larger infarctions are more likely to undergo hemorrhagic transformation and are one
contraindication to thrombolytic therapy.
Epidemiology
Occurrence in the United States
Each year in the United States, approximately 795,000 people experience new or recurrent
stroke. Of these, approximately 610,000 represent initial attacks, and 185,000 represent recurrent
strokes. Epidemiologic studies indicate that approximately 87% of strokes in the United States
are ischemic, 10% are secondary to intracerebral hemorrhage, and another 3% may be secondary
to subarachnoid hemorrhage.
[7, 23]

A 2010 retrospective review from a stroke center found that 40.9% of the 757 patients in the
study had suffered hemorrhagic strokes.
[24]
The researchers speculate that improved availability
and implementation of computed tomography (CT) scanning may have unmasked a previous
underestimation of the actual percentage of hemorrhagic strokes, or increased use of antiplatelet
agents and warfarin may have led to a higher incidence of hemorrhage. Alternatively, this higher
rate may represent referral bias of patients with intracerebral hemorrhages to medical centers
with neurosurgical capabilities.
The incidence of stroke varies with age, sex, ethnicity, and socioeconomic status. For example,
American Heart Association (AHA) researchers found that rates of intracerebral hemorrhage are
higher in Mexican Americans, Latin Americans, blacks, Native Americans, Japanese people, and
Chinese people than they are in whites.
[7]

Flaherty et al found that excess risk of intracranial hemorrhage in African Americans is largely
attributable to higher hemorrhage rates in young and middle-aged persons, particularly for deep
cerebral and brainstem locations. Hypertension is the predominant risk factor.
[25]

International occurrence
According to the World Health Organization (WHO), 15 million people suffer stroke worldwide
each year. Of these, 5 million die and another 5 million are left permanently disabled.
[26]

The global incidence of stroke has at least a modest variation from nation to nation, suggesting
the importance of genetics and environmental factors, such as disparities in access to health care
in developing countries. The age-adjusted incidence of total strokes per 1000 person-years for
people 55 years or older has been reported in the range of 4.2 to 6.5. The highest incidences have
been reported in Russia, Ukraine, and Japan.
In a prospective, population-based registry study from Italy, the crude annual incidence rate of
intracerebral hemorrhage was 36.9 per 100,000 population. When standardized to the 2006
European population, the rate was 32.9 per 100,000 population; standardized to the world
population, the rate was 15.9 per 100,000 population.
[27]

Overall, the incidence of acute stroke has demonstrated a constant decline over the past several
decades, most notably during the 1970s-1990s, although in recent years the rate trend has begun
to plateau. However, the increased survival among stroke victims will place an increased demand
on health-care systems globally.
[10, 28]

Stroke subtypes also vary greatly in different parts of the world and between different races. For
example, the proportion of hemorrhagic strokes may be higher in certain populations, such as the
Chinese population, in which it has been reported to be up to 39.4%, and the Japanese, in which
it is reportedly up to 38.7%.
[28, 3]

Prognosis
The prognosis in patients with hemorrhagic stroke varies depending on the severity of stroke and
the location and the size of the hemorrhage. Lower Glasgow Coma Scale (GCS) scores are
associated with poorer prognosis and higher mortality rates. A larger volume of blood at
presentation is also associated with a poorer prognosis. Growth of the hematoma volume is
associated with a poorer functional outcome and increased mortality rate.
The intracerebral hemorrhage score is the most commonly used instrument for predicting
outcome in hemorrhagic stroke. The score is calculated as follows:
 GCS score 3-4: 2 points
 GCS score 5-12: 1 point
 GCS score 13-15: 0 points
 Age ≥80 years: Yes, 1 point; no, 0 points
 Infratentorial origin: Yes, 1 point; no, 0 points
 Intracerebral hemorrhage volume ≥30 cm
3
: 1 point
 Intracerebral hemorrhage volume < 30 cm
3
: 0 points
 Intraventricular hemorrhage: Yes, 1 point; no, 0 points
In a study by Hemphill et al, all patients with an Intracerebral Hemorrhage Score of 0 survived,
and all of those with a score of 5 died; 30-day mortality increased steadily with the Score.
[29]

Other prognostic factors include the following:
 Nonaneurysmal perimesencephalic stroke has a less severe clinical course and, in general, a
better prognosis
 The presence of blood in the ventricles is associated with a higher mortality rate; in one study,
the presence of intraventricular blood at presentation was associated with a mortality increase
of more than 2-fold
 Patients with oral anticoagulation-associated intracerebral hemorrhage have higher mortality
rates and poorer functional outcomes
In studies, withdrawal of medical support or issuance of Do Not Resuscitate (DNR) orders
within the first day of hospitalization predict poor outcome independent of clinical factors.
Because limiting care may adversely impact outcome, American Heart Association/American
Stroke Association (AHA/ASA) guidelines suggest that new DNR orders should probably be
postponed until at least the second full day of hospitalization. Patients with DNRs should be
given all other medical and surgical treatment, unless the DNR explicitly says otherwise.
[2]

