Denise Nassisi, MD,
Assistant Professor, Department of Emergency
Medicine, Mount Sinai Medical Center
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Francisco Talavera, PharmD, PhD,
Senior Pharmacy Editor,
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J Stephen Huff, MD,
Associate Professor, Emergency Medicine and
Neurology, Department of Emergency Medicine, University of
Virginia Health Sciences Center
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John D Halamka, MD, MS,
Associate Professor of Medicine, Harvard
Medical School, Beth Israel Deaconess Medical Center; Chief
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Medicine, Beth Israel Deaconess Medical
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Richard S Krause, MD,
Senior Faculty, Department of Emergency
Medicine, State University of New York at Buffalo School of
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Rick Kulkarni, MD,
Assistant Professor of Surgery, Section of
Emergency Medicine, Yale-New Haven Hospital
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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.
Acute ischemic stroke refers to stroke caused by thrombosis or embolism and is more common than hemorrhagic stroke. Prior literature indicates that only 8-18% of strokes were hemorrhagic. However, a recent retrospective review from a stroke center found that 40.9% of 757 strokes were hemorrhagic. However, the authors state that the increased percentage of hemorrhagic stroke may be due to improvement of CT scan availability and implementation unmasking a previous underestimation of the actual percentage, or it may be due to an increase in therapeutic use of antiplatelet agents and warfarin causing an increase in the incidence of hemorrhage.
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.
An intracerebral hemorrhage is shown in the CT below.
Large intracerebral hemorrhage with midline shift.
In intracerebral hemorrhage (ICH), 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.
Intracerebral hemorrhage accounts for 10-15% of all strokes. Recent reports indicate an incidence exceeding 500,000 new strokes of all types per year.
Stroke is a leading killer and disabler. Combining all types of stroke, it is the third leading cause of death and the first leading cause of disability.
Morbidity is more severe and mortality rates are higher for hemorrhagic stroke than for ischemic stroke. Only 20% of patients regain functional independence.
The 30-day mortality rate for hemorrhagic stroke is 40-80%. Approximately 50% of all deaths occur within the first 48 hours.
A recent study of 474 ICH patients found that for those younger than 75 years of age, male sex predicted a poor outcome. Within 28 days, 20% of women and 23% of men died (P=0.38); in those 75 years or older, the corresponding figures were 26% and 41%, respectively (P=0.02). Other independent predictors of death were high age, central and brainstem hemorrhage location, intraventricular hemorrhage, increased volume, and decreased level of consciousness.
African Americans have a higher incidence of hemorrhagic and ischemic strokes than other races in the United States. The incidence of hemorrhagic stroke in the Japanese population is increased.
Patients' symptoms vary depending on the area of the brain affected and the extent of the bleeding.
Hemorrhagic strokes are more likely to exhibit symptoms of increased intracranial pressure than other types of stroke.
Headache, often severe and sudden onset
Nausea and/or vomiting
Seizures are more common in hemorrhagic stroke than in ischemic stroke. They occur in up to 28% of hemorrhagic strokes and generally occur at the onset of the intracerebral hemorrhage (ICH) or within the first 24 hours.
Intracerebral hemorrhage (ICH) may be clinically indistinguishable from ischemic stroke.
Hypertension is commonly a prominent finding.
An altered level of consciousness 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 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 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 a 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.
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 (ICH), ranging from mild headache to neurologic devastation. At times, a cerebral hemorrhage may present as a new-onset seizure.
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. It may identify complications including intraventricular hemorrhage, brain edema, or hydrocephalus. Either noncontrast CT or MRI of the brain is the modality of choice.
Noncontrast CT of the brain
Noncontrast CT differentiates hemorrhagic stroke from ischemic stroke.
It is useful in distinguishing stroke from other intracranial pathology.
Noncontrast CT can identify virtually all intracerebral hematomas greater than 1 cm in diameter.
CTs of intracerebral hemorrhage are shown below.
CT scan of right frontal intracerebral hemorrhage complicating thrombolysis of an ischemic stroke.
A 59-year-old female with hypertension who presented with left-sided weakness demonstrated a right putaminal hemorrhage on noncontrast CT examination ....
