Hemorrhagic Stroke

Background
The terms intracerebral hemorrhage (ICH) and hemorrhagic stroke are used interchangeably in this discussion and are regarded as separate entities from hemorrhagic transformation of ischemic stroke. Intracerebral hemorrhage accounts for 10-15% of all strokes and is associated with higher mortality rates than cerebral infarctions.[1] Acute ischemic stroke refers to stroke caused by thrombosis or embolism and is more common than hemorrhagic stroke. Previous literature indicates that only 8-18% of strokes were hemorrhagic. (See Etiology.) Although a 2010 retrospective review from a stroke center found that 40.9% of 757 strokes were hemorrhagic,[2] nonetheless, the authors stated that the increased percentage of hemorrhagic stroke may be due to improvement of computed tomography (CT) scanning availability and implementation, unmasking a previous underestimation of the actual percentage (see Workup), or it may be due to an increase in therapeutic use of antiplatelet agents and warfarin causing an increase in the incidence of hemorrhage (see Treatment and Management).[2] Patients with hemorrhagic stroke present with similar focal neurologic deficits but tend to be more ill than patients with ischemic stroke. Patients with intracerebral bleeds are more likely to have headache, altered mental status, seizures, nausea and vomiting, and/or marked hypertension; however, none of these findings reliably distinguishes between hemorrhagic stroke and ischemic stroke. (See Clinical Presentation.) An intracerebral hemorrhage is shown in the CT scan below.

Axial noncontrast computed tomography scan of the brain in a 60-year-old male with history of acute onset of left-sided weakness demonstrates 2 areas of intracerebral hemorrhage 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.

Anatomy
Knowledge of cerebrovascular arterial anatomy and the territories supplied by each 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 comprise 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 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 to arise 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: the A1 segment extends from the internal carotid artery (ICA) bifurcation to the anterior communicating artery; A2 extends to the junction of the rostrum and genu of the corpus callosum; A3 extends into the bend of the genu of the corpus callosum; 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. The image below shows the supratentorial vascular territories of the major cerebral arteries.

The supratentorial vascular territories of the major cerebral arteries are demonstrated superimposed on axial (left) and coronal (right) T2-weighted images through the level of the basal ganglia and thalami. The middle cerebral artery (red) supplies the lateral aspects of the hemispheres, including the lateral frontal, parietal, and anterior temporal lobes, insula, and basal ganglia. The anterior cerebral artery (blue) supplies the medial frontal and parietal lobes. The posterior cerebral artery (green) supplies the thalami and occipital and inferior temporal lobes. The anterior choroidal artery (yellow) supplies the posterior limb of the internal capsule and part of the hippocampus extending to the anterior and superior surface of the occipital horn of the lateral ventricle.

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.

Etiology
The etiologies of stroke are varied, but they can be broadly categorized into ischemic or hemorrhagic infarctions. Approximately 80-87% of strokes are from ischemic infarction due to thrombotic or embolic cerebrovascular occlusion. Hemorrhagic infarctions comprise most of the remainder of strokes, with a smaller number due to aneurysmal subarachnoid hemorrhage.[3, 4, 5, 6] Furthermore, 20-40% of patients with ischemic infarction may develop hemorrhagic transformation within 1 week after ictus.[7, 8] Differentiating between these different types of stroke is an essential part of the initial workup of these patients, as the subsequent management of each will be vastly different.