For more information, see Motor Recovery in Stroke.
History
Obtaining an adequate history includes determining the onset and progression of symptoms, as
well as assessing for risk factors and possible causative events. Such risk factors include the
following:
 Previous transient ischemic attack (TIA) and stroke
 Hypertension
 Diabetes
 Smoking
 Arrhythmia and valvular disease
 Illicit drug use
 Use of anticoagulants
 Risk factors for thrombosis
A history of trauma, even if minor, may be important, as extracranial arterial dissections can
result in ischemic stroke.
Hemorrhagic versus ischemic stroke
Symptoms alone are not specific enough to distinguish ischemic from hemorrhagic stroke.
However, generalized symptoms, including nausea, vomiting, and headache, as well as an altered
level of consciousness, may indicate increased intracranial pressure and are more common with
hemorrhagic strokes and large ischemic strokes.
Seizures are more common in hemorrhagic stroke than in the ischemic kind. Seizures occur in up
to 28% of hemorrhagic strokes, generally at the onset of the intracerebral hemorrhage or within
the first 24 hours.
Focal neurologic deficits
The neurologic deficits reflect the area of the brain typically involved, and stroke syndromes for
specific vascular lesions have been described. Focal symptoms of stroke include the following:
 Weakness or paresis that may affect a single extremity, one half of the body, or all 4 extremities
 Facial droop
 Monocular or binocular blindness
 Blurred vision or visual field deficits
 Dysarthria and trouble understanding speech
 Vertigo or ataxia
 Aphasia
Subarachnoid hemorrhage
Symptoms of subarachnoid hemorrhage may include the following:
 Sudden onset of severe headache
 Signs of meningismus with nuchal rigidity
 Photophobia and pain with eye movements
 Nausea and vomiting
 Syncope - Prolonged or atypical
The most common clinical scoring systems for grading aneurysmal subarachnoid hemorrhage are
the Hunt and Hess grading scheme and the World Federation of Neurosurgeons (WFNS) grading
scheme, which incorporates the Glasgow Coma Scale. The Fisher Scale incorporates findings
from noncontrast computed tomography (NCCT) scans.
Physical Examination
The assessment in patients with possible hemorrhagic stroke includes vital signs; a general
physical examination that focuses on the head, heart, lungs, abdomen, and extremities; and a
thorough but expeditious neurologic examination.
[2]
However, intracerebral hemorrhage may be
clinically indistinguishable from ischemic stroke. (Though stroke is less common in children, the
clinical presentation is similar.)
Hypertension (particularly systolic blood pressure [BP] greater than 220 mm Hg) is commonly a
prominent finding in hemorrhagic stroke. Higher initial BP is associated with early neurologic
deterioration, as is fever.
[2]

An acute onset of neurologic deficit, altered level of consciousness/mental status, or coma is
more common with hemorrhagic stroke than with ischemic stroke. Often, this is caused by
increased intracranial pressure. Meningismus may result from blood in the subarachnoid space.
Examination results can be quantified using various scoring systems. These include the Glasgow
Coma Scale (GCS), the Intracerebral Hemorrhage Score (which incorporates the GCS; see
Prognosis), and the National Institutes of Health Stroke Scale.
Focal neurologic deficits
The type of deficit depends upon the area of brain involved. If the dominant hemisphere (usually
the left) is involved, a syndrome consisting of the following may result:
 Right hemiparesis
 Right hemisensory loss
 Left gaze preference
 Right visual field cut
 Aphasia
 Neglect (atypical)
If the nondominant (usually the right) hemisphere is involved, a syndrome consisting of the
following may result:
 Left hemiparesis
 Left hemisensory loss
 Right gaze preference
 Left visual field cut
Nondominant hemisphere syndrome may also result in neglect when the patient has left-sided
hemi-inattention and ignores the left side.
If the cerebellum is involved, the patient is at high risk for herniation and brainstem
compression. Herniation may cause a rapid decrease in the level of consciousness and may result
in apnea or death.
Specific brain sites and associated deficits involved in hemorrhagic stroke include the following:
 Putamen - Contralateral hemiparesis, contralateral sensory loss, contralateral conjugate gaze
paresis, homonymous hemianopia, aphasia, neglect, or apraxia
 Thalamus - Contralateral sensory loss, contralateral hemiparesis, gaze paresis, homonymous
hemianopia, miosis, aphasia, or confusion
 Lobar - Contralateral hemiparesis or sensory loss, contralateral conjugate gaze paresis,
homonymous hemianopia, abulia, aphasia, neglect, or apraxia
 Caudate nucleus - Contralateral hemiparesis, contralateral conjugate gaze paresis, or confusion
 Brainstem - Quadriparesis, facial weakness, decreased level of consciousness, gaze paresis,
ocular bobbing, miosis, or autonomic instability
 Cerebellum – Ipsilateral ataxia, facial weakness, sensory loss; gaze paresis, skew deviation,
miosis, or decreased level of consciousness
Other signs of cerebellar or brainstem involvement include the following:
 Gait or limb ataxia
 Vertigo or tinnitus
 Nausea and vomiting
 Hemiparesis or quadriparesis
 Hemisensory loss or sensory loss of all 4 limbs
 Eye movement abnormalities resulting in diplopia or nystagmus
 Oropharyngeal weakness or dysphagia
 Crossed signs (ipsilateral face and contralateral body)
Many other stroke syndromes are associated with intracerebral hemorrhage, ranging from mild
headache to neurologic devastation. At times, a cerebral hemorrhage may present as a new-onset
seizure.
Diagnostic Considerations
Intracerebral hemorrhage may be clinically indistinguishable from ischemic stroke, and a
thorough history and physical examination are important. An acute onset of neurologic deficit,
altered level of consciousness/mental status, or coma is more common with hemorrhagic stroke
than with ischemic stroke. A history of trauma, even if minor, may be important, as extracranial
arterial dissections can result in ischemic stroke.
Seizures are more common in hemorrhagic stroke than in ischemic stroke and occur in up to 28%
of hemorrhagic strokes, generally at the onset of the intracerebral hemorrhage or within the first
24 hours. Postictal (Todd) paralysis and hyperosmolality should also be considered.
Other problems to consider are as follows:
 Hyponatremia or hypernatremia
 Migraine headache
 Hyperosmolar hyperglycemic nonketotic coma
Differential Diagnoses
 Encephalitis
 Headache, Migraine
 Hypernatremia
 Hyperosmolar Hyperglycemic Nonketotic Coma
 Hypertensive Emergencies
 Hypoglycemia
 Hyponatremia
 Labyrinthitis Ossificans
 Meningitis
 Neoplasms, Brain
 Stroke, Ischemic
 Subarachnoid Hemorrhage
 Subdural Hematoma
 Transient Ischemic Attack
Approach Considerations
Laboratory tests should include a complete blood count, a metabolic panel, and—particularly in
patients taking anticoagulants—coagulation studies (ie, prothrombin time or international
normalized ratio [INR] and an activated partial thromboplastin time).
[2]

