AHA/ASA Guideline

Guidelines for the Management of Spontaneous
Intracerebral Hemorrhage
A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association
The American Academy of Neurology affirms the value of this guideline
as an educational tool for neurologists.
Endorsed by the American Association of Neurological Surgeons, the Congress
of Neurological Surgeons, and the Neurocritical Care Society

J. Claude Hemphill III, MD, MAS, FAHA, Chair; Steven M. Greenberg, MD, PhD, Vice-Chair;
Craig S. Anderson, MD, PhD; Kyra Becker, MD, FAHA; Bernard R. Bendok, MD, MS, FAHA;
Mary Cushman, MD, MSc, FAHA; Gordon L. Fung, MD, MPH, PhD, FAHA;
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Joshua N. Goldstein, MD, PhD, FAHA; R. Loch Macdonald, MD, PhD, FRCS;
Pamela H. Mitchell, RN, PhD, FAHA; Phillip A. Scott, MD, FAHA;
Magdy H. Selim, MD, PhD; Daniel Woo, MD, MS; on behalf of the American Heart Association
Stroke Council, Council on Cardiovascular and Stroke Nursing, and Council on Clinical Cardiology

Purpose—The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and
treatment of spontaneous intracerebral hemorrhage.
Methods—A formal literature search of PubMed was performed through the end of August 2013. The writing committee
met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart
Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the
class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members
of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee.
Results—Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics
focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain
injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future
considerations. Results of new phase 3 trials were incorporated.
Conclusions—Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted.
These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.
(Stroke. 2015;46:000-000. DOI: 10.1161/STR.0000000000000069.)
Key Words: AHA Scientific Statements ◼ blood pressure ◼ coagulopathy ◼ diagnosis ◼ intracerebral hemorrhage
◼ intraventricular hemorrhage ◼ surgery ◼ treatment

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 guideline was approved by the American Heart Association Science Advisory and Coordinating Committee on January 28, 2015, and the American
Heart Association Executive Committee on February 16, 2015. A copy of the document is available at http://my.americanheart.org/statements by selecting
either the “By Topic” link or the “By Publication Date” link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.
The American Heart Association requests that this document be cited as follows: Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok
BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D; on behalf of the American Heart Association Stroke
Council, Council on Cardiovascular and Stroke Nursing, and Council on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral
hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:•••–•••.
Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines
development, visit http://my.americanheart.org/statements and select the “Policies and Development” link.
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.heart.org/HEARTORG/General/Copyright-
Permission-Guidelines_UCM_300404_Article.jsp. A link to the “Copyright Permissions Request Form” appears on the right side of the page.
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STR.0000000000000069


2  Stroke  July 2015

S pontaneous, nontraumatic intracerebral hemorrhage
(ICH) remains a significant cause of morbidity and mor-
tality throughout the world. Although ICH has traditionally
Association ICH guideline, published in 2010, incorpo-
rating the results of new studies published in the interim.2
Another equally important purpose is to remind clinicians
lagged behind ischemic stroke and aneurysmal subarach- of the importance of their care in determining ICH outcome
noid hemorrhage in terms of evidence from clinical trials and to provide an evidence-based framework for that care.
to guide management, the past decade has seen a dramatic To make this review brief and readily useful to practic-
increase in studies of ICH intervention. Population-based ing clinicians, background details of ICH epidemiology are
studies show that most patients present with small ICHs limited, with references provided for readers seeking more
that are readily survivable with good medical care.1 This details.1,3,4 Ongoing studies are not discussed substantively
suggests that excellent medical care likely has a potent, because the focus of this guideline is on currently available
direct impact on ICH morbidity and mortality. This guide- therapies; however, the increase in clinical studies related to
line serves several purposes. One is to provide an update ICH is encouraging, and those interested may go to http://
to the last American Heart Association/American Stroke www.strokecenter.org/trials/ for more information. Also, this

Table 1.  Applying Classification of Recommendations and Level of Evidence
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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. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful
or effective.
*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.
†For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve
direct comparisons of the treatments or strategies being evaluated.

Hemphill et al   Management of Spontaneous ICH   3

guideline is generally concerned with adults, with issues of Table 2.  Definition of Classes and Levels of Evidence Used in
hemorrhagic stroke in children and neonates covered in a AHA/ASA Recommendations
separate American Heart Association scientific statement on Class I Conditions for which there is evidence for and/
“Management of Stroke in Infants and Children.”5 or general agreement that the procedure or
This document serves to update the last ICH guidelines treatment is useful and effective
published in 2010,2 and the reader is referred to these guide- Class II Conditions for which there is conflicting
lines for additional relevant references not contained here. The evidence and/or a divergence of opinion about
development of this update was purposely delayed for 1 year the usefulness/efficacy of a procedure or
from the intended 3-year review cycle so that results of 2 pivotal treatment
phase 3 ICH clinical trials could be incorporated. Differences  Class IIa The weight of evidence or opinion is in favor
from recommendations in the 2010 guideline are specified in of the procedure or treatment
the current work. The writing group met by phone to determine  Class IIb Usefulness/efficacy is less well established by
subcategories to evaluate. These included 15 sections that cov- evidence or opinion
ered the following: emergency diagnosis and assessment of Class III Conditions for which there is evidence and/
ICH and its causes; hemostasis and coagulopathy; blood pres- or general agreement that the procedure
sure (BP) management; inpatient management, including gen- or treatment is not useful/effective and in
some cases may be harmful
eral monitoring and nursing care, glucose/temperature/seizure
management, and other medical complications; procedures, Therapeutic recommendations
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including management of intracranial pressure (ICP), intra-  Level of Evidence A Data derived from multiple randomized clinical
ventricular hemorrhage, and the role of surgical clot removal; trials or meta-analyses
outcome prediction; prevention of recurrent ICH; rehabilita-  Level of Evidence B Data derived from a single randomized trial or
tion; and future considerations. Each subcategory was led by nonrandomized studies
a primary author, with 1 or 2 additional authors making contri-  Level of Evidence C Consensus opinion of experts, case studies, or
butions. Full PubMed searches were conducted of all English standard of care
language articles regarding relevant human disease treatment Diagnostic recommendations
from 2009 through August 2013. Drafts of summaries and rec-  Level of Evidence A Data derived from multiple prospective
ommendations were circulated to the entire writing group for cohort studies using a reference standard
feedback. Several conference calls were held to discuss indi- applied by a masked evaluator
vidual sections, focusing on controversial issues. Sections were  Level of Evidence B Data derived from a single grade A study or
revised and merged by the Chair. The resulting draft was sent to one or more case-control studies, or studies
using a reference standard applied by an
the entire writing group for comment. Comments were incorpo- unmasked evaluator
rated by the Chair and Vice-Chair, and the entire committee was
 Level of Evidence C Consensus opinion of experts
asked to approve the final draft. Changes to the document were
made by the Chair and Vice-Chair in response to peer review, AHA/ASA indicates American Heart Association/American Stroke Association.
and the document was again sent to the entire writing group
for suggested changes and approval. Recommendations follow
the American Heart Association/American Stroke Association's Ischemic Stroke.”9 The primary objective is to provide airway
methods of classifying the level of certainty of the treatment management if needed, provide cardiovascular support, and
effect and the class of evidence (Tables 1 and 2). All Class I transport the patient to the closest facility prepared to care for
recommendations are listed in Table 3. patients with acute stroke.10 Secondary priorities for EMS pro-
viders include obtaining a focused history regarding the tim-
Emergency Diagnosis and Assessment ing of symptom onset (or the time the patient was last normal);
ICH is a medical emergency. Rapid diagnosis and attentive information about medical history, medication, and drug use;
management of patients with ICH is crucial, because early and contact information for family. EMS providers should
deterioration is common in the first few hours after ICH onset. provide advance notice to the ED of the impending arrival
More than 20% of patients will experience a decrease in the of a potential stroke patient so that critical pathways can be
Glasgow Coma Scale (GCS) of 2 or more points between the initiated and consulting services alerted. Advance notice by
prehospital emergency medical services (EMS) assessment EMS has been demonstrated to significantly shorten time to
and the initial evaluation in the emergency department (ED).6 computed tomography (CT) scanning in the ED.11 Two studies
Furthermore, another 15% to 23% of patients demonstrate have shown that prehospital CT scanning with an appropri-
continued deterioration within the first hours after hospital ately equipped ambulance is feasible and may allow for tri-
arrival.7,8 The risk for early neurological deterioration and the age to an appropriate hospital and initiation of ICH-specific
high rate of poor long-term outcomes underscore the need for therapy.12,13
aggressive early management.
ED Management
Prehospital Management Every ED should be prepared to treat patients with ICH or
Prehospital management for ICH is similar to that for ischemic have a plan for rapid transfer to a tertiary care center. The
stroke, as detailed in the recent American Heart Association crucial resources necessary to manage patients with ICH
“Guidelines for the Early Management of Patients With Acute include neurology, neuroradiology, neurosurgery, and critical

or via transfer) and ini- valuable tool for hospitals without on-site presence of consul. (New recommendation) Rapid neuroimaging with CT or MRI is recommended to distinguish ischemic stroke from ICH (Class I.ahajournals. 4  Stroke  July 2015 Table 3. the most widely used and externally validated to an intensive care unit. or other hospital. emergency providers should arrange for should be performed efficiently. Level of Evidence B). ICH. (Unchanged from the previous guideline) DVT Prophylaxis Patients with ICH whose INR is elevated because of VKA should have their VKA withheld. Both hyperglycemia and hypoglycemia should be avoided (Class I. early neurocritical care management in the ED may ameliorate A routine part of the evaluation should include a stan. because such scales can help stream. MRI. (Unchanged from the previous guideline) Management of Medical A formal screening procedure for dysphagia should be performed in all patients before the initiation of oral intake to reduce Complications the risk of pneumonia (Class I. Level of Evidence B). is the ICH Score. Level of Evidence C).28. deep vein thrombosis. (Unchanged from the previous guideline) Prevention of Recurrent ICH BP should be controlled in all ICH patients (Class I. (Unchanged from the previous guideline) Patients with a change in mental status who are found to have electrographic seizures on EEG should be treated with antiseizure drugs (Class I. The protocols specific to the management of ICH. Level of Evidence A). Consultants should be contacted as quickly as pos.  Class I Recommendations Section Class I Recommendations Emergency Diagnosis and Assessment A baseline severity score should be performed as part of the initial evaluation of patients with ICH (Class I. stroke unit. sible while the patient is in the ED. respectively (Class I. magnetic resonance imaging. and VKA.39 These pathways emphasize that consciousness on initial presentation. Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate factor Antiplatelet Agents. and diagnostic studies that should ED lead to worse outcomes. vitamin K antagonist. Level of Evidence A). Level of Evidence B). computed tomography. few have line assessment and communication between providers. although another suggested that be obtained in the ED. this effect. electroencephalography. care facilities that include adequately trained nurses and phy. Numerous grading scales exist spe.38 Such pathways National Institutes of Health Stroke Scale (NIHSS) score. and reversal of coagulopathy should be initiated in the ED to cifically for ICH. systolic blood pressure. (Unchanged from the previous guideline) Hemostasis and Coagulopathy.15 Table 4 describes the integral components of the his. with physicians and nurses rapid admission to a stroke unit or neuroscience intensive care working in parallel.26–32 Although the optimal severity scale is which the patient presents rather than waiting until after transfer not yet clear. ICH patients more often have depressed Neurocritical Care Society. and the clinical evaluation After diagnosis. (Unchanged from the previous guideline) Patients with ICH should have intermittent pneumatic compression for prevention of venous thromboembolism beginning the day of hospital admission (Class I. (Revised from the previous guideline) Seizures and Antiseizure Drugs Clinical seizures should be treated with antiseizure drugs (Class I. (Revised from the Downloaded from http://stroke. EEG. and replacement therapy or platelets. (New recommendation) Rehabilitation and Recovery Given the potentially serious nature and complex pattern of evolving disability and the increasing evidence for efficacy. Level of Evidence A). standardized. A single-center study found that prolonged patient stays in the tory. DVT. receive therapy to replace vitamin K–dependent factors and correct the INR. Level of Evidence B). Level of Evidence C).14.37 Although many centers have critical pathways dardized severity score.org/ by guest on February 6. and integrated man- commonly used for ischemic stroke. (Revised from the previous guideline) General Monitoring and Nursing Care Initial monitoring and management of ICH patients should take place in an intensive care unit or dedicated stroke unit with physician and nursing neuroscience acute care expertise (Class I. acute lowering of SBP to 140 mm Hg is safe (Class I.24. CT. it is recommended that all patients with ICH have access to multidisciplinary rehabilitation (Class I. developed for the treatment of acute ischemic stroke.36. Level of Evidence A) and can be effective for improving functional outcome (Class IIa. 2017 previous guideline) Glucose Management Glucose should be monitored. and receive intravenous vitamin K (Class I. intracerebral hemorrhage. SBP. physical examination. may also be useful in agement of patients with acute ICH. one is available from the ICH. . (New recommendation) Surgical Treatment of ICH Patients with cerebellar hemorrhage who are deteriorating neurologically or who have brainstem compression and/or hydrocephalus from ventricular obstruction should undergo surgical removal of the hemorrhage as soon as possible (Class I. Consultation via telemedicine can be a unit (at their own hospital if available. (Revised from the previous guideline) Blood Pressure For ICH patients presenting with SBP between 150 and 220 mm Hg and without contraindication to acute BP treatment. Level of Evidence B). Level of Evidence C).33–35 These severity scales should not be sicians. INR. Level of Evidence A).25 However. international normalized ratio. Level of Evidence C). tiate early management while the patient is awaiting this bed. tants. and this may diminish urgent treatment of time-sensitive issues including BP lowering the utility of the NIHSS. Level of Evidence A). (Revised from the previous guideline) Measures to control BP should begin immediately after ICH onset (Class I. used as a singular indicator of prognosis. (Revised from the previous guideline) BP indicates blood pressure.30. Level of Evidence A). may allow for more efficient.

