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. Key Words: AHA Scientific Statements blood pressure coagulopathy diagnosis intracerebral hemorrhage intraventricular hemorrhage surgery treatment 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; 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 TheAmerican HeartAssociation 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;46:2032 2060. 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 AHA/ASA Guideline Hemphill et al Management of Spontaneous ICH 2033 Spontaneous, nontraumatic intracerebral hemorrhage (ICH) remains a significant cause of morbidity and mor- tality throughout the world. Although ICH has traditionally lagged behind ischemic stroke and aneurysmal subarach- noid hemorrhage in terms of evidence from clinical trials to guide management, the past decade has seen a dramatic increase in studies of ICH intervention. Population-based studies show that most patients present with small ICHs that are readily survivable with good medical care.1 This suggests that excellent medical care likely has a potent, direct impact on ICH morbidity and mortality. This guide- line serves several purposes. One is to provide an update to the last American Heart Association/American Stroke 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 of the importance of their care in determining ICH outcome and to provide an evidence-based framework for that care. To make this review brief and readily useful to practic- ing clinicians, background details of ICH epidemiology are limited, with references provided for readers seeking more Ongoing studies are not discussed substantively because the focus of this guideline is on currently available therapies; however, the increase in clinical studies related to ICH is encouraging, and those interested may go to http:// www.strokecenter.org/trials/ for more information. Also, this Table 1. Applying Classification of Recommendations and Level of Evidence 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. guideline is generally concerned with adults, with issues of hemorrhagic stroke in children and neonates covered in a separate American Heart Association scientific statement on Management of Stroke in Infants and Children. 5 This document serves to update the last ICH guidelines published in 2010,2 and the reader is referred to these guide- lines for additional relevant references not contained here. The development of this update was purposely delayed for 1 year from the intended 3-year review cycle so that results of 2 pivotal phase 3 ICH clinical trials could be incorporated. Differences from recommendations in the 2010 guideline are specified in the current work. The writing group met by phone to determine subcategories to evaluate. These included 15 sections that cov- ered the following: emergency diagnosis and assessment of ICH and its causes; hemostasis and coagulopathy; blood pres- sure (BP) management; inpatient management, including gen- eral monitoring and nursing care, glucose/temperature/seizure management, and other medical complications; procedures, including management of intracranial pressure (ICP), intra- ventricular hemorrhage, and the role of surgical clot removal; outcome prediction; prevention of recurrent ICH; rehabilita- tion; and future considerations. Each subcategory was led by a primary author, with 1 or 2 additional authors making contri- butions. Full PubMed searches were conducted of all English language articles regarding relevant human disease treatment from 2009 through August 2013. Drafts of summaries and rec- ommendations were circulated to the entire writing group for feedback. Several conference calls were held to discuss indi- vidual sections, focusing on controversial issues. Sections were revised and merged by the Chair. The resulting draft was sent to the entire writing group for comment. Comments were incorpo- rated by the Chair andVice-Chair, and the entire committee was asked to approve the final draft. Changes to the document were made by the Chair and Vice-Chair in response to peer review, 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 methods of classifying the level of certainty of the treatment effect and the class of evidence (Tables 1 and 2). All Class I recommendations are listed in Table 3. Emergency Diagnosis and Assessment ICH is a medical emergency. Rapid diagnosis and attentive management of patients with ICH is crucial, because early deterioration is common in the first few hours after ICH onset. More than 20% of patients will experience a decrease in the Glasgow Coma Scale (GCS) of 2 or more points between the prehospital emergency medical services (EMS) assessment and the initial