Brain imaging is a crucial step in the evaluation of suspected hemorrhagic stroke and must be
obtained on an emergent basis. Brain imaging aids diagnosing hemorrhage, and it may identify
complications such as intraventricular hemorrhage, brain edema, or hydrocephalus. Either
noncontrast computed tomography (NCCT) scanning or magnetic resonance imaging (MRI) is
the modality of choice.
Computed tomography (CT)-scan studies can also be performed in patients who are unable to
tolerate a magnetic resonance examination or who have contraindications to MRI, including
pacemakers, aneurysm clips, or other ferromagnetic materials in their bodies. Additionally, CT-
scan examination is more easily accessible for patients who require special equipment for life
support. See the image below.
Noncontrast computed tomography scan of the brain (left)
demonstrates an acute hemorrhage in the left gangliocapsular region, with surrounding white matter
hypodensity consistent with vasogenic edema. T2-weighted axial magnetic resonance imaging scan
(middle image) again demonstrates the hemorrhage, with surrounding high-signal edema. The coronal
gradient-echo image (right) demonstrates susceptibility related to the hematoma, with markedly low
signal adjacent the left caudate head. Gradient-echo images are highly sensitive for blood products.
CT angiography and contrast-enhanced CT scanning may be considered for helping identify
patients at risk for hematoma expansion. Extravasation of contrast within the hematoma indicates
high risk.
When clinical or radiologic findings suggest an underlying structural lesion, useful techniques
include CT angiography, CT venography, contrast-enhanced CT scanning, contrast-enhanced
MRI, magnetic resonance angiography (MRA), or magnetic resonance venography.
[2]

Conventional angiography is the gold standard in evaluating for cerebrovascular disease and for
providing less-invasive endovascular interventions. This modality can be performed to clarify
equivocal findings or to confirm and treat disease seen on MRA, CTA, transcranial Doppler, or
neck ultrasonograms. However, Zhu et al found that in patients with spontaneous intracranial
hemorrhage, angiographic yield was significantly lower in patients older than 45 years and those
who had preexisting hypertension.
[30]

Although the traditional approach to excluding underlying vascular abnormalities in patients
with spontaneous intracerebral hemorrhage is to use digital subtraction angiography (DSA) in the
acute and subacute phases, Wong et al found that MRA was able to detect most structural
vascular abnormalities in the subacute phase in most patients. Consequently, they recommend
MRA as the screening test.
Approach Considerations
The treatment and management of patients with acute intracerebral hemorrhage depends on the
cause and severity of the bleeding. Basic life support, as well as control of bleeding, seizures,
blood pressure (BP), and intracranial pressure, are critical. Medications used in the treatment of
acute stroke include the following:
 Anticonvulsants - To prevent seizure recurrence
 Antihypertensive agents - To reduce BP and other risk factors of heart disease
 Osmotic diuretics - To decrease intracranial pressure in the subarachnoid space
Management begins with stabilization of vital signs. Perform endotracheal intubation for patients
with a decreased level of consciousness and poor airway protection. Intubate and hyperventilate
if intracranial pressure is elevated, and initiate administration of mannitol for further control.
Rapidly stabilize vital signs, and simultaneously acquire an emergent computed tomography
(CT) scan. Glucose levels should be monitored, with normoglycemia recommended.
[2]
Antacids
are used to prevent associated gastric ulcers.
Currently, no effective targeted therapy for hemorrhagic stroke exists. Studies of recombinant
factor VIIa (rFVIIa) have yielded disappointing results. Evacuation of hematoma, either via open
craniotomy or endoscopy, may be a promising ultra-early-stage treatment for intracerebral
hemorrhage that may improve long-term prognosis.
Management of Seizures
Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage; these seizures
are often nonconvulsive.
[31, 32]
According to American Heart Association/American Stroke
Association (AHA/ASA) 2010 guidelines for the management of spontaneous intracerebral
hemorrhage, patients with clinical seizures or electroencephalographic (EEG) seizure activity
accompanied by a change in mental status should be treated with antiepileptic drugs.
[2]

Patients for whom treatment is indicated should immediately receive a benzodiazepine, such as
lorazepam or diazepam, for rapid seizure control. This should be accompanied by phenytoin or
fosphenytoin loading for longer-term control.
Prophylaxis
The utility of prophylactic anticonvulsant medication remains uncertain. In prospective and
population-based studies, clinical seizures have not been associated with worse neurologic
outcome or mortality. Indeed, 2 studies have reported worse outcomes in patients who did not
have a documented seizure but who received antiepileptic drugs (primarily phenytoin).
[2]

The 2010 AHA/ASA guidelines do not offer recommendations on prophylactic anticonvulsants,
but suggest that continuous EEG monitoring is probably indicated in patients with intracranial
hemorrhage whose mental status is depressed out of proportion to the degree of brain injury
Prophylactic anticonvulsant therapy has been recommended in patients with lobar hemorrhages
to reduce the risk of early seizures. One large, single-center study showed that prophylactic
antiepileptic drugs significantly reduced the number of clinical seizures in these patients.
[31]