abdomen. and extremities  A focused neurological examination A structured examination such as the National Institutes of Health Stroke Scale can be completed in minutes and provides a quantification that allows easy communication of the severity of the event to other caregivers. and death. Neuroimaging The high rate of early neurological deterioration after ICH The abrupt onset of focal neurological symptoms is presumed is related in part to active bleeding that may proceed for hours to be vascular in origin until proven otherwise.42 Time. stimulants (including diet pills). Serum and urine tests  Complete blood count.17 and glucose  Prothrombin time (with INR) and an activated partial thromboplastin time Warfarin-related hemorrhages are associated with an increased hematoma volume. cost.21  Toxicology screen to detect cocaine and other Cocaine and other sympathomimetic drugs are associated with ICH sympathomimetic drugs of abuse  Urinalysis and urine culture. 28% to 38% have hematoma expan- coma or decreased level of consciousness.45 As such. CT CT and magnetic resonance imaging (MRI) are both reasonable angiography (CTA) and contrast-enhanced CT may identify for initial evaluation. sion of greater than one third of the initial hematoma volume gression over minutes or hours all suggest ICH. blood urea nitrogen and creatinine.56 identification of prior hemorrhage.7.50–54 echo and T2* susceptibility-weighted MRI are as sensitive as A larger number of contrast spots suggests even higher risk of CT for detection of acute hemorrhage and are more sensitive for expansion. and smoking  Medications Anticoagulant drugs. greater risk of expansion. Physical Examination.7. often termed a spot sign. GCS. however. the identification of patients at of these findings are specific.43 patients. lungs. GCS score is similarly well known and easily computed.23 CT indicates computed tomography. magnetic resonance imaging. hypertension. ICH. because ICH may be related to hyperperfusion after such procedures  Dementia Associated with amyloid angiopathy  Alcohol or illicit drug use Cocaine and other sympathomimetic drugs are associated with ICH. Higher serum glucose is associated with worse outcome16.19  Cardiac-specific troponin Elevated troponin levels are associated with worse outcome20. systolic BP (SBP) >220 mm Hg.55.41. ECG abnormalities can mark concomitant myocardial injury22. diabetes mellitus. as well as a pregnancy test in a woman of childbearing age Other routine tests  Neuroimaging CT or MRI. Glasgow Coma Scale. proximity to Early diagnosis of underlying vascular abnormalities can the ED. Risk factors for underlying vascular abnormalities are .org/ by guest on February 6. 3 hours of ICH onset. and symptom pro. it is after symptom onset. preclude emergent MRI in many cases.40 risk for hematoma expansion is an active area of research. 2017  Vital signs  A general physical examination focusing on the head. CT is very sensitive for identifying acute patients at high risk of ICH expansion based on the presence hemorrhage and is considered the “gold standard”. severe headache. sympathomimetic drugs  Recent trauma or surgery Carotid endarterectomy or carotid stenting. and MRI. however. and increased morbidity and mortality18. neuroimaging is thus mandatory.44–49 Among patients undergoing head CT within Vomiting. heart. although none on follow-up CT. consider contrast-enhanced or vascular imaging  ECG To assess for active coronary ischemia or prior cardiac injury. electrolytes. stimulants  Seizures  Liver disease May be associated with coagulopathy  Cancer and hematologic disorders May be associated with coagulopathy Physical examination Downloaded from http://stroke.  Integral Components of the History. Hemphill et al   Management of Spontaneous ICH   5 Table 4. antiplatelet agents. intracerebral hemorrhage. gradient of contrast within the hematoma. INR. and Workup of the Patient With ICH in the Emergency Department Comments History  Time of symptom onset (or time the patient was last normal)  Initial symptoms and progression of symptoms  Vascular risk factors History of stroke or ICH. patient tolerance. Hematoma expansion tends to occur impossible to know whether symptoms are caused by ischemia early after ICH and increases risk of poor functional outcome or hemorrhage on the basis of clinical characteristics alone. international normalized ratio. clinical status. and MRI availability both influence clinical management and guide prognosis in ICH may. antihypertensive medications.ahajournals.

58 MRI. lobar ICH. can be reconstituted and administered rapidly Patients at risk include those taking oral anticoagulant drugs in a small volume (20–40 mL). but more recently.74 It is important that providers caring along the margins of the ICH. PCC does not require cross Underlying hemostatic abnormalities can contribute to ICH.4 by this time. Level of Evidence A). contrast. used.72 and apixaban. although 17% of patients and tumors when there is clinical or radiological sus.65 Radiological evidence suggestive of vascu.56 unusual hematoma shape. VKA reversal strategies in a dose of 5 to 10 mg. or abnormal per 100 U of heparin (maximum dose 50 mg). tor VIII inhibitor bypassing activity). presence of edema out patients with ICH. (OACs). and CTA.77 Fresh frozen plasma (FFP). with adjustment signal in the cerebral sinuses on routine neuroimaging suggests based on time elapsed since discontinuation of heparin infu- cerebral vein thrombosis. Level of Evidence B). appropriate interventions. and catheter and often requires large volumes for full INR correction. magnetic resonance angiography. or of an underlying coagulopathy in the initial evaluation of age path.75 Similar dosing can be used in patients who are receiv- In summary. Onset of action begins by 2 expansion (Class IIb. and absence of a history of hypertension tal coagulation factor deficiencies. PCCs are plasma-derived factor concentrates originally Medical Treatment for ICH developed to treat factor IX deficiency (hemophilia B). and those with inherited or coagulopathy. intraven. and has been processed to . Level of Evidence B). CTA and contrast-enhanced CT may be consid.79 Shortcomings of FFP have led to interest in alternative agents for VKA reversal. often with the assistance of a consultant hema- higher likelihood of identification of a secondary cause of ICH tologist.78 CT venography. usually given ered to help identify patients at risk for hematoma slowly via the intravenous route. rapid correction of the international normalized Recommendations ratio (INR) is recommended.57. sion. 6  Stroke  July 2015 age <65 years. (Unchanged FFP administered in this manner may be insufficient for rapid from the previous guideline) correction of coagulopathy. matching. and cerebral vein lation and increased use of anticoagulant drugs in recent thrombosis. then protamine resonance venography or CT venography should be performed sulfate can be given by intravenous injection at a dose of 1 mg if hemorrhage location. car- enhanced MRI. rhage location. reversal may be diagnosed and managed promptly. those with acquired or congeni- tricular extension. so that the treatment strategy can include of proportion to the time of presumed ICH.67. Rapid neuroimaging with CT or MRI is recom. and no history of hypertension have a or platelets.76 For ICH patients tak- Emergency Diagnosis and Assessment: ing VKA. with ICH. Antiplatelets. enlarged vessels or calcifications of ICH than VKAs. and magnetic resonance venography.67–69 a rate that has increased with the aging popu- venous malformations.58. including dabigatran. age <55 years. ICH is a medical emergency that should be ing low-molecular-weight heparin. female sex. nonsmoker.66 An magnetic undergoing an intravenous heparin infusion. Three- Hemostasis and Coagulopathy. contrast-enhanced CT. Patients with lobar hemorrhage or platelet disorder. and factor PCC contains factors II. (New recommendation) complex concentrates (PCCs). including arterio.71 rivaroxaban. (Class I.73 lar abnormalities as causative for ICH can include the presence These new agents appear to be associated with a lower risk of subarachnoid hemorrhage. and X whereas 4-factor Deep Vein Thrombosis Prophylaxis PCC also contains factor VII.62–64 A catheter angiogram may be considered if clinical do not require laboratory monitoring and do not necessarily suspicion is high or noninvasive studies are suggestive of an prolong coagulation screening tests are being increasingly underlying lesion.ahajournals. or acquired qualitative or quantitative platelet abnormali- magnetic resonance venography. is indicated.org/ by guest on February 6. prothrombin Level of Evidence B). and recombinant acti- mended to distinguish ischemic stroke from ICH vated factor VIIa (rFVIIa) have emerged as potential therapies. are the most frequently prescribed OAC. FFP administration requires thawing and cross matching. the activated PCC FEIBA (fac- 2. an unusual hemor. moyamoya.39 early deterioration are common within the first few hours after onset. IX. 2017 in the brain (like a mass).59–61 CTA has been more widely studied and is decades.70 Vitamin K antagonists (VKAs) such as warfarin highly sensitive and specific for detecting vascular abnormali. VKA-Related ICH Guidelines exist for reversal of OACs. hyperattenuation within a dural for ICH patients recognize the use of antithrombotic drugs venous sinus or cortical vein along the presumed venous drain. and the presence of other abnormal structures For patients with a known coagulation factor deficiency Downloaded from http://stroke. but new agents that ties. still did not have an INR <1. A baseline severity score should be performed as part along with vitamin K. tumors.76. replacement of the appropriate factor location. Patients taking OACs constitute 12% to 20% of patients can identify specific causes of hemorrhage. antiplatelet agents. however. hours and is maximal at ≈24 hours if liver function is normal. 1. which suggests that picion (Class IIa. angiography can be useful to evaluate for underlying Likelihood of INR correction at 24 hours was linked to time structural lesions including vascular malformations to FFP administration in 1 study. If spontaneous ICH occurs in a patient from additional MRI beyond noncontrast CT. (Unchanged from the Administration of intravenous vitamin K alone is insufficient previous guideline) for reversal in the first hours but should be part of all acute 3. magnetic resonance angiography ries a risk of allergic and infectious transfusion reactions. the United States for years. Hematoma expansion and incomplete. relative edema volume. and CTA or CT venography ties. has been the mainstay of treatment in of the initial evaluation of patients with ICH (Class I.

95 are taking an OAC. licensed to treat hemophilia patients with high growth and improved clinical outcome relative to placebo. Analogous randomized trials have not been performed to directly evaluate 3-factor and 4-factor PCCs against each rFVIIa in ICH Not Related to Anticoagulant Agents other. New Anticoagulant Medication–Related ICH Thromboprophylaxis in ICH Patients There are no randomized trials of reversing agents for newer Patients with ICH have a high risk of thromboembolic dis- anticoagulants among patients with ICH or other major bleed.114 Finally.107 4.86 PCCs may increase the risk of thrombotic has not been fully studied. a subsequent phase 3 trial did not find clinical benefit. Hemphill et al   Management of Spontaneous ICH   7 inactivate infectious agents. or rivaroxaban was taken within the previous graduated compression stockings than in those with thigh- couple of hours.96–99 but these data are preliminary. has gar. intermittent pneumatic available for a few years. 2. DVT. Although rFVIIa can rapidly normal.94 Thus. A case series of 45 ICH patients complications. Additionally.108. Several studies have shown that Antiplatelet Medication–Related ICH PCCs rapidly normalize the INR (within minutes) in patients Studies addressing the effect of prior antiplatelet agent use or taking VKAs.106.3 to <1. rFVIIa has also been tested in patients with non-OAC ICH. but currently its benefits in ICH patients.6% for FFP. CLOTS 1 enrolled 2518 stroke patients (232 with ICH) and whereas other PCCs may be better for the factor Xa inhibitors found that thigh-high compression stockings did not reduce rivaroxaban and apixaban.102 Others patient clinical outcome with PCC.100 Hemodialysis has been noted as an option high graduated compression stockings. graduated compression stockings versus calf-high stockings.87 In this study. those sion and clinical outcome. 2017 apy was 62. min K is not useful. and because these agents have only been randomized trial of 151 ICH patients.83–85 In 1 randomized trial have suggested that platelet dysfunction as measured by plate- comparing the use of a PCC (Konyne) to supplement FFP let function assays may be associated with hematoma expan- versus FFP alone in patients with VKA-related ICH.5. CLOTS 3 for dabigatran.9%). primarily attributable to tions and guiding hemostatic interventions. the receiving platelet transfusion at the discretion of their phy- first large phase 3 randomized controlled trial demonstrated sician demonstrated improved platelet reactivity after trans- noninferiority of 4-factor PCC to FFP for urgent reversal of fusion with the VerifyNow-ASA assay. FFP is of unclear utility.115 CLOTS 2 found Activated charcoal can be used if the most recent dose of dabi. Stroke) consisted of 3 different randomized trials (CLOTS 1. Reported antiplatelet agent use was not correction of INR with vitamin K and PCC than vitamin K associated with hematoma expansion or clinical outcome in and FFP. ease. occurrence of asymptomatic deep vein thrombosis (DVT) rivaroxaban. includ- Potential reversal strategies using FEIBA. but this approach fluid overload. or death.2% for PCC and 9.109 nered attention as a potential treatment for spontaneous and Use of rFVIIa was associated with an increased frequency of OAC-associated ICH.8% with PCC and 6. thromboembolic events compared with placebo (7% versus ize INR in the setting of VKA-associated ICH. Thromboembolic pendence at 3 months.105 Subgroup analysis warfarin in a cohort of 202 patients with acute bleeding (24 of in those at high risk of hemorrhage growth suggested that whom had intracranial hemorrhage). experience with reversal is limited.110–112 In a ing complications.7% versus ranging from 5 to 15 hours. other PCCs. Two randomized controlled trials are event rates were similar (7.89–93 it does not 2%) in the phase 2 trial and significantly more arterial events replenish all of the vitamin K–dependent factors and may not in the phase 3 trial.80 In 2013.90 Specific antidotes for tent pneumatic compression begun as early as the day of hos- these medications are in early clinical development.114–117 may be better for the direct thrombin inhibitor dabigatran.104 Platelet function monitoring who were given FFP alone received a higher volume of FFP could be helpful in assessing exposure to antiplatelet medica- and developed more adverse events.101 pital admission reduced the occurrence of proximal DVT. 15. the specific INR target for VKA correc. none have clearly demonstrated an improvement in the placebo group of an ICH neuroprotective study. or ing graduated compression stockings versus none. rFVIIa is not currently recommended for routine use in war. the rate of platelet transfusion within 12 hours of symptom onset was achieving an INR <1. and 3) that assessed several different treatments. compression together with elastic stockings reduced the Currently available agents in the United States (dabigatran.103. ongoing to evaluate the effectiveness of platelet transfusion in and fluid overload was more common with FFP (12. with various studies cited Although a phase 2 randomized trial showed that treatment here and elsewhere using targets ranging from <1. although this risk appears low. It has been suggested that FEIBA or rFVIIa and intermittent pneumatic compression versus none. pulmonary embolism (PE). apixaban.110 Women and blacks may be at greater risk.113 The CLOTS trials (Clots in Legs or Stockings After tial thromboplastin time and prothrombin time and consulta. titer inhibitors or congenital factor VII deficiency. and apixaban) have relatively short half-lives after ICH compared with elastic stockings alone (4.8% versus ICH patients taking antiplatelet agents. remain unproven.3 within 30 minutes of completing ther.ahajournals.9%). tion in OAC-related ICH is unclear. that DVT was more common in patients who had below-knee gatran. thigh-high rFVIIa might be considered. but less so for rivaroxaban or apixaban because enrolled 2876 patients (376 with ICH) and found that intermit- these are more highly protein bound. whether or not they farin reversal. Evaluation of the activated par. rFVIIa might benefit a particular subset of patients with ICH. tion with a hematologist are reasonable to individualize care. associated with smaller final hemorrhage outcome and inde- Downloaded from http://stroke. and vita. with .80–82 Although nonrandomized retrospective platelet dysfunction on ICH growth and outcome have found reviews and a small case-control study have shown more rapid conflicting results.org/ by guest on February 6. It remains to be determined whether restore thrombin generation as effectively as PCCs.88 with rFVIIa within 4 hours after ICH onset limited hematoma rFVIIa.4% with FFP).