evaluation in the emergency department (ED).6 Furthermore, another 15% to 23% of patients demonstrate continued deterioration within the first hours after hospital The risk for early neurological deterioration and the high rate of poor long-term outcomes underscore the need for aggressive early management. Prehospital Management Prehospital management for ICH is similar to that for ischemic stroke, as detailed in the recent American Heart Association Guidelines for the Early Management of Patients With Acute The primary objective is to provide airway management if needed, provide cardiovascular support, and transport the patient to the closest facility prepared to care for patients with acute stroke.10 Secondary priorities for EMS pro- viders include obtaining a focused history regarding the tim- ing of symptom onset (or the time the patient was last normal); information about medical history, medication, and drug use; and contact information for family. EMS providers should provide advance notice to the ED of the impending arrival of a potential stroke patient so that critical pathways can be initiated and consulting services alerted. Advance notice by EMS has been demonstrated to significantly shorten time to computed tomography (CT) scanning in the ED.11 Two studies have shown that prehospital CT scanning with an appropri- ately equipped ambulance is feasible and may allow for tri- age to an appropriate hospital and initiation of ICH-specific ED Management Every ED should be prepared to treat patients with ICH or have a plan for rapid transfer to a tertiary care center. The crucial resources necessary to manage patients with ICH include neurology, neuroradiology, neurosurgery, and critical Table 2. Definition of Classes and Levels of Evidence Used in AHA/ASA Recommendations Class I Conditions for which there is evidence for and/ or general agreement that the procedure or treatment is useful and effective Class II Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment Class IIa The weight of evidence or opinion is in favor of the procedure or treatment Class IIb Usefulness/efficacy is less well established by evidence or opinion Class III Conditions for which there is evidence and/ or general agreement that the procedure or treatment is not useful/effective and in some cases may be harmful Therapeutic recommendations Level of Evidence A Data derived from multiple randomized clinical trials or meta-analyses Level of Evidence B Data derived from a single randomized trial or nonrandomized studies Level of Evidence C Consensus opinion of experts, case studies, or standard of care Diagnostic recommendations Level of Evidence A Data derived from multiple prospective cohort studies using a reference standard applied by a masked evaluator Level of Evidence B Data derived from a single grade A study or one or more case-control studies, or studies using a reference standard applied by an unmasked evaluator Level of Evidence C Consensus opinion of experts AHA/ASA indicates American Heart Association/American Stroke Association. Hemphill et al Management of Spontaneous ICH 2035 care facilities that include adequately trained nurses and phy- sicians. Consultants should be contacted as quickly as pos- sible while the patient is in the ED, and the clinical evaluation should be performed efficiently, with physicians and nurses working in parallel. Consultation via telemedicine can be a valuable tool for hospitals without on-site presence of consul- Table 4 describes the integral components of the his- tory, physical examination, and diagnostic studies that should be obtained in the ED. A routine part of the evaluation should include a stan- dardized severity score, because such scales can help stream- line assessment and communication between providers. The National Institutes of Health Stroke Scale (NIHSS) score, commonly used for ischemic stroke, may also be useful in However, ICH patients more often have depressed consciousness on initial presentation, and this may diminish the utility of the NIHSS. Numerous grading scales exist spe- cifically for ICH.26 32 Although the optimal severity scale is not yet clear, the most widely used and externally validated is the ICH Score.28,30,33 35 These severity scales should not be used as a singular indicator of prognosis. After diagnosis, emergency providers should arrange for rapid admission to a stroke unit or neuroscience intensive care unit (at their own hospital if available, or via transfer) and ini- tiate early management while the patient is awaiting this bed. A single-center study found that prolonged patient stays in the ED lead to worse outcomes, although another suggested that early neurocritical care management in the ED may ameliorate Although many centers have critical pathways developed for the treatment of acute ischemic stroke, few have protocols specific to the management of ICH.38 Such pathways may allow for more efficient, standardized, and integrated man- agement of patients with acute ICH; one is available from the Neurocritical Care Society.39 These pathways emphasize that urgent treatment of time-sensitive issues including BP lowering and reversal of coagulopathy should be initiated in the ED to which the patient presents rather than waiting until after transfer to an intensive care unit, stroke unit, or other hospital. Table 3. 