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Mayo Clin Proc. March, 2005;80:420-433

Emerging Medical and Surgical Management Strategies in the Evaluation and Treatment of Intracerebral Hemorrhage

From the Department of Neurology (E.M.M., J.R.F., E.F.M.W.) and Department of Neurologic Surgery (J.L.D.A.), Mayo Clinic College of Medicine, Rochester, Minn.


Intracerebral hemorrhage (ICH) accounts for approximately 10% of all strokes and causes high morbidity and mortality. Rupture of the small perforating vessels of the cerebral arteries is caused by chronic hypertension, which induces pathologic changes in the small vessels and accounts for most cases of ICH; however, amyloid angiopathy and other secondary causes are being seen more frequently with the increasing age of the population. Recent computed tomographic studies have revealed that ICH is a dynamic process with up to one third of initial hemorrhages expanding within the first several hours of ictus. Secondary injury is believed to result from the development of cerebral edema and the release of specific neurotoxins associated with the breakdown products of hemoglobin. Treatment is primarily supportive. Surgical evacuation is the treatment of choice for patients with neurologic deterioration from infratentorial hematomas. Randomized trials comparing surgical evacuation to medical management have shown no benefit of surgical removal of supratentorial hemorrhages. New strategies focusing on early hemostasis, improved critical care management, and less invasive surgical techniques for clot evacuation are promising to decrease secondary neurologic injury. We review the pathophysiology of ICH, its medical management, and new treatment strategies for improving patient outcome.

Mayo Clin Proc. 2005;80(3):420-433


CBF = cerebral blood flow; CPP = cerebral perfusion pressure; CSF = cerebrospinal fluid; CT = computed tomography; FFP = fresh frozen plasma; GCS = Glasgow Coma Scale; ICH = intracerebral hemorrhage; ICP = intracranial pressure; IV = intravenous; IVH = intraventricular hemorrhage; MAP = mean arterial pressure; SAH = subarachnoid hemorrhage; STICH = Surgical Trial in Intracerebral Haemorrhage

Intracerebral hemorrhage (ICH) is a common devastating neurologic event that causes high morbidity and mortality with profound economic implications. Unlike the declining mortality with subarachnoid hemorrhage (SAH) due to improvements in surgical and critical care techniques, the morbidity and mortality of ICH have remained relatively unchanged throughout the past several decades. Recent advances in our understanding of the pathophysiology involved in the development and progression of ICH have suggested a considerable amount of neurologic damage after the initial ICH event. New medical strategies and surgical techniques have been developed to prevent or treat secondary complications. We review our current understanding of these mechanisms and treatment options.


Intracerebral hemorrhage is bleeding that occurs directly into the brain parenchyma. It is differentiated from intraventricular hemorrhage (IVH) and SAH, which involve bleeding into the brain’s ventricular system and subarachnoid space, respectively. Often, ICH is classified as primary (unrelated to congential or acquired lesions), secondary (directly related to congenital or acquired conditions), and/or spontaneous (not secondary to trauma or surgery).

Intracerebral hemorrhage is common, with an estimated prevalence of 37,000 cases per year in the United States.1 It is twice as prevalent as SAH2 and accounts for approximately 10% of all strokes. The prevalence of ICH is expected to increase as the population ages and the racial demographics change in the United States.3

Incidence rates vary on the basis of age, race, and demographics. The most recent population-based studies using computed tomographic (CT) verification estimate that the overall incidence of ICH is between 12 and 15 cases per 100,000 population.4 There is a slight male predominance.1 The incidence of ICH increases exponentially with increasing age, with rates doubling every 10 years after age 35 years.2 The overall mean age for patients with ICH is 61 years.5 Incidence rates are estimated to be twice as high in African American, Hispanic, and Japanese populations.6-9 The reason for the large discrepancy among populations is unclear but probably is accounted for by differences in education, poor control of hypertension, and lack of health care availability.6 Alcohol consumption and low serum cholesterol levels have been theorized to account for some differences in the Japanese population.7,8 Hispanics may have an increased rate of cavernous angiomas.9

The economic burden of ICH is substantial. Estimated lifetime costs, including patient care and lost productivity, are $125,000 per person per year with an aggregate cost of $6 billion per year in the United States. In comparison, estimated lifetime costs are $5.6 billion per year for SAH and $29.0 billion per year for ischemic stroke.10-12

Morbidity and mortality associated with ICH are dismal, with 30-day mortality ranging between 30% and 40% in hospital-based studies13,14 to as high as 52% in community-based studies.15,16 The annual mortality rate after 30-day survival was 8% per year for 5 years in 1 community-based study with almost half of all later deaths attributed to complications of the original hemorrhage (myocardial infarction, sudden death, extracranial hemorrhage, pneumonia, etc).17 Only 21% to 38% of patients with ICH were independent at 6 months.15