Level of CI.126 be considered over FFP (Class IIb. as well as the optimal anticoagulation regi.57–1.7% versus 2.0%. 95% CI. 8  Stroke  July 2015 the effect being particularly prominent in patients with hem. High SBP is 2. and death and dependency after ICH. (Unchanged from the variety of factors. 2017 guide decision making on IVC filter placement versus anti. Level of Evidence the perihematomal rim of low attenuation seen on CT being C). Level of Evidence A). respectively Elevated BP is very common in acute ICH121.122–124 Compared to replace vitamin K–dependent factors and correct the with ischemic stroke.120 account several factors.116 A meta-analysis tain (Class IIb. of Evidence C). Level of Evidence C). The coagulant therapy if the risk of bleeding resolves. Evidence A). General guidelines for the use of IVC filters in the probably indicated in ICH patients with symptom- setting of acute DVT suggest a conventional course of anti. 0.44–1. For patients with ICH who are taking dabigatran.3%. 1.36. 0. (Revised from of anticoagulant drugs for thromboprophylaxis that included the previous guideline) 1000 ICH patients from 4 trials (2 randomized) and evalu. lowering to an SBP target of <140 mm Hg within several hours roxaban was taken <2 hours earlier. including time from hem- orrhage onset. Level of Evidence A). cause of hemor- rhage. pain.03). Hemodialysis of ICH.34) or hematoma enlargement matic compression for prevention of venous throm- (8. The usefulness of platelet transfusions in ICH orrhagic stroke (6. Although rFVIIa can limit the extent of hematoma ated the early use of enoxaparin or heparin (from 1 to 6 days expansion in noncoagulopathic ICH patients. (Revised from the previous guideline) related to extravasated plasma.76. but no difference in DVT (4. rFVIIa is not recommended shown no significant ischemic penumbra in ICH. and Safety of Early Intensive BP-Lowering Treatment although the INR may be lowered.9%. 0. (Unchanged from the previous guideline) 7. (Unchanged from the previ- toma size on neuroimaging. Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate BP and Outcome in ICH factor replacement therapy or platelets. treatment with FEIBA. After documentation of cessation of bleeding. Protamine sulfate may be considered to reverse hep.80). or apixaban. however. receive therapy rioration. including stress. observation alone is not rec.125 only 1 study of ICH has shown a and correct the INR more rapidly than FFP and might poor outcome at low SBP levels (<140 mm Hg). is an increase in thromboembolic risk with rFVIIa relative risk [RR]. Patients with ICH whose INR is elevated because of associated with greater hematoma expansion. therefore. Antiplatelet Agents.0% versus 4. increased ICP. Level of outcomes were seen in the group with the lowest achieved Evidence C).77. Activated charcoal might be used if within the perihematomal region related to early intensive BP the most recent dose of dabigatran. Level of Evidence C).or J-shaped asso- INR. Level of Evidence B). low- ommended. unfractionated heparin may be considered for pre- coagulation. or riva. Level of Evidence C).9%.7% versus 17. Patients with ICH should have intermittent pneu- RR. 4. (New recommendation) an SBP target of <160 mm Hg at a mean of 30 minutes (range. PCCs may have fewer complications outcome have been shown. Only very limited information is available to dose subcutaneous low-molecular-weight heparin or Downloaded from http://stroke. and overall patient condition (Class IIa. decision between these 2 options should take into these are not ICH specific.118 boembolism beginning the day of hospital admission ICH patients who develop DVT or PE may be consid- (Class I.124 Both the Antihypertensive Treatment . 0. 0.2% versus 3. 5.127 with for VKA reversal in ICH (Class III. odds ratio [OR].129 In a clinical cohort of 211 patients who received a might be considered for dabigatran (Class IIb. 8. and receive intravenous vitamin K (Class I. IIb. Level standard protocol of nicardipine-based BP lowering to reach of Evidence C). a nonsignificant and no clear clinical benefit in unselected patients.ahajournals.75). rivaroxaban.17–0.122 because of a (Class I. 15–45 minutes) within 3 hours of the onset of ICH. or rFVIIa might be considered on an no clinically significant reduction in cerebral blood flow individual basis. 0. patients with a history of antiplatelet use is uncer- 95% confidence interval. 95% CI. neurological dete- VKA should have their VKA withheld. atic DVT or PE (Class IIa. the best arin in patients with acute ICH (Class IIb. and the practical ability to remove an IVC filter at a 9. vention of venous thromboembolism in patients with men. rFVIIa is not recommended (Class III. Level Hemostasis and Coagulopathy. using CT perfusion in primarily small and medium ICH found other PCCs. Given the generally accepted improve outcome (Class III. RR.0%. in which consistent U.1% versus 20. documentation of stable hema. there after admission) found a reduction in PE (1. 95% CI. hematoma stability.37.128 A randomized clinical trial 3.42. rFVIIa does not replace all clotting factors. Level of Evidence B). 95% Thus.17–0. reduction in mortality (16. 0. Systemic anticoagulation or IVC filter placement is later date. RR. 6. Level ciations between SBP nadir of 140 and 150 mm Hg and poor of Evidence C). and previous guideline) premorbid acute or persistent elevations in BP. (New recommendation) and DVT Prophylaxis: Recommendations 1. (New recommendation) SBP (<135 mm Hg). clotting may not be Observational studies with advanced neuroimaging have restored in vivo.119 Considerations include the posthemorrhage date on lack of mobility after 1 to 4 days from onset (Class which DVT/PE is diagnosed. 0. [CI] 0. recurrence rate of nonfatal PE is 12% to 15% in nontreated (Revised from the previous guideline) patients (not specific to ICH). lobar versus deep hematoma ous guideline) location. Graduated compres- ered for full systemic anticoagulation or placement of an sion stockings are not beneficial to reduce DVT or inferior vena cava (IVC) filter.57–3.53). apixaban.org/ by guest on February 6.

0%) receiving intensive treatment (to an SBP target of <140 mm Hg within 1 hour of randomiza. Level of Evidence B). Analysis of secondary end cated stroke unit rather than an intensive care unit. and (<20 mL) hematomas.137 This document also recommends that nurses of death and major disability. cerebral perfusion pressure (CPP). a phase 3 trial Evidence C). 0. with a favorable trend ing and complication prevention in which nurses should seen toward a reduction in the conventional clinical end point be trained. and pulse oximetry better physical and mental health–related quality of life on probe should be standard. comorbidities. patients within 6 hours of ICH131 found rapid reduction of SBP to <140 mm Hg to be safe. Care of ICH patients in a dedicated neuroscience intensive ment (SBP <180 mm Hg) had a primary outcome of death or care unit is associated with a lower mortality rate.55±0. electrocardiographic telemetry. the main phase BP: Recommendations INTERACT2 trial has shown no increase in death or serious adverse events from early intensive BP lowering in eligible 1.134 Among 2794 participants Inpatient Management and Prevention of for whom the primary outcome could be determined. neurological assessments. pharmaco- Hemorrhage (INTERACT1) trial in 404 mainly Chinese logical profile. P=0. There are fewer data avail.134 Several observational studies and 220 mm Hg and without contraindication to have demonstrated that small ischemic lesions identified on acute BP treatment. BP. potential side effects. current evidence indicates that early intensive BP document from the Brain Attack Coalition on comprehensive lowering is safe and feasible and that surviving patients show stroke centers delineates these as specific areas of monitor- modestly better functional recovery. intensive treatment. (Revised from the previous across studies. 785 of 1412 participants (55. General Monitoring tion and for a duration of 7 days.39 versus standard group 0. patients. patients similar to those enrolled in INTERACT2 to receive including standardized scales such as the NIHSS. of ICP. Level of Evidence A) and can impact on outcome and relationship with BP lowering vary be effective for improving functional outcome (Class IIa. and (3) prevention of complications of hours).77 to 1.130 and the pilot ery (bolus versus infusion) and clinical features. GCS. large and more severe ICH. 719 of Secondary Brain Injury 1382 participants (52. fever.06). and most (75%) presented with mild to moderate size immobility through positioning. reduction will vary according to the agent and method of deliv- ering in 80 patients within 3 hours of ICH. acute lowering of SBP to 140 diffusion-weighted MRI are common after ICH. (2) titration and implementation of protocols growth. Moreover. mechanical ventilation. 0. following protocols that Patients with ICH are frequently medically and neurologically included locally available intravenous agents) compared with unstable. Although INTERACT2 demonstrated consistency of the Nursing Care treatment effect across several prespecified patient subgroups.132. 2017 of intensive BP lowering is INTERACT2. and hemody- cant effect of intensive BP-lowering treatment on hematoma namic function.6%) receiving standard treat. Efficacy of Early Intensive BP-Lowering it may be reasonable to consider aggressive reduc- Treatment tion of BP with a continuous intravenous infusion The largest randomized clinical trial evaluating the efficacy and frequent BP monitoring (Class IIb.87. only one third of patients achieved the for management of ICP. particularly within the first few days after onset. Hemphill et al   Management of Spontaneous ICH   9 of Acute Cerebral Hemorrhage (ATACH) trial. For ICH patients presenting with SBP >220 mm Hg. and early treatment targeted to an SBP level <140 mm Hg to the Glasgow Outcome Scale. surgical decompression. the mm Hg is safe (Class I. Continuous intra-arterial BP moni- the EQ-5D scale (mean health utility scores. The specific nursing care required for ICH patients in inten- there was no clear relationship between outcome and the time sive care units may include (1) surveillance and monitoring from onset of ICH to commencing treatment and no signifi. (New recommendation) undertaken in 2839 patients with SBP between 150 and 220 mm Hg within 6 hours of ICH. 95% CI.40. improve their chances of achieving better functional recovery In a Canadian study of 49 hospitals that included ICH should they survive the condition.04) and BP cuff. and hospital .01. however.134 Frequent points indicated significantly better functional recovery on an vital sign checks.org/ by guest on February 6. 0.00.135 guideline) 2. the choice of phase Intensive Blood Pressure Reduction in Acute Cerebral agent should take into account the practicability. and cost. a higher proportion of registered nurses at the hos- able pertaining to the safety and effectiveness of such treatment pital and better nurse-physician communication were inde- in patients with very high BP (sustained SBP >220 mm Hg) on pendently associated with lower 30-day mortality even after presentation. Because the speed and degree of BP escalation study of intravenous nicardipine-based BP low. intensive group toring should be considered in patients receiving intravenous 0. For ICH patients presenting with SBP between 150 patients with elevated SBP.75–1. and those requiring adjustment for disease severity.133 Most recently. P=0. mobilization within physiological tolerance.136 Many major disability (modified Rankin scale score ≥3. P=0. patients in the INTERACT2 study were cared for in a dedi- 95% CI.60±0.002) from vasoactive medications. and continuous ordinal analysis of scores on the modified Rankin scale (OR cardiopulmonary monitoring including a cycled automated for greater disability. The consensus Overall. Level of Downloaded from http://stroke. a 4-tier dose. It is therefore reasonable for ICH be trained in detailed assessment of neurological function. 0.87. target SBP level within 1 hour (half achieved the target by 6 and serum glucose.ahajournals. OR. airway maintenance.

152 Fever may also be associated the previous guideline) with hematoma growth. Level of Evidence C). indepen. Hypoglycemia should be avoided.169. zure drugs. The frequency of clinical seizures early (within 1 week) after tional living after 3 months in patients with ICH (OR.8). especially in patients Seizures and Antiseizure Drugs: with intraventricular hemorrhage. Treatment of fever after ICH may be reasonable (Class mended (Class III. 0.153 Although these data provide a rationale found to have electrographic seizures on EEG for treatment of fever in ICH patients. drugs (Class I. however.166 A small randomized trial of 1-month increased incidence of systemic and cerebral hypoglycemic prophylactic treatment with valproic acid showed no reduc- events and possibly even an increased risk of mortality in tion in incident seizures over 1-year follow-up (19. maintenance of nor. prophylactic antiseizure drugs significantly reduced Recommendation the number of clinical seizures after lobar ICH.159 Cortical involvement of ICH is the most impor- tant risk factor for early seizures. (Revised from the previous guideline) of ICH patients. treatment with mild hypothermia in ICH patients with depressed mental status that is should be considered investigational in ICH at this time. 22. (Unchanged from the previous to outcome.145–148 A cluster randomized the treatment group.54–0.149 At present. Temperature Management Fever worsens outcome in experimental models of brain injury.169. High blood glucose on admission predicts an increased risk Most studies suggest that prophylactic antiseizure of mortality and poor outcome in patients with ICH.68). Level of Evidence C). should be treated with antiseizure drugs (Class I. mortality. Clinical seizures should be treated with antiseizure is related to outcome and appears to be an independent prog. Level of Evidence A). 80–110 mg/dL) using insulin infusions in mainly come in those who survived beyond 5 days after ICH.org/ by guest on February 6. (New recommendation) from the previous guideline) . However.165–167 although a recent study Downloaded from http://stroke. Studies of continuous electroencephalography (EEG) roscience acute care expertise (Class I.168 trial of a set of interventions (managing glucose.60. demonstrated to be beneficial. Initial monitoring and management of ICH patients ciation between clinical seizures and neurological outcome or should take place in an intensive care unit or dedi. 3. comes in a mixed cohort of ischemic and hemorrhagic stroke Clinical seizures or electrographic seizures in patients patients. Continuous EEG monitoring is probably indicated mal edema.155.160.138 In a Swedish study of 86 hospitals. Level of Evidence B). Both hyperglyce- mia and hypoglycemia should be avoided (Class be less in older patients. 2.5% in patients treated with this regimen. Level of Evidence C).170 Risk factors for epilepsy I.160. 0. ICH is as high as 16%.156 However. Prophylactic antiseizure medication is not recom- 1. in ICH patients with depressed mental status that is dispropor- tionate to the degree of brain injury.164 The clinical impact of subclini- Glucose Management cal seizures detected on EEG is unclear. In patients surviving the Recommendations first 72 hours after hospital admission. more recent studies have demonstrated an previous reports. drugs (primarily phenytoin) are associated with increased dent of the presence of diabetes mellitus. 10  Stroke  July 2015 characteristics. although a cause-effect relation. (Unchanged from nostic factor in these patients.139 onset. and Prophylactic anticonvulsant medication has thus not been swallowing dysfunction in stroke units) found improved out. the optimal management of hypergly. have shown no asso- 1.158–160 In a large single-center General Monitoring and Nursing Care: study.154 Preliminary animal and human studies have guideline) suggested that therapeutic cooling may reduce perihemato. stroke Seizures and Antiseizure Drugs unit care was associated with a lower risk of death or institu. (Revised from the previous Temperature Management: Recommendation guideline) 4.151 Fever is common after ICH. (Unchanged IIb.140–144 A randomized death and disability in ICH. surgical critical care patients141 has increased the use of this which highlights the possible influence of confounding in therapy.2% in the placebo group. despite most having received prophylactic antiseizure medications.150. guideline) and delayed initial seizures.158.170 There are no data to sug- gest that early use of antiseizure drugs will prevent lesion- related epilepsy. fever.157 out of proportion to the degree of brain injury (Class IIa. with a change in mental status should be treated with antisei- cemia in ICH and the target glucose level remains to be clari. mothermia has not been clearly demonstrated as beneficial Level of Evidence C).149.162–164 cated stroke unit with physician and nursing neu. Continuous EEG monitoring should be considered fied. the risk of poststroke epilepsy may 1. cortical location of the hematoma. P=0. Level of report electrographic seizures in 28% to 31% of select cohorts Evidence B).ahajournals. with the majority occurring at or near 95% CI. Patients with a change in mental status who are ship is unclear. Glucose should be monitored. 2017 trial showing improved outcomes with tight glucose control found no association between antiseizure drugs and out- (range. the duration of fever 1.161 Prospective and population-based studies. Glucose Management: Recommendation Epilepsy occurs in up to 10% of young patients (18– 50 years) with ICH.159. (Revised from the previous include stroke severity.