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; Level of Evidence B). (New recommendation) Rapid neuroimaging with CT or MRI is recommended to distinguish ischemic stroke from ICH (Class I; Level of Evidence A). (Unchanged from the previous guideline) Hemostasis and Coagulopathy, Antiplatelet Agents, and DVT Prophylaxis Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate factor replacement therapy or platelets, respectively (Class I; Level of Evidence C). (Unchanged from the previous guideline) Patients with ICH whose INR is elevated because of VKA should have their VKA withheld, receive therapy to replace vitamin K dependent factors and correct the INR, and receive intravenous vitamin K (Class I; Level of Evidence C). (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; Level of Evidence A). (Revised from the previous guideline) Blood Pressure For ICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mmHg is safe (Class I; Level of Evidence A) and can be effective for improving functional outcome (Class IIa; Level of Evidence B). (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; Level of Evidence B). (Revised from the previous guideline) Glucose Management Glucose should be monitored. Both hyperglycemia and hypoglycemia should be avoided (Class I; Level of Evidence C). (Revised from the previous guideline) Seizures and Antiseizure Drugs Clinical seizures should be treated with antiseizure drugs (Class I; Level of Evidence A). (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; Level of Evidence C). (Unchanged from the previous guideline) Management of Medical Complications A formal screening procedure for dysphagia should be performed in all patients before the initiation of oral intake to reduce the risk of pneumonia (Class I; Level of Evidence B). (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; Level of Evidence B). (Unchanged from the previous guideline) Prevention of Recurrent ICH BP should be controlled in all ICH patients (Class I; Level of Evidence A). (Revised from the previous guideline) Measures to control BP should begin immediately after ICH onset (Class I; Level of Evidence A). (New recommendation) Rehabilitation and Recovery Given the potentially serious nature and complex pattern of evolving disability and the increasing evidence for efficacy, it is recommended that all patients with ICH have access to multidisciplinary rehabilitation (Class I; Level of Evidence A). (Revised from the previous guideline) BP indicates blood pressure; CT, computed tomography; DVT, deep vein thrombosis; EEG, electroencephalography; ICH, intracerebral hemorrhage; INR, international normalized ratio; MRI, magnetic resonance imaging; SBP, systolic blood pressure; and VKA, vitamin K antagonist. Neuroimaging The abrupt onset of focal neurological symptoms is presumed to be vascular in origin until proven otherwise; however, it is impossible to know whether symptoms are caused by ischemia or hemorrhage on the basis of clinical characteristics alone. Vomiting, systolic BP (SBP) >220 mmHg, severe headache, coma or decreased level of consciousness, and symptom pro- gression over minutes or hours all suggest ICH, although none of these findings are specific; neuroimaging is thus mandatory.40 CT and magnetic resonance imaging (MRI) are both reasonable for initial evaluation. CT is very sensitive for identifying acute hemorrhage and is considered the gold standard ; gradient echo and T2* susceptibility-weighted MRI are as sensitive as CT for detection of acute hemorrhage and are more sensitive for identification of prior hemorrhage.41,42 Time, cost, proximity to the ED, patient tolerance, clinical status, and MRI availability may, however, preclude emergent MRI in many cases.43 The high rate of early neurological deterioration after ICH is related in part to active bleeding that may proceed for hours after symptom onset. Hematoma expansion tends to occur early after ICH and increases risk of poor functional outcome Among patients undergoing head CT within 3 hours of ICH onset, 28% to 38% have hematoma