In addition, AHA/ASA guidelines from 2012 suggest that prophylactic anticonvulsants may be
considered for patients with aneurysmal subarachnoid hemorrhage. In such cases, however,
anticonvulsant use should generally be limited to the immediate post-hemorrhagic period.
Routine long-term use is not recommended, but it may be considered in patients with a prior
seizure history, intracerebral hematoma, intractable hypertension, or infarction or aneurysm at
the middle cerebral artery.
[33]

Blood Pressure Control
No controlled studies have defined optimum BP levels for patients with acute hemorrhagic
stroke, but greatly elevated BP is thought to lead to rebleeding and hematoma expansion. Stroke
may result in loss of cerebral autoregulation of cerebral perfusion pressure.
Suggested agents for use in the acute setting are beta blockers (eg, labetalol) and angiotensin-
converting enzyme inhibitors (ACEIs) (eg, enalapril). For more refractory hypertension, agents
such as nicardipine and hydralazine are used. Avoid nitroprusside because it may raise
intracranial pressure.
The 2010 AHA/ASA guidelines acknowledge that evidence for the efficacy of managing BP in
hemorrhagic stroke is currently incomplete. With that caveat, the AHA/ASA recommendations
for treating elevated BP are as follows
[2]
:
 If systolic BP is over 200 mm Hg or mean arterial pressure (MAP) is over 150 mm Hg, then
consider aggressive reduction of BP with continuous IV infusion; check BP every 5 minutes
 If systolic BP is over 180 mm Hg or MAP is over 130 mm Hg and intracranial pressure may be
elevated, then consider monitoring intracranial pressure and reducing BP using intermittent or
continuous intravenous medications, while maintaining a cerebral perfusion pressure of 60 mm
Hg or higher
 If systolic BP is over 180 or MAP is over 130 mm Hg and there is no evidence of elevated
intracranial pressure, then consider modest reduction of BP (target MAP of 110 mm Hg or target
BP of 160/90 mm Hg) using intermittent or continuous intravenous medications to control it,
and perform clinical reexamination of the patient every 15 minutes
 In patients presenting with a systolic BP of 150 to 220 mm Hg, acute lowering of systolic BP to
140 mm Hg is probably safe
For patients with aneurysmal subarachnoid hemorrhage, the 2012 AHA/ASA guidelines
recommend lowering BP below 160 mmHg acutely to reduce rebleeding.
[33]

The ongoing Antihypertensive Treatment in Acute Cerebral Hemorrhage-II (ATACH-II) phase 3
randomized clinical trial is designed to determine whether the likelihood of death or disability at
3 months after spontaneous supratentorial intracerebral hemorrhage is lower when systolic BP
has been reduced to 180 mm Hg or below or to 140 mm Hg or below. In ATACH-II, intravenous
nicardipine is started within 3 hours of stroke onset and continued for the next 24 hours.
Intracranial Pressure Control
Elevated intracranial pressure may result from the hematoma itself, from surrounding edema, or
from both. The frequency of increased intracranial pressure in patients with intracerebral
hemorrhage is not known.
Elevate the head of the bed to 30°. This improves jugular venous outflow and lowers intracranial
pressure. The head should be midline and not turned to the side. Provide analgesia and sedation
as needed. Antacids are used to prevent gastric ulcers associated with intracerebral hemorrhage.
More aggressive therapies, such as osmotic therapy (ie, mannitol, hypertonic saline), barbiturate
anesthesia, and neuromuscular blockage, generally require concomitant monitoring of
intracranial pressure and BP with an intracranial pressure monitor to maintain adequate cerebral
perfusion pressure of greater than 70 mm Hg. A randomized, controlled study of mannitol in
intracerebral hemorrhage failed to demonstrate any difference in disability or death at 3
months.
[34]

Hyperventilation (partial pressure of carbon dioxide [PaCO
2
] of 25 to 30-35 mm Hg) is not
recommended, because its effect is transient, it decreases cerebral blood flow, and it may result
in rebound elevated intracranial pressure.
[4]
Glucocorticoids are not effective and result in higher
rates of complications with poorer outcomes.
Hemostatic Therapy
The use of hemostatic therapy with rFVIIa to stop ongoing hemorrhage or prevent hematoma
expansion has generated much interest. However, research to date has failed to support this off-
label use of rFVIIa.
[35, 36, 37]

A preliminary study of treatment rFVIIa demonstrated reduced mortality and improved
functional outcomes. Unfortunately, the results of a subsequent randomized trial that was larger
than the preliminary study revealed no overall benefit from treatment; hemostatic therapy with
rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome.
[38]

Diringer et al found that a higher dose of rFVIIa was associated with a small increase in the risk
of arterial thromboembolic events in patients who presented less than 3 hours after spontaneous
intracerebral hemorrhage. Arterial events were also associated with the presence of cardiac or
cerebral ischemia at presentation, with advanced age, and with antiplatelet use.
[39]

The investigators also found that with the use of 20 or 80 mcg/kg rFVIIa, the rates of venous
events were similar to those with placebo.
Treatment of Anticoagulation-associated Intracranial Hemorrhage
Patients on warfarin have an increased incidence of hemorrhagic stroke. Morbidity and mortality
for warfarin-associated bleeding is high, with over one half of patients dying within 30 days.
Most episodes occur with a therapeutic international normalized ratio (INR), but
overanticoagulation is associated with an even greater risk of bleeding.
The need to reverse warfarin anticoagulation is a true medical emergency, and reversal must be
accomplished as quickly as possible to prevent further hematoma expansion. Options for reversal
therapy include the following:
 Intravenous vitamin K
 Fresh frozen plasma (FFP)
 Prothrombin complex concentrates (PCC)
 rFVIIa
FFP versus PCC
Because vitamin K requires more than 6 hours to normalize the INR, it should be administered
with either FFP or PCC. FFP is the standard of care in the United States
[40]
; however, FFP needs
to be given in a dose of 15-20 mL/kg and therefore requires a large-volume infusion. PCC
contains high levels of vitamin K-dependent cofactors and thus involves a smaller-volume
infusion than FFP and more rapid administration.
[41, 42]
However, PCC is associated with high
rates of thrombotic complications.
No randomized, controlled trial has studied the safety and efficacy of FFP versus PCC for
reversing the effects of warfarin in patients with intracranial hemorrhage. The International
Normalised ratio normalisation in patients with Coumarin-related intracranial Haemorrhages
(INCH) trial, a prospective, randomized, controlled, multicenter trial comparing the 2 agents,
began recruiting subjects in 2009.
[43]