Screening and monitoring are keys to detecting these In a prospective multicenter study. although this was not associated The frequency of medical complications after acute stroke with 30-day mortality. PE (1. and post- particulate exogenous substances. however. Neurogenic Hematoma and NXY Treatment]) in patients with sponta. 40% of which were serious well documented in subarachnoid hemorrhage but prevalent (ie.172 In another German study of 208 ICH patients. use of a formal screen- events. aspiration (2. or were fatal). 0. be performed in all patients before the initiation of found that 0. 68% could not tolerate oral feed- dL to a level of at least 1.21 In ICP Monitoring and Treatment another study of 49 patients with supratentorial ICH. these should be consid- monia rate of sites with a formal dysphagia screen was 2.177 is high. and sepsis were independent risk factors for dyspha- result of overall medical status rather than this particular pro- gia and percutaneous endoscopic gastrostomy placement. 95% CI. usually after 7 days of hospitaliza. respira.10. In a meta-analysis of 65 996 stroke patients Level of Evidence C). impaired nutritional status. management. an elevated troponin level >0. exclud. cations were pneumonia (5. acute respiratory distress syndrome formal screen (OR. were immediately in ICH as well. occlusive hydrocephalus.6%).175 These patients not only experienced higher in.176 the annual risk of MI was 2. resulted in prolonged hospitalization. of 3 days.5 years. which included 4984 ICH patients.4 ng/mL was found in 15% within 24 hours of admission Procedures/Surgery and was associated with increased in-hospital mortality. Systematic screening for myocardial ischemia or ing pneumonia and progressive stroke. Level of Evidence B). a 3% absolute risk treatment strategies for other medical complications will also reduction.173 In period and was no more frequent in those who underwent this study. 2017 development of pneumonia. however. In a retrospective study that included 90 Oleinik et al181 as a rise in creatinine of at least 25% or 0. For ICH patients. includ. ways to prevent this have not been studied. 20% its management in patients with ICH. History of prior MI infarction with electrocardiogram and cardiac and severity of deficits on admission are associated with the enzyme testing after ICH is reasonable (Class IIa.181 which suggests that kidney injury was a lation. attention impairments in swallowing efficiency and safety. hyponatremia. gastrointestinal bleeding.171 pulmonary edema.4% ered areas for future study. at present.45). cedure. pulmonary edema is an increase in interstitial and alveolar neous ICH. water swallow test) for all targeting these complications as they arise. it is indistinguishable from cardiogenic tory failure/distress (2%). Resolution usually occurs within several Approximately 50% of deaths after stroke are attributed to days. Management at this time is focused on prevention and ing protocol for dysphagia (eg. at least 1 adverse event was reported in 88% fluid in the setting of an acute central nervous system injury of the placebo-treated patients.org/ by guest on February 6.182–185 A recently reported . oxygen delivery. (New recommendation) hospital mortality but also had greater complications. it is reasonable Downloaded from http://stroke. A formal screening procedure for dysphagia should Stroke Unit Registry. infarction. Intubation with mechanical ventilator support is often medical complications. or uncon- safety and tolerability of NXY-059 (CHANT [Cerebral trolled hypertension in the setting of acute ICH.3%). Stroke patients who experience medical complications ICH patients may be at risk for acute respiratory distress syn- while in the hospital have increased mortality up to 4 years drome from multiple different origins179.6%). urinary tract infections. The identification of preventive or versus 5. required for airway protection and maximum oxygen delivery. Serious cardiac events and cardiac death after stroke may be caused by acute myocardial infarction (MI). heart failure. In a trial of the emia. and sepsis (1. to use ventilation strategies used in non-neurological patients lowing impairment of the upper digestive tract and includes (such as low-tidal-volume ventilation)180. Concurrent stroke and MI are not uncommon. although there is substantially more information Heart failure can occur as the result of myocardial isch- reported for ischemic stroke than ICH. occurrence of MI.ahajournals. Management of Medical Complications: ventricular arrhythmias including ventricular tachycardia/ Recommendations fibrillation.4% of those without a screen. 25% of patients (8%) admitted to a single institution over a 5-year patients required percutaneous endoscopic gastrostomy. Acute nephropathy (defined in a study by into the airways. and cardiac arrest. and acute kidney injury. or endogenous secretions stroke depression. Aspiration in this population is a sign Other medical complications in ICH patients include of severe dysphagia and refers to abnormal entry of fluid.3% of patients had an MI over a median duration oral intake to reduce the risk of pneumonia (Class I.178 Neurogenic pulmonary edema presents life threatening. mechanical venti- CT angiography. Recent data from the prospective Austrian 1. after the initial event. require further studies focused on ICH patients. Hemphill et al   Management of Spontaneous ICH   11 Management of Medical Complications had elevated troponin levels. abruptly and progresses quickly after the neurological insult. Dysphagia is defined by swal.7%).5 mg/ Japanese ICH patients. stress-induced cardiomyopathy. Limited data exist regarding the frequency of elevated ICP and ing those who died within 12 hours or were moribund. When ICH patients Dysphagia and aspiration are major risk factors for the develop acute respiratory distress syndrome. 2. and frank aspiration.30–0. (New recommendation) with a mean follow-up of ≈3. GCS. The most common compli. with delays should be paid to avoid ICP elevations or inadequate cerebral in the timing of movements.2 %. acute kidney injury.5 mg/dL) occurred in 41 of 539 ICH ing. reduced range of movements.174 The pneu. tion. 0. Because of lim- patients admitted with ischemic stroke was associated with ited information regarding ICH-specific issues related to ven- a significantly reduced risk of pneumonia compared with no tilator-associated events. Radiographically.

associated with brain tissue hypoxia and poor outcome. and the use of warfarin may require reversal of coagulopathy before Intraventricular Hemorrhage placement. Level of Evidence higher with VC than with parenchymal catheters. obstruction caused by hydrocephalus or a trapped ventricle. because ICP is measured by use of devices inserted into the brain they are not effective in ICH and increase complications. Corticosteroids should not be administered for treat- Before insertion of a monitoring device.202. and hypertonic Increased ICP also may be more common in younger patients saline may be more effective. VC use alone may be ineffec- tion. A parenchymal ICP device is limited data. The decision to use a VC or a parenchymal cath.184. which could potentially increase the risk of infection.195. Salvage therapies might include barbiturate coma or (23% of all patients. Pooled analysis of 13 studies found IVH in association with Because of limited data regarding indications for monitor.196 In 1 study of multimodality episode of intracranial hypertension (defined as an ICP >20 monitoring in 18 ICH patients. CPP <70 to 80 mm Hg was mm Hg).190.3% in patients with to 70 mm Hg may be reasonable to maintain depend- coagulopathies).195. and CSF from the ventricles. ated with worsened outcome in acute ICH.205 Although the 8 and maintenance of an ICP <20 mm Hg and a CPP of 50 insertion of a VC should theoretically aid in drainage of blood to 70 mm Hg. Ventricular drainage as treatment for hydrocephalus with ICP monitors include infection and intracranial hemor. Fiber optic technology can Small case series have described the use of brain tissue be used in both types of devices. although B). ICH. 377 had IVH. The absence of published stud- ies showing that management of elevated ICP has an effect on ICP Monitoring and Treatment: Recommendations ICH outcome makes the decision whether to monitor and treat elevated ICP unclear in patients with ICH. originating as an extension of an ICH. patients with small hematomas and that might constrict cervical veins. elevated ICP are usually generalized from those for traumatic or secondary. the use of hydrocephalus from IVH or mass effect from the hematoma mild sedation.1% (15. ICP was >20 mm Hg at the time considered in ICH patients with a GCS score of ≤8 that is of ventricular catheter (VC) insertion in 14 patients. ICP was not frequently elevated during monitoring evidence of transtentorial herniation. especially in patients with decreased rhage.org/ by guest on February 6.200. (New recommendation) may justify platelet transfusion before the procedure. ICH increased the risk of death from 20% without to 51% ing and treatment of ICP in ICH. is reasonable.201 Because of the small numbers of patients and which can help reduce ICP. In a 1997 series of 108 intrapa. no recommendation can be made regarding the inserted into the brain parenchyma and allows for monitoring use of these technologies at this time. ferential pressure gradients in at least some cases of ICH. so Methods of treating elevated ICP are generally borrowed that ICP may be elevated in and around the hematoma but not from traumatic brain injury guidelines as well.195 ysis in 100 patients with intraventricular hemorrhage (IVH) Thus.199 parenchyma or cerebral ventricles. evidence of transtentorial herniation. oxygen and cerebral microdialysis monitoring in patients with eral ventricle allows for drainage of cerebrospinal fluid (CSF). ous guideline) tions.186 Because the usual causes of elevated ICP are ples include elevation of the head of the bed to 30°.185 In a randomized trial of intraventricular thrombol.184 Overall. management principles for with IVH. but these patients had multiple intrathecal injec.185 Hydrocephalus is associ. (Revised from the previous guideline) data on these rates are not derived from patients with ICH but 2. depending on the status of cerebral autoregula. IVH is secondary and related to hypertensive hemorrhages ment of an ICP monitor in patients with a GCS score of 3 to involving the basal ganglia and thalamus. or those with significant and VC drainage in these patients. IVH or hydrocephalus. but not CSF drainage.184 3. The risk of hemorrhage or infection is thought to be level of consciousness (Class IIa. There is evidence for dif. confined to the ventricles. Most brain injury. ICP monitoring and subsequent treatment might be and ICH smaller than 30 mm3. the rate of infection was 2.203 CSF to treat hydrocephalus or elevated ICP.197 Mannitol or hypertonic limited IVH usually will not require treatment to lower ICP. A CPP of 50 of intracranial hemorrhage was 2.192–194 Data from small.9% and the rate ered for ICP monitoring and treatment. retrospectively analyzed cohorts tive because of difficulty maintaining catheter patency and the . A VC inserted into the lat. 55% of those with IVH). of ICP. (Unchanged from the previ- ventriculitis. and 208 of these had hydrocephalus of ICH. IVH occurs in ≈45% of patients with spontaneous ICH and is eter device should be based on whether there is a need to drain an independent factor associated with poor outcome. Prior use of antiplatelet agents Evidence B). Risks associated 1. Corticosteroids should not be used. Patients with a GCS score of ≤8. ment of elevated ICP in ICH (Class III. 2017 patients with follow-up data who were randomized into the decompressive craniectomy (DC) are options for treating ele- international Surgical Trial for Intracerebral Haemorrhage vated ICP and are discussed in the section on Surgical Treatment (STICH). of whom 40 (70%) had at least 1 associated with mortality.202.204 IVH can be primary. Hematoma evacuation and Downloaded from http://stroke.ahajournals. those with clinical however. and avoidance of collar-endotracheal tube ties (or surrounding edema).187–189 Among 902 CSF drainage should be considered. Basic princi- distant from it.191 Two of 22 patients (9%) patients in the pla.198 In patients with CSF outflow and those with supratentorial ICH. those with clinical principally from those with traumatic brain injury or aneurys. saline may be used to treat acute ICP elevations. Level of tion status should be evaluated. significant IVH or hydrocephalus might be consid- renchymal devices. ing on the status of cerebral autoregulation (Class cebo arm of a trial of intraventricular thrombolysis developed IIb. the patient’s coagula. in which current guidelines recommend place. Level of Evidence C).190 mild hypothermia. presumed related to hematoma mass effect. 12  Stroke  July 2015 cohort study of 243 consecutive ICH patients described ICP of ICH patients suggest that rising ICP and declining CPP are monitoring in 57 (23%). or those with mal subarachnoid hemorrhage.