Some of the many causes of ICH are listed in approximate descending order in Table 1. Intracerebral hemorrhage secondary to pathologic changes initiated by chronic hypertension is responsible for approximately 75% of all cases of primary ICH.18 More recent clinical and pathologic series have reported a lower percentage.19 Cerebral amyloid angiopathy, the next most common cause of primary ICH, is distinct from systemic amyloidosis and leads to the infiltration of amyloid protein into the media and adventitia of the cortical arterioles of the brain. Its prevalence increases with age; more than 60% of autopsy samples from patients older than 90 years exhibit some degree of amyloid deposition. Cerebral amyloid angiopathy is estimated to account for more than 20% of all ICH in patients older than 70 years.20

Underlying vascular abnormalities such as arteriovenous malformations, cerebral aneurysms, or cavernous angiomas are an important cause of secondary ICH. The exact frequency of their occurrence is difficult to establish but may approximate 5% of all ICH. Vascular abnormalities occur primarily in younger populations, accounting for approximately 38% of ICH in patients younger than 45 years.21 Bleeding directly into primary or metastatic brain tumors is another cause of secondary ICH but accounts for less than 10% of all ICH.22

A growing source of secondary ICH, anticoagulant or fibrinolytic use accounts for approximately 10% of all ICH. Long-term anticoagulant use increases the risk of ICH 10-fold.22,23 The National Institute of Neurological Disorders and Stroke (NINDS) trial rated the overall risk of ICH after tissue plasminogen activator use for ischemic stroke to be 6.4%.24 A recent reanalysis of these data cited several risk factors for ICH: age older than 70 years, serum glucose level greater than 300 mg/dL, National Institutes of Health stroke score higher than 20, and early ischemic changes detected on CT.25

Sudden severe elevation in blood pressure is another source of ICH seen commonly in malignant hypertension but rarely after carotid endarterectomy. Intracranial hemorrhage due to cocaine, amphetamine, or phenylpropanolamine use may be secondary to sudden elevation in blood pressure, multifocal cerebral vessel spasm, or drug-induced vasculitis.22

Causes of Spontaneous Intracerebral Hemorrhage*



Secondary hemorrhages into brain areas after ischemic stroke or due to cerebral venous thrombosis can occur and reflect bleeding into compromised brain. Small areas of microhemorrhage can coalesce in a delayed fashion after severe head trauma. This occurs commonly at gray and white matter interfaces and usually reflects substantial pathologic damage.

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The most notable and modifiable risk factor for ICH is the presence of hypertension.26 Hypertension, detected in most patients with ICH, is the basis for the term hypertensive hemorrhage. Risk of ICH appears to be related to the severity and the duration of hypertension. The exact quantification of risk is difficult to ascertain, but a response curve similar to the pack-year concept with smoking probably exists.4 Thus, short-term severe hypertension may have the same risk and effect as mild hypertension sustained for a longer period. Control of hypertension notably decreases the risk of ICH, although this effect appears to have plateaued in the 1980s.19

Several case-control studies have implicated heavy alcohol intake as a risk factor for ICH.27-31 This effect may be mediated partially by hypertension, although studies controlling for hypertension have supported an independent effect of alcohol.29,30 The reason for this may relate to impaired coagulation or platelet function or an increase in cardiac arrhythmias leading to increased cardioembolic hemorrhagic infarctions.31

The Multiple Risk Factor Intervention Trial32 and a recent case-control study33 reported that cholesterol levels lower than 160 mg/dL imparted a 3-fold increased risk of ICH in hypertensive middle-aged men. However, this finding was not verified by other cohort studies.34,35 Similarly, cardiac studies evaluating reductase inhibitors observed no increase in ICH, although these studies were not designed to study this effect.36,37 The effect of low cholesterol levels on ICH requires further confirmation.38


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

A higher incidence of a point mutation in the gene involved in the formation of factor XIII, responsible for fibrin cross-linking, has been reported in patients with ICH.39 Other reported risk factors include aspirin use, epistaxis, and smoking.40,41 Also, there may be some seasonal variation in the incidence of ICH, with a greater occurrence of ICH reported in the colder months.42

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Intracranial hemorrhage secondary to hypertension occurs in areas of the brain that are perfused by the perforating arteries that arise directly from the large basal cerebral arteries (Figure 1). These perforating arteries are directly exposed to the effects of hypertension because they lack the protection normally afforded by a preceding gradual decrease in vessel caliber.43 Chronic hypertension induces a series of pathologic changes that lead to segmental constriction of these vessels. This process was labeled lipohyalinosis by Fisher.44

Lipohyalinosis represents 2 pathologic processes that include atherosclerosis of the larger (100-500 ?m) perforating arteries and arteriolosclerosis of the smaller (<100 ?m) perforating vessels. Atherosclerosis occurs most commonly at the branch points of vessels and is characterized by subintimal fibroblast proliferation accompanied by deposition of lipid-filled macrophages. Arteriolosclerosis involves the replacement of smooth muscle cells in the tunica media with collagen.43 These processes result in the development of noncompliant, narrowed vessels that are susceptible to both sudden closure (lacunar infarction) or rupture (ICH). The mechanism of actual hemorrhage is presumably due to rupture of these fragile vessels, but this has been difficult to prove pathologically. Cerebral micro-aneurysms, described by Charcot and Bouchard45 and further delineated by Fisher,46 are described in only a small number of patients. Hemorrhagic expansion of fibrin or bleeding globules of tissue have been described but are believed to be limited to ICH secondary to sudden elevations in blood pressure.43