Risk factors
The risk of stroke is increased with the following factors:

Advanced age Hypertension (up to 60% of cases) Previous history of stroke Alcohol and illicit drug use, such as cocaine and other sympathomimetic drugs

Causes of hemorrhagic stroke include the following:

Cerebral amyloidosis (affects people who are elderly and may cause up to 10% of intracerebral hemorrhages) Coagulopathies (eg, due to underlying systemic disorders such as bleeding diathesis or liver disease) Anticoagulant therapy Thrombolytic therapy for acute myocardial infarction (MI) and acute ischemic stroke (can cause iatrogenic hemorrhagic transformation) Arteriovenous malformation Intracranial aneurysm Vasculitis Intracranial neoplasm

To see complete information on Genetic and Inflammatory Mechanisms in Stroke, please go to the main article by clicking here. To see complete information on Blood Dyscrasias and Stroke, please go to the main article by clicking here. In addition, complete information on the following metabolic disease and stroke can be found in the main articles:

Metabolic Disease and Stroke - Methylmalonic Acidemia Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia Metabolic Disease and Stroke - Fabry Disease Metabolic Disease and Stroke - MELAS Metabolic Disease and Stroke - Hyperglycemia/Hypoglycemia

Hypertension
The most common etiology of primary hemorrhagic stroke (intracerebral hemorrhage) is hypertension, with at least two thirds of patients with primary intraparenchymal hemorrhage 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.

Axial noncontrast computed tomography scan of the brain in a 60-year-old male with history of acute onset of left-sided weakness demonstrates 2 areas of intracerebral hemorrhage 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. 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 image (middle image) redemonstrates 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.

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 aneurysm or saccular aneurysms. Aneurysms may less commonly be related to altered hemodynamics associated with arteriovenous malformations, collagen vascular disease, polycystic kidney disease, septic emboli, and neoplasms.

Nonaneurysmal perimesencephalic subarachnoid hemorrhage may also be seen and is thought to arise from capillary or venous rupture. It has a less severe clinical course and, in general, better prognosis. Berry aneurysms are most commonly isolated lesions that form due to 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. These include the junction of the anterior communication arteries and anterior cerebral arteriesmost commonly, the MCA bifurcationthe supraclinoid internal carotid artery at the origin of the posterior communicating artery, and the bifurcation of the internal carotid artery (ICA). The pathologic effects of subarachnoid hemorrhage (SAH) on the brain are multifocal. SAH results in elevated intracranial pressure and impairs cerebral autoregulation. This, in combination with acute vasoconstriction, microvascular platelet aggregation, and loss of microvascular perfusion are also seen, resulting in profound reduction in blood flow and cerebral ischemia.[9] See the images below.

Noncontrast computed tomography (CT) scanning was performed emergently in a 71-year-old male 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 graywhite differentiation. The fluid-attenuated inversion-recovery (FLAIR) image (right) demonstrates high signal throughout the cortical sulci, basilar cisterns and in the dependent portions of the ventricles. FLAIR is highly sensitive to acute subarachnoid hemorrhage, owing to the suppression of high cerebrospinal fluid signal lending to greater conspicuity of subarachnoid hemorrhage compared with conventional magnetic resonance image

sequences. The patient above subsequently underwent a computed tomographic angiography examination and subsequent cerebral angiography. 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.

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 more frank intraparenchymal hematoma.
[6, 7, 10]

To see complete information on Reperfusion Injury in Stroke, please go to the main article by clicking here. Hemorrhagic transformation of an ischemic infarct occurs within 2-14 days post ictus, usually within the first week. It is more commonly seen following cardioembolic strokes and is more likely with larger infarct size.[6, 8, 11] Hemorrhagic transformation is also more likely following administration of tissue plasminogen activator (tPA) and with noncontrast CT scans demonstrating areas of hypodensity.[12, 13, 10] See the image below.

Noncontrast computed tomography scan (left) obtained after a 75-year-old male was admitted for cerebrovascular accident 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.

Vascular malformations and amyloid angiography

The remaining cases of spontaneous intraparenchymal hemorrhage may be secondary to vascular malformations (eg, arteriovenous malformations and cavernous malformations) or amyloid angiopathy.[6, 7, 14, 15, 16]

Epidemiology
United States statistics
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. 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.[3, 17] The incidence of stroke varies depending on age, sex, ethnicity, and socioeconomic status. For example, American Heart Association (AHA) researchers found that black persons had a 3-fold higher multivariate-adjusted risk ratio of lacunar stroke than white individuals.[3]

International statistics
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 for developing countries. According to the World Health Organization (WHO), 15 million people suffer stroke worldwide each year. 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. 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 this trend has begun to plateau. However, the increased survival among stroke victims will place an increased demand on healthcare systems globally.[6, 18] Stroke subtypes also vary greatly in different parts of the world and between different races. For example, the proportion of hemorrhagic strokes may be even 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%.[18, 19] Also, an increased proportion of intracerebral hemorrhage and lacunar infarcts have been reported in Asia.