2 prospective randomized trials and 3 meta-analyses have There was symptomatic rebleeding in 9 rtPA patients (12%) been completed that compared surgery versus conservative and 1 patient given placebo (5%.32. study reported improved outcome on the Glasgow Outcome ventricular administration of fibrinolytic agents.189 In a study comparing 16 patients treated ventricular urokinase found death occurred in 21 patients with VC and lumbar drainage for ICH with IVH to 39 histori- (50%) and ventriculitis in 11 (26%). or lumbar drainage.184. treating neurosurgeon determined that uncertainty of preferred . 0. with 2 patients in the rtPA group diagnosed with ventriculitis.207 Mortality was reduced from require permanent CSF diversion. because these patients were not included tomy. intervention. reducing ICP. (New recommendation) or VC with intraventricular fibrinolysis (n=167) found a sig- nificant decrease in mortality from 47% to 23% (pooled Peto OR. 78 rtPA) with IVH attributable to spon. the current recommendations randomized CLEAR III trial is in progress.223 Among recent interest in the use of thrombolytic agents as adjuncts to the 46 patients treated with endoscopy compared with 44 VC use in the setting of IVH. including Scale at 2 months with endoscopy but did not report the rate urokinase.189 30% to 10% in the group treated with rtPA. remains controversial. bacterial ventriculitis these trials can be questioned. patients managed study compared 48 patients with IVH (caused by ICH in 40 with VC plus lumbar drainage had a longer median duration [83%]) treated with intraventricular rtPA to 49 matched control of external CSF drainage but were significantly less likely to patients treated with VC alone. who were treated with intra. One Animal studies and clinical series have reported that intra. the generalizability of the results of taneous ICH <30 mm3. with urokinase and 44% with VC alone (P=0. of permanent CSF diversion. underlying structural lesions such as aneurysms and arteriove- such as endoscopic surgical evacuation and ventriculos. 95% CI. and mortality was 19%.33). niation were likely excluded and the largest and most recent Patients treated with rtPA had significantly lower intracranial studies had high rates of treatment group crossover from con- pressures. because patients at risk for her- occurred in 3 patients with rtPA (4%) and 2 with placebo (9%).218 CLEAR-IVH included 100 agement have not demonstrated a clear benefit for surgical patients (22 placebo. Level of Evidence B).52).184.223 In 1 of the studies. and recombinant tissue-type plas. Moreover. tain (Class IIb. Craniotomy for Supratentorial Hemorrhage pared with 50% of 48 historical control patients treated with On the basis of inconclusive evidence from prior trials.org/ by guest on February 6. uloperitoneal shunting. Studies with rtPA have used various dose niation.22). and decreasing the pathophysiological regimens ranging from 1 to 4 mg every 8 to 12 hours. fewer VC obstructions that required replacement. with the difference occurring Surgical Treatment of ICH (Clot Removal) principally in patients treated with urokinase.217.224 endoscopic third ventriculostomy. 2017 randomized to VC or VC plus urokinase. The theoretical rationale for hematoma sion between subjects treated with intraventricular fibrinolytic evacuation revolves around the concepts of preventing her- agents and VC alone.188 Thus. P=0. Permanent CSF treatment for ICH. Since the last guidelines.209 There was no The role of surgery for most patients with spontaneous ICH difference in complications or need for permanent CSF diver. In a small pro. with no possible role for craniectomy in ameliorating increased ICP significant difference between placebo and rtPA. The efficacy of endoscopic treatment of IVH is IVH secondary to spontaneous ICH treated with VC (n=149) uncertain (Class IIb. servative management to surgery. the CLEAR-IVH trial (Clot Lysis: Evaluating Accelerated Randomized trials comparing surgery to conservative man- Resolution of IVH).221.214 Clearance of IVH 1. STICH VC alone. 0. Median 30-day modified Rankin scale Additionally. streptokinase. Mortality at 6 months was 14% IVH appears to have a fairly low complication rate. recent retrospective studies have suggested a score was 5 in both groups. in IVH may reduce morbidity and rates of permanent CSF diversion after endoscopy. and there the efficacy and safety of this treatment are uncer- were no significant differences between groups in require. 16 patients with IVH and ICH <30 mm3 were Downloaded from http://stroke. and nonsignificantly shorter duration of VC requirement.27). Outcome on the modified Rankin scale was simi. treated with VC.206 Another prospective cal control patients treated with VC alone.217–219 Overall. patients (P=0. IVH: Recommendations spective trial.230–234 In addition. Meta-analysis of the previous recommendation) 4 randomized and 8 observational studies of patients with 2.220–223 A comparison of 48 patients with IVH secondary in the described ICH surgery trials. do not apply to intracranial hemorrhage caused by trauma or There are now reports of alternative procedures for IVH. to ICH and other causes and treated with endoscopic removal of IVH found 17% required permanent CSF diversion com. mortality was not significantly different. there has been urokinase was also used in both treatment groups.225 88% attributable to primary ICH. Two randomized trials have been reported comparing mortality and improves neurological outcome compared with endoscopic removal of IVH with VC in patients with IVH conservative management for supratentorial ICH when the secondary to primary ICH <30 mm3. (Revised from ment for permanent shunts or ventriculitis.221 Other mortality by accelerating blood clearance and clot lysis.223 The other suggested lower minogen activator (rtPA). nous malformations.ahajournals. The phase 3 caused by ICH.215–218 impact of the hematoma on surrounding tissue by decreas- The largest trial of intraventricular fibrinolysis to date is ing mass effect or the cellular toxicity of blood products. Level of Evidence B). was undertaken to determine whether early surgery reduces lar. Although intraventricular administration of rtPA in was faster with urokinase.206–214 reported management strategies for IVH include early ventric- Retrospective analysis of 42 consecutive patients with IVH.19–0.184.226–229 Several other studies have examined diversion was required in 14% of placebo and 6% of rtPA minimally invasive approaches compared with craniotomy. Hemphill et al   Management of Spontaneous ICH   13 slow removal of intraventricular blood.

but meth- of STICH and STICH II on early surgery leave unclarified odological issues with this analysis have been raised. it is unlikely that a randomized trial could be con- surgery. uation included 5 patients with recalcitrant elevated ICP.227 The Minimally Invasive Surgery rioration can occur quickly in cerebellar hemorrhage caused Plus Recombinant Tissue-Type Plasminogen Activator for by obstructive hydrocephalus or local mass effect on the ICH Evacuation Trial II (MISTIE II) aimed to determine the brainstem. evacuation of brainstem hemorrhages may be harm- with 24% in the medical arm. ful in many cases. A nonpre.229. Given the broad lack of clinical equipoise cally significant difference in mortality or functional outcome for surgical evacuation of cerebellar hemorrhages. 3-month neurological outcome was bet- Because of the narrow confines of the posterior fossa.231.org/ by guest on February 6.241–243 A als.228 A significant advantage for surgery was shown when all Minimally Invasive Surgical Evacuation of ICH patients were considered. was 8.232–234. Although there was no significant Craniotomy for Posterior Fossa Hemorrhage impact on mortality. narrow patient-based inclusion criteria. volume was 61. but high crossover rates of patients to surgical interven. there was no ation for both putaminal and lobar ICH found that patients advantage to early surgery for patients in the good prognosis with putaminal hemorrhage had greater reduction in midline category. particularly in patients those with worse prognosis.ahajournals. Twenty-six percent of the patients with compressed cisterns. A comes with surgical decompression. The study randomized patients to early surgery agement.236 of the first STICH trial. Good VC insertion alone.240 A systematic review of studies in ized to initial medical management ultimately underwent which DC was performed in the setting of spontaneous ICH surgery. Notably. dete. large within 48 hours of ictus. Thus.233 meta-analysis of surgical trials reporting on 3366 patients. aspiration of basal ganglia hemorrhages (25–40 mm3) to med- ical management alone.234 specified subgroup analysis that included only patients with This small cohort fared better than matched control subjects a poor prognosis (as defined by a specific equation used in from the authors’ institutional prospective ICH database. On the basis of the results observations. or ICP that did not normalize with medical man- participated. The primary outcome control subjects via propensity score. 14  Stroke  July 2015 treatment was present. STICH found no overall statisti. however. but there was significant heteroge. and may actually be harmful. the STICH II trial was undertaken. such as Scale at 6 months was used as the primary end point. especially between treatment groups.232 Median hematoma was a prognosis-based dichotomized (favorable or unfavor. The STICH II authors performed an updated and might improve outcomes. and the focus minimally invasive approaches over craniotomy.3 mm3. On the basis of these ICH has not been well studied.244 whether surgery may benefit specific groups of patients with A recent randomized study of 465 patients compared needle supratentorial ICH.239 In contrast to cerebellar hemor- in the surgical arm achieved a favorable outcome compared rhage. Three patients in the study group died compared with Forty-one percent of patients in the early surgery group had 8 in the control group. Seventy-eight centers in 27 countries hematomas.240 superficial lobar hemorrhage of 10 to 100 mm3 within 1 cm of Patients in these studies tended to be those in coma (GCS the cortical surface and without IVH and who were admitted score <8) and those who had significant midline shift.237–239 Attempting to con- favorable outcome on the 8-point extended Glasgow Outcome trol ICP via means other than hematoma evacuation. A STICH) showed that such patients were more likely to have a retrospective study of DC in addition to hematoma evacu- favorable outcome with early surgery. 26% of patients initially those >3 cm in diameter occurring in potentially salvageable assigned to conservative management ultimately underwent patients. meta-analysis of 12 clinical trials suggested superiority of tion. Additional subgroup analysis suggested that Craniectomy for ICH the risk for a poor outcome was increased for patients who The potential of DC to improve outcomes for patients with presented as comatose (GCS score ≤8). is not recom- outcome was dichotomized. with the most common reason described as patient suggested that DC with hematoma evacuation might be safe deterioration. Several recent randomized studies have compared minimally neity in the data. better outcomes with less invasive approaches. A nonsignificant survival advantage was noted for shift and a trend toward better neurological outcome than the surgical arm. matched control subjects. Twenty-one percent of patients random. ter in the aspiration group.227. 1033 patients from 83 or patients in whom cerebellar hemorrhage is associated with centers in 27 countries were randomized to early surgery (<24 brainstem compression or hydrocephalus have better out- hours of randomization) or initial conservative treatment. This study compared 79 surgical patients with 39 . 2017 The STICH II trial addressed the question of whether outcomes could potentially be improved with DC for selected early surgery would be beneficial for conscious patients with patients with high ICP and mass effect related to ICH. good outcome. Another study on DC without hematoma evac- this difference was not statistically significant. with lower expectations set for mended. early hematoma evacuation has not invasive aspiration to standard craniotomies and suggested been shown to be beneficial in the 2 largest randomized tri. Subgroup analysis suggested that patients with lobar ducted to compare surgery versus conservative treatment. One study of DC without hematoma evacuation (within 12 hours of randomization) plus medical manage.235 In this trial. several authors have suggested that Downloaded from http://stroke. hemorrhages within 1 cm of the cortical surface might ben- efit from surgery. Several nonrandomized studies have suggested safety of minimally invasive surgery plus rtPA in the setting that patients with cerebellar hemorrhages >3 cm in diameter of ICH. and median preoperative GCS score able) outcome of the extended Glasgow Outcome Scale. whereas 9 patients had a study-defined a favorable outcome compared with 38% in the medical arm. is considered insufficient. matched 12 consecutive patients with supratentorial ICH to ment or medical management alone.226.

248 talization.247 Ultra-early craniotomy (within 4 hours from identified withdrawal of medical support and other early care ictus) was associated with an increased risk of rebleeding in a limitations. and the riorating neurologically or who have brainstem overall aggressiveness of ICH care at a hospital is associated compression and/or hydrocephalus from ventricu.260–262 By defi- Downloaded from http://stroke. Providers guideline) Specific exceptions and potential subgroup should therefore be cautious about offering precise prog- considerations are outlined below in recommenda. noses early after ICH.ahajournals. The study demonstrated a significant reduc. or have elevated ICP refrac. 2017 nition.258 Palliative care is an important aspect of care onset. Initial treatment of these patients with poor outcome. and this is discussed on before 21 hours from ictus. Hemphill et al   Management of Spontaneous ICH   15 medical patients. but existing prognostic IIb. a DNAR order means that there should be no attempt at Surgical Treatment of ICH: Recommendations resuscitation should a cardiopulmonary arrest occur. A policy of early hematoma evacuation is not orders. patients. These of other major vascular disease.–256 ized phase 3 clinical trial of minimally invasive hematoma None of these prediction models. and studies show that current outcome predic- ventricular drainage rather than surgical evacuation tion models are overly pessimistic because of the failure to is not recommended (Class III. (New recommendation) undertaken. Timing of Surgery Most patients who die of ICH do so during the initial Timing of surgery for ICH remains controversial.267 The cumulative risk of . DC with or without hematoma evacuation might reduce mortality for patients with supratentorial 1. have hemorrhage. (Unchanged from the previous guideline) account for these care limitations. Patients with preex- Evidence C).257. the Prognostication early after ICH is often desired by usefulness of surgery is not well established (Class physicians. Level of Evidence C). and families. DNAR status should not limit appropriate medical and surgical interventions Outcome Prediction and Withdrawal of unless otherwise explicitly indicated (Class III. 4.263 The decision to limit care early the hemorrhage as soon as possible (Class I. even after controlling for specific indi- lar obstruction should undergo surgical removal of vidual characteristics. have large hematomas with ment of new DNAR orders until at least the second significant midline shift. with patient outcomes. impact of care limitations such as do-not-attempt-resuscitation (DNAR) orders or the withdrawal of technological support. guideline-concordant therapy is clearly beneficial compared with hematoma evacu. full day of hospitalization is probably recommended tory to medical management (Class IIb. however. prediction models include individual patient characteristics tion in perihematomal edema in the hematoma evacuation such as score on the GCS or NIHSS.266 Aggressive. in substantially more detail in the recently released American analysis of 2186 patients from 8 trials of surgery for ICH found Heart Association scientific statement on “Palliative and End- that surgery improved outcome if performed within 8 hours of of-Life Care in Stroke. however.26. and location. Patients with cerebellar hemorrhage who are dete. Level of account for the influence of withdrawal of support Evidence B). as independent predictors of outcome. Level of Evidence C). aggressive care when administered early after ICH. and the presence and amount of IVH. Level of Evidence A). DNAR orders are a proxy for overall lack of 1.231 A random.136. however. patients early after ICH are biased by failure to out thrombolytic usage is uncertain (Class IIb. Level of after ICH may therefore result in self-fulfilling prophecies of Evidence B). The effectiveness of minimally invasive clot evacuation mendation. hematoma volume group with a trend toward improved outcomes. (Revised from the previous guideline) Observational and epidemiological studies have identified a wide range of factors associated with outcome after acute Prevention of Recurrent ICH ICH. Level of Evidence B). account for the evacuation (MISTIE III) is currently in progress.264.265 2.246 Subgroup analyses of patients in STICH II for patients with severe ICH and their families whether or not suggested a trend toward better outcome for patients operated withdrawal of support is being pursued. identification of these factors led to the development of Patients with ICH are at high risk of a recurrent event and models to predict mortality and functional outcome. Level of (Class IIa. (New recommendation) isting DNAR orders are not included in this recom- 6.”259 Several studies. Level of advanced directives specifying that such care should not be Evidence A). such as DNAR orders within the first day of hospi- study that involved 24 patients.245. Supratentorial hematoma evacuation in deteriorating patients might be considered as a life-saving measure Outcome Prediction and Withdrawal of (Class IIb. thus recommended for patients with ICH who do not have ation when patients deteriorate (Class IIb. nostication is to consider withdrawal of support or DNAR 3.org/ by guest on February 6. Aggressive care early after ICH onset and postpone- ICH who are in a coma. For most patients with supratentorial ICH.226 An individual patient meta. age. Randomized acute hospitalization.226. (New recommendation) Technological Support: Recommendation 5. (Revised from the previous models are biased by limitation-of-care decisions. In practi- cal use. especially if the purpose of prog- tions 3 through 6. and these deaths usually occur in the prospective trials to date have reported on a wide time frame setting of withdrawal of support because of presumed poor for surgery that ranges from 4 to 96 hours after symptom prognosis. Current prognostic models for individual with stereotactic or endoscopic aspiration with or with. Level Technological Support of Evidence C). (Revised from the previous guideline) and early DNAR orders.