A substantial amount of tissue damage occurs after an initial hemorrhage. Traditionally, ICH was believed to cause secondary damage by the local mass effect of an expanding hematoma. However, animal models have failed to reveal a local pressure effect of an introduced nonhemorrhagic focal mass.47 It is now believed that the initial hemorrhage dissects along the white matter tissue planes of the brain, encircling islands of intact neural tissue. Neurologic deterioration after this point often is attributed to the development of cerebral edema,48 which appears within hours secondary to clot retraction with extrusion of plasma proteins into the underlying white matter. Later, delayed thrombin formation may contribute directly to neural toxicity or indirectly through damage to the blood-brain barrier with subsequent worsening of vasogenic edema. Peak edema occurs 3 to 7 days after the hemorrhage and correlates with lysis of red blood cells. Both hemoglobin and its degradation products have been implicated in direct and indirect neural toxicity.48,49 The importance of the development of cerebral edema in ICH has been supported by retrospective evidence suggesting that patients with a larger amount of cerebral edema relative to the initial hemorrhage volume have worse clinical outcomes.50

The role of ischemia in the pathophysiology of ICH is unclear. Numerous cerebral blood flow (CBF) studies have described an area of decreased perfusion surrounding a cerebral hemorrhage,51-53 suggesting that large areas of brain surrounding ICH may be at risk of ischemia. Glutamate and other excitotoxins have been reported in cases of ICH.54,55 Similarly, DNA markers of cell damage and apoptosis have been noted in perihematomal tissue.56,57 However, recent positron emission tomographic data have caused researchers to question the role of ischemia in ICH.58 Zazulia et al58 reported a normal oxygen extraction ratio in the perihematomal region, suggesting that this region is not ischemic and that the decreased perfusion occurs in response to decreased cerebral metabolism.

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The clinical presentation of ICH depends on the size, location, and presence of intraventricular extension of the hemorrhage. Headache of variable intensity always occurs and may be accompanied by nausea and vomiting, focal signs, and progressive neurologic deficits. The deficits may not follow a typical infarction distribution pattern seen in patients with large artery strokes.4 Seizures occur in approximately 10% of all patients with ICH and in almost one half of patients with lobar hemorrhage.20,59 Almost all seizures occur at onset of bleeding or within the first 24 hours of ictus and are not predictive of the development of delayed epilepsy.60

Patients with large hemorrhages present in stupor or coma. This may be secondary to elevated intracranial pressure (ICP) leading to decreased cerebral perfusion or due to direct infiltration or distortion of diencephalic or brainstem structures.3 Patients with blood extending into the ventricular system often experience a reduced level of alertness because of ventricular ependymal irritation or the development of hydrocephalus.

Clinically, putaminal hemorrhages present with contralateral motor deficits, gaze paresis, aphasia, or hemineglect. Thalamic hemorrhages also present with contralateral sensory loss. Pupillary and oculomotor abnormalities may coexist if the thalamic hemorrhage extends into the rostral brainstem. It is important to recognize cerebellar hemorrhages, which present with nausea, vomiting, ataxia, nystagmus, decreased level of consciousness, and ipsilateral gaze palsies or facial paralysis. Pontine hemorrhages are not subtle, presenting with coma, pinpoint pupils, disturbed respiratory patterns, autonomic instability, quadriplegia, and gaze paralysis. Almost all pontine hemorrhages are fatal. Lobar hemorrhages present according to the location of the hemorrhage.3,20,60,61

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The diagnostic study of choice in ICH is noncontrasted head CT. Clinical criteria alone are insufficient for diagnosis.1 Head CT provides a substantial amount of information, including the size and location of the hemorrhage and the presence of intraventricular, subarachnoid, or subdural blood. It clearly differentiates ICH from nonhemorrhagic cerebral infarctions and may reveal an underlying structural abnormality. Hemoglobin appears bright on noncontrasted head CT but in extremely rare instances such as severe anemia may become isodense.1,60

Magnetic resonance imaging is sensitive for detecting ICH; it is useful for dating hemorrhages and for identifying small vascular lesions that may be missed with conventional CT. Magnetic resonance imaging is limited in early detection of ICH by the time required to obtain imaging and by the limited ability to monitor a patient while in the scanner.1,60,61

The location of a hemorrhage may provide information about the underlying etiology. Hemorrhages that originate in the deep subcortical structures (putamen, caudate, thalamus), pons, cerebellum, or periventricular deep white matter (Figure 1), particularly in patients with a history of hypertension, result from rupture of the deep perforating arteries. Single or multiple hemorrhages in elderly persons that extend to the cortical surface are most likely attributable to amyloid angiopathy. A system has been proposed and supported by neuropathologic studies for the diagnosis of ICH related to cerebral amyloid angiopathy.62,63