Prognosis
The prognosis of hemorrhagic stroke varies depending on the severity of stroke and the location and the size of the hemorrhage. Lower Glasgow Coma Scale scores are associated

with poorer prognosis and higher mortality rate. A larger volume of blood at presentation is associated with a poorer prognosis. Growth of the hematoma volume is associated with a poorer functional outcome and increased mortality rate. Nonaneurysmal perimesencephalic 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 more than a 2-fold increase in death. Patients with oral anticoagulation-associated intracerebral hemorrhage have higher mortality rates and poorer functional outcomes. Endoscopic hematoma evacuation may be a promising ultra-early stage treatment for intracerebral hemorrhage that improves long-term prognosis (see Treatment and Management).[20] The 2010 guideline for management of spontaneous ICH from the American Heart Association (AHA) and American Stroke Association (ASA) notes that in studies, withdrawal of medical support or issuance of DNR orders within the first day of hospitalization are predictors of poor outcome independent of clinical factors. The writing committee has concern that current methods of early prognostication do not account for the effects of limiting care after a pessimistic estimate of prognosis. Therefore, initial therapy should probably be aggressive, and 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.[21] For more information, see Motor Recovery in Stroke.

Patient Education
For excellent patient education resources, visit eMedicine's Stroke Center. Also, see eMedicine's patient education article Stroke.

History
Obtaining an adequate history includes the onset and progression of symptoms as well as an assessment for risk factors and possible causative events. These include previous transient ischemic attack (TIA) and stroke, hypertension, diabetes, smoking, arrhythmia and valvular disease, illicit drug use, and risk factors for thrombosis. History of trauma, even if minor, may be important, as extracranial arterial dissections can result in ischemic stroke.

Symptoms alone are not specific enough to distinguish ischemic from hemorrhagic infarction. 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 or large ischemic strokes. 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. Other, more focal, symptoms of stroke include 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; and aphasia. The neurologic deficits reflect the area of the brain typically involved, and stroke syndromes for specific vascular lesions have been described. Symptoms of subarachnoid hemorrhage may include sudden onset of headache, signs of meningismus with nuchal rigidity, photophobia and pain with eye movements, nausea, and vomiting. 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 CT (NCCT) scans.

Physical Examination
Intracerebral hemorrhage may be clinically indistinguishable from ischemic stroke. Hypertension is commonly a prominent finding. 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 due to an increase in intracranial pressure. Meningismus may result from blood in the ventricles.

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 right hemiparesis, right hemisensory loss, left gaze preference, right visual field cut, and aphasia may result. If the nondominant (usually the right) hemisphere is involved, a syndrome of left hemiparesis, left hemisensory loss, right gaze preference, and left visual field cut may result. 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 of herniation and brainstem compression. Herniation may cause a rapid decrease in the level of consciousness, apnea, and death. Specific brain sites and 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 - Ataxia (usually beginning in the trunk), ipsilateral facial weakness, ipsilateral 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 and range 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.