which median 69-week follow-up period.9–1. 1. only BP and the use of anti. P<0. whereas none who did not restart warfarin had recurrent intracranial BP Management bleeding. the HR for recurrent ICH with rent) are more common in Asians. Eckman stolic and lowered the risks of first and recurrent ICH (adjusted et al296 found that withholding anticoagulation improved HR. 5 patients in the nonrestarted group devel- Among the preceding risk factors. tial event. However. 95% prevention of ICH in patients with established small-vessel CI.03). 1 had a recurrent ICH and 2 subsequently had traumatic intracranial hemorrhage.295 Using a Markov deci- with perindopril (4 mg daily) and indapamide reduced base.7. The optimal timing for resumption of anticoagulation heart failure. older age.272.69] and 0. rapid reduction of SBP to <140 mm Hg within a few hours was safe.44 [95% CI. the ongoing risk extends for years.134 rhage (deep versus lobar) are important risk factors for ICH recurrence. discontinued.293 In a ret- In whites. In PROGRESS. 60%.7. P=0.269. should also be studies of patients with anticoagulant-related ICH found .269.37. with a higher risk of subsequent ICH (OR.org/ by guest on February 6. 0. as is seen for ischemic stroke or warfarin users.50–9. 0. CAA is an important cause of was directly related to the degree of BP lowering. In a cohort of 284 consecutive patients Downloaded from http://stroke. and location of the initial hemor. treatment in the group who restarted warfarin.271 Increased The rising use of anticoagulant agents in an aging population risk in the elderly is attributed to a higher prevalence of cere. sion model and estimates for 1-year risk of ICH recurrence line BP by an average of 12 mm Hg systolic and 5 mm Hg dia. There is a marked paucity of prospective population-based thrombotic medications with accumulating comorbidities. In INTERACT2. P difference between pooled HR.37 [95% CI.275 the rates of bleeding events were not increased. and the presence of microbleeds was associated have their BP lowered to or beyond the targets currently rec. as well as other vascular events. of whom 234 to be lobar. P<0.3. might also be a pre.271 High BP is associated with an increase in the Management of Antithrombotic Drugs recurrence of both deep and lobar hemorrhages.33.ahajournals. those with prior in patients with deep hemorrhage if the risk of thromboem- ICH derived the greatest benefit. which led to the conclusion that anticoagula- patients with the lowest follow-up BP levels (median. is associated with increased risk of ICH and its recurrence.001). 3.2) during a stroke. 1. patients with warfarin-associated ICH.6–4.272 data on the risk of ICH recurrence and mortality after reini- CAA is a recognized risk factor for recurrent ICH.267 Although the also associated with increased ICH risk287–291 and should be risk of ICH recurrence is highest in the first year after the ini.3 quality-adjusted life-years trial.284 data are available to guide the decision.6 (95% CI. microbleeds were more frequent in war- the greatest benefit of “more intensive” BP lowering is on the farin users with ICH than in nonwarfarin users (OR.278 began taking warfarin again. significantly reduced the risk of ICH (risk reduction. particularly tiation of warfarin. 0. 0. 0.68). Frequent alcohol use (>2 drinks per hazard ratio (HR) for ICH recurrence among subjects with day)285 and illicit drug use have been linked to elevated BP and prior ICH relative to a first ICH in subjects with prior isch. of 23 patients who dictor of ICH recurrence.001) but were not more frequent in warfarin stroke disease and that lowering target SBP to <130 mm Hg users with ischemic stroke or transient ischemic attack (OR. The presence clear evidence of a lower threshold below which the benefit of microbleeds might increase the risk of ICH recurrence in attenuated or even reversed. ICH286 and should be avoided in ICH patients. 2017 in lobar locations.4– ommended in other high-risk groups (<130 mm Hg systolic–269 In the Perindopril considered despite the lack of systematic data regarding their Protection Against Recurrent Stroke Study (PROGRESS).274 and patients with a greater number of microbleeds restarted warfarin in the hospital: 31. and echo MRI appear to be at higher risk for ICH recurrence.276 A history of ischemic resumption of warfarin was 5.38].001) and 48% versus 61% at 1 year (P=0.28–0. P=0.4% at 30 (particularly microbleeds in lobar brain locations) on gradient days (P<0.5. if necessary. 4.292 bral amyloid angiopathy (CAA) and increased use of anti. the effect on ICH recurrence. In a coronary artery disease. had warfarin-associated ICH.60 (95% CI.9% versus 54.04). most of the initial and recurrent hemorrhages tend rospective cohort study of 2869 ICH patients. 12. and other lifestyle modifications. with no warfarin-associated lobar ICH in the elderly.281 which suggests that ICH patients should OR. 0. is uncertain. 95% CI. such after ICH. Tobacco use is emic stroke was 6. the presence of obstructive sleep apnea.297 and 80 mm Hg diastolic in the presence of diabetes mellitus. whereas deep hemorrhages (both initial and recur.294 In another study of 48 shares a common pathogenesis with ICH. although there are no prospective data. 112 tion should be avoided after lobar ICH but can be considered mm Hg systolic and 72 mm Hg diastolic) 280. quality-adjusted life-year expectancy by 1. Results of the Secondary Prevention pooled analysis of ICH and ischemic stroke or transient isch- of Small Subcortical Strokes (SPS3) study have shown that emic attack patients.270 to prevent recurrence is unknown.10–1. or chronic kidney disease). particularly of the small-vessel “lacunar” type.273.8–17.282 Other factors.273 patients with previous ICH before the present.1% for deep ICH.9 quality-adjusted respectively).01). and the size of the benefit bolism is particularly high. 16  Stroke  July 2015 ICH recurrence is 1% to 5% per year.4. 95% CI. soon as possible after ICH onset. Stroke Network.267. Risk Factors which indicates that such treatment can be safely initiated as Hypertension. the lowest risk of stroke recurrence was seen among after deep ICH. and no randomized trial as BP variability. oped thromboembolism (2 with stroke) compared with none thrombotic agents are modifiable.279 In that life-years after lobar ICH and 0. 2. particularly in The optimal timing for initiating BP lowering after ICH patients with lobar ICH. 1.271 Carriers of the apolipoprotein E ε2 or with warfarin-related ICH in the Registry of the Canadian ε4 alleles. of 15% after lobar ICH versus 2. Several observational obesity.269. mortality rates were lower in those who ing ICH.277.

 The usefulness of dabigatran. Level of Evidence C).310 A Markov analysis evaluating the risks and ben. recommendation) tion patients. In patients with pros- age. the opposite was true. The optimal timing to resume oral anticoagula- recurrent ischemic stroke was offset in part by an increased tion after anticoagulant-related ICH is uncertain. particularly in patients with lobar guideline) Downloaded from http://stroke.71. of BP <130 mm Hg systolic and 80 mm Hg diastolic Although dabigatran.306 but the tive sleep apnea.301 antiplatelet monotherapy302 or percutaneous left 2. (3) presence and number of microbleeds on gra- thetic heart valves. early resumption of anticoagulation may dient echo MRI. 1. and having ICH as the qualifying stroke for weeks. (New recommendation) If indicated. Level of hematoma expansion52. in patients without mechanical heart valves.308 However. the timing often depends to consider the following risk factors for ICH recur- rence: (1) lobar location of the initial ICH. Lifestyle modifications. (New recommendation) statins should be considered in patients with ICH. ban in patients with atrial fibrillation and past ICH efits of statin therapy in patients with prior ICH concluded to decrease the risk of recurrence is uncertain (Class that if statin use does increase the risk of ICH.32. risk of ICH. It remains unclear whether statins should be continued with early resumption of anticoagulation exceeded the risk or discontinued in ICH patients.88). (Unchanged from the previous with the presence and number of microbleeds.294 A survival model based on these data Prevention of Recurrent ICH: Recommendations found that the total risk of ischemic plus hemorrhagic stroke was minimized when anticoagulation was reinitiated after 1. Avoidance of oral anticoagulation for at least 4 increasing age.ahajournals. and apixaban are reported is reasonable (Class IIa. (Revised from the previous rence with antiplatelet use. the benefit of high-dose atorvastatin in reducing 6. BP should be controlled in all ICH patients (Class atrial appendage closure303 might be safer alternatives to I.88–1.102 and therefore appear to be gener. 127 survivors of lobar hemorrhage (HR. study enrollment were factors associated with later ICH might decrease the risk of ICH recurrence (Class occurrence. (New recommendation) A long-term goal ally safe for use after ICH. Level of Evidence B). as well as treatment of obstruc- modest increases in ICH incidence305 and mortality. in ICH patients. 8.313 In contrast. including ICH caused by CAA. (2) older on the indication for anticoagulation.org/ by guest on February 6. Secondary analysis found that statin treatment. Level of Evidence B). 1. 0.312 There are no data on whether the study of 234 patients with warfarin-related ICH followed up reported propensity for ICH with statin use is dose depen- for a median of 34 weeks found that the risk of rebleeding dent. There are conflicting reports regarding the use of statins particularly when there are strong indications for in patients with ICH. Meta-analyses suggest that aspirin use is associated with and illicit drug use. Hemphill et al   Management of Spontaneous ICH   17 low rates of cardioembolic events while not receiving anti.272.298–300 but the results are limited by relatively cal improvement and reduced 6-month mortality in a small small sample sizes and short durations of follow-up. Antiplatelet ous guideline) Measures to control BP should begin agents do not appear to dramatically increase the risk of immediately after ICH onset (Class I. When stratifying a patient’s risk for recurrent ICH ≈10 weeks.307 let monotherapy after any ICH might be considered. hol use greater than 2 drinks per day.311 Concordant with these con. clusions. 0. rivaroxaban. and the authors suggested a delay of at least 1 may affect management decisions. particu.2. Level of Evidence B).308–312 In the Stroke Prevention With these agents (Class IIb. rivaroxaban. and (5) be necessary because of the high risk of embolism. avoidance of IIb. 0. statin use and age were independently associated Level of Evidence C).08. continued coagulation therapy or recurrent ICH when anticoagulation statin use after ICH was associated with early neurologi- was resumed. cortical locations. Evidence A). Level of Evidence B). (Revised Aggressive Reduction in Cholesterol Levels (SPARCL) from the previous guideline) study. 95% 5. it is reasonable month after ICH. There are insufficient data to recommend restric- larly those with lobar ICH. (New to convey a lower risk of ICH than warfarin in atrial fibrilla.305 A small observational study found that is probably recommended after warfarin-associated antiplatelet use was common after ICH and did not appear to spontaneous lobar ICH because of the relatively high be associated with an increase in the risk of ICH recurrence in risk of recurrence (Class IIa. Anticoagulation after nonlobar ICH and antiplate- CI. Level of Evidence B). a meta-analysis of 31 randomized IIb. 95% CI. tions on the use of statins in ICH patients (Class IIb.304 their usefulness as alternatives to warfarin 3.3. of thromboembolism from withholding it. tobacco use. although the optimal found no significant association between statin use and ICH timing is uncertain (Class IIa.1–14. or apixa- therapy. Avoidance of long-term anticoagulation with warfa- small relative to the absolute numbers of MIs and ischemic rin as a treatment for nonvalvular atrial fibrillation strokes prevented. all strokes and (New recommendation) all-cause mortality were significantly reduced with statin 7. 95% CI. Level of Evidence A).294 In practice. whereas later. (Unchanged from the previous guideline) P=0. (Revised from the previ- warfarin in some patients with atrial fibrillation. Although presence of apolipoprotein E ε2 or ε4 alleles (Class there are conflicting reports regarding the risk of ICH recur.72. aspirin monotherapy can probably be controlled trials that included 91 588 statin-treated patients restarted in the days after ICH. A larger retrospective study.47). including avoidance of alco- after ICH remains to be determined. P=0. 2017 ICH. P=0.3. IIa. (Revised from previous guideline) absolute ICH risk in unselected populations appears to be 4.3–2. especially in guideline) . are probably beneficial (Class IIa.8.73) and 80 survivors of deep hemorrhage (HR. (4) ongoing anticoagulation. (OR. 0. Level of Evidence B). Level of Evidence B).

