ICH Guidline AHA
ICH Guidline AHA
ICH Guidline AHA
Purpose—The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and
treatment of acute spontaneous intracerebral hemorrhage.
Methods—A formal literature search of MEDLINE was performed. Data were synthesized with the use of evidence tables.
Writing committee members met by teleconference to discuss data-derived recommendations. The American Heart
Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease
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review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council
Scientific Statements Oversight Committee and Stroke Council Leadership Committee. It is intended that this guideline
be fully updated in 3 years’ time.
Results—Evidence-based guidelines are presented for the care of patients presenting with intracerebral hemorrhage. The
focus was subdivided into diagnosis, hemostasis, blood pressure management, inpatient and nursing management,
preventing medical comorbidities, surgical treatment, outcome prediction, rehabilitation, prevention of recurrence, and
future considerations.
Conclusions—Intracerebral hemorrhage is a serious medical condition for which outcome can be impacted by early,
aggressive care. The guidelines offer a framework for goal-directed treatment of the patient with intracerebral
hemorrhage. (Stroke. 2010;41:2108-2129.)
Key Words: AHA Scientific Statements 䡲 intracerebral hemorrhage 䡲 treatment 䡲 diagnosis
䡲 intracranial pressure 䡲 hydrocephalus 䡲 surgery
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside
relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required
to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on May 19, 2010. A copy of the
statement is available at http://www.americanheart.org/presenter.jhtml?identifier⫽3003999 by selecting either the “topic list” link or the “chronological
list” link (No. KB-0044). To purchase additional reprints, call 843-216-2533 or e-mail [email protected].
The American Heart Association requests that this document be cited as follows: Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick
JP, Connolly ES Jr, Greenberg SM, Huang JN, Macdonald RL, Messé SR, Mitchell PH, Selim M, Tamargo RJ; on behalf of the American Heart
Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline
for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2010;41:2108 –2129.
Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development,
visit http://www.americanheart.org/presenter.jhtml?identifier⫽3023366.
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml?
identifier⫽4431. A link to the “Permission Request Form” appears on the right side of the page.
© 2010 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STR.0b013e3181ec611b
2108
Morgenstern et al Intracerebral Hemorrhage Guideline 2109
*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior
myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak.
Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may
be a very clear clinical consensus that a particular test or therapy is useful or effective.
†In 2003, the ACCF/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline
recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from
the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will
increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.
neuroimaging is thus mandatory.19 CT and magnetic resonance follow-up CT.8,25 Hematoma expansion is predictive of
imaging (MRI) are both reasonable for initial evaluation. CT is clinical deterioration and increased morbidity and mortali-
very sensitive for identifying acute hemorrhage and is consid- ty.8,10,15,25 As such, identifying patients at risk for hematoma
ered the gold standard; gradient echo and T2*susceptibility- expansion is an active area of research. CT angiography and
weighted MRI are as sensitive as CT for detection of acute blood contrast-enhanced CT may identify patients at high risk of
and are more sensitive for identification of prior hemorrhage.20,21 ICH expansion based on the presence of contrast extravasa-
Time, cost, proximity to the ED, patient tolerance, clinical status, tion within the hematoma.26 –30 MRI/angiogram/venogram
and MRI availability may, however, preclude emergent MRI in and CT angiogram/venogram are reasonably sensitive at
a sizeable proportion of cases.22 identifying secondary causes of hemorrhage, including arte-
The high rate of early neurological deterioration after ICH is riovenous malformations, tumors, moyamoya, and cerebral
in part related to active bleeding that may proceed for hours after vein thrombosis.31–33 A catheter angiogram may be consid-
symptom onset. The earlier time from symptom onset to first ered if clinical suspicion is high or noninvasive studies are
neuroimage, the more likely subsequent neuroimages will suggestive of an underlying vascular cause. Clinical suspicion
demonstrate hematoma expansion.15,23,24 Among patients of a secondary cause of ICH may include a prodrome of
undergoing head CT within 3 hours of ICH onset, 28% to headache, neurological, or constitutional symptoms. Radio-
38% have hematoma expansion of greater than one third on logical suspicions of secondary causes of ICH should be
Morgenstern et al Intracerebral Hemorrhage Guideline 2111
Table 2. Definition of Classes and Levels of Evidence Used in useful to evaluate for underlying structural lesions,
American Heart Association Stroke Council Recommendations including vascular malformations and tumors when
there is clinical or radiological suspicion (Class IIa;
Class I Conditions for which there is evidence for
Level of Evidence: B). (New recommendation)
and/or general agreement that the
procedure or treatment is useful and
effective Medical Treatment for ICH
Class II Conditions for which there is conflicting Hemostasis/Antiplatelets/Deep Vein
evidence and/or a divergence of Thrombosis Prophylaxis
opinion about the usefulness/efficacy Underlying hemostatic abnormalities can contribute to ICH.
of a procedure or treatment Patients at risk include those on oral anticoagulants (OACs),
Class IIa The weight of evidence or opinion is in those with acquired or congenital coagulation factor deficien-
favor of the procedure or treatment cies, and those with qualitative or quantitative platelet abnormal-
Class IIb Usefulness/efficacy is less well ities. Patients undergoing treatment with OACs constitute 12%
established by evidence or opinion to 14% of patients with ICH,34,35 and with increased use of
Class III Conditions for which there is evidence warfarin, the proportion appears to be increasing.36 Recognition
and/or general agreement that the
of an underlying coagulopathy thus provides an opportunity to
procedure or treatment is not
useful/effective and in some cases
target correction in the treatment strategy. For patients with a
may be harmful coagulation factor deficiency and thrombocytopenia, replace-
Therapeutic recommendations
ment of the appropriate factor or platelets is indicated.