Differentials

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
Brain imaging is a crucial step in a patient's evaluation and must be obtained on an emergent basis. Brain imaging aids in making the diagnosis of hemorrhage, and it may identify complications such as intraventricular hemorrhage, brain edema, or hydrocephalus. Either NCCT scanning or magnetic resonance imaging (MRI) of the brain is the modality of choice. Imaging has greatly evolved in the past 2 decades, and advanced CT and magnetic resonance neuroimaging techniques have been developed for improved physiologic imaging of acute stroke. These techniques allow clinicians to assess for the core infarct size and to characterize cerebral blood volume and cerebral blood flow to identify potentially salvageable tissue at risk for infarction (ie, ischemic penumbra). Some examples of these techniques include diffusion-weighted MRI (DWI) and perfusion imaging of acute stroke with magnetic resonance and CT scanning. CT scanning and magnetic resonance angiography (MRA) can give useful information regarding large-vessel occlusion, which is an important consideration, as intraarterial interventions for acute ischemic stroke are available. Although the sensitivity of CT scanning and MRI for large-vessel occlusion is conceivably similar, CT angiography (CTA) may be more practical for several reasons. For example, its more rapid image acquisition makes CTA less susceptible to motion artifacts, more accurate at depicting vascular anatomy, and more sensitive for stenosis, occlusion, vascular malformations, and aneurysms. Imaging with CT studies has multiple logistic advantages for patients with acute stroke; it is able to more rapidly acquire images than magnetic resonance studies, allowing for assessment with an examination that includes NCCT, CTA, and CT perfusion in less than 10 minutes. Expedient acquisition is of the utmost importance in acute stroke imaging

because of the narrow window of time available for definitive ischemic stroke treatment with pharmacologic agents and mechanical devices. CT 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 examination is more easily accessible for patients who require special equipment for maintaining and monitoring life support. Ultrasonography has multiple uses in the workup of stroke patients. This examination is usually performed on a nonemergent basis to evaluate cerebrovascular ischemic disease preoperatively or in the acute setting after evaluation with CT scanning or MRI. Transthoracic and transesophageal echocardiography (TTE and TEE, respectively) may also be used in assessing for cardioembolic disease and patent foramen ovale or, more acutely, to exclude thoracic aortic dissection. Conventional angiography is the gold standard in evaluating for cerebrovascular disease, as well as for disease involving the aortic arch and great vessels in the neck, 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. Angiography is also useful in preoperative evaluation for hemodynamically significant or flow limiting lesions and to confirm the presence of trickle flow versus occlusion seen on ultrasonography when considering carotid endarterectomy. Angiography is also more sensitive than MRA for detecting ulceration and is superior to both MRA and CTA for detecting vasculitis. Angiography allows for endovascular treatment with intraarterial thrombolytic therapy or mechanical thrombectomy in acute stroke and for stenting of patients with arterial stenosis intracranially or in the neck. It can also be used to characterize and treat aneurysms and vascular malformations using stents and embolic agents, such as coils or other embolic material.

Approach Considerations
The treatment and management 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. For more information, see Acute Stroke Management.

Medical Treatment

Medications used in the treatment of acute stroke include anticonvulsants to prevent seizure recurrence, antihypertensive agents to reduce BP and other risk factors of heart disease, and osmotic diuretics to decrease intracranial pressure in the subarachnoid space.

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 increased, and initiate administration of mannitol for further control. Rapidly stabilize vital signs, and simultaneously acquire emergent CT scan.

Management of seizures
Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage, and these seizures are often nonconvulsive seizures.[22, 20] Seizure activity should be rapidly controlled with a benzodiazepine, such as lorazepam or diazepam, accompanied by either phenytoin or fosphenytoin loading. Prophylactic anticonvulsant therapy is recommended in patients with lobar hemorrhages to reduce the risk of early seizures.[1, 22] However, the use of prophylactic anticonvulsant therapy in all cases of intracerebral hemorrhage is controversial, as no prospective controlled trials have demonstrated a clear benefit. According to the AHA/ASA 2010 guidelines for management of spontaneous ICH, patients with a change in mental status and whose EEG shows electrographic seizures should receive antiepileptic drugs.[21]

Blood pressure control

No controlled studies define optimum BP levels, but greatly elevated BP is thought to lead to rebleeding and hematoma expansion. Patients who have had a stroke may lose their cerebral autoregulation of cerebral perfusion pressure. Rapid or aggressive BP lowering may compromise cerebral perfusion. Nicardipine, labetalol, esmolol, and hydralazine are agents that may be used when necessary for BP control. Avoid nitroprusside because it may raise intracranial pressure. The American Heart Association guidelines for treating elevated BP are as follows[1] :