expan- sion of greater than one third of the initial hematoma volume on follow-up CT.7,45 As such, the identification of patients at risk for hematoma expansion is an active area of research. CT angiography (CTA) and contrast-enhanced CT may identify patients at high risk of ICH expansion based on the presence of contrast within the hematoma, often termed a spot sign.50 54 A larger number of contrast spots suggests even higher risk of Early diagnosis of underlying vascular abnormalities can both influence clinical management and guide prognosis in ICH patients. Risk factors for underlying vascular abnormalities are Table 4. Integral Components of the History, Physical Examination, 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, hypertension, diabetes mellitus, and smoking Medications Anticoagulant drugs, antiplatelet agents, antihypertensive medications, stimulants (including diet pills), sympathomimetic drugs Recent trauma or surgery Carotid endarterectomy or carotid stenting, 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, stimulants Seizures Liver disease May be associated with coagulopathy Cancer and hematologic disorders May be associated with coagulopathy Physical examination Vital signs A general physical examination focusing on the head, heart, lungs, 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. GCS score is similarly well known and easily computed. Serum and urine tests Complete blood count, electrolytes, blood urea nitrogen and creatinine, and glucose Higher serum glucose is associated with worse outcome16,17 Prothrombin time (with INR) and an activated partial thromboplastin time Warfarin-related hemorrhages are associated with an increased hematoma volume, greater risk of expansion, and increased morbidity and mortality18,19 Cardiac-specific troponin Elevated troponin levels are associated with worse outcome20,21 Toxicology screen to detect cocaine and other sympathomimetic drugs of abuse Cocaine and other sympathomimetic drugs are associated with ICH Urinalysis and urine culture, as well as a pregnancy test in a woman of childbearing age Other routine tests Neuroimaging CT or MRI; consider contrast-enhanced or vascular imaging ECG To assess for active coronary ischemia or prior cardiac injury; ECG abnormalities can mark concomitant myocardial injury22,23 CT indicates computed tomography; GCS, Glasgow Coma Scale; ICH, intracerebral hemorrhage; INR, international normalized ratio; and MRI, magnetic resonance imaging. Hemphill et al Management of Spontaneous ICH 2037 age <65 years, female sex, nonsmoker, lobar ICH, intraven- tricular extension, and absence of a history of hypertension MRI, magnetic resonance angiography, magnetic resonance venography, and CTA or CT venography can identify specific causes of hemorrhage, including arterio- venous malformations, tumors, moyamoya, and cerebral vein CTA has been more widely studied and is highly sensitive and specific for detecting vascular abnormali- A catheter angiogram may be considered if clinical suspicion is high or noninvasive studies are suggestive of an Radiological evidence suggestive of vascu- lar abnormalities as causative for ICH can include the presence of subarachnoid hemorrhage, enlarged vessels or calcifications along the margins of the ICH, hyperattenuation within a dural venous sinus or cortical vein along the presumed venous drain- unusual hematoma shape, presence of edema out of proportion to the time of presumed ICH, an unusual hemor- rhage location, and the presence of other abnormal structures in the brain (like a mass). Patients with lobar hemorrhage location, age <55 years, and no history of hypertension have a higher likelihood of identification of a secondary cause of ICH from additional MRI beyond noncontrast CT.66 An magnetic resonance venography or CT venography should be performed if hemorrhage location, relative edema volume, or abnormal signal in the cerebral sinuses on routine neuroimaging suggests cerebral vein thrombosis. In summary, ICH is a medical emergency that should be diagnosed and managed promptly. Hematoma expansion and early deterioration are common within the first few hours after onset. Emergency Diagnosis and Assessment: Recommendations 1. A baseline severity score should be performed as part of the initial evaluation of patients with ICH (Class I; Level of Evidence B). (New recommendation) Rapid neuroimaging with CT or MRI is recom- mended to distinguish ischemic stroke from ICH (Class I; Level of Evidence A). (Unchanged from the previous guideline) CTA and contrast-enhanced CT may be consid- ered to help identify patients at risk for hematoma expansion (Class IIb; Level of Evidence B), and CTA, CT venography, contrast-enhanced