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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.[1] However, hemorrhagic stroke is associated with higher mortality rates than is ischemic stroke. (See Epidemiology.)[2] 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.)[3] 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.

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.

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.[4] See the images below.

Noncontrast computed tomography (CT) scanning was performed emergently in a 71year-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 fluidattenuated 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.

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.[5, 6, 7, 8] In 20-40% of patients with ischemic infarction, hemorrhagic transformation may occur within 1 week after ictus.[9, 10] 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[8, 9, 11, 12, 13] : 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.[14] 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-WeberRendu 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 patients 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 arteriesmost 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 predispositioninherited in an autosomal dominant fashionto 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.[15] 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.[16] 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.[8, 9, 17] (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.[8, 10, 18] 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.[19, 20, 17] 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.

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 cm3: 1 point Intracerebral hemorrhage volume < 30 cm3: 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.[27] 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.[28]

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.[28] 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.[28] 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, andparticularly in patients taking anticoagulantscoagulation studies (ie, prothrombin time or international normalized ratio [INR] and an activated partial thromboplastin time).[28]

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, contrastenhanced CT scanning, contrast-enhanced MRI, magnetic resonance angiography (MRA), or magnetic resonance venography.[28] 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.[29] 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.[28] 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.[30, 31] 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.[28]

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).[28] 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.[30] 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.[32]

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[28] : 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.[32] 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.[33] Hyperventilation (partial pressure of carbon dioxide [PaCO2] 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.[2] 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.[34, 35, 36] 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.[37] 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.[38] 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[39] ; 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 smallervolume infusion than FFP and more rapid administration.[40, 41] 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.[42] 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 antagonistrelated coagulopathy using a combination of low-dose FVIIa with PCC, although they note the need for caution in patients at high risk for thrombosis.[39] Patients on heparin (either unfractionated or low molecular weight heparin [LMWH]) who develop a hemorrhagic stroke should immediately have anticoagulation reversed with protamine.[2] 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.[28] 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.[28]

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.[43] 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[44] : 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.[45] A study in this group of patients (STICH II) has been completed, but results are still pending.[46] 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.[47] 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.[47, 48] 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.[49] Outcomes at 3-year follow-up of the BRAT patients continued to favor coil embolization, though the difference no longer reached statistical significance.[50] Endovascular treatment of aneurysms may be favored over surgical clipping under the following circumstances[51] : 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.[52]

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 fourthventricle 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.[28] 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.[53] 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.[28] 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),[53] 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.[54] 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.[55] 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.[56] Although this drug alone was not superior to placebo, the combination of perindopril with indapamide (a thiazide diuretic) substantially reduced the recurrence of stroke.[56] 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.[57] 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.[58] 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).[59] 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.[53] 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 [VO2max] < 25.2 mL/kg/min) was more than 3 times greater than in men with the highest degree of physical fitness (VO2max >35.3 mL/kg/min).[60] 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.[53]

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 hemorrhages 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.
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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.
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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.[28] Prophylactic use of anticonvulsants is controversial and should be used judiciously, if at all.
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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.
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Fosphenytoin (Cerebyx) Fosphenytoin is a diphosphate ester salt of phenytoin that acts as watersoluble 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.
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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.
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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.

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.
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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 hearts 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 firstline 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 reninangiotensin 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 reninangiotensin 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.

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 lifethreatening 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/L.
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Prothrombin complex concentrate (Bebulin VH, Profilnine SD) Prothrombin complex concentrate (PCC) is a mixture of vitamin Kdependent 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.

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.