The role of cerebral angiography in ICH has been addressed by 2 studies. Zhu et al64 reported low yield from cerebral angiography in identifying an underlying lesion in patients older than 45 years who had a history of hypertension and had hemorrhages in deep subcortical structures. However, Halpin et al65 reported finding an underlying lesion in 84% of patients (32/38) that appeared to have some structural abnormality detected on previous neuroimaging. Findings on CT that should prompt cerebral angiography include the presence of subarachnoid or intraventricular blood, an abnormal calcification or prominent draining vein, or blood that extends to the perisylvian or interhemispheric fissure (Figure 2).65 Current recommendations are to consider angiography for young patients with no clear source of hemorrhage who may be surgical candidates. Angiography is not required for older patients with hemorrhages in locations typically associated with hypertension.1


FIGURE 2. Expansion of an initial intracerebral hemorrhage. An 82-year-old man with a history of hypertension and cigarette smoking presented to the emergency department immediately after developing a severe headache and right-sided hemiparesis. The initial computed tomogram (left) revealed an intracerebral hemorrhage into the left basal ganglia. Approximately 3 hours after ictus, the patient abruptly deteriorated neurologically into a coma. Emergent computed tomogram (right) revealed a large increase in size of the initial hemorrhage with extension into the ventricular system.

A complete laboratory evaluation, including a complete blood cell count, serum electrolytes, and coagulation profile, as well as chest radiography and electrocardiography, is important to detect underlying infections, hemorrhages, electrolyte disturbances, or myocardial ischemia that may accompany ICH.


Traditionally, ICH was believed to be a monophasic event. Subsequent neurologic deterioration was attributed to the development of cerebral edema. It is now accepted that a large percentage of patients will develop hemorrhagic expansion of their initial bleeding. Brott et al,66 in a prospective observational study of patients evaluated within the first 3 hours after ictus, described ICH expansion in 26% of patients within the first hour after hospital admission (Figure 2). Another 12% of patients experienced ICH volume expansion within 20 hours after admission. Hematoma expansion after the first 24 hours is rare.67 The ICH volume can increase by as much as 40% and is associated with neurologic deterioration.67 Attempts to identify predictive factors for hematoma expansion have been limited; however, 1 study suggested that poorly controlled diabetes mellitus and systolic blood pressure greater than 200 mm Hg on hospital admission were associated with hematoma volume expansion.68

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Initial evaluation begins with obtaining a thorough patient history of proceeding or initiating events and a thorough general physical and neurologic examination. Previous or current drug use, hemorrhages, or known structural lesions can provide important information about a potential source of hemorrhage. Left ventricular hypertrophy on electrocardiography or an enlarged heart on chest radiography or physical examination is helpful for identifying a patient with chronic hypertension. The presence of amyloid angiopathy is suggested by a history of cortical hemorrhages.

The patient’s level of consciousness must be monitored closely because neurologic deterioration can occur quickly with hematoma expansion or with rupture into the ventricular system. Poor airway control or a Glasgow Coma Scale (GCS) score of 8 or less should prompt consideration of elective endotracheal intubation. A GCS score of 8 or less is used to select patients for intubation on the basis of retrospective analysis from the traumatic coma data bank that discovered an increased rate of aspiration pneumonia in comatose patients.69 More recent evidence suggests that an adequate cough and clearance of secretions may be all that is necessary to maintain airway patency.70 However, episodic oxygen desaturation or other evidence of presumptive respiratory insufficiency should prompt immediate intubation.

Endotracheal intubation must be performed in a controlled setting by an experienced physician. Patients with large cerebral hemorrhages or obstructive hydrocephalus are at increased risk of elevated ICP. Pharmacological agents and intubation techniques should be used to ensure rapid and smooth airway control along with medications designed to block increases in ICP. Lidocaine (1.0-2.0 mg/kg of body weight intravenously [IV]) is administered to blunt a cough reflex that can increase ICP during intubation. Short-acting barbiturates (thiopental, 1.0-1.5 mg/kg of body weight, or propofol, 10-20 mg in incremental doses) can be used for induction.60 Etomidate (0.1-0.2 mg/kg of body weight IV) minimally affects ICP and can be used for intubation. Fasciculations can occur with use of etomidate and often are misinterpreted as seizures. Midazolam generally is avoided because of unfavorable effects on ICP60 during induction, although the clinical importance of this is uncertain. Neuromuscular paralysis ideally should be avoided and may be unnecessary in many instances. When required for airway control, a short-acting nondepolarizing agent such as atracurium besylate (0.3-0.4 mg/kg of body weight IV) or vecuronium bromide (0.2-0.3 mg/kg of body weight IV) is preferred. Paralysis should be discontinued as quickly as possible to allow for monitoring of the neurologic examination.60

Once the airway is secure, mechanical ventilation should be set to ensure adequate oxygenation and ventilation. If elevated ICP is suspected, an intermittent mandatory ventilation volume and rate should be set to attain a PCO2 of 30 to 35 mm Hg.