For patients being treated with OACs who have life-threatening
Level of Evidence A Data derived from multiple randomized
clinical trials or meta-analyses
bleeding, such as intracranial hemorrhage, the general recommen-
dation is to correct the international normalized ratio (INR) as
Level of Evidence B Data derived from a single randomized
trial or nonrandomized studies
rapidly as possible.37,38 Infusions of vitamin K and fresh-frozen
plasma (FFP) have historically been recommended, but more
Level of Evidence C Consensus opinion of experts, case
studies, or standard of care recently, prothrombin complex concentrates (PCCs) and recom-
binant factor VIIa (rFVIIa) have emerged as potential therapies.
Diagnostic recommendations
Vitamin K remains an adjunct to more rapidly acting initial
Level of Evidence A Data derived from multiple prospective
therapy for life-threatening OAC-associated hemorrhage be-
cohort studies using a reference
standard applied by a masked cause even when given intravenously, it requires hours to correct
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spite the lack of large, well-controlled, randomized trials, (7% versus 2%).60 A subsequent phase 3 study comparing
PCCs are being increasingly recommended as an option in placebo with 20 g/kg and 80 g/kg of rFVIIa failed to show
guidelines promulgated for warfarin reversal in the setting differences in clinical outcome, despite confirming the ability
of OAC-associated life-threatening or intracranial hemor- of both doses to diminish hematoma enlargement.61 Although
rhages.37,38,50 –52 Table 5 provides a list of several products overall serious thromboembolic adverse events were similar,
for factor replacement in warfarin reversal that are commer- the higher rFVIIa (80 g/kg) group had significantly more
cially available in the United States at the present time. arterial events than the placebo group. The authors noted
rFVIIa, licensed to treat hemophilia patients with high titer imbalances in the treatment groups, particularly the greater
inhibitors or congenital factor VII deficiency, has garnered number of patients with IVH in the higher-dose rFVIIa
attention as a potential treatment for spontaneous and OAC- group.60 It remains to be determined whether rFVIIa will
associated ICH. Although rFVIIa can rapidly normalize INR benefit a particular subset of patients with ICH, but currently
in the setting of OAC-associated ICH,53–57 it does not its benefits in ICH patients, whether or not they are under-
replenish all of the vitamin K– dependent factors and there- going treatment with OACs, remain unproven.
fore may not restore thrombin generation as well as PCCs.58 Studies of the effect of prior antiplatelet agent use or
In light of the limited data, a recent American Society of platelet dysfunction on ICH hematoma growth and outcome
Hematology evidence-based review recommended against have found conflicting results. Reported antiplatelet agent use
routine use of rFVIIa for warfarin reversal.59 was not associated with hematoma expansion or clinical
rFVIIa has also been tested in patients with non-OAC ICH. outcome in the placebo group of an ICH neuroprotective
A phase 2 randomized trial showed that treatment with study.62 However, others have suggested that platelet dys-
rFVIIa within 4 hours after ICH onset limited hematoma function as measured by platelet function assays may be
growth and improved clinical outcomes relative to placebo, associated with hematoma expansion and clinical out-
though with increased frequency of thromboembolic events come.63,64 The utility and safety of platelet transfusion or
Morgenstern et al Intracerebral Hemorrhage Guideline 2113
Medications Anticoagulants, antiplatelet agents, ECG To assess for active coronary ischemia or
decongestants, antihypertensive prior cardiac injury that may indicate
medications, stimulants (including diet poor cardiac function and to obtain a
pills), sympathomimetics baseline in the event of
cardiopulmonary issues during
Recent trauma or surgery Carotid endarterectomy or carotid stenting hospitalization
in particular, as ICH may be related to
hyperperfusion after such procedures Chest radiograph
Alcohol or illicit drug use Cocaine and other sympathomimetic GCS indicates Glasgow Coma Scale; ECG, electrocardiogram.
drugs are associated with ICH,
stimulants
other agents in patients with a normal platelet count, but use
Seizures of antiplatelet agents or platelet dysfunction, is not known.