If systolic BP is >200 mm Hg or mean arterial pressure (MAP) is >150 mm Hg, then consider aggressive reduction of BP with continuous IV infusion with frequent BP (every 5 min) checks. If systolic BP is >180 mm Hg or MAP is >130 mm Hg and there is evidence or suspicion of elevated intracranial pressure, then consider monitoring of intracranial pressure and reducing BP using intermittent or continuous IV medications to maintain cerebral perfusion pressure >60-80 mm Hg. If systolic BP is >180 or MAP is >130 mm Hg and there is NOT evidence or suspicion of elevated intracranial pressure, then consider modest reduction of BP

(target MAP of 110 mm Hg or target BP of 160/90 mm Hg) with BP checks every 15 minutes. One prospective study found a hazard ratio of 1.89 for the risk of poor outcome for each 10% decrease in systolic BP in the first 24 hours of an acute stroke.[23] Another study found that the use of calcium channel blockers acutely lowered diastolic BP and was associated with worse outcomes.[24] Current recommendations include avoiding more than 10% reduction of BP within the first 24 hours, unless values exceed certain thresholds. These values, which are not based on any specific randomized studies, are 220 mm Hg systolic (some recommend 200 mm Hg systolic) and 115 mm Hg diastolic. Suggested agents for use in the acute setting are betablockers (eg, labetalol) and angiotensin-converting enzyme inhibitors (ACEIs) (eg, enalapril). For more refractory hypertension, agents such as nicardipine, nitroprusside, and hydralazine are used.

Medical treatment of increased intracranial pressure

Elevated intracranial pressure may result from the hematoma itself, surrounding edema, or both. The frequency of increased intracranial pressure in patients with intracerebral hemorrhage is not known. Elevate the head of the bed to 30 degrees. 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. More aggressive therapies such as osmotic therapy (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 (CPP) 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.[25] Hyperventilation (partial pressure of carbon dioxide [PaCO2] of 25 to 30-35 mm Hg) is not recommended, because its effect is transient, it decreases CBF, and it may result in rebound elevated intracranial pressure.[1] Glucocorticoids are not effective and result in higher rates of complications with poorer outcomes. Antacids are used to prevent gastric ulcers associated with intracerebral hemorrhage.

Ventriculostomy
Ventriculostomy (CSF drainage by intraventricular catheter drainage) 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 high rates of complications, including bacterial meningitis.

Endoscopic hematoma evacuation

Endoscopic hematoma evacuation may be a promising ultra-early stage treatment for intracerebral hemorrhage that improves long-term prognosis.[20]

Hemostatic therapy
Much interest has been generated to determine if treatment with hemostatic therapy to stop ongoing hemorrhage or prevent hematoma expansion may be effective. A preliminary study of treatment with recombinant factor VIIa demonstrated reduced mortality and improved functional outcomes. Unfortunately, the results of the larger randomized trial revealed no overall benefit of treatment. Hemostatic therapy with recombinant activated factor VIIa (rFVIIa) reduced growth of the hematoma but did not improve survival or functional outcome.[26] Diringer et al found that higher doses of rFVIIa in a high-risk population are associated with a small increased risk of what are usually minor cardiac events.[27] Their study randomized the use of 20 or 80 mcg/kg rFVIIa or placebo in 841 patients who presented less than 3 hours after spontaneous intracerebral hemorrhage.[27] Although venous events were similar among the groups, arterial events were associated with receiving 80 mcg/kg dose of rFVIIa, cardiac or cerebral ischemia at presentation , advanced age, or antiplatelet use.[27] The investigators concluded that additional research is needed to measure the benefit of hemorrhage control in patients with cerebral hemorrhage with the risk for arterial thromboembolic events. Currently, no effective targeted therapy for hemorrhagic stroke exists. Further studies are necessary to develop other potential treatment options.