Isotonic IV fluids should be initiated and adjusted to correct for any electrolyte abnormalities. The goal is to achieve euvolemia and to maintain adequate intravascular volume to optimize cerebral perfusion.71 Hypervolemia worsens cerebral edema and should be avoided.

Glucose-containing solutions also should be avoided except in patients with symptomatic hypoglycemia. Hyperglycemia is detrimental to damaged brain and should be corrected. However, this correction should occur slowly because a rapid decrease in the serum glucose level decreases serum osmolality and may worsen cerebral edema.72

Patients receiving anticoagulant medications have larger hematomas and worse outcomes.73 Bleeding progresses slowly over several hours in most of these patients, necessitating immediate discontinuation and reversal of anticoagulation.71,73 The effects of warfarin can be reversed with fresh frozen plasma (FFP) and vitamin K, although the optimal dose for reversing anticoagulation is unclear. Vitamin K administered parenterally is the most rapid way to provide long-term reversal of warfarin-induced anticoagulation. Substantial improvement in anticoagulation reversal has been shown within 4 hours with use of 2 mg of IV vitamin K.74 Infusion of IV vitamin K imparts a small risk of anaphylaxis and should be given slowly. Immediate changes in coagulation require procoagulant factors usually administered as units of FFP. Full replacement of all coagulant factors can be estimated by giving FFP at 15 mL/kg of body weight. A 70-kg man requires approximately 8 U of FFP to reverse anticoagulation.75 However, rapid administration of this volume can be problematic for patients with limited cardiac reserve or intracranial compliance. Preliminary studies suggest that a prothrombin complex or factor VII concentrate may be faster and more effective in reversing anticoagulation while avoiding the difficulties of volume overload.76-78 However, use is restricted by limited availability. Anticoagulation in patients receiving heparin should be reversed with protamine sulfate.

Experience is limited in the treatment of ICH caused by thrombolytic therapy. Red blood cells, fibrinogen, cryoprecipitate, FFP, and platelets have all been recommended. The efficacy of aminocaproic acid taken as a 5-g loading dose followed by a dosage of 1 g/h is unknown.71

Seizure activity increases CBF and ICP that can result in neuronal injury and destabilization of a critically ill patient.1 Seizures should be treated immediately with IV lorazepam followed by a loading dose of phenytoin or fosphenytoin.

The role of prophylactic anticonvulsant use in ICH is controversial. American Heart Association guidelines for the management of ICH recommend prophylactic anticonvulsant therapy for 1 month, after which time therapy should be discontinued in the absence of seizures.1 Because most seizures occur at the time of ICH or shortly thereafter, our practice has been to avoid routine anticonvulsant use in ICH. Anticonvulsants are considered for patients with lobar hemorrhages, known or suspected structural lesions, or a history of seizures.

Short-term management of hypertension after ICH has been an issue of considerable debate. Hypertension after ICH is common and may persist for a few days before returning to baseline. This may be attributed to headache, high circulating levels of catecholamine, or withdrawal of antihypertensive medications. Hypertension after ICH also may be initiated by brainstem-mediated release of catecholamines in response to increased ICP. Sympathetic outflow can be substantial and has important management implications.

Advocates of aggressive blood pressure control express concerns of hematoma expansion and worsening cerebral edema after ICH.78 Hypertension after ICH has been reported as a poor prognostic indicator in some outcome studies,79,80 and 1 observational study reported better outcomes in patients with ICH whose blood pressure was maintained below a mean arterial pressure (MAP) of 125 mm Hg.81 The only randomized trial comparing antihypertensive treatment after ICH to placebo was performed in the era before CT and has been criticized for significant differences between treatment groups.82

Cerebral blood flow studies consistently have described an area of decreased blood flow surrounding an intracerebral hematoma that is close to ischemic levels.51,83,84 Sudden decreases in blood pressure can lead to extension of this area with subsequent hematoma expansion or worsening ischemia. Support for these concerns was provided by an elevated lower limit of cerebral autoregulation shown in patients with ICH.85 Similarly, increased cerebral oxygen extraction, suggestive of early ischemia, was shown by jugular venous oxygen monitoring in patients with large hematomas who had received aggressive blood pressure treatment.86

Recent evidence suggests that modest control of blood pressure after ICH is probably safe. Qureshi et al,87 using an ICH dog model, found no difference in perihematomal blood flow between the controls and animals treated with labetalol. Powers et al88 randomized 14 patients with ICH and MAP greater than 120 mm Hg to a control group or to a 15% reduction in blood pressure with use of labetalol or nicardipine. Regional CBF measured at baseline and after treatment using positron emission tomography revealed no difference between groups. Larger decreases in blood pressure have not been studied.