Liver disease May be associated with coagulopathy Patients with ICH have a high risk of thromboembolic
Cancer and hematologic May be associated with coagulopathy disease.65 Women and African Americans appear to be at greater
disorders risk.65– 67 Intermittent pneumatic compression combined with
Physical examination elastic stockings has been shown by a randomized trial to be
Vital signs Fever is associated with early neurologic superior to elastic stockings alone in reducing occurrence of
deterioration10 asymptomatic deep vein thrombosis after ICH (4.7% versus
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Higher initial blood pressure is associated 15.9%).68 Graduated compression stockings alone are ineffec-
with early neurologic deterioration and tive in preventing deep vein thrombosis.69 Less clear, however, is
increased mortality11 the role of adding anticoagulation to pneumatic compression. Two
A general physical small randomized studies found no difference in deep vein throm-
examination focusing on
bosis incidence, and no increase in bleeding, in patients given low-
the head, heart, lungs,
abdomen, and extremities dose subcutaneous heparin initiated at day 4 or at day 10 after
ICH.70,71 An uncontrolled study of treatment initiated on day 2
A thorough but time-urgent A structured examination such as the
neurologic examination National Institutes of Health Stroke found a reduction in thromboembolic disease without increased
Scale can be completed in minutes and rebleeding.70
provides a quantification that allows
easy communication of the severity of Recommendations
the event to other caregivers. GCS 1. Patients with a severe coagulation factor deficiency or
score is similarly well known and severe thrombocytopenia should receive appropriate fac-
easily computed, and the initial GCS tor replacement therapy or platelets, respectively (Class I;
score is a strong predictor of long-term
Level of Evidence: C). (New recommendation)
outcome.12,13 These can be
2. Patients with ICH whose INR is elevated due to OACs
supplemented as needed
should have their warfarin withheld, receive therapy to
Serum and urine tests replace vitamin K– dependent factors and correct the
Complete blood count, Higher creatinine is associated with INR, and receive intravenous vitamin K (Class I; Level
electrolytes, blood urea hematoma expansion. Higher serum of Evidence: C). PCCs have not shown improved
nitrogen and creatinine, glucose is associated with hematoma outcome compared with FFP but may have fewer
and glucose expansion and worse outcome complications compared with FFP and are reasonable
(although there are no data to suggest
to consider as an alternative to FFP (Class IIa; Level of
that normalization improves
Evidence: B). rFVIIa does not replace all clotting
outcome)11,14
factors, and although the INR may be lowered, clotting
Prothrombin time or INR Warfarin-related hemorrhages are may not be restored in vivo; therefore, rFVIIa is not
and an activated partial associated with an increased
routinely recommended as a sole agent for OAC re-
thromboplastin time hematoma volume, greater risk of
versal in ICH (Class III; Level of Evidence: C). (Revised
expansion, and increased morbidity and
mortality15–17
from the previous guideline).
3. Although rFVIIa can limit the extent of hematoma
(Continued)
expansion in noncoagulopathic ICH patients, there
2114 Stroke September 2010
Table 5. Products Commercially Available in the United States for Coagulation Factor Replacement
Dose (Consultation With a Hematologist
Product Factor(s) Is Recommended for Specific Dosing) Uses
Fresh-frozen plasma I (fibrinogen), II, V, VII, IX, X, XI, 10 –15 mL/kg with ideal recovery OAC reversal
XIII, antithrombin would raise factor levels 15%–20% Consumptive coagulopathy
Hepatic dysfunction
Cryoprecipitate I, VIII, XIII, vWF 1–2 U/10 kg Hypo/a-fibrinogenemia
Lack of factor-specific products for
factor VIII deficiency or vWD
Factor XIII deficiency
Prothrombin complex II, IX, X (small amounts of VII) Assayed in factor IX activity Factor IX deficiency (hemophilia B)
concentrates
Bebulin VH (Baxter), Profilnine Both Bebulin and Profilnine are OAC reversal (not FDA-approved)
SD (Grifols) 3-factor PCCs that have
approximately 1/10th the factor VII
activity relative to factor IX activity.
The amounts of factor II and X
relative to IX is variable, but for
Bebulin X⬎II⬎IX and for Profilnine
II⬎X⬃IX
Dosing for factor IX deficiency—
1 U/kg raises activity by 1%
Dosing for OAC reversal has not been
well established
NovoSeven RT (Novo Nordisk) Recombinant activated VII Higher risk of thromboembolic Factor VIII or IX deficiency with inhibitors
complications with higher doses to factor VIII or IX
For hemophilia A or B patients with Congenital factor VII deficiency
inhibitors, 90 g/kg every 2 h Not recommended for spontaneous ICH
For factor VII–deficient patients, 15–30 or OAC reversal
g/kg every 4–6 h
Factor VIII concentrates VIII Each factor VIII unit/kg raises the Factor VIII deficiency (hemophilia A)
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is an increase in thromboembolic risk with rFVIIa from this therapy is needed before any recommenda-
and no clear clinical benefit in unselected patients. tion for its use can be made.
Thus rFVIIa is not recommended in unselected 4. The usefulness of platelet transfusions in ICH pa-
patients. (Class III; Level of Evidence: A). (New tients with a history of antiplatelet use is unclear and
recommendation) Further research to determine is considered investigational (Class IIb; Level of
whether any selected group of patients may benefit Evidence: B). (New recommendation)
Morgenstern et al Intracerebral Hemorrhage Guideline 2115
5. Patients with ICH should have intermittent pneu- Table 6. Suggested Recommended Guidelines for Treating
matic compression for prevention of venous throm- Elevated BP in Spontaneous ICH
boembolism in addition to elastic stockings (Class I;
1. If SBP is ⬎200 mm Hg or MAP is ⬎150 mm Hg, then consider
Level of Evidence: B). (Unchanged from the previous aggressive reduction of BP with continuous intravenous infusion, with
guideline) frequent BP monitoring every 5 min.
6. After documentation of cessation of bleeding, low-
2. If SBP is ⬎180 mm Hg or MAP is ⬎130 mm Hg and there is the
dose subcutaneous low-molecular-weight heparin or
possibility of elevated ICP, then consider monitoring ICP and reducing BP
unfractionated heparin may be considered for pre- using intermittent or continuous intravenous medications while
vention of venous thromboembolism in patients with maintaining a cerebral perfusion pressure ⱖ60 mm Hg.
lack of mobility after 1 to 4 days from onset (Class
3. If SBP is ⬎180 mm Hg or MAP is ⬎130 mm Hg and there is not
IIb; Level of Evidence: B). (Revised from the previous
evidence of elevated ICP, then consider a modest reduction of BP (eg,
guideline) MAP of 110 mm Hg or target BP of 160/90 mm Hg) using intermittent or
continuous intravenous medications to control BP and clinically
Blood Pressure reexamine the patient every 15 min.