FVIIa
Based upon the available medical evidence, the use of FVIIa is currently not recommended over
other agents. The PCC available in the United States contains only low levels of FVII, however,
and Sarode et al have described successful, rapid reversal of vitamin K antagonist–related
coagulopathy using a combination of low-dose FVIIa with PCC, although they note the need for
caution in patients at high risk for thrombosis.
[40]

Patients on heparin (either unfractionated or low molecular weight heparin [LMWH]) who
develop a hemorrhagic stroke should immediately have anticoagulation reversed with
protamine.
[4]
The dose of protamine is dependent upon the dose of heparin that was given and the
time elapsed since that dose.
Patients with severe deficiency of a specific coagulation factor who develop spontaneous
intracerebral hemorrhage should receive factor replacement therapy.
[2]

Reversal of antiplatelet therapy and platelet dysfunction
There is controversy about whether patients on antiplatelet medications (eg, aspirin,
aspirin/dipyridamole [Aggrenox], clopidogrel) should be given desmopressin (DDAVP) and/or
platelet transfusions. Patients with renal failure and platelet dysfunction may also benefit from
the administration of desmopressin (DDAVP). The 2010 AHA/ASA guideline for management
of spontaneous intracerebral hemorrhage recommends platelet transfusions only when such
hemorrhaging complicates severe thrombocytopenia.
[2]

Invasive Therapy
A potential treatment for hemorrhagic stroke is surgical evacuation of the hematoma. However,
the role of surgical treatment for supratentorial intracranial hemorrhage remains controversial.
Outcomes in published studies are conflicting. The international multicenter Trial in
Intracerebral Haemorrhage (STICH), which compared early surgery with initial conservative
treatment, failed to demonstrate a surgery-related benefit.
[44]

In contrast, a meta-analysis of trials for surgical treatment of spontaneous supratentorial
intracerebral hemorrhage found evidence for improved outcome with surgery if any of the
following applied
[45]
:
 Surgery undertaken within 8 hours of ictus
 Volume of the hematoma 20-50 mL
 Glasgow coma score 9-12
 Patient age 50-69 years
In addition, evidence suggests that a subset of patients with lobar hematoma but no
intraventricular hemorrhage may benefit from intervention.
[46]
A study in this group of patients
(STICH II) has been completed, but results are still pending.
[47]

In patients with cerebellar hemorrhage, surgical intervention has been shown to improve
outcome if the hematoma is greater than 3 cm in diameter. It can be lifesaving in the prevention
of brainstem compression.
Endovascular treatment of aneurysms
Endovascular therapy using coil embolization, as an alternative to surgical clipping, has been
increasingly employed in recent years with great success (see the following images), although
controversy still exists over which treatment is ultimately superior.
A cerebral angiogram was performed in a 57-year-old man with a
family history of subarachnoid hemorrhage and who was found on previous imaging to have a left distal
internal carotid artery (ICA) aneurysm. The lateral projection from this angiogram demonstrates a
narrow-necked aneurysm arising off the posterior aspect of the distal supraclinoid left ICA, with an
additional nipplelike projection off the inferior aspect of the dome of the aneurysm. There is also a mild,
lobulated dilatation of the cavernous left ICA. Follow-up cerebral
angiogram after coil embolization in a 57-year-old man with a left distal internal carotid artery
aneurysm. Multiple coils were placed with sequential occlusion of the aneurysm, including the nipple at
its inferior aspect. A small amount of residual filling is noted at the proximal neck of the aneurysm,
which may thrombose over time.
The International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus
endovascular coiling reported that independent survival was higher at 1 year with endovascular
coiling and that the survival benefit continued for at least 7 years.
[48]
This randomized,
multicenter, international trial included 2143 patients. The investigators also noted that the risk
of late rebleeding was small in both groups but higher in the endovascular coiling group,
reconfirming the higher long-term anatomic cure rate of surgery.
[48, 49]

More recently, the Barrow Ruptured Aneurysm Trial (BRAT), which included 358 patients,
demonstrated superior functional outcome at 1 year with endovascular coil embolization than
with microsurgical clipping for acutely ruptured intracerebral aneurysm. Further, in contrast to
the ISAT results, no patient in the endovascular embolization group suffered a recurrent
hemorrhage.
[50]
Outcomes at 3-year follow-up of the BRAT patients continued to favor coil
embolization, though the difference no longer reached statistical significance.
[51]

Endovascular treatment of aneurysms may be favored over surgical clipping under the following
circumstances
[52]
:
 The aneurysm is in a location that is difficult to access surgically, such as the cavernous internal
carotid artery (ICA) or the basilar terminus
 The aneurysm is small-necked and located in the posterior fossa
 The patient is elderly
 The patient has a poor clinical grade
The following factors militate against endovascular treatment:
 Wide-based aneurysms or those without an identifiable neck
 Aneurysms with a vessel extending off the aneurysm dome
 Severely atherosclerotic or tortuous vessels that limit the endovascular approach
Although vasospasm may be treated with intra-arterial pharmaceutical agents, such as verapamil
or nicardipine, balloon angioplasty can be used for opening larger vessels (see the images
below). The combination of the 2 treatments appears to provide safe and long-lasting therapy for
severe, clinically significant vasospasm.
[53]