org/ by guest on February 6. previous guideline) and social support all influence recovery. ICH volume and location. level of con. it is recommended that all patients others for activities of daily living.  separate intrinsic from adaptive recovery. multidisciplinary inpatient other outstanding questions.27 INTERACT2. Another rational but still stroke units that include rehabilitation services demonstrate unproven approach to acute ICH treatment is neuroprotec- improved outcomes compared with other models of stroke tion of surrounding brain tissue from the toxic effects of unit care. As documented above. The success of rehabilitation depends on caregiver train- ing between ICH and ischemic stroke is complicated by ing and support. the previous guideline) tional areas. 2017 rule as to when recovery ends. The translation of biological data on neuro- The majority of studies do not differentiate ICH patients protection from animals to human ICH patients may face from those with ischemic stroke.322 for acute ICH.134 acute lowering of BP can now be considered The provision of stroke rehabilitation services has safe and potentially effective for improving outcome in most received considerable attention in recent years. model system and a clinically relevant time frame for treat- pared to standard ward and medical care. and faster gains in recovery than patients with ischemic stroke. Given the potentially serious nature and complex but may continue for many months after ICH. 18  Stroke  July 2015 Rehabilitation and Recovery was too small to make any sensible comparisons to those with Knowledge of differences in the natural history of recovery ischemic stroke. but the number of ICH patients lyzed.318 Given that ICH is often located in lobar regions and complicated by intraventricular extension. Improvement was ment. in neuroprotection field. of BP lowering and refine the BP ranges and targets that sures on costly health services. However. These studies will also address the benefits of well-organized. rehabilitation can be beneficial 2. and there is no hard tion (Class I. the community as part of a well-coordinated (“seam- sciousness at admission.319 whereas home-based therapy for stable minimally invasive surgery231 can provide the advantages patients has been shown to produce comparable outcomes of hematoma removal with less surgical trauma and there- to conventional outpatient rehabilitation. Cognition. Level of Evidence A). and caregiver burden as important issues to ing evidence that patients with ICH make slightly greater address with the patient and caregivers. depression. a recent random. the likely configuration of services the lower rate of ICH compared with ischemic stroke and in any region will depend on available resources and fund- the lumping of subarachnoid hemorrhage and ICH together ing options.325 tional nondedicated stroke wards.31. Given strong evidence for should be applied in practice. (Unchanged from techniques may also be useful with lesions in specific func.323 patterns and prognosis for residual disability and function. Thanks largely to therapy in rehabilitation. Level of Evidence B). motivation. patients vary with ICH have access to multidisciplinary rehabilita- in their speed and degree of recovery. mood. and pre-ICH cognitive impairment less”) program of accelerated hospital discharge and has been shown to predict independence at 90 days. (Revised from the Downloaded from http://stroke. in rehabilitation to allow detection of clinically meaning. In part this instances of ICH. Even so.28.316 with pattern of evolving disability and the increasing evi- approximately half of all survivors remaining dependent on dence for efficacy. A simple prognostic when begun as early as possible and continued in score that uses age.30 However. benefit from BP lowering. as ATACH II.314–317 Rehabilitation and Recovery: Recommendations In general. A key portion of rehabilitation should include in many studies. There are also problems associated with education for the patient and caregiver regarding secondary the insensitivity of many of the outcome measures used stroke prevention and means to achieve rehabilitation goals. but prognostic imaging ery (Class IIa. some patients Future Considerations with specific cognitive deficits or delayed recovery that is dis.320 Comprehensive fore greater net benefit to patients. such represents a need to tailor services to ensure optimal recov. recovery.326 Emerging methods such as prehospital administra- significantly greater for the rehabilitation group. other neuroimaging findings identify patients more likely to and returning home compared with care provided in conven. and it is difficult to Where possible. such as identifying the correct animal which a 3 stage in-hospital rehabilitation program was com. measured tion of candidate neuroprotectants327 should increase the by Fugl-Meyer and Barthel scales over 6 months.321 the hematoma. there is grow. Rehabilitation programs should consider lifestyle changes. studies will community. Specifically. Ongoing and future studies in this area.319 efforts have been made Although current evidence does not establish a general to extend this service model of coordinated care into the strategy of early surgery for supratentorial ICH.ahajournals.324 will seek to solidify the evidence for efficacy ery for patients. the same difficulties encountered by the ischemic stroke ized trial in 364 patients in China was specific to ICH.30 Such home-based resettlement to promote ongoing recov- scores are useful across all patients. such as whether the spot sign or (stroke unit) care in terms of improved survival. Another and home-based rehabilitation programs have been shown to major focus in future years will be determining whether be cost-effective. early supported hospital discharge continue to seek subgroups of patients who benefit. A similar result was seen in an Australian trial of very early As targeted treatments for acute ICH continue to be ana- mobilization in 72 patients. it is important to note that many of the gains seen in . recovery is more rapid in the first few weeks 1. and in part it is attributable to fiscal pres. ful differences between groups. the acute treatment of spontaneous proportionate to the size of the lesion may require specialized ICH remains under intense investigation. with the range of feasible treatment approaches and time windows greatest improvement evident in the first month after stroke. however.

role of the newer direct OACs in patients at increased ICH Acute ICH treatment. or 5% or more of the person’s gross income. Hemphill et al   Management of Spontaneous ICH   19 ICH outcome have resulted from improved hospital care. Physicians Services Incorporated Foundation* Pamela H. this is a major goal for ongoing and future tri- than revolutionary but can sum to substantial benefits to als. Disclosures Writing Group Disclosures Writing Group Other Research Speakers’ Bureau/ Expert Ownership Consultant/ Member Employment Research Grant Support Honoraria Witness Interest Advisory Board Other Downloaded from http://stroke. Canadian Therapeutics* Pharmaceuticals* Institutes of Health Research*.72.ahajournals. None None None None CSL Behring* None Hospital NINDS† R. Selim Harvard Medical Faculty NIH/NINDS† None None None None Daiichi-Sankyo* None Physicians Daniel Woo University of Cincinnati NINDS† None None None None None None This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire. Scott University of Michigan NIH/NINDS† None None None None None None Magdy H. Anderson The George Institute for The National Health None Takeda China*. NIH/NINDS* None None None None None None San Francisco Steven M.273. Another important question to be addressed is the possible patients and remain a key part of future ICH research.328 There remains no improving outcome from this devastating form of stroke. 2017 J. BP control can ICH recovery. NIH/NINDS† None None None None None None Gordon L Fung University of California San None None None None None None None Francisco Medical Center Joshua N. Royal Prince (NHMRC) of Australia† Company* Alfred Hospital Kyra Becker University of Washington NINDS† None None None None None None School of Medicine Bernard R. †Significant. there are no spe- recovery that has the greatest potential for reducing overall cific treatments or therapies established for enhancing post- disease burden. Claude Hemphill III University of California. University and Medical Research Covidien*. In the area of ICH prevention. like acute ischemic stroke treatment. it is improved ICH prevention and to trigger intracranial bleeding. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition. Bayer* Medicines of Sydney. Greenberg Massachusetts General Avid None None None None None None Hospital Radiopharmaceuticals†. or owns $10 000 or more of the fair market value of the entity. for this reason. Bendok Northwestern Medical NIH† None None None None None None Faculty Foundation Mary Cushman University of Vermont NIH/NHLBI†. risk and the identification of the subgroup that might derive is fundamentally limited in its ability to reduce stroke-related the greatest benefit from the reduced tendency of these agents disability. which highlights a tremendous opportunity for be considered as established treatment. Mitchell University of Washington NIH† None None None None None None Phillip A. disease-modifying treatment for prevention of CAA-related Improvements in hospital care tend to be incremental rather ICH.73. None None Pfizer*. *Modest. however. or (b) the person owns 5% or more of the voting stock or share of the entity. Heart and Stroke Foundation of Canada*.304 Finally. NINDS†. which all members of the writing group are required to complete and submit. NIH†. Craig S. Goldstein Massachusetts General CSL Behring†. NIH*. . The None Global Health.org/ by guest on February 6. A relationship is considered to be “significant” if (a) the person receives $10 000 or more during any 12-month period. Loch Macdonald Independent Medical Brain Aneurysm None None None Edge Actelion None Practitioner Foundation*.

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Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association J.ahajournals. Once the online version of the published article for which permission is being requested is located. Print ISSN: 0039-2499. Goldstein. R. published online May 28.org/content/suppl/2016/04/04/STR. Further information about this process is available in the Permissions and Rights Question and Answer document.lww. Craig S.org/ by guest on February 6.DC1 Permissions: Requests for permissions to reproduce figures. Gordon L. Joshua N. a service of the Copyright Clearance Center.0000000000000069. Inc. along with updated information and services. Claude Hemphill III. Bernard R. Steven M.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke. is located on the World Wide Web at: http://stroke. Stroke is published by the American Heart Association. Bendok. Pamela H. Scott. Phillip A. Anderson.ahajournals.0000000000000069 Data Supplement (unedited) at: http://stroke. Magdy H. not the Editorial Office. 2017 Mitchell. TX 75231 Copyright © 2015 American Heart Association. or portions of articles originally published in Stroke can be obtained via RightsLink. click Request Permissions in the middle column of the Web page under Services. Fung. Loch Macdonald. Kyra Becker. Online ISSN: 1524-4628 The online version of this article. 7272 Greenville Avenue. Dallas. Greenberg.org//subscriptions/ .ahajournals.ahajournals. Selim and Daniel Woo Stroke. Reprints: Information about reprints can be found online at: http://www. Mary Cushman. tables. 2015.org/content/early/2015/05/28/STR. All rights reserved. Downloaded from http://stroke.

Scott. Stroke 日 本 語 版 Vol.5. FAHA. MS.1161/STR. Magdy H. MD.0000000000000069. and Council on Clinical Cardiology Stroke. PhD. FAHA. MAS. Steven M. Daniel Woo. the Congress of Neurological Surgeons. Fung. FAHA. Vice-Chair. Anderson. PhD. MPH. PhD.73:1088 )はその一つである。止血と凝固障害への 救命手段として考慮することが認められ,開頭減圧術に 対応( 表 3 )では,主として薬剤性凝固障害につき述べ より死亡率の低下が期待されるとしている。生命維持処 られており,新しい経口抗凝固薬( NOAC )服用者に対 置( 表 9 )について新しい推奨はない。ICH の再発予防 する FEIBA や血液透析の適応が述べられ,一時注目さ ( 表 10 )については ICH 発症直後から血圧コントロール れた活性型第 VII 因子は ICH には一般的に推奨されな が推奨され,長期的には 130 以下 /80mmHg が妥当とし いとしている。NOAC の新しい拮抗薬についてはまだ ている。ICH 後の経口抗凝固薬の開始時期はまだ確定し PDLQLQGG 30 . Selim.3. FAHA. PhD. MD. PhD. FAHA. PhD. Loch Macdonald. Joshua N. R. MD. Goldstein. Craig S. Bernard R. 本ガイドラインは英文 Stroke 誌 7 月号に掲載された 臨床試験の段階であり,記載はない。血圧の管理( 表 4 ) 脳内出血( ICH )の管理に関する米国心臓協会/米国脳卒 では INTERACT2 試験の結果を受けて,収縮期血圧が 中協会( AHA/ASA )ガイドラインで,2010 年のガイド 150 ∼ 220mmHg の場合に 140mmHg まで下げることは ラ イ ン( Stroke 41:2108-2129. Pamela H. PhD. Mitchell. MS. MD. on behalf of the American Heart Association Stroke Council. Gordon L. MD. MD. Endorsed by the American Association of Neurological Surgeons. Council on Cardiovascular and Stroke Nursing. MD. MSc. and the Neurocritical Care Society J. 安全であり,220mmHg 以上の場合には薬剤の持続点滴 No. Bendok. MD. Kyra Becker. Phillip A. Claude Hemphill III. 35-39 )の改訂版である。推奨には AHA/ASA の とモニタリングで急激に低下させることを推奨してい エビデンスクラスとレベルが用いられている( 表 1 )。 る。入院管理と二次的脳損傷の予防( 表 5 )では ICH 患 ICH の治療法は虚血性脳卒中の治療ほど注目されてな 者の管理に ICU に加えて設備の整った SCU が加えら いが,微小出血( microbleeds: MB )の認識,スポットサ れている。ICH 患者では持続した発熱が転帰に影響を インによる再出血の予測,再出血予防のための血圧管理 及ぼすとされることから,発熱の治療には肯定的である など新しい動きがある。本稿には救急診断からリハビリ が,軽度であっても低体温療法はまだ研究の段階である テーションにおよぶ項目で提唱された全ての推奨を表 2 としている。 内科的合併症の管理( 表 6 )では,誤嚥性 から表 11 に掲載しているが,表自体は英文原著の表と 肺炎予防のため,経口摂取前に嚥下障害のスクリーニン 関係がないことにご注意いただきたい。また紙面が限ら グ( 例えば飲水テスト )をすることが推奨され,脳卒中 れているため,以下の要約は新しい推奨の簡単な紹介に 後に急性心筋梗塞,心不全,心室性不整脈が起こること 限定させていただいた。 から,心電図および血中心筋酵素のスクリーニングが新 救急診断と評価( 表 2 )では,意識障害のため ICH 患 たに勧められている。ICH 後の 頭蓋内圧亢進症の治療 者に NIHSS が使いにくく,病状が急速に悪化するこ ( 表 7 )には副腎皮質ステロイドを禁忌とする一文が加え と が 多 い た め, 来 院 時 に ま ず ICH の 重 症 度 ス コ ア を られた。ICH と脳室内出血の 脳外科的治療( 表 8 )にお 評価すべきとしている。現時点で NIHSS のように普 いて,早期の血腫除去は臨床的な悪化後の血腫除去と比 遍化されたスケールはないが,ICH Score( Neurology 較して明らかな有益性を認めないが,悪化した患者では 2009. Mary Cushman. FAHA. FRCS. 脳卒中の一次予防に関するガイドライン 29 AHA/ASA Guideline 脳内出血の管理に関するガイドライン Guidelines for the Management of Spontaneous Intracerebral Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. 2015. Greenberg. DOI: 10. MD.46:2032-2060. FAHA. Chair. MD. FAHA. MD. RN. MD.