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: over one half of patients die within 30 days. Most episodes occur with a therapeutic international normalized ratio (INR), but overanticoagulation is further associated with an increased risk of bleeding. Reversal of warfarin anticoagulation is a true medical emergency and must be accomplished as quickly as possible to prevent further hematoma expansion. Warfarin reversal options include IV vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrates (PCC), and rFVIIa. Because vitamin K requires more than 6 hours to normalize the INR, it should be administered with either FFP or PCC. FFP needs to be

given 15-20 mL/kg and therefore requires a large volume infusion. PCC contains high levels of vitamin K-dependent cofactors, with a smaller volume of infusion than FFP, resulting in more rapid administration. If available, PCC is preferable over FFP as a reversal agent.[28, 29] Based upon the available medical evidence, the use of FVIIa is currently not recommended over other agents. Patients on heparin (either unfractionated or low molecular weight heparin [LMWH]) who develop a hemorrhagic stroke should immediately have anticoagulation reversed with protamine.[1] The dose of protamine is dependent upon the dose of heparin that was given and the time elapsed since that dose. Fore more information, see the article on Reperfusion Injury in Stroke. The 2010 AHA/ASA guideline for management of spontaneous ICH recommends factor replacement therapy for patients with spontaneous ICH and a severe coagulation factor deficiency.[21]

Reversal of antiplatelet therapy and platelet dysfunction

Patients on antiplatelet medications including aspirin, aspirin/dipyridamole (Aggrenox), and clopidogrel should be given desmopressin (DDAVP) and platelet transfusion. 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 ICH recommends platelet therapy for patients with spontaneous ICH and severe thrombocytopenia.[21]

Management of glucose
The 2010 AHA/ASA guideline for spontaneous ICH states that glucose levels should be monitored, with normoglycemia recommended.[21]

Surgical Intervention
Craniotomy and clot evacuation
A potential treatment of hemorrhagic stroke is surgical evacuation of the hematoma. The role of surgical treatment for supratentorial intracranial hemorrhage remains controversial. Outcomes in published studies are conflicting. A published meta-analysis of studies suggested some promise for early surgical intervention. However, one study comparing early surgery versus initial conservative treatment failed to demonstrate a benefit with surgery.[30] Surgical intervention for cerebellar hematoma has been shown to improve outcome. It can be lifesaving in the prevention of brainstem compression.

Endovascular treatment of aneurysms

Endovascular therapy using coil embolization has been increasingly used in recent years with great success as an alternative to surgical clipping (see the following images), although controversy still exists over which treatment is ultimately superior.

A cerebral angiogram was performed in a 57-year-old male 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 in the same patient as above following coil embolization. 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.[31] This randomized, multicenter trial was conducted mainly in the United Kingdom and Europe and was the largest of its type, with 2143 patients. The investigators also noted that the small risk of late rebleeding found in both groups was higher in the endovascular coiling group, reconfirming the higher long-term anatomic cure rate of surgery.[31, 32] Endovascular treatment of aneurysms may be favored over surgical clipping when the aneurysm is in a location that is difficult to access surgically, such as cavernous ICA or basilar terminus; when the aneurysms are small-necked and located in the posterior fossa; when the patients are elderly; and when the patients have a poor clinical grade.[33]

Factors mitigating against endovascular treatment include wide-based aneurysms or those without an identifiable neck; aneurysms with a vessel extending off the aneurysm dome; and patients with severely atherosclerotic or tortuous vessels that limit the endovascular approach. Vasospasm may be treated with intra-arterial pharmaceutical agents, such as verapamil or nicardipine, or with balloon angioplasty for opening larger vessels (see the images below). The combination of the 2 treatments appears to provide safe and long-lasting therapy of severe clinical significant vasospasm.[34]

Frontal view from a cerebral angiogram in a 41-year-male who presented 7 days before with subarachnoid hemorrhage from a ruptured anterior communicating artery (ACA) aneurysm 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 the same patient as above (image on left) with superimposed road map image to demonstrate placement of a wire across the left M1 segment and balloon angioplasty. The left proximal anterior communicating artery (ACA) and supraclinoid internal carotid artery (ICA) were also angioplastied and intraarterial 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. For more information, see Mechanical Thrombolysis in Acute Stroke and Cerebral Revascularization.