CT, contrast- enhanced MRI, magnetic resonance angiography and magnetic resonance venography, and catheter angiography can be useful to evaluate for underlying structural lesions including vascular malformations and tumors when there is clinical or radiological sus- picion (Class IIa; Level of Evidence B). (Unchanged from the previous guideline) Medical Treatment for ICH Hemostasis and Coagulopathy, Antiplatelets, and Deep Vein Thrombosis Prophylaxis Underlying hemostatic abnormalities can contribute to ICH. Patients at risk include those taking oral anticoagulant drugs (OACs), antiplatelet agents, those with acquired or congeni- tal coagulation factor deficiencies, and those with inherited or acquired qualitative or quantitative platelet abnormali- ties. Patients taking OACs constitute 12% to 20% of patients a rate that has increased with the aging popu- lation and increased use of anticoagulant drugs in recent Vitamin K antagonists (VKAs) such as warfarin are the most frequently prescribed OAC, but new agents that do not require laboratory monitoring and do not necessarily prolong coagulation screening tests are being increasingly used, including dabigatran,71 These new agents appear to be associated with a lower risk of ICH than VKAs.74 It is important that providers caring for ICH patients recognize the use of antithrombotic drugs or of an underlying coagulopathy in the initial evaluation of patients with ICH, so that the treatment strategy can include appropriate interventions. For patients with a known coagulation factor deficiency or platelet disorder, replacement of the appropriate factor or platelets, often with the assistance of a consultant hema- tologist, is indicated. If spontaneous ICH occurs in a patient undergoing an intravenous heparin infusion, then protamine sulfate can be given by intravenous injection at a dose of 1 mg per 100 U of heparin (maximum dose 50 mg), with adjustment based on time elapsed since discontinuation of heparin infu- Similar dosing can be used in patients who are receiv- ing low-molecular-weight heparin; however, reversal may be VKA-Related ICH Guidelines exist for reversal of OACs.76 For ICH patients tak- ing VKA, rapid correction of the international normalized ratio (INR) is recommended.76,77 Fresh frozen plasma (FFP), along with vitamin K, has been the mainstay of treatment in the United States for years, but more recently, prothrombin complex concentrates (PCCs), the activated PCC FEIBA (fac- tor VIII inhibitor bypassing activity), and recombinant acti- vated factorVIIa (rFVIIa) have emerged as potential therapies. Administration of intravenous vitamin K alone is insufficient for reversal in the first hours but should be part of all acute VKA reversal strategies in a dose of 5 to 10 mg, usually given slowly via the intravenous route. Onset of action begins by 2 hours and is maximal at 24 hours if liver function is normal.78 FFP administration requires thawing and cross matching, car- ries a risk of allergic and infectious transfusion reactions, and often requires large volumes for full INR correction. Likelihood of INR correction at 24 hours was linked to time to FFP administration in 1 study, although 17% of patients still did not have an INR <1.4 by this time, which suggests that FFP administered in this manner may be insufficient for rapid correction of coagulopathy.79 Shortcomings of FFP have led to interest in alternative agents for VKA reversal. PCCs are plasma-derived factor concentrates originally developed to treat factor IX deficiency (hemophilia B). Three- factor PCC contains factors II, IX, and X whereas 4-factor PCC also contains factor VII. PCC does not require cross matching, can be reconstituted and administered rapidly in a small volume (20 40 mL), and has been processed to inactivate infectious agents. Several studies have shown that PCCs rapidly normalize the INR (within minutes) in patients Although nonrandomized retrospective reviews and a small case-control study have shown more rapid correction of INR with vitamin K and PCC than vitamin K and FFP, none have clearly demonstrated an improvement in patient clinical outcome with PCC.83 85 In 1 randomized trial comparing the use of a PCC (Konyne) to supplement FFP versus FFP alone in patients with VKA-related ICH, those who were given FFP alone received a higher volume of FFP and developed more adverse events, primarily attributable to PCCs may increase the risk of thrombotic complications, although this risk appears low.80 In 2013, the first large phase 3 randomized controlled trial demonstrated noninferiority of 4-factor PCC to FFP for urgent reversal of warfarin in a cohort of 202 patients with acute bleeding (24 of whom