Frontal view from a cerebral angiogram in a 41-year-man who presented 7
days earlier with subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA)
aneurysm (which was treated with surgical clipping). There is significant narrowing of the proximal left
ACA, left M1 segment, and left supraclinoid internal carotid artery, indicating vasospasm.
Angiographic view in a 41-year-man who presented 7 days earlier with
subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA) aneurysm (which was
treated with surgical clipping). Superimposed road map image demonstrates placement of a wire across
the left M1 segment and balloon angioplasty. The left proximal ACA and supraclinoid internal carotid
artery (ICA) were also angioplastied, and intra-arterial verapamil was administered. Follow-up image on
the right after treatment demonstrates resolution of the left M1 segment and distal ICA, which are now
widely patent. Residual narrowing is seen in the left proximal ACA.
Ventriculostomy
Placement of an intraventricular catheter for cerebrospinal fluid drainage (ie, ventriculostomy) is
often used in the setting of obstructive hydrocephalus, which is a common complication of
thalamic hemorrhage with third-ventricle compression and of cerebellar hemorrhage with fourth-
ventricle compression. Ventriculostomies are associated with a risk of infection, including
bacterial meningitis.
Prevention of Hemorrhagic Stroke
Antihypertensives
The 2010 AHA/ASA guidelines for spontaneous ICH recommend that after acute intracerebral
hemorrhage, patients without medical contraindications should have BP well controlled,
especially for hemorrhage in typical hypertensive vasculopathy locations.
[2]
In addition, the
guidelines strongly recommend maintenance of BP below 140/90 mm Hg to prevent a first
stroke. In patients with hypertension plus either diabetes or renal disease, the treatment goal is
BP below 130/80 mm Hg.
[54]

BP-lowering medications include thiazide diuretics, calcium channel blockers, angiotensin-
converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). For patients
with diabetes, the use of ACEIs and ARBs to treat hypertension is a class I-A recommendation
(strongest and best-documented), according to the 2011 AHA/ASA primary prevention
guidelines.
[2]
Beta blockers are considered second-line agents given their inferiority in preventing
vascular events, despite producing similar reductions in BP. (Adverse effects of ACEIs include
cough [10%], which is less common with ARBs.)
Although statin therapy is recommended for primary prevention of ischemic stroke (class I-A
recommendation),
[54]
especially if other risk factors are present, some studies have found an
increased risk of intracerebral hemorrhage with statin use. However, a meta-analysis of 31
randomized, controlled trials of statin therapy found that active statin therapy was not associated
with a significant increase in intracerebral hemorrhage.
[55]

In the Heart Outcomes Prevention Evaluation (HOPE) study, the addition of the ACEI ramipril
to all other medical therapy, including antiplatelet agents, reduced the relative risk of stroke,
death, and myocardial infarction by 32% compared with placebo.
[56]
Only 40% of the efficacy of
ramipril could be attributed to its BP-lowering effects. Other postulated mechanisms included
endothelial protection.
Whether the beneficial effect of ramipril represents a class effect of ACEIs or whether it is a
property unique to ramipril is unclear.
In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a regimen based on
perindopril, an ACEI, was superior to placebo.
[57]
Although this drug alone was not superior to
placebo, the combination of perindopril with indapamide (a thiazide diuretic) substantially
reduced the recurrence of stroke.
[57]
Much of the effect in reducing stroke recurrence was
attributable to the lowering of BP, in contrast to findings for ramipril from the HOPE study.
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
showed slight superiority of chlorthalidone (a thiazide diuretic) over lisinopril (an ACEI) in
terms of stroke occurrence.
[58]

The Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE) demonstrated
that an ARB (losartan) was superior to a beta blocker (atenolol) in reducing the occurrence of
stroke.
[59]

The Morbidity and Mortality after Stroke, Eprosartan Compared With Nitrendipine for
Secondary Prevention (MOSES) study found that the ARB eprosartan was superior to the
calcium channel blocker nitrendipine in the secondary prevention of stroke and transient
ischemic attack (TIA).
[60]
This was true despite comparable BP reductions. The absolute annual
difference in stroke and TIA risk was approximately 4%. The study was relatively small, and
most events were TIAs.
Lifestyle interventions
Smoking cessation, a low-fat diet (eg, Dietary Approaches to Stop Hypertension [DASH] or
Mediterranean diets), weight loss, and regular exercise should be encouraged as strongly as
pharmacologic treatment. Written prescriptions for exercise and medications for smoking
cessation (ie, nicotine patch, bupropion, varenicline) increase the likelihood of success with these
interventions.
Reducing sodium intake and increasing consumption of foods high in potassium to reduce BP
may also help in primary prevention.
[54]
High alcohol intake should be reduced, as drinking more
than 30 drinks per month has been tied to increased risk of intracerebral hemorrhage.
Exercise
A Finnish study showed that the likelihood of stroke in men with the lowest degree of physical
fitness (maximal oxygen uptake [VO
2max
] < 25.2 mL/kg/min) was more than 3 times greater than
in men with the highest degree of physical fitness (VO
2max
>35.3 mL/kg/min).
[61]
level of
physical fitness was a more powerful risk factor than low-density lipoprotein cholesterol level,
body mass index, and smoking, and it was nearly comparable to hypertension as a risk factor.
The 2011 AHA/ASA guidelines for the primary prevention of stroke, which address hemorrhagic
and ischemic stroke, emphasize exercise and other lifestyle modifications. The guidelines
endorse the 2008 Physical Activity Guidelines for Americans, which include a recommendation
of at least 150 minutes per week of moderate-intensity aerobic physical activity.
[54]