急性 ICH 患者では,ヘパリンの中和にプロタミン硫酸塩を考慮してもよいだろう。 クラス IIb;エビデンスレベル C (新たな推奨) 5. 脳内出血( ICH)患者の初期評価の一環として,ベースライン重症度スコアを算定すべきである クラス I;エビデンスレベル B (新たな推奨) 2. 抗血小板薬の投与歴を有する ICH 患者における血小板輸血の有用性は確定していない。 クラス IIb;エビデンスレベル C (前回のガイドラインから変更 ) 6. 4 ていないが,機械弁のない患者では4週間は待つよう推 る。リハビリテーション( 表 11 )の新しい推奨はないが, 奨されている。心房細動をもつ ICH 患者の再発予防の 全ての ICH 患者が集学的リハビリテーションを受けら ための NOAC の有用性はまだ確立されていないが,ア れるよう推奨レベルが格上げされた。 スピリンの単独投与は発症数日後には再開に肯定的であ ( 文責:柳原武彦) 表 1 AHA/ASA の推奨に用いられているエビデンスの分類とレベルの定義 クラス I 手技または治療法の有用性および有効性を示すエビデンス,または一般的合意がある。 クラス II 手技または治療法の有用性および有効性に関して相反するエビデンス,または意見の相違がある。  クラス IIa エビデンスまたは意見は手技または治療法を支持する。  クラス IIb エビデンスまたは意見による有用性および有効性の確立が十分でない。 クラス III 手技または治療法の有用性および有効性がなく,場合によっては有害となりうることを示すエビデンス,または一般的合意がある。 治療に関する推奨  エビデンスレベル A 複数の無作為臨床試験またはメタ解析から得られたデータ  エビデンスレベル B 単一の無作為試験または複数の非無作為試験から得られたデータ  エビデンスレベル C 専門家の意見,症例研究または標準的治療 診断に関する推奨  エビデンスレベル A 盲検化された評価者による参照基準を用いた複数の前向きコホート研究から得られたデータ  エビデンスレベル B 単一のグレード A 試験,1 つ以上の症例対照研究,または盲検化されていない評価者による参照基準を用いた複数の試験から得 られたデータ  エビデンスレベル C 専門家の意見 AHA/ASA:American Heart Association/American Stroke Association 表 2 救急診断と評価に関する推奨 推 奨 エビデンスのクラスとレベル 1. 10. 虚血性脳卒中と ICH の鑑別のために CT または MRI による迅速な脳神経画像検査が推奨される クラス I;エビデンスレベル A (前回のガイドラインから変更なし ) 3. ダビガトラン,リバーロキサバンまたはアピキサバンを服用している ICH 患者では,症例によっては,血液凝固 クラス IIb;エビデンスレベル C 因子抗体迂回活性複合体(FEIBA),その他の PCC または rFVIIa の投与を考慮してもよいだろう。直近のダビガ (新たな推奨) トラン,アピキサバンまたはリバーロキサバンの服用から 2 時間未満であれば活性炭を使用してもよいだろう。 ダビガトランについては血液透析を考慮してもよいかもしれない。 4. 重度の凝固因子欠乏症患者および重度の血小板減少症患者には,適切な凝固因子および血小板補充療法を行うべ クラス I;エビデンスレベル C きである。 (前回のガイドラインから変更なし ) 2. 30 Stroke 日本語版 Vol. No. 静脈血栓塞栓症予防のため,ICH 患者には入院当日から間欠的空気圧迫法を行うべきである。 クラス I;エビデンスレベル A 深部静脈血栓症( DVT)の低減または転帰の改善に,段階式着圧ストッキングは有効ではない。 クラス III;エビデンスレベル A (前回のガイドラインから変更 ) (次ページに続く) PDLQLQGG 30 . 血腫拡大のリスクを有する患者を特定できるよう CTA および造影 CT を考慮してもよい クラス IIb;エビデンスレベル B また,血管奇形や腫瘍など根底にある構造的病変が臨床的にまたは画像から疑われる場合,その評価のために クラス IIa;エビデンスレベル B CTA,CT 静脈造影法,造影 CT,造影 MRI,MR 血管造影法,MR 静脈造影法,カテーテル血管造影法が有用と (前回のガイドラインから変更なし ) 考えられる 表 3 止血と凝固障害,抗血小板薬,深部静脈血栓症予防に関する推奨 推 奨 エビデンスのクラスとレベル 1. 凝固障害のない ICH 患者において,rFVIIa は血腫の拡大を制限するが,FVIIa には血栓塞栓症のリスクの増加が クラス III;エビデンスレベル A 認められるため,非選択的な患者には明らかな臨床的有益性はない。したがって,rFVIIa は推奨されない。 (前回のガイドラインから変更なし ) 7. ビタミン K 拮抗薬(VKA)により INR が高値の脳内出血(ICH)患者では,VKA 投与を中止し,ビタミン K 依存性 クラス I;エビデンスレベル C 因子の補充療法,INR の補正,ビタミン K の静脈内投与を行うべきである。 プロトロンビン複合体濃縮製剤(PCC)は新鮮凍結血漿(FFP)と比較して合併症が少なく,INR を迅速に補正す クラス IIb;エビデンスレベル B るため,FFP ではなく PCC を考慮してもよいだろう。 遺伝子組換え活性型第 VII 因子製剤(rFVIIa)はすべての凝固因子を補充するものではなく,INR は低下しうるが, クラス III;エビデンスレベル C in vivo において凝固能は回復しない可能性があるため,ICH における VKA の中和に rFVIIa は推奨されない。 (前回のガイドラインから変更 ) 3.

血糖値をモニタリングすべきである。高血糖および低血糖はいずれも回避すべきである。 クラス I;エビデンスレベル C (前回のガイドラインから変更 ) 3. 脳内出血における頭蓋内圧亢進症の治療に副腎皮質ステロイドを投与すべきではない クラス III;エビデンスレベル B (新たな推奨) 表 8 脳内出血と脳室内出血の脳外科的治療に関する推奨 推 奨 エビデンスのクラスとレベル 1. 収縮期血圧(SBP)が 150 ∼ 220 mmHg で急性期降圧療法が禁忌でない脳内出血(ICH)患者では,SBP クラス I;エビデンスレベル A , 140 mm Hg までの急激な降圧は安全である。 また,このような降圧処置は機能的転帰の改善に有効と考えられる。 クラス IIa;エビデンスレベル B (前回のガイドラインから変更 ) 2. 発症後 1 ∼ 4 日間可動不能な患者では,静脈血栓塞栓症の予防のため,止血の確認後,低分子量ヘパリンまたは クラス IIb;エビデンスレベル B 未分画ヘパリンの低用量皮下投与を考慮してもよい。 (前回のガイドラインから変更なし ) 9. 経口摂取の開始前に,肺炎のリスクを軽減するためすべての患者に対して嚥下障害の正式なスクリーニングを行 クラス I;エビデンスレベル B うべきである (新たな推奨) 2. 水頭症の治療としての脳室ドレナージは,特に意識レベルが低下した患者には妥当である クラス IIa;エビデンスレベル B (前回のガイドラインから変更 ) 2. グラスゴー コーマ スケールが 8 以下の患者,テント切痕ヘルニアの臨床的所見を有する患者,あるいは重度の脳 クラス IIb;エビデンスレベル C 室内出血または水頭症を有する患者では,頭蓋内圧のモニタリングおよび治療を考慮してもよいだろう。脳自動 (前回のガイドラインから変更なし ) 調節能に応じて,脳灌流圧 50 ∼ 70 mm Hg を維持するのが適切だろう。 3. ICH 後の発熱の治療は妥当と考えられる。 クラス IIb;エビデンスレベル C (新たな推奨) 4. 臨床的けいれん発作には抗てんかん薬を投与すべきである。 クラス I;エビデンスレベル A (前回のガイドラインから変更なし ) 精神状態の変化を呈し,脳波検査で脳波的けいれん発作波が認められる患者には抗てんかん薬を投与すべきであ クラス I;エビデンスレベル C る (前回のガイドラインから変更なし ) 脳損傷の程度と不釣り合いな意識レベルの低下を呈する ICH 患者は持続的脳波モニタリングの適応があるだろう。 クラス IIa;エビデンスレベル C (前回のガイドラインから変更 ) 抗てんかん薬の予防的投与は推奨されない。 クラス III;エビデンスレベル B (前回のガイドラインから変更なし ) 表 6 内科的合併症の管理に関する推奨 推 奨 エビデンスのクラスとレベル 1. 脳内出血( ICH)患者の初期のモニタリングおよび管理は,医師および神経系疾患の急性期看護知識をもった看護 クラス I;エビデンスレベル B 師がいる集中治療室または stroke unit で行うべきである。 (前回のガイドラインから変更 ) 2. 脳室内出血(IVH)における組換え型組織プラスミノゲン活性化因子(rt-PA)の脳室内投与は合併症発症率がかな クラス IIb;エビデンスレベル B り低いように思われるが,その有効性および安全性は確実でない。 (前回の推奨から変更 ) IVH の内視鏡治療の有効性は確実でない。 クラス IIb;エビデンスレベル B (新たな推奨) (次ページに続く) PDLQLQGG 30 . SBP が 220 mm Hg を超える ICH 患者では,持続静注による積極的な降圧および頻回な血圧測定を考慮するのが クラス IIb;エビデンスレベル C 妥当かもしれない。 (新たな推奨) 表 5 入院管理と二次的脳損傷の予防に関する推奨 推 奨 エビデンスのクラスとレベル 1. 症候性 DVT または肺塞栓症(PE )を有する ICH 患者には,抗凝固薬の全身投与または下大静脈フィルター留置の クラス IIa;エビデンスレベル C 適応があるだろう。 この 2 つの選択肢からの決定には,出血後の時間,血腫の安定性,出血の原因,患者の総合的状態などいくつか クラス IIa;エビデンスレベル C の要素を考慮すべきである。 (新たな推奨) 表 4 血圧に関する推奨 推 奨 エビデンスのクラスとレベル 1. 脳内出血後の心電図および心筋酵素検査による心筋虚血または心筋梗塞の系統的なスクリーニングは妥当である クラス IIa;エビデンスレベル C (新たな推奨) 表 7 頭蓋内圧モニタリングと頭蓋内圧亢進症の治療に関する推奨 推 奨 エビデンスのクラスとレベル 1. 脳卒中の一次予防に関するガイドライン 31 表 3 止血と凝固障害,抗血小板薬,深部静脈血栓症予防に関する推奨  (前ページより続く) 推 奨 エビデンスのクラスとレベル 8.

早期の血腫除去は患者が悪化した時点での血腫除去と比較して明らかな有益性は認められない。 クラス IIb;エビデンスレベル A (新たな推奨) 5. 4 表 8 脳内出血と脳室内出血の脳外科的治療に関する推奨  (前ページより続く) 推 奨 エビデンスのクラスとレベル 2. 血腫除去の併用の有無に関わらず,開頭減圧術(DC )により,昏睡状態にある,著明な正中偏位を伴う大きな血 クラス IIb;エビデンスレベル C 腫を有する,または内科的治療に抵抗性の頭蓋内圧亢進を有するテント上脳内出血患者の死亡率が低下するかも (新たな推奨) しれない。 7. 10. 非脳葉性 ICH 後の抗凝固療法および全ての ICH 後の抗血小板薬単独投与は,特にこれらの薬剤に強い適応がある クラス IIb;エビデンスレベル B 場合には考慮してもよいだろう。 (前回のガイドラインから変更 ) 6. 脳内出血( ICH)発症後早期の積極的な治療および新たな延命治療中止(DNAR)指示の少なくとも入院 2 日目まで クラス IIa;エビデンスレベル B の延期は推奨されるだろう。 DNAR の指示が既に出されている患者はこの推奨の対象とならない。現在の ICH 発症後早期の個々の患者の予後 クラス III;エビデンスレベル C 予測モデルには,生命維持支援の中止および早期の DNAR 指示の影響を考慮していないというバイアスがかかっ (前回のガイドラインから変更 ) ている。特に明示されてない限り, DNAR 指示の有無が適切な内科的介入および外科的介入を制限すべきではない。 表 10 脳内出血の再発予防に関する推奨 推 奨 エビデンスのクラスとレベル 1. 悪化した患者では救命手段としてテント上血腫除去を考慮してもよいだろう。 クラス IIb;エビデンスレベル C (新たな推奨) 6. 心房細動を有し,ICH の既往がある患者の再発リスクを低下させるためのダビガトラン,リバーロキサバンまた クラス IIb;エビデンスレベル C はアピキサバンの有用性は確立していない。 (新たな推奨) 8. 可能であれば,リハビリテーションをできるだけ速やかに開始し,連携のとれた(シームレスな)早期退院と在宅 クラス IIa;エビデンスレベル B 復帰プログラムの一環として継続することは,回復を促進するために有益と考えられる。 (前回のガイドラインから変更なし ) PDLQLQGG 30 . テント上脳内出血患者の大部分において,手術の有用性は十分に確立されていない。 クラス IIb;エビデンスレベル A (前回のガイドラインから変更 ) 具体的な例外および考慮すべきサブグループを推奨 4 ∼ 7 に示す。 4. ワルファリンに関連する自然発症の脳葉性 ICH 後は再発のリスクが比較的高いため,非弁膜症性心房細動の治療 クラス IIa;エビデンスレベル B としてワルファリンによる長期抗凝固療法は避けたほうがよいだろう。 (前回のガイドラインから変更なし ) 5. 32 Stroke 日本語版 Vol. 血栓溶解薬併用の有無に関わらず定位的吸引または内視鏡的吸引による低侵襲的血栓除去の有効性は確実でない。 クラス IIb;エビデンスレベル B (前回のガイドラインから変更 ) 表 9 転帰予測と生命維持支援の中止に関する推奨 推 奨 エビデンスのクラスとレベル 1. 機能障害が重篤で,かつ進行パターンが複雑であり,リハビリテーションの有効性を示すエビデンスが蓄積され クラス I;エビデンスレベル A ていることから,すべての脳内出血患者に集学的リハビリテーションを受けさせることが推奨される。 (前回のガイドラインから変更 ) 2. ICH 患者においてスタチン剤の使用制限を推奨するデータは不十分である。 クラス IIb;エビデンスレベル C (前回のガイドラインから変更なし ) 表 11 リハビリテーションと回復に関する推奨 推 奨 エビデンスのクラスとレベル 1. 1 日 2 杯を超える飲酒,喫煙および違法薬物の使用を控える等の生活習慣の改善とともに,閉塞性睡眠時無呼吸 クラス IIa;エビデンスレベル B の治療は有益だろう。 (前回のガイドラインから変更 ) 4. 神経学的悪化を認める小脳出血患者,または脳幹圧迫および脳室閉塞による水頭症またはそのいずれかを有する クラス I;エビデンスレベル B 小脳出血患者では,できるだけ速やかに出血の外科的除去を行うべきである。 このような患者では,外科的除去ではなく脳室ドレナージによる初期治療は推奨されない。 クラス III;エビデンスレベル C (前回のガイドラインから変更なし ) 3. No. 抗凝固療法に関連する ICH 後の経口抗凝固療法再開の最適時期は確立していない。機械弁を植え込んでいない患 クラス IIb;エビデンスレベル B 者では,少なくとも 4 週間は経口抗凝固療法を控えることにより ICH 再発のリスクが低下する可能性がある。 (新たな推奨) アスピリン単独投与が適応となる場合には,最適時期は確定していないが,ICH 発症から数日後に投与を再開す クラス IIa;エビデンスレベル B ることが有益と思われる。 (新たな推奨) 7. すべての ICH 患者において血圧をコントロールすべきである。 クラス I;エビデンスレベル A (前回のガイドラインから変更 ) 血圧コントロールは ICH 発症後直ちに開始すべきである。 クラス I;エビデンスレベル A (新たな推奨) 収縮期血圧 130 mm Hg 未満,拡張期血圧 80 mm Hg 未満を長期目標とすることが妥当である。 クラス IIa;エビデンスレベル B (新たな推奨) 3. 脳内出血( ICH)再発のリスクを層別化することが治療方針の決定に影響を及ぼす場合には,以下の ICH 再発の危 クラス IIa;エビデンスレベル B 険因子を考慮に入れることが妥当である。(1 )最初の ICH をきたした脳葉の位置,(2)高齢であること,(3)グ (前回のガイドラインから変更 ) ラディエントエコー MRI での微小出血の有無および数,(4)抗凝固療法を実施中であるか否か,(5)アポリポ蛋 白 E の ε2 または ε4 アレルの有無。 2.