had intracranial hemorrhage).87 In this study, the rate of achieving an INR <1.3 within 30 minutes of completing ther- apy was 62.2% for PCC and 9.6% for FFP. Thromboembolic event rates were similar (7.8% with PCC and 6.4% with FFP), and fluid overload was more common with FFP (12.8% versus 4.9%). Analogous randomized trials have not been performed to directly evaluate 3-factor and 4-factor PCCs against each other. Additionally, the specific INR target for VKA correc- tion in OAC-related ICH is unclear, with various studies cited here and elsewhere using targets ranging from <1.3 to <1.5.88 rFVIIa, licensed to treat hemophilia patients with high titer inhibitors or congenital factor VII deficiency, has gar- nered attention as a potential treatment for spontaneous and OAC-associated ICH. Although rFVIIa can rapidly normal- ize INR in the setting of VKA-associated ICH,89 93 it does not replenish all of the vitamin K dependent factors and may not restore thrombin generation as effectively as PCCs.94 Thus, rFVIIa is not currently recommended for routine use in war- New Anticoagulant Medication Related ICH There are no randomized trials of reversing agents for newer anticoagulants among patients with ICH or other major bleed- ing complications, and because these agents have only been available for a few years, experience with reversal is limited. Currently available agents in the United States (dabigatran, rivaroxaban, and apixaban) have relatively short half-lives ranging from 5 to 15 hours. Evaluation of the activated par- tial thromboplastin time and prothrombin time and consulta- tion with a hematologist are reasonable to individualize care. Potential reversal strategies using FEIBA, other PCCs, or rFVIIa might be considered. FFP is of unclear utility, and vita- min K is not useful. It has been suggested that FEIBA or rFVIIa may be better for the direct thrombin inhibitor dabigatran, whereas other PCCs may be better for the factor Xa inhibitors rivaroxaban and apixaban,96 99 but these data are preliminary. Activated charcoal can be used if the most recent dose of dabi- gatran, apixaban, or rivaroxaban was taken within the previous couple of hours.100 Hemodialysis has been noted as an option for dabigatran, but less so for rivaroxaban or apixaban because these are more highly protein bound.90 Specific antidotes for these medications are in early clinical development.101 Antiplatelet Medication Related ICH Studies addressing the effect of prior antiplatelet agent use or platelet dysfunction on ICH growth and outcome have found conflicting results. Reported antiplatelet agent use was not associated with hematoma expansion or clinical outcome in the placebo group of an ICH neuroprotective study.102 Others have suggested that platelet dysfunction as measured by plate- let function assays may be associated with hematoma expan- sion and clinical outcome.103,104 Platelet function monitoring could be helpful in assessing exposure to antiplatelet medica- tions and guiding hemostatic interventions, but this approach has not been fully studied. A case series of 45 ICH patients receiving platelet transfusion at the discretion of their phy- sician demonstrated improved platelet reactivity after trans- fusion with the VerifyNow-ASA assay.105 Subgroup analysis in those at high risk of hemorrhage growth suggested that platelet transfusion within 12 hours of symptom onset was associated with smaller final hemorrhage outcome and inde- pendence at 3 months. Two randomized controlled trials are ongoing to evaluate the effectiveness of platelet transfusion in ICH patients taking antiplatelet agents.106,107 rFVIIa in ICH Not Related to Anticoagulant Agents rFVIIa has also been tested in patients with non-OAC ICH. Although a phase 2 randomized trial showed that treatment with rFVIIa within 4 hours after ICH onset limited hematoma growth and improved clinical outcome relative to placebo, a subsequent phase 3 trial did not find clinical benefit.108,109 Use of rFVIIa was associated with an increased frequency of thromboembolic events compared with placebo (7% versus 2%) in the phase 2 trial and significantly more arterial events in the phase 3 trial. It remains to be determined whether rFVIIa might benefit a particular subset of patients with ICH, but currently its benefits in ICH patients, whether or not they are taking an OAC, remain unproven. Thromboprophylaxis in ICH Patients Patients with ICH have a high risk of thromboembolic dis- Women and blacks may be at greater risk.110 112 In a randomized trial of 151 ICH patients, intermittent pneumatic compression together with elastic stockings reduced the occurrence of asymptomatic deep vein thrombosis (DVT) after ICH compared