Blood Pressure and Outcome in ICH Note that these recommendations are Class C. SBP indicates systolic blood
Blood pressure (BP) is frequently, and often markedly, pressure; MAP, mean arterial pressure.
elevated in patients with acute ICH; these elevations in BP
are greater than that seen in patients with ischemic stroke.72,73 and absolute growth in hematoma volumes from baseline to
Although BP generally falls spontaneously within several 24 hours in the intensive treatment group compared with the
days after ICH, high BP persists in a substantial proportion of control group. In addition, there was no excess of neurolog-
patients.72,73 Potential pathophysiologic mechanisms include ical deterioration or other adverse events related to intensive
stress activation of the neuroendocrine system (sympathetic BP lowering, nor were there any differences across several
nervous system, renin-angiotensin axis, or glucocorticoid sys- measures of clinical outcome, including disability and quality
tem) and increased intracranial pressure. Hypertension theoreti- of life between groups, although the trial was not powered to
cally could contribute to hydrostatic expansion of the hematoma, detect such outcomes. The study provides an important proof
peri-hematoma edema, and rebleeding, all of which may con- of concept for early BP lowering in patients with ICH, but the
tribute to adverse outcomes in ICH, although a clear association data are insufficient to recommend a definitive policy. An-
between hypertension within the first few hours after ICH and other study, the Antihypertensive Treatment in Acute Cere-
the risk of hematoma expansion (or eventual hematoma volume) bral Hemorrhage (ATACH) trial,81 also confirms the feasi-
bility and safety of early rapid BP lowering in ICH.82 This
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onset. Care of ICH patients in a dedicated neuroscience treatment with outcome. Similarly, therapeutic cooling has not
intensive care unit is associated with a lower mortality rate.83 been systematically investigated in ICH patients.
Frequent vital sign checks, neurological assessments, and
continuous cardiopulmonary monitoring including a cycled Seizures and Antiepileptic Drugs
automated BP cuff, electrocardiographic telemetry, and O2 The incidence of clinical seizures within the first 2 weeks after
saturation probe should be standard. Continuous intra-arterial ICH has been reported to range from 2.7% to 17%, with the
BP monitoring should be considered in patients receiving majority occurring at or near onset.96 –100 Studies of continuous
intravenous vasoactive medications. electroencephalography (EEG) have reported electrographic sei-
zures in 28% to 31% of select cohorts of ICH patients, despite
Nursing Care most having received prophylactic anticonvulsants.101,102 In a
The specific nursing care required for ICH patients in large, single-center study, prophylactic antiepileptic drugs did
intensive care units may include (1) surveillance and moni- significantly reduce the number of clinical seizures after lobar
toring of ICP, cerebral perfusion pressure and hemodynamic ICH.98 However, in prospective and population-based
function; (2) titration and implementation of protocols for studies, clinical seizures have not been associated with
management of ICP, BP, mechanical ventilation, fever, and worsened neurological outcome or mortality.97,103,104 The
serum glucose; and (3) prevention of complications of im- clinical impact of subclinical seizures detected on EEG is also
mobility through positioning, airway maintenance, and mo- not clear. A recent analysis from the placebo arm of an ICH
bilization within physiological tolerance. The consensus doc- neuroprotectant study found that patients who received anti-
ument from the Brain Attack Coalition on comprehensive epileptic drugs (primarily phenytoin) without a documented
stroke centers delineates these as specific areas of monitoring seizure were significantly more likely to be dead or disabled
and complication prevention in which nurses should be at 90 days, after adjusting for other established predictors of
trained. This document also recommends that nurses be ICH outcome.105 Another recent single-center observational
trained in detailed assessment of neurological function in- study had similar findings, specifically for phenytoin.106 Thus
cluding standardized scales such as the National Institutes of only clinical seizures or electrographic seizures in patients
Health Stroke Scale, GCS, and the Glasgow Outcome Scale. with a change in mental status should be treated with
In a Canadian study of 49 hospitals that included ICH antiepileptic drugs. Continuous EEG monitoring should be
patients, a higher proportion of registered nurses and better considered in ICH patients with depressed mental status out
nurse–physician communications were independently associ- of proportion to the degree of brain injury. The utility of
ated with lower 30-day mortality even after adjusting for prophylactic anticonvulsant medication remains uncertain.