Several agents are effective for lowering blood pressure in ICH. There are theoretical advantages to using ?-blockers, nicardipine, labetalol, and angiotensin-converting enzyme inhibitors because they have little effect on ICP and do not compromise CBF. Sodium nitroprusside and nitrates are readily accessible and easily titratable but cause cerebral venodilation, which can suddenly increase ICP; although never proved detrimental in neurologic patients, these agents generally are avoided in patients with elevated ICP. Hydralazine can decrease CBF, but its effects are negligible. Sublingual nifedipine may decrease blood pressure precipitously and is usually not used for patients with brain injuries. Hypertension after ICH may be self-limiting; therefore, use of short-acting parenteral medications for blood pressure control may be prudent. Delayed hypotension can occur with enteral use of antihypertensive medications because enteral medications become effective as ICH-induced hypertension begins to resolve.

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Medical Management of ICH

Once the patient is stabilized initially, medical therapy for ICH becomes supportive. Care is focused on neurologic monitoring, treatment of elevated ICP or cerebral ischemia, and prevention and treatment of secondary medical complications.

Monitoring is accomplished through a series of neurologic examinations, preferably performed in a neurologic intensive care unit by experienced nurses, physicians, and other medical personnel. When this level of specialization is unavailable, standardized neurologic examinations including the GCS should be used. Intracranial pressure monitoring, which may be useful in selected patients,60 is reserved generally for patients with large hemorrhages, those with intraventricular extension of the original hemorrhage, and patients with a GCS score of 8 or less. Patients who need to be sedated or pharmacologically restrained compromise monitoring of the neurologic examination and are candidates for ICP monitoring. Although not proved to improve outcome in ICH,89,90 ICP monitoring may be useful to measure the response to various stimuli and maneuvers commonly used in the intensive care unit (eg, changes in head elevation, responses to fluid administration, and ventilator settings).60

Monitoring of ICP is accomplished by use of ICP bolts or ventriculostomies. The ICP bolt system uses a fiberoptic wire placed directly on the surface of the brain to measure changes in brain tension. The ICP bolts are less invasive and pose less risk of infection compared with ventriculostomies but are prone to drift and cannot be recalibrated once placed.91 Ventriculostomies or external ventricular drains are catheters placed through the brain into the ventricles that allow direct measurement of cerebrospinal fluid (CSF) pressure in the ventricular system. Cerebrospinal fluid can be withdrawn from ventriculostomies, which can help in the management of elevated ICP. Insertion presents a small risk of hemorrhage, and infection rates increase with prolonged use. Traditionally, ventriculostomies were changed every 7 days92; however, more recent evidence suggests that, with close monitoring for infection, they can be used for longer periods.93 Common practice is to use prophylactic antibiotics and to obtain routine scheduled CSF Gram stains, white blood cell counts, and cultures for evidence of infection.

The role of ventricular drainage of CSF to treat hydrocephalus in ICH is unclear. In acute hydrocephalus, early placement of an external ventricular drain may be lifesaving.94 However, once hydrocephalus is established, use of external CSF drainage may be limited. One retrospective series showed no benefit with CSF drainage; the authors hypothesized that irreversible damage had occurred by the time of external ventricular placement.95

Ventricular drains may be useful for the application of thrombolytic agents to decrease the size of IVH. The volume of IVH proportionately affects mortality in ICH.96,97 A preliminary study has suggested that use of intraventricular thrombolysis within 72 hours of IVH can decrease intraventricular hematoma size and improve 30-day mortality.98 Further work in this area is pending.

Patients with IVH or large amounts of intracerebral blood are at high risk of developing elevated ICP and/or cerebral edema with subsequent neurologic injury and deterioration. Treatment is focused on controlling ICP while maintaining adequate cerebral perfusion to avoid secondary ischemic complications. Although the absolute values necessary to ensure adequate cerebral perfusion cannot be given, in general, attempts are made to maintain ICP at 20 mm Hg or less and cerebral perfusion pressure (CPP) at 70 mm Hg or greater (CPP is equal to MAP minus ICP).

Numerous methods are used to lower elevated ICP. Hyperventilation is highly effective and can be used to rapidly lower ICP. Hyperventilation induces cerebral vasoconstriction with subsequent decreases in cerebral blood volume and pressure. It is believed to be mediated by changes in CSF hydrogen ion concentrations.99 However, its effects are short-lived because the choroid plexus begins to equilibrate hydrogen ion concentrations within a few hours.100 Sustained hyperventilation may be deleterious to ischemic brain, although this has not been directly tested in ICH.101 Traditionally, PCO2 is lowered incrementally to approximately 25 to 30 mm Hg. Practically, hyperventilation is used to gain immediate control of elevated ICP, whereas other methods are initiated to improve ICP control.