A 62-year-old female with hypertension who presented with acute-onset ataxia and confusion. Noncontrast CT examination of the head showed a large righ....
In the past, noncontrast CT was the criterion standard for diagnosing hemorrhagic stroke. Recent progress has demonstrated that current MRI techniques are capable of accurately diagnosing hemorrhagic stroke.
MRI, especially newer techniques such as diffusion-weighted imaging, has been shown to identify ischemic stroke earlier and more reliably than CT scanning. MRI is being used with increasing frequency in the evaluation of ischemic stroke.
MRI may identify an underlying vascular malformation or lesion that caused the bleeding.
Intracerebral hemorrhage associated with a right frontal arteriovenous malformation is shown below.
Fluid-attenuated inversion-recovery, T2-weighted, and gradient echo MRI illustration of intracerebral hemorrhage associated with a right frontal arter....
Head CT should be obtained in patients with contraindications to MRI.
Chest radiography should be obtained to screen for comorbid conditions.
Assess the ABCs. Address any compromise in the patient's status as clinically indicated.
Establish intravenous (IV) access.
Obtain bedside glucose determination.
Hypoglycemia may mimic stroke.
Hyperglycemia has been associated with poorer outcomes in patients experiencing stroke. (Also see Metabolic Disease & Stroke: Hyperglycemia/Hypoglycemia.)
Institute cardiac monitoring and obtain an ECG.
Intubation should be performed for patients who demonstrate potential loss of airway protective mechanisms or signs of brainstem dysfunction. If intubation is needed, rapid sequence intubation should be performed with technique and medications aimed at limiting any increase in intracranial pressure.
Early seizure activity occurs in 4-28% of patients with intracerebral hemorrhage, and these seizures are often nonconvulsive seizures.[5, 6]
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.[5, 1] 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.
Careful blood pressure (BP) monitoring is important.
No controlled studies define optimum BP levels.
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:
If systolic BP is >200 mm Hg or mean arterial pressure (MAP) is >150 mm Hg, then consider aggressive reduction of BP with continuous intravenous 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 (ICP), then consider monitoring of ICP and reducing BP using intermittent or continuous intravenous 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 ICP, 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.
Intracranial pressure control:
Elevated intracranial pressure (ICP) may result from the hematoma itself, surrounding edema, or both. The frequency of increased ICP in patients with intracerebral hemorrhage (ICH) is not known.
Elevate the head of the bed to 30 degrees. This improves jugular venous outflow and lowers ICP. 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 ICP and BP with an ICP monitor to maintain adequate cerebral perfusion pressure (CPP) of above 70 mmHg. A randomized controlled study of mannitol in ICH failed to demonstrate any difference in disability or death at 3 months.
Hyperventilation (paCO2 of 25-30-35 mm Hg) is not recommended. Its effect is transient, it decreases cerebral blood flow, and it may result in rebound elevated intracranial pressure.
Glucocorticoids are not effective and result in higher rates of complications with poorer outcomes.
Ventriculostomy (cerebrospinal fluid drainage by intraventricular catheter drainage) is often used in the setting of obstructive hydrocephalus. Obstructive hydrocephalus 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.
Much interest has been generated to determine if treatment with hemostatic therapy to stop ongoing hemorrhage or prevent hematoma expansion may be effective.
Recombinant factor VIIa
A preliminary study of treatment with recombinant factor VIIa demonstrated reduced mortality and improved functional outcomes. However, unfortunately, the results of the larger randomized trial revealed no overall benefit of treatment. Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome.
Diringer et al conducted a study using recombinant activated factor VIIa (rFVIIa) in patients (n=841) presenting less than 3 hours after spontaneous intracerebral hemorrhage. Patients considered at higher risk for thromboembolic events (eg, Glasgow Coma Scale score < 5, planned early surgery, coagulopathy, recent thromboembolic event) were excluded. Participants were randomized to receive 20 or 80 mcg/kg of rFVIIa, or placebo. Venous events were similar between groups. Arterial events were associated with receiving 80 mcg/kg dose of rFVIIa (P=0.031), cardiac or cerebral ischemia at presentation (P=0.01), advanced age (P=0.0123), or antiplatelet use (P=0.035). 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.