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heme oxygenase-1 and inhibits hemoglobin-mediated glutamate ICP monitor insertion and use include infection and intracra-
excitotoxicity and hypoxia inducible factor prolyl hydroxy- nial hemorrhage. In general, the risk of hemorrhage or
lases.116 –119 Further studies in this area are warranted, but no infection is thought to be higher with VC than with paren-
current therapeutic recommendation can be made at present. chymal catheters, although data on these rates are not derived
from patients with ICH, but rather principally from those with
Procedures/Surgery traumatic brain injury or aneurysmal subarachnoid hemor-
ICP Monitoring and Treatment rhage. In a 1997 series of 108 intraparenchymal devices, the
ICP monitoring is often performed in patients with ICH. rate of infection was 2.9% and the rate of intracranial
However, only very limited published data exist regarding the hemorrhage was 2.1% (15.3% in patients with coagulopa-
frequency of elevated ICP and its management in patients thies).123 A direct comparison of the complications associated
with ICH.120,121 There is evidence for differential pressure with each type of monitoring device was reported in a 1993 to
gradients in at least some cases so that ICP may be elevated 1997 series of 536 intracerebral monitoring devices (274 VCs,
in and around the hematoma but not distant from it.122 229 intraparenchymal parenchymal catheters, and 33 other types
Because the usual causes of elevated ICP are hydrocephalus of devices) in which the overall rate of infection was 4% and the
from IVH or mass effect from the hematoma (or surrounding overall rate of intracranial hemorrhage was 3%.124 Before
edema), patients with small hematomas and limited IVH insertion of a monitoring device, the patient’s coagulation status
usually will not require treatment to lower ICP. should be evaluated. Prior use of antiplatelet agents may justify
ICP is measured using devices inserted into the brain platelet transfusion before the procedure, and the use of warfarin
parenchyma, typically at the bedside. Fiberoptic technology may require reversal of coagulopathy before placement. The
can be used in both types of devices. A ventricular catheter decision to use a VC or a parenchymal catheter device should be
(VC) inserted into the lateral ventricle allows for drainage of based on the specific need to drain cerebrospinal fluid in patients
cerebrospinal fluid, which can help reduce ICP in patients with hydrocephalus or trapped ventricle and the balance of
with hydrocephalus. A parenchymal catheter ICP device is monitoring risks with the unknown utility of ICP management in
inserted into the brain parenchyma and allows for monitoring patients with ICH.
of ICP, but not cerebrospinal fluid drainage. The absence of ICP treatment should be directed at the underlying cause,
published studies showing that management of elevated ICP especially if due to hydrocephalus or mass effect from the
impacts on ICH outcome makes the decision whether to hematoma. Because of limited data regarding ICP in ICH,
monitor and treat elevated ICP unclear. Risks associated with management principles for elevated ICP are borrowed from
2118 Stroke September 2010
traumatic brain injury guidelines, which emphasize maintaining Some reports suggest alternative procedures for IVH such
a cerebral perfusion pressure of 50 to 70 mm Hg, depending on as endoscopic surgical evacuation and ventriculostomy,144 –146
the status of cerebral autoregulation125,126 (see Figure). ICH ventriculoperitoneal shunting,147 or lumbar drainage for hy-
patients with a GCS score of ⱕ8, those with clinical evidence of drocephalus.148 Few data exist to support these strategies.
transtentorial herniation, or those with significant IVH or hydro-
cephalus may be considered for ICP monitoring and treatment. Recommendation
Numerous studies have assessed ventricular size and effects 1. Although intraventricular administration of recom-
of enlargement on ICH outcome.127–130 Among 902 patients binant tissue-type plasminogen activator in IVH
with follow-up data randomized into the international Surgical appears to have a fairly low complication rate,
Trial of Intracerebral Hemorrhage (STICH) trial of early hema- efficacy and safety of this treatment is uncertain and
toma evacuation, 377 had IVH and 208 of these had hydroceph- is considered investigational (Class IIb; Level of
alus (23% of all patients, 55% of those with IVH).131 Hydro- Evidence: B). (New recommendation)
cephalus predicted poor outcome in this study, as well as other
previous studies.127 Thus, hydrocephalus is an important cause Clot Removal
of ICH-related morbidity and mortality,1 and treatment should Surgical Treatment of ICH
be considered in patients with decreased level of consciousness. The decision about whether and when to surgically remove
Small case series have described the use of brain tissue ICH remains controversial. The pathophysiology of brain
oxygen and cerebral microdialysis monitoring in patients injury surrounding the hematoma is due to the mechanical
with ICH.132,133 Because of the small numbers of patients and effects of the growing mass of blood as well as the subsequent
limited data, no recommendation can be made regarding the toxic effects of blood in the surrounding brain tissue. Early
use of these technologies at this time. surgery to limit the mechanical compression of brain and the
toxic effects of blood may limit injury, but the surgical risks
Recommendations
in a patient with ongoing bleeding may be greater. In
1. Patients with a GCS score of <8, those with clinical
addition, operative removal of hemorrhage by craniotomy in
evidence of transtentorial herniation, or those with
significant IVH or hydrocephalus might be consid- all but the most superficial hemorrhages involves cutting
ered for ICP monitoring and treatment. A cerebral through uninjured brain. Among the limitations of ICH surgical
perfusion pressure of 50 to 70 mm Hg may be trials is that young and middle-aged patients at risk of herniation
reasonable to maintain depending on the status of from large ICHs were unlikely to be randomized for treatment.
cerebral autoregulation (Class IIb; Level of Evi- Recommendations for these patients are uncertain.