Consultations
Emergent neurosurgical or neurologic consultation is often indicated; local referral patterns may
vary. The need for invasive intracranial pressure monitoring and for emergent cerebral
angiography should be assessed by the neurosurgeon. Patients in whom the hemorrhage’s cause
is unclear and who would otherwise be candidates for surgery should be considered for
angiographic evaluation. Also see Stroke Team Creation and Primary Stroke Center
Certification.
Medication Summary
Medications used in the treatment of acute stroke include anticonvulsants such as diazepam, to
prevent seizure recurrence; antihypertensive agents such as labetalol, to reduce blood pressure
(BP) and other risk factors for heart disease; and osmotic diuretics such as mannitol, to decrease
intracranial pressure in the subarachnoid space.
As previously mentioned, the treatment and management of patients with acute intracerebral
hemorrhage depends on the cause and severity of the bleeding. However, there is currently no
effective targeted therapy for hemorrhagic stroke.
Anticonvulsants, Other
Class Summary
Benzodiazepines are commonly used to control seizure activity and recurrence. Agents such as
lorazepam and diazepam are often used acutely, in combination with either phenytoin or
fosphenytoin loading.
View full drug information
Diazepam (Diastat, Diazemuls, Valium)

Diazepam controls active seizures by modulating the postsynaptic effects of gamma-
aminobutyric acid type A (GABA-A) transmission, resulting in an increase in presynaptic
inhibition. It appears to act on part of the limbic system, the thalamus, and hypothalamus, to
induce a calming effect. It also acts as an effective adjunct for the relief of skeletal muscle spasm
caused by upper motor neuron disorders.
Diazepam should be augmented by longer-acting anticonvulsants, such as phenytoin or
phenobarbital, because it rapidly distributes to other body fat stores.
View full drug information
Lorazepam (Ativan)

Lorazepam is a short-acting acting benzodiazepine with a moderately long half-life. It has
become the drug of choice in many centers for treating active seizures.
Anticonvulsants, Hydantoins
Class Summary
Anticonvulsants prevent seizure recurrence and terminate clinical and electrical seizure activity.
These agents are used routinely to avoid seizures that may be induced by cortical damage.
According to the American Heart Association/American Stroke Association (AHA/ASA) 2010
guidelines for management of spontaneous intracranial hemorrhage, treatment with antiepileptic
drugs is indicated for those patients with clinical seizures or with electroencephalographic (EEG)
seizure activity accompanied by a change in mental status.
[2]
Prophylactic use of anticonvulsants
is controversial and should be used judiciously, if at all.
View full drug information
Phenytoin (Dilantin)

Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity, as well as
in the brainstem centers responsible for the tonic phase of grand mal seizures. All doses should
be individualized. The antiepileptic effect of phenytoin is not immediate. Concomitant
administration of an intravenous benzodiazepine will usually be necessary to control status
epilepticus. In addition, a larger dose before retiring should be administered if the dose cannot be
divided equally.
View full drug information
Fosphenytoin (Cerebyx)

Fosphenytoin is a diphosphate ester salt of phenytoin that acts as water-soluble prodrug of
phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
To avoid the need to perform molecular-weight-based adjustments when converting between
fosphenytoin and phenytoin sodium doses, express the dose as phenytoin sodium equivalents.
Although fosphenytoin can be administered intravenously or intramuscularly, the intravenous
route is the route of choice and should be used in emergency situations.
The antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is
not immediate. Concomitant administration of an intravenous benzodiazepine will usually be
necessary to control status epilepticus.
Beta Blockers, Alpha Activity
Class Summary
Beta blockers are used to reduce BP and risk factors for heart disease. They are first-line agents
for acute BP reduction in hemorrhagic stroke, but they are second-line agents for stroke
prevention. Selective beta blockers obstruct access to beta-1 receptors more than they do to beta-
2 receptors; nonselective beta blockers obstruct access to beta-1 and beta-2 receptors.
View full drug information
Labetalol (Trandate)

Labetalol blocks beta1-, alpha-, and beta2-adrenergic receptor sites to decrease BP. It is
administered as a 5-20 mg intravenous bolus over 2 minutes, then as a continuous infusion at 2
mg/min (not to exceed 300 mg/dose).
Beta Blockers, Beta-1 Selective
Class Summary
Beta blockers are used to reduce BP and risk factors for heart disease. They are first-line agents
for acute BP reduction in hemorrhagic stroke, but they are second-line agents for stroke
prevention. Selective beta blockers obstruct access to beta-1 receptors more than they do to beta-
2 receptors; nonselective beta blockers obstruct access to beta-1 and beta-2 receptors.
View full drug information
Esmolol (Brevibloc)

Esmolol is an ultra-short-acting agent that selectively blocks beta-1 receptors with little or no
effect on beta-2 receptor types. This drug is particularly useful in patients with elevated arterial
pressure, especially if surgery is planned, and its short half-life of 8 minutes allows for titration
and quick discontinuation, if necessary.
Esmolol is also useful in patients at risk for experiencing complications from beta blockade,
particularly those with reactive airway disease, mild to moderate left-ventricular dysfunction,
and/or peripheral vascular disease.
Vasodilators
Class Summary
Vasodilators lower BP through direct vasodilation and relaxation of the vascular smooth muscle.
They are used more for BP lowering in refractory situations.
View full drug information
Hydralazine (Apresoline)

Hydralazine decreases systemic resistance through direct vasodilation of arterioles and is used to
treat hypertensive emergencies. The use of a vasodilator will reduce the stroke volume ratio
(SVR), which, in turn, may allow forward flow, improving cardiac output. Hydralazine is
typically not a first-line agent, because of its side-effect profile.
Calcium Channel Blockers
Class Summary
Calcium channel blockers are used to lower BP by relaxing the blood vessels and increasing the
amount of blood and oxygen that is delivered to the heart, while reducing the heart’s workload.
In acute situations, intravenous calcium channel blockers are frequently used to control BP.
These are first-line agents for long-term BP control in stroke patients (along with thiazides,
ACEIs, and angiotensin receptor blockers [ARBs]).
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Nicardipine (Cardene, Cardene IV, Cardene SR)

Nicardipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn,
improves myocardial oxygen delivery and reduces myocardial oxygen consumption.
Angiotensin-converting Enzyme Inhibitors
Class Summary
ACEIs prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor,
resulting in lower aldosterone secretion. These are first-line agents for emergent and long-term
BP control in hemorrhagic stroke patients.
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Enalapril (Vasotec)

Enalapril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor,
resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It helps to
control BP and proteinuria.
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Ramipril (Altace)

Ramipril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor,
resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
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Lisinopril (Zestril)

Lisinopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor,
resulting in lower aldosterone secretion.
Angiotensin Receptor Blockers
Class Summary
ARBs may be used as an alternative to ACEIs in patients who develop adverse effects, such as a
persistent cough.
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Losartan (Cozaar)

Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may
induce a more complete inhibition of the renin-angiotensin system than ACEIs do. In addition, it
does not affect the response to bradykinin and is less likely to be associated with cough and
angioedema.
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Candesartan (Atacand)

Candesartan blocks vasoconstriction and the aldosterone-secreting effects of angiotensin II. It
may induce a more complete inhibition of the renin-angiotensin system than ACEIs do. In
addition, it does not affect response to bradykinin and is less likely to be associated with cough
and angioedema.
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Valsartan (Diovan)

Valsartan produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from
the AT1 receptor and may lower BP by antagonizing AT1-induced vasoconstriction, aldosterone
release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic
responses.
Diuretics, Thiazide
Class Summary
Thiazide diuretics inhibit sodium and chloride reabsorption in the distal tubules of the kidney,
resulting in increased urinary excretion of sodium and water.
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Hydrochlorothiazide (Microzide)

Hydrochlorothiazide inhibits the reabsorption of sodium in distal tubules, causing increased
excretion of sodium and water, as well as potassium and hydrogen ions.
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Chlorthalidone (Diuril)

Chlorthalidone inhibits the reabsorption of sodium in distal tubules, causing increased excretion
of sodium and water, as well as potassium and hydrogen ions.
Diuretics, Osmotic Agents
Class Summary
Osmotic diuretics, such as mannitol, may be used to decrease intracranial pressure in the
subarachnoid space. As water diffuses from the subarachnoid space into the intravascular
compartment, pressure in the subarachnoid compartment may decrease.
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Mannitol (Osmitrol)

Mannitol reduces cerebral edema with the help of osmotic forces. It also decreases blood
viscosity, resulting in reflex vasoconstriction and lowering of intracranial pressure.
Analgesics, Other
Class Summary
Because hyperthermia may exacerbate neurologic injury, these agents may be given to reduce
fever and relieve pain.
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Acetaminophen (Tylenol, FeverAll, Aspirin Free Anacin)

Acetaminophen reduces fever, maintains normothermia, and reduces headache.
Hemostatics
Class Summary
Vitamin K is used to promote the formation of clotting factors. Phytonadione can overcome the
competitive block produced by warfarin and other related anticoagulants. A fresh frozen plasma
(FFP) infusion followed by oral vitamin K should be given without delay in the emergency
department to manage warfarin-related intracranial hemorrhage.
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Vitamin K1 (phytonadione; vitamin K, Mephyton, AquaMephyton)

Phytonadione can overcome the competitive block produced by warfarin and other related
anticoagulants. Vitamin K3 (menadione) is not effective for this purpose. There is a delay of the
clinical effect for several hours while liver synthesis of the clotting factors is initiated and plasma
levels of clotting factors II, VII, IX, and X are gradually restored.
Phytonadione should not be administered prophylactically and is used only if evidence of
anticoagulation exists. The required dose varies with the clinical situation, including the dose and
duration of action of the anticoagulant ingested. Intravenous phytonadione is recommended for
life-threatening bleeding, including intracerebral hemorrhage complicating warfarin therapy,
although it carries a small risk of anaphylaxis.
Blood Components
Class Summary
These agents are indicated for the correction of abnormal hemostatic parameters.
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Fresh frozen plasma

Plasma, the fluid component of blood, contains the blood's soluble clotting factors. FFP is
created by separating plasma from a unit of blood and freezing it for use in patients with blood-
product deficiencies.
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Platelets

Platelets are fragments of large bone marrow cells found in the blood that play a role in blood
coagulation. A single random donor unit of platelets per 10 kg is administered in adults when the
platelet count drops below 50,000/µL.
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Prothrombin complex concentrate (Bebulin VH, Profilnine SD)

Prothrombin complex concentrate (PCC) is a mixture of vitamin K-dependent clotting factors
found in normal plasma that replaces deficient clotting factors, provides an increase in plasma
levels of factor IX, and can temporarily correct a coagulation defect in patients with factor IX
deficiency. PCC is usually reserved for situations in which volume overload is a concern.
Antidotes, Other
Class Summary
Protamine is used to neutralize the effects of anticoagulants.
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Protamine

Protamine sulfate forms a salt with heparin and neutralizes its effects. The dosage administered
is dependent on the amount of time that has passed since heparin was given.
Vasopressin-Related
Class Summary
These agents improve bleeding time and hemostasis.
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Desmopressin acetate (DDAVP, Stimate)

Desmopressin releases von Willebrand protein from endothelial cells. It improves bleeding time
and hemostasis in patients with mild and moderate von Willebrand disease without abnormal
molecular forms of von Willebrand protein. It is effective in uremic bleeding. Tachyphylaxis
usually develops after 48 hours, but the drug can be effective again after several days.