Patients on warfarin have an increased incidence of hemorrhagic stroke. Morbidity and mortality for warfarin associated bleeding is high, over half of patients die within 30 days. Most episodes occur with a therapeutic 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 recombinant factor VIIa.
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. Prothrombin complex concentrate 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.[10, 11]
Based upon the available medial evidence, the use of factor VIIa is currently not recommended over other agents.
Patients on heparin (either unfractionated or low molecular weight heparin) who develop a hemorrhagic stroke should immediately have anticoagulation reversed with protamine.
The dose of protamine is dependent upon the dose of heparin that was given and the time elapsed since that dose.
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).
Emergent neurosurgical or neurological consultation often is indicated; local referral patterns may vary.
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.
Surgical intervention for cerebellar hematoma has been shown to improve outcome. It can be lifesaving in the prevention of brainstem compression.
Need for invasive intracranial pressure monitoring should be assessed by the neurosurgeon.
Need 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.
Diphosphate ester salt of phenytoin that acts as water-soluble prodrug of phenytoin. Following administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde and phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
To avoid need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express dose as phenytoin sodium equivalents (PE). Although can be administered IV and IM, IV route is 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.
Useful in controlling active seizures and should be augmented by longer-acting anticonvulsants, such as phenytoin or phenobarbital.
Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. Also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.
Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.
Individualize dosage and increase cautiously to avoid adverse effects.
Ultra–short-acting agent that selectively blocks beta1-receptors with little or no effect on beta2-receptor types. Particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Shown to reduce episodes of chest pain and clinical cardiac events compared to placebo. Can be discontinued abruptly if necessary. Useful in patients at risk for experiencing complications from beta-blockade; particularly those with reactive airway disease, mild-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.
Decreases systemic resistance through direct vasodilation of arterioles. Used to treat hypertensive emergencies. The use of a vasodilator will reduce SVR, which, in turn, may allow forward flow, improving cardiac output.
These agents are used in an attempt to lower pressure in the subarachnoid space. As water diffuses from the subarachnoid space into the intravascular compartment, pressure in the subarachnoid compartment may decrease.
Can overcome competitive block produced by warfarin and other related anticoagulants. Vitamin K-3 (menadione) is not effective for this purpose. Clinical effect is delayed several hours while liver synthesis of clotting factors is initiated and plasma levels of clotting factors II, VII, IX, and X are gradually restored.
Not to be administered prophylactically. Use only if evidence of anticoagulation exists. Required dose varies with clinical situation, including amount of anticoagulant ingested and whether it is a short-acting or long-acting anticoagulant.
A mixture of vitamin K–dependent clotting factors found in normal plasma. Replaces deficient clotting factors. Provides increase in plasma levels of factor IX and can temporarily correct coagulation defect of patients with factor IX deficiency.
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.
Increased intracranial pressure and herniation are the dreaded complications of intracerebral hemorrhage. Worsening cerebral edema is often implicated in neurologic deterioration in the first 24-48 hours.
Early hemorrhage growth is associated with neurologic deterioration. Expansion of the hematoma is the most common cause of neurologic deterioration in the first 3 hours.
In patients who are initially alert, 25% will have a decrease in consciousness within the first 24 hours.
Poststroke seizures may develop.
Stroke is the leading cause of permanent disability.
The prognosis varies depending on the severity of stroke and the location and the size of the hemorrhage.
Lower Glasgow Coma 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.
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.
Other complicating medical comorbidities also affect the prognosis.
Large intracerebral hemorrhage with midline shift.
CT scan of right frontal intracerebral hemorrhage complicating thrombolysis of an ischemic stroke.
A 59-year-old female with hypertension who presented with left-sided weakness demonstrated a right putaminal hemorrhage on noncontrast CT examination of the head. Tiny hyperdense foci in the basal ganglia and pineal gland represent calcifications.
A 62-year-old female with hypertension who presented with acute-onset ataxia and confusion. Noncontrast CT examination of the head showed a large right cerebellar hemorrhage, which was evacuated to relieve the mass effect on the brainstem and fourth ventricle.
Fluid-attenuated inversion-recovery, T2-weighted, and gradient echo MRI illustration of intracerebral hemorrhage associated with a right frontal arteriovenous malformation.