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By contrast, patients in the STICH study with an ICH ⬎1 and/or hydrocephalus from ventricular obstruction
cm from the cortical surface or with a GCS score of ⱕ8 should undergo surgical removal of the hemorrhage as
tended to do worse with surgical removal as compared with soon as possible (Class I; Level of Evidence: B). (Revised
medical management. Another study randomized 108 patients from the previous guideline) Initial treatment of these
with supratentorial subcortical or putaminal ICH ⬎30 mL in patients with ventricular drainage alone rather than
volume to craniotomy or medical management within 8 hours of surgical evacuation is not recommended (Class III; Level
onset.158 Good outcome (good recovery or moderate disability of Evidence: C). (New recommendation)
3. For patients presenting with lobar clots >30 mL and
on the Glasgow Outcome Scale at 1 year) was significantly
within 1 cm of the surface, evacuation of supraten-
better in those treated with surgery, but there was no difference torial ICH by standard craniotomy might be consid-
in overall survival. Other randomized trials have had too few ered (Class IIb; Level of Evidence: B). (Revised from
patients to determine outcomes in subgroups by location, ran- the previous guideline)
domized only patients with deep ICH, or did not report these 4. The effectiveness of minimally invasive clot evacua-
results.159 –161 Enthusiasm for surgical evacuation of thalamic tion utilizing either stereotactic or endoscopic aspi-
and pontine ICH has been limited.154,162,163 ration with or without thrombolytic usage is uncer-
tain and is considered investigational (Class IIb;
Minimally Invasive Surgical Removal of ICH Level of Evidence: B). (New recommendation)
If the indications for surgical evacuation of intracerebral 5. Although theoretically attractive, no clear evidence at
hematomas are controversial, the means by which to achieve present indicates that ultra-early removal of supraten-
this evacuation are even less well established. Several groups torial ICH improves functional outcome or mortality
have developed minimally invasive clot removal techniques. rate. Very early craniotomy may be harmful due to
These techniques tend to make use of stereotactic guidance increased risk of recurrent bleeding (Class III; Level of
combined with either thrombolytic-enhanced or endoscopic- Evidence: B). (Revised from the previous guideline)
enhanced aspiration. Both randomized trials of thrombolytic-
enhanced aspiration for subcortical ICH149,161,164 and Outcome Prediction and Withdrawal of
endoscopic-enhanced aspiration165–167 with or without ste- Technological Support
reotaxis have reported increased clot removal and de- Many observational and epidemiological studies have identified a
creased mortality in those subjects treated surgically wide range of factors that are predictive of outcome after acute ICH.
within 12 to 72 hours, but improved functional outcome From these studies numerous outcome prediction models have been
has not been consistently demonstrated. developed for mortality and functional outcome. Features found in
most of these prediction models include individual patient charac-
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Timing of Surgery teristics such as the score on the GCS or National Institutes of
One key issue has been the lack of consensus on the time frame Health Stroke Scale, age, hematoma volume and location, and the
of what constitutes early surgery. Clinical studies have reported presence and amount of IVH.12,172–180 No outcome prediction
a wide variability in the timing of surgery, ranging from within model for ICH, however, has considered the impact of care
4 hours up to 96 hours from the onset of symptoms to time of limitations such as do not resuscitate (DNR) orders or withdrawal of
operation.156,158,161,168 Such time variance among the studies has technological support.
made direct comparison and analysis of the impact of surgical Most patients that die from ICH do so during the initial acute
timing difficult. A retrospective Japanese series of surgical hospitalization, and these deaths usually occur in the setting of
removal of 100 putaminal ICHs within 7 hours of onset (60 withdrawal of support due to presumed poor prognosis.181,182
within 3 hours) reported better than expected outcomes.169 Several studies, however, have now identified withdrawal of
However, subsequent randomized trials that treated subjects medical support and other early care limitations, such as DNR
within 12 hours of onset reported mixed results.158,161,168 An orders within the first day of hospitalization, as independent
increased risk of rebleeding was noted in the small trial of outcome predictors.2,183,184 It is likely that current outcome
subjects randomized within 4 hours of onset.170 prediction models as well as more informal methods of early
Trials that randomized patients within 24 hours,171 48 prognostication after ICH are biased by the failure to account for
hours,159,165 72 hours,149,160 and 96 hours156 have also demon- these care limitations. Concern has been raised that decisions by
strated no clear benefit for surgery as compared with initial physicians to limit care early after ICH are resulting in self-
medical management except for improved outcome in the fulfilling prophecies of poor outcome due to inaccurately pessi-
subgroup of patients in the STICH trial with superficial ICH and mistic prognostication and failure to provide initial aggressive
decreased mortality in those patients with subcortical hemor- therapy in severely ill ICH patients who nonetheless still have
rhages treated with minimally invasive methods within 12 to 72 the possibility of favorable outcome.
hours, as noted above. Although a DNR order by definition means that no attempt
at resuscitation should be made in the event that a cardiopul-
Recommendations
monary arrest occurs, in practical use, when administered
1. For most patients with ICH, the usefulness of sur-
early after ICH, it is a proxy for overall lack of aggres-
gery is uncertain (Class IIb; Level of Evidence: C).
(New recommendation) Specific exceptions to this siveness of care.2 This implies that the overall aggressive-
recommendation follow ness of ICH care at a hospital may be critically important
2. Patients with cerebellar hemorrhage who are deteriorat- in determining patients’ outcome, irrespective of specific
ing neurologically or who have brainstem compression individual characteristics.2,83,185
2120 Stroke September 2010
Although prognostication early after ICH may be desired Committee on Prevention, Detection, Evaluation, and Treatment
by physicians, patients, and families, it is currently based on of High Blood Pressure.197
uncertain ground. Given this uncertainty and the potential for Oral anticoagulation is associated with worse ICH out-
self-fulfilling prophecies of poor outcome, great caution come198,199 and increased risk of recurrence,188 raising the
should be undertaken in attempting precise prognostication question of whether the benefits of anticoagulation for prevent-
early after ICH, especially if the purpose is to consider ing thromboembolism outweigh its risks after initial ICH. For a
withdrawal of support or DNR orders.186 Thus, aggressive hypothetical 69-year-old man with nonvalvular atrial fibrillation
guideline-concordant therapy is recommended for all ICH and prior lobar ICH, Markov modeling predicted that long-term
patients who do not have advanced directives specifying that anticoagulation would shorten quality-adjusted survival because
this should not be undertaken. Care limitations such as DNR of the high risk of recurrence after lobar ICH.200 The results for
orders or withdrawal of support should not be recommended anticoagulation after deep hemispheric ICH were less clear-cut
by treating physicians during the first few days after ICH. and varied depending on assumptions about risk of future
thromboembolism or ICH. The effects of antiplatelet agents on
Recommendation ICH recurrence and severity appear to be substantially smaller
1. Aggressive full care early after ICH onset and than for anticoagulation,16,62,189,201 suggesting that antiplatelet
postponement of new DNR orders until at least the treatment may be a safer alternative to anticoagulation after ICH.