with elastic stockings alone (4.7% versus The CLOTS trials (Clots in Legs or Stockings After Stroke) consisted of 3 different randomized trials (CLOTS 1, 2, and 3) that assessed several different treatments, includ- ing graduated compression stockings versus none, thigh-high graduated compression stockings versus calf-high stockings, and intermittent pneumatic compression versus none.114 117 CLOTS 1 enrolled 2518 stroke patients (232 with ICH) and found that thigh-high compression stockings did not reduce DVT, pulmonary embolism (PE), or death.115 CLOTS 2 found that DVT was more common in patients who had below-knee graduated compression stockings than in those with thigh- high graduated compression stockings.114 Finally, CLOTS 3 enrolled 2876 patients (376 with ICH) and found that intermit- tent pneumatic compression begun as early as the day of hos- pital admission reduced the occurrence of proximal DVT, with Hemphill et al Management of Spontaneous ICH 2039 the effect being particularly prominent in patients with hem- orrhagic stroke (6.7% versus 17.0%, odds ratio [OR], 0.36; 95% confidence interval, [CI] 0.17 0.75).116 A meta-analysis of anticoagulant drugs for thromboprophylaxis that included 1000 ICH patients from 4 trials (2 randomized) and evalu- ated the early use of enoxaparin or heparin (from 1 to 6 days after admission) found a reduction in PE (1.7% versus 2.9%; relative risk [RR], 0.37; 95% CI, 0.17 0.80), a nonsignificant CI, 0.57 1.03), but no difference in DVT (4.2% versus 3.3%; RR, 0.77; 95% CI, 0.44 1.34) or hematoma enlargement ICH patients who develop DVT or PE may be consid- ered for full systemic anticoagulation or placement of an inferior vena cava (IVC) filter. Given the generally accepted recurrence rate of nonfatal PE is 12% to 15% in nontreated patients (not specific to ICH), observation alone is not rec- ommended. Only very limited information is available to guide decision making on IVC filter placement versus anti- coagulation, as well as the optimal anticoagulation regi- Considerations include the posthemorrhage date on which DVT/PE is diagnosed, documentation of stable hema- toma size on neuroimaging, lobar versus deep hematoma location, and the practical ability to remove an IVC filter at a later date. General guidelines for the use of IVC filters in the setting of acute DVT suggest a conventional course of anti- coagulant therapy if the risk of bleeding resolves; however, these are not ICH specific.120 Hemostasis and Coagulopathy, Antiplatelet Agents, and DVT Prophylaxis: Recommendations 1. Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate factor replacement therapy or platelets, respectively (Class I; Level of Evidence C). (Unchanged from the previous guideline) Patients with ICH whose INR is elevated because of VKA should have their VKA withheld, receive therapy to replace vitamin K dependent factors and correct the INR, and receive intravenous vitamin K (Class I; Level of Evidence C). PCCs may have fewer complications and correct the INR more rapidly than FFP and might be considered over FFP (Class IIb; Level of Evidence B). rFVIIa does not replace all clotting factors, and although the INR may be lowered, clotting may not be restored in vivo; therefore, rFVIIa is not recommended for VKA reversal in ICH (Class III; Level of Evidence C). (Revised from the previous guideline) For patients with ICH who are taking dabigatran, rivaroxaban, or apixaban, treatment with FEIBA, other PCCs, or rFVIIa might be considered on an individual basis. Activated charcoal might be used if the most recent dose of dabigatran, apixaban, or riva- roxaban was taken <2 hours earlier. Hemodialysis might be considered for dabigatran (Class IIb; Level of Evidence C). (New recommendation) Protamine sulfate may be considered to reverse hep- arin in patients with acute ICH (Class IIb; Level of Evidence C). (New recommendation) The usefulness of platelet transfusions in ICH patients with a history of antiplatelet use is uncer- tain (Class IIb; Level of Evidence C). (Revised from the previous guideline) Although rFVIIa can limit the extent of hematoma expansion in noncoagulopathic ICH patients, there is an increase in thromboembolic risk with rFVIIa and no clear clinical benefit in unselected patients. Thus, rFVIIa is not recommended (Class III; Level of Evidence A). (Unchanged from the previous guideline) Patients with ICH should have intermittent pneu- matic compression for prevention of venous throm- boembolism beginning the day of hospital admission (Class I; Level of Evidence A). Graduated compres- sion stockings are not beneficial to reduce DVT or improve outcome (Class III; Level of Evidence A). (Revised from the previous guideline) After