Prevention of Hemorrhagic Stroke

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).[35] In this analysis, level of physical fitness was a more powerful risk factor than LDL cholesterol level, body mass index, and smoking, and it was nearly comparable to hypertension as a risk factor.

Antihypertensives
The 2010 AHA/ASA guideline for spontaneous ICH recommends that after acute ICH, patients without medical contraindications should have blood pressure well controlled, especially for ICH in typical hypertensive vasculopathy locations.[21] BP-lowering medications include thiazide diuretics, ACEIs, and angiotensin receptor blockers (ARBs). In the Heart Outcomes Prevention Evaluation (HOPE) study, the addition of the ACE inhibitor ramipril to all other medical therapy, including antiplatelet agents, reduced the relative risk of stroke, death, and myocardial infarction by 32% compared with placebo.[36] Only 40% of the efficacy of ramipril could be attributed to its BP-lowering effects. Postulated mechanisms included endothelial protection. In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a regimen based on perindopril, an ACEI, was superior to placebo.[37] However, perindopril alone was not superior to placebo, but the combination of perindopril with indapamide (a thiazide diuretic) substantially reduced the recurrence of stroke.[37] Much of the effect in reducing stroke recurrence was due to the lowering of BP, in contrast to findings from the HOPE study. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed slight superiority of chlorthalidone (a thiazide diuretic) compared with lisinopril (an ACEI) in terms of stroke occurrence.[38] 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.[39] The Morbidity and Mortality after Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention (MOSES) study found that the ARB eprosartan was superior in the secondary prevention of stroke and TIA compared with the calcium channel blocker nitrendipine.[40] This was true despite comparable BP reductions.[40] The absolute annual difference in stroke and TIA risk was approximately 4%. The study was relatively small, and most events were TIAs.

Whether the beneficial effect of ramipril represents a class effect of ACEIs or whether it is a property unique to ramipril is unclear. Adverse effects of ACEIs include cough (10%), which is less common with ARBs. At this time, first-line agents for the treatment of hypertension in stroke include thiazide diuretics, calcium channel blockers, ACEIs, and ARBs. Beta-blockers are considered second-line agents given their inferiority in preventing events despite similar reductions in blood pressure.

Lifestyle interventions
Smoking cessation, BP control, diabetes control, 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 the medications described above. Written prescriptions for exercise and medications for smoking cessation (nicotine patch, bupropion, varenicline) increase the likelihood of success with these interventions.

Consultations
Emergent neurosurgical or neurologic consultation is often indicated; local referral patterns may vary. Need for invasive intracranial pressure monitoring and for emergent cerebral angiography should be assessed by the neurosurgeon. Patients with no clear cause of the hemorrhage 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
The goals of pharmacotherapy for hemorrhagic stroke are to reduce morbidity and to prevent complications. Medications used in the treatment of acute stroke include anticonvulsants such as diazepam to prevent seizure recurrence, antihypertensive agents such as labetalol to reduce BP and other risk factors of heart disease, and osmotic diuretics such as mannitol to decrease intracranial pressure in the subarachnoid space.

Anticonvulsants
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. 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 IV and intramuscularly (IM), the IV route is the route of choice and should be used in emergency situations. Concomitant administration of an IV benzodiazepine will usually be necessary to control status epilepticus. The antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate. 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. In addition, a larger dose before retiring should be administered if the dose cannot be divided equally.