second full day of hospitalization is probably recom- Recently, the ACTIVE A (Atrial Fibrillation Clopidogrel Trial
mended (Class IIa; Level of Evidence: B). Patients with Irbesartan for Prevention of Vascular Events–Aspirin)
with preexisting DNR orders are not included in this study reported on a randomized, double-blind study of the safety
recommendation. Current methods of prognostica- and efficacy of adding clopidogrel 75 mg daily to aspirin 75 to
tion in individual patients early after ICH are likely
100 mg daily in patients with high-risk atrial fibrillation and a
biased by failure to account for the influence of
withdrawal of support and early DNR orders. Pa- contraindication to warfarin. Although previous ICH was listed
tients who are given DNR status at any point should as one of the many reasons for study entry, the authors did not report
receive all other appropriate medical and surgical the proportion of subjects with previous ICH, and therefore the
interventions unless otherwise explicitly indicated. study results may not directly apply to those with previous ICH.
(Revised from the previous guideline) Subjects who received clopidogrel added to aspirin had a 0.8% per
year absolute risk reduction of major vascular events at the cost of
Prevention of Recurrent ICH 0.7% per year increase in major bleeding events.202
The recent Stroke Prevention with Aggressive Reductions in
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4. Avoidance of long-term anticoagulation as treatment rehabilitation should include education for the patient and
for nonvalvular atrial fibrillation is probably recom- caregiver regarding secondary stroke prevention and means to
mended after spontaneous lobar ICH because of the achieve rehabilitation goals. Rehabilitation programs should
relatively high risk of recurrence (Class IIa; Level of consider lifestyle changes, depression, and caregiver burden as
Evidence: B). Anticoagulation after nonlobar ICH important issues to work on with the patient and caregivers.
and antiplatelet therapy after all ICH might be
considered, particularly when there are definite in-
dications for these agents (Class IIb; Level of Evi- Recommendations
dence: B). (Unchanged from the previous guideline) 1. Given the potentially serious nature and complex pat-
5. Avoidance of heavy alcohol use can be beneficial tern of evolving disability, it is reasonable that all
(Class IIa; Level of Evidence: B). There is insufficient patients with ICH have access to multidisciplinary
data to recommend restrictions on use of statin rehabilitation (Class IIa; Level of Evidence: B). Where
agents or physical or sexual activity (Class IIb; Level possible, rehabilitation can be beneficial when begun as
of Evidence: C). (New recommendation) early as possible and continued in the community as
part of a well-coordinated (seamless) program of ac-
celerated hospital discharge and home-based resettle-
Rehabilitation and Recovery ment to promote ongoing recovery (Class IIa; Level of
Knowledge of differences in the natural history of recovery Evidence: B). (New recommendation)
patterns and prognosis for residual disability and functioning
between ICH and ischemic stroke is complicated by the Future Considerations
disproportionately lower rate of ICH compared with ischemic The future of ICH treatment centers on a cluster of targets.
stroke and the lumping of subarachnoid hemorrhage and ICH The first is clearly prevention. Community-based projects to
together in many studies. There are also problems associated reduce BP through healthy lifestyles and medication adher-
with the insensitivity of many of the outcome measures used in ence are likely to be quite successful in reducing ICH
rehabilitation to allow detection of clinically meaningful differ- incidence.212 Animal studies aimed at preventing cerebral
ences between groups. Even so, there is some evidence that amyloid angiopathy show early promise.213,214
patients with ICH make slightly greater and faster gains in Once an ICH has occurred, efforts to mobilize communities to
recovery206 –208 compared with patients with ischemic stroke. facilitate prompt treatment are similar to efforts aimed at acute
In general, recovery is more rapid in the first few weeks but ischemic stroke treatment.215 Advanced imaging currently may
may continue for many months after ICH,208,209 with approxi- identify patients with ongoing bleeding and provides a target for
mately half of all survivors remaining dependent on others for improved patient selection for testing of hemostatic agents.28
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activities of daily living.176 However, patients vary in their speed Hemostatic agents’ efficacy must be clearly weighed against
and degree of recovery, and there is no hard rule regarding when potential arterial and venous thrombotic risk.
recovery is over. Cognition, mood, motivation, and social BP control theoretically may reduce hematoma growth
support all influence recovery, and it is difficult to separate and/or reduce cerebral edema. Early studies suggest that a
intrinsic from adaptive recovery. A simple prognostic score randomized controlled BP-lowering study is feasible.79,81
utilizing age, ICH volume and location, level of consciousness at Safety and efficacy remain to be shown in larger studies.