Mannitol is used commonly to treat elevated ICP. Mannitol is a metabolically inert and poorly permeant hexose sugar used as an osmotic diuretic.102 It has several putative mechanisms of action. Osmotic agents are widely believed to exert their effect by inducing an osmotic gradient between brain and blood that leads to the extraction of water from the cerebral extracellular space into the intravascular compartment.103 Animal models of middle cerebral artery strokes have shown reduced water content of both edematous and normal brain with repeated use of mannitol.104 Despite these findings, the effects on cerebral water content with use of mannitol may be limited clinically. The immediate effect of mannitol is mediated probably through the hemodynamic and rheologic effects of a rapid infusion of an osmotic agent. The increase in intravascular blood volume initiated with a dose of mannitol is believed to increase cardiac output and decrease serum viscosity, which leads to a compensatory decrease in cerebral blood volume and ICP.105

Mannitol is administered parenterally in doses of 0.25 to 1.0 g/kg of body weight. Peak effect is in approximately 20 to 30 minutes and may have duration of action for several hours.106 The preferred treatment of sudden elevation in ICP is administration of IV boluses of mannitol as needed. Scheduled or repetitive doses of mannitol are avoided because of concerns that mannitol may leak into damaged brain tissue and worsen cerebral edema and/or cerebral tissue shifts.107 However, these concerns may be overstated because multiple doses of mannitol infusions induced no significant changes in horizontal or vertical displacement of brain tissue in large middle cerebral artery strokes.108 Careful attention must be paid to replace fluid and electrolyte losses with mannitol use.

Other methods to help control ICP elevation include mild sedation, aggressive treatment of fever, and changes in head position to lower ICP and optimize CPP. Barbiturates and induced hypothermia are reserved for ICP elevation recalcitrant to other treatment methods. Corticosteroids generally are not recommended for ICH on the basis of a randomized study of patients given dexamethasone at 20 mg/d vs placebo. The study was terminated prematurely because of findings of similar 21-day mortalities between the groups and an increased rate of medical complications in the treatment group.109 However, a subset of patients could potentially benefit from use of corticosteroids. In this study, a subset of patients with midsized hematomas showed a trend for improvement during the first week of treatment and deteriorated only after discontinuation of corticosteroids.110

Prevention and treatment of medical complications are crucial to the management of ICH. Patients with ICH are at risk of stress-induced gastric ulcers and should be treated with prophylactic H2 receptor antagonist or proton pump inhibitors. Immobilized and critically ill patients are at risk of deep venous thrombosis. Sequential compression devices may be used in place of subcutaneous heparin if continued bleeding is a consideration. Hyperthermia is deleterious to ischemic neurons. Therefore, all fevers should be aggressively evaluated and treated. Pharmacological and external methods to control fever have had limited success.111 Intravascular cooling devices are being evaluated currently to control fever in both hemorrhagic and ischemic stroke.

Information is limited about how long anticoagulants can be discontinued safely in patients at high risk of cerebral embolism after ICH.109,112 A Mayo retrospective study found that the 30-day probability of ischemic stroke after warfarin cessation was 2.9% and concluded that temporary discontinuation of warfarin therapy for 7 to 14 days after ICH is probably safe.112 Similarly, the exact time at which anticoagulants can be restarted safely is unknown. One study using a statistically based decision model suggested that anticoagulants should not be restarted only in patients with atrial fibrillation.109 However, most authors believe that anticoagulants can be restarted safely 10 to 14 days after ICH.113

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Surgical Treatment of ICH

The role for surgical evacuation of ICH is uncertain. Despite several controlled studies that have shown no benefit with surgery,114-116 surgical removal of ICH is common. The reasons for the use of surgery are that proper randomized trials with adequate size and power have not been performed, and observational studies and anecdotal experience have suggested that surgery may benefit selected patients.

In practice, surgery may be performed as a lifesaving measure in patients with large hematomas or in young patients with cortical hemorrhages and secondary neurologic deterioration. Patients with profound and prolonged neurologic deficits (GCS score ?4) are believed to have little chance for functional recovery and are considered poor surgical candidates.1 Deep hemorrhages rarely are evacuated. Patients with small hemorrhages (?10 cm3) or minimal neurologic deficits are treated medically.

There is general consensus that urgent surgical removal is necessary for infratentorial hematomas 3 cm or larger in diameter or for smaller hematomas that are neurologically deteriorating from brainstem compression. Remarkable recoveries from cerebellar hematomas are possible, but early intervention is critical. Rabinstein et al117 reported that all patients who had lost upper brainstem reflexes or had shown extensor posturing died despite surgical intervention. External ventricular drainage of CSF in cerebellar hematomas must be performed judiciously to avoid the potential complication of upward herniation.