Benzodiazepines
Class Summary
Benzodiazepines are commonly used to control seizure activity and recurrence. Agents such as lorazepam and diazepam are often used in combination with either phenytoin or fosphenytoin loading. View full drug information

Diazepam (Diastat, Diazemuls, Valium)

Diazepam is used to control 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, as well as 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 that has become the drug of choice in many centers for treating active seizures.

Beta-adrenergic blockers
Class Summary
Beta-blockers are used to reduce blood pressure and risk factors for heart disease. Selective beta-blockers block beta-1 receptors more than beta-2 receptors; nonselective beta-blockers block both 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 IV bolus over 2 minutes, then as a continuous infusion at 2 mg/min, not to exceed 300 mg/dose. View full drug information

Esmolol (Brevibloc)

Esmolol is an ultra-short-acting agent that selectively blocks beta1-receptors with little or no effect on beta2-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 betablockade, particularly those with reactive airway disease, mild to moderate left-ventricular dysfunction, and/or peripheral vascular disease.

Vasodilators
Class Summary
Vasodilators lower blood pressure through direct vasodilation and relaxation of the vascular smooth muscle. 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.

Calcium channel blockers

Class Summary
Calcium channel blockers are used to lower blood pressure by relaxing the blood vessels and increasing the amount of blood and oxygen that is delivered to the heart while reducing the hearts workload. View full drug information

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
ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. Some examples of ACE inhibitors include enalapril (Vasotec), ramipril (Altace) and lisinopril (Zestril). View full drug information

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 control blood pressure and proteinuria. View full drug information

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. View full drug information

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
Angiotensin-receptor blockers may be used as an alternative to ACE inhibitors in patients who develop adverse effects, such as a persistent cough. Examples of angiotensin receptor blockers are losartan (Cozaar), valsartan (Diovan), and candesartan (Atacand). View full drug information

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 ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. View full drug information

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 ACE inhibitors, does not affect response to bradykinin, and is less likely to be associated with cough and angioedema. View full drug information

Valsartan

Valsartan produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.

Thiazide Diuretics
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. Examples of thiazide diuretics are hydrochlorothiazide and chlorthalidone. View full drug information

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. View full drug information

Chlorthalidone (Thalitone)

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

Osmotic Diuretics
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. View full drug information

Mannitol (Osmitrol)

Mannitol reduces cerebral edema with help of osmotic forces as well as decreases blood viscosity, resulting in reflex vasoconstriction and lowering of intracranial pressure.

Antipyretics, Analgesics
Class Summary
As hyperthermia may exacerbate neurologic injury, these agents may be given to reduce fever and relieve pain. View full drug information

Acetaminophen (Tylenol, Feverall, Aspirin Free Anacin)

Acetaminophen reduces fever, maintains normothermia, and reduces headache.

Vitamin, Fat Soluble

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. View full drug information

Phytonadione (Mephyton)

Phytonadione can overcome the competitive block produced by warfarin and other related anticoagulants. Vitamin K-3 (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 amount of anticoagulant ingested and whether it is a short-acting or long-acting anticoagulant.

Blood products
Class Summary
These agents are indicated for the correction of abnormal hemostatic parameters. View full drug information

Fresh Frozen Plasma

Fresh frozen plasma is the fluid component of blood containing the soluble clotting factors that has been separated from a unit of blood and frozen to be used in patients with bloodproduct deficiencies. View full drug information

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. View full drug information

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.

Heparin antidote
Class Summary
This agent is used to neutralize the effects of anticoagulants.

Protamine sulfate

Protamine sulfate forms a salt with heparin and neutralizes its effects. The dosage administered is dependent on the time since heparin was given.

Hemostatic Agents
Class Summary
These agents improve bleeding time and hemostasis. View full drug information

Desmopressin acetate (DDAVP, Stimate)

Releases von Willebrand protein from endothelial cells. Improves bleeding time and hemostasis in patients with some vWf (mild and moderate von Willebrand disease without abnormal molecular forms of von Willebrand protein). Effective in uremic bleeding. Tachyphylaxis usually develops after 48 h, but the drug can be effective again after several days.