admission, and pre-ICH cognitive impairment has been shown There is active research on interfering with oxidative injury
to predict independence at 90 days.176 Given that ICH is often after ICH. Iron-chelating agents such as deferoxamine are being
located in lobar regions and complicated by intraventricular studied in early-phase trials.107,115 Pathways that center around
extension, some patients with specific cognitive deficits or hypoxia-inducible factors and prolyl hydroxylases offer other
delayed recovery that is disproportionate to the size of the lesion potential targets for intervention centered around oxidative
may require specialized therapy in rehabilitation. stress.216 The role of microglia and macrophages in hematoma
The provision of stroke rehabilitation services has received resolution is getting more attention.217 Autophagy may be a cellular
considerable attention in recent years. In part this represents a process that could be altered to prevent ICH-related cell death.218
need to tailor services to ensure optimal recovery for patients and There are probably many factors that contribute to injury after
in part is due to fiscal pressures on costly health services. Given ICH, including mass effect, toxicity related to blood, and
strong evidence for the benefits of well-organized, multidisci- displacement of underlying tissue. Seemingly, a simple solution
plinary inpatient (stroke unit) care in terms of improved survival, is hematoma removal. To date, however, surgery has not proved
recovery, and returning home compared with conventional to be the panacea for this condition. New efforts utilizing
nondedicated stroke wards,210 efforts have been made to extend minimally invasive surgical techniques that may remove blood’s
this service model of coordinated care into the community. toxic and pressure effects while avoiding the damage caused by
Specifically, early supported hospital discharge and home-based more invasive procedures, as well as new treatments to dissolve and
rehabilitation programs have been shown to be cost-effective,210 drain intraventricular blood, are currently being studied.143,164
whereas home-based therapy in stable patients has been shown Priorities for ICH research have been published and reviewed
to produce comparable outcomes to conventional outpatient extensively.13 An aggressive, collaborative approach to both
rehabilitation.211 The success of these programs depends on basic and clinical research in this field is likely to promote the
caregiver training and support. However, the likely configura- highest yield. In the mean time, it is clear that our ability to
tion of stroke rehabilitation services in any region will depend on prognosticate about ICH is limited,184 and that aggressive care
available resources and funding options. A key portion of now, and hope for the future, are both clearly indicated.
2122 Stroke September 2010
Disclosures
Writing Group Disclosures
Writing Group Other Research Speakers’ Expert Ownership Consultant/Advisory
Member Employment Research Grant Support Bureau/Honoraria Witness Interest Board Other
Lewis B. University of NIH (R01 NS057127) None None None None None Medical adjudication
Morgenstern Michigan Consultant—Safety and board member
Tolerability of Wyeth*
Deferoxamine in Acute
Cerebral Hemorrhage
(generic study drug)*;
NINDS (U01 NS052510)
Co-I (Deferoxamine
therapy for
intracerebral
hemorrhage—animal
translational grant
examining generic
deferoxamine in ICH)†;
NIH (R01 NS38916)
PI—Brain Attack
Surveillance in Corpus
Christi (observational
study of stroke in a
biethnic community)†
Craig Anderson George Institute, The Australian National None Boehringer-Ingelheim*; None None Boehringer-Ingelheim* None
Sydney, Health & Medical Servier*;
Australia Research Council Sanofi-Aventis*
(employer); Senior
Principal Research
Fellowship (632918);
Program Grant
(571281); Project Grant
(INTERACT 2
study—512402) †;
NINDS (IMSIII Trial 1
Downloaded from http://ahajournals.org by on November 12, 2018
V01 NSO52220-02;
subaward SRS#19449
SAP-G100121-
1005817)†; FIA
(RO1NS39512 R-01-NS
36695)†
Kyra Becker University of None None None None None None None
Washington
Joseph P. University of NINDS R-01 NS36695 Novo None None None None None
Broderick Cincinnati (Genetic and Nordisk-
Environmental Risk supplies-
Factors for Hemorrhagic Factor VIIa for
Stroke—Co- NINDS-funded
Investigator)†; STOP-IT trial*
NIH/NINDS (P50
SPOTRIAS
NS44283—PI of PPG)†
E. Sander Columbia None None None None None None None
Connolly, Jr University
Steven M. Massachusetts NIH (R01 NS057127, None None None None None None
Greenberg General Hospital Consultant)—Safety
and Tolerability of
Deferoxamine in Acute
Cerebral Hemorrhage
(generic study drug)†
J. Claude University of NIH/NINDS; U10 None None None None Novo Nordisk* None
Hemphill III California at San NS058931 (PI)†;
Francisco (SF-NET: San Francisco
Neurological
Emergencies Trials
Network—national
network for phase III
clinical trials—no
current ICH trials); Novo
Nordisk (PI)†
(Continued)
Morgenstern et al Intracerebral Hemorrhage Guideline 2123
Reviewer Disclosures
Other
Research Speakers’ Expert Ownership Consultant/Advisory
Reviewer Employment Research Grant Support Bureau/Honoraria Witness Interest Board Other
Tamilyn Bakas Indiana University None None None None None None None
Purdue University
Indianapolis
John Cole University of None None None None None None None
Maryland
Matthew University of None None None None None None None
Flaherty Cincinnati
Academic Health
Center
Karen C. University of NIH-NINDS R01 NS050192 - None Multiple grand rounds, None None Diffussion Pharmaceuticals, AAN as associate
Johnston Virginia GRASP trial† national talks on Inc.*; Remedy editor of neurology
stroke* Pharmaceuticals, Inc.* through July
2009†
Christina University of None None None None None None None
Stewart-Amidei Central Florida
Greg Zipfel Washington None None None None None None None
University
This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure
Questionnaire, which all reviewers are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10 000 or more
during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns
$10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
*Modest.
†Significant.
2124 Stroke September 2010
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