The proper management of medium-sized hematomas is debatable. In most cases, no benefit with surgery has been reported for spontaneous supratentorial ICH.114-116 All these studies114-117 have been criticized for inadequate sample size, lack of adequate controls, and variable implementations and timing of intervention and surgical techniques.118 A meta-analysis of these trials reported an increased trend toward death and dependency after surgery; however, when studies were included only from the more modern post-CT era, a trend for improvement with surgery was found.119

The role of surgery in ICH is being reevaluated in light of recent technological advances.118 The goal of surgery is to decrease the size of the hematoma and subsequently limit local increases in ICP and neurotoxic edema secondary to blood-degradation products. To that purpose, minimally invasive techniques designed to decrease hematoma size while limiting surgical trauma have been developed. In 1985, Niizuma et al120 reported a CT-guided technique of hematoma aspiration and lysis using urokinase. In 1989, a series of randomized patients reported by Auer et al121 showed a decrease in 6-month mortality in the surgical group (42% vs 70%; P<.01) and an improved quality of life in patients with small ICH. The benefit in this series was suggested to be due to the minimally invasive approach, although benefit appeared to be limited to lobar hemorrhages with larger intracranial hematoma volumes. Recent studies have shown the safety and feasibility of CT-guided thrombolysis and aspiration of intracranial hematomas.122-125 This led to a multicenter randomized controlled trial of stereotactic treatment of ICH with plasminogen activator. In this study, 71 patients were randomized to either medical therapy or stereotactic placement of a catheter into the hematoma with scheduled periodic instillation of urokinase and clot aspiration. Hematoma volume was followed by serial CT imaging. In this study, there was a modest reduction in hematoma volume with instillation of urokinase and aspiration of clot; however, there was no difference in mortality. The authors speculated that a larger reduction in hematoma volume may be required to improve mortality.125

It is unknown whether emergent early open surgery provides any benefit over a more delayed approach of stereotactic catheter placement and instillation of urokinase for hematoma evacuation. Two pilot studies that successfully randomized patients to surgical or medical treatments within 12 hours of hemorrhage showed the feasibility of early surgical evacuation.126,127 Both studies suggested a benefit with early surgery (<12 hours) but were limited by small numbers. A recent surgical evaluation of ultra-early evacuation of ICH (<3 hours) was stopped after interim analysis because of an increased rate of rebleeding.128

Because of the continued uncertainty and variation in clinical practice, a new prospective randomized controlled trial is under way and near completion. The international Surgical Trial in Intracerebral Haemorrhage (STICH) compares early surgical evacuation to conservative treatment. Patients are randomized to an “uncertainty principle” based on whether the surgeon is uncertain about the best possible treatment. Patients who are included have hemorrhage volumes between 20 and 80 mL and present with a GCS score of 5 to 15.129 The trial was completed recently and showed no benefit with surgical intervention.130

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Numerous clinical series using logistic regression models to define predictors of outcome in ICH have been undertaken.79,80,96,131-136 The most consistent predictors across studies are the size of the hemorrhage, GCS score at presentation, and the presence and volume of IVH. The most powerful individual predictor appears to be the volume of ICH measured on initial CT.133 This is estimated by using the equation for calculating the volume of an ellipsoid obtained by measuring the length, width, and depth of the hematoma and then dividing by 2. A comatose patient with an ICH volume greater than 60 cm3 has a 30-day mortality of 91%.133

Other inconsistent predictors of poor outcome have included advanced age, hydrocephalus, deep location of ICH, and elevated blood pressure on hospital admission. Increased cerebral edema relative to the initial hemorrhage size may be a marker for increased secondary neurologic injury and has been reported as an adverse prognostic sign.49 Not surprisingly, patients who require mechanical ventilation have worse clinical outcomes.137

Finally, Becker et al138 have found that “withdrawal of care” orders initiated by physicians may introduce bias regarding which prognostic factors are identified.


It is hoped that an improved understanding of the pathophysiological changes that result in hematoma expansion, the development of cerebral edema, and the identity of hemoglobin degradation neurotoxins will lead to more focused pharmacological treatments. A preliminary trial of aminocaproic acid was unsuccessful for preventing rebleeding in ICH139; however, Mayer140 has suggested there may be a role for ultra-early hemostatic therapy with recombinant factor VIIa to prevent further hematoma expansion.

Further distillation of prognostic factors in ICH will help identify subgroups of patients who may be enrolled in future clinical trials. Best medical management has yet to be defined and may include future treatments of blood pressure and hypothermia, tight glucose control, and selected use of glucocorticoids. Results from the STICH have provided important information about the utility of surgical evacuation of ICH but do not address questions about the timing, approach, and technique of other procedures. Lysis and removal of IVH associated with ICH needs to be addressed in controlled randomized studies.

Progress in the field of neurorehabilitation may promote recovery after ICH. Transplanted neural human stem cells have been shown to improve functional recovery in an animal model of ICH.141


Intracerebral hemorrhage will continue to be an important problem as the population ages in the United States. Treatment is limited currently and is primarily supportive. Despite historically poor outcomes in ICH, there is considerable hope that the identification of factors involved in neurologic morbidity, early hemostasis, and removal of intracerebral hematomas will improve the short-term treatment of ICH. Algorithms for treatment and therapeutic options are provided in Figures 3 and 4.


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


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

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Medical Progress: Spontaneous Intracerebral Hemorrhage
Adnan I. Qureshi, Stanley Tuhrim, Joseph P. Broderick, H. Hunt Batjer, Hideki Hondo, Daniel F. Hanley
The New England Journal of Medicine -- May 10, 2001 -- Vol. 344, No. 19