documentation of cessation of bleeding, low- dose subcutaneous low-molecular-weight heparin or unfractionated heparin may be considered for pre- vention of venous thromboembolism in patients with lack of mobility after 1 to 4 days from onset (Class IIb; Level of Evidence B). (Unchanged from the previ- ous guideline) Systemic anticoagulation or IVC filter placement is probably indicated in ICH patients with symptom- atic DVT or PE (Class IIa; Level of Evidence C). The decision between these 2 options should take into account several factors, including time from hem- orrhage onset, hematoma stability, cause of hemor- rhage, and overall patient condition (Class IIa; Level of Evidence C). (New recommendation) BP and Outcome in ICH Elevated BP is very common in acute ICH121,122 because of a variety of factors, including stress, pain, increased ICP, and premorbid acute or persistent elevations in BP. High SBP is associated with greater hematoma expansion, neurological dete- rioration, and death and dependency after ICH.122 124 Compared with ischemic stroke, in which consistent U- or J-shaped asso- ciations between SBP nadir of 140 and 150 mmHg and poor outcome have been shown,125 only 1 study of ICH has shown a poor outcome at low SBP levels (<140 mmHg).126 Safety of Early Intensive BP-Lowering Treatment Observational studies with advanced neuroimaging have shown no significant ischemic penumbra in ICH,127 with the perihematomal rim of low attenuation seen on CT being related to extravasated plasma.128 A randomized clinical trial using CT perfusion in primarily small and medium ICH found no clinically significant reduction in cerebral blood flow within the perihematomal region related to early intensive BP lowering to an SBP target of <140 mmHg within several hours In a clinical cohort of 211 patients who received a standard protocol of nicardipine-based BP lowering to reach an SBP target of <160 mmHg at a mean of 30 minutes (range, 15 45 minutes) within 3 hours of the onset of ICH, the best outcomes were seen in the group with the lowest achieved Both the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) trial, a 4-tier dose- escalation study of intravenous nicardipine-based BP low- ering in 80 patients within 3 hours of ICH,130 and the pilot phase Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage (INTERACT1) trial in 404 mainly Chinese patients within 6 hours of ICH131 found rapid reduction of SBP to <140 mmHg to be safe.132,133 Most recently, the main phase INTERACT2 trial has shown no increase in death or serious adverse events from early intensive BP lowering in eligible patients with elevated SBP.134 Several observational studies have demonstrated that small ischemic lesions identified on diffusion-weighted MRI are common after ICH; however, the impact on outcome and relationship with BP lowering vary Efficacy of Early Intensive BP-Lowering Treatment The largest randomized clinical trial evaluating the efficacy of intensive BP lowering is INTERACT2, a phase 3 trial undertaken in 2839 patients with SBP between 150 and 220 mmHg within 6 hours of ICH.134 Among 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment (to an SBP target of <140 mmHg within 1 hour of randomiza- tion and for a duration of 7 days, following protocols that included locally available intravenous agents) compared with 785 of 1412 participants (55.6%) receiving standard treat- ment (SBP <180 mmHg) had a primary outcome of death or major disability (modified Rankin scale score 3; OR, 0.87; 95% CI, 0.75 1.01; P=0.06). Analysis of secondary end points indicated significantly better functional recovery on an ordinal analysis of scores on the modified Rankin scale (OR better physical and mental health related quality of life on the EQ-5D scale (mean health utility scores, intensive group intensive treatment. Although INTERACT2 demonstrated consistency of the treatment effect across several prespecified patient subgroups, there was no clear relationship between outcome and the time from onset of ICH to commencing treatment and no signifi- cant effect of intensive BP-lowering treatment on hematoma growth. Moreover, only one third of patients achieved the target SBP level within 1 hour (half achieved the target by 6 hours), and most (75%) presented with mild to moderate size (<20 mL) hematomas. Overall, current evidence indicates that early intensive BP lowering is safe and feasible and that surviving patients show modestly better functional recovery, with a favorable trend seen toward a reduction in the conventional clinical end point of death and major disability. It is therefore reasonable for ICH patients similar to those enrolled in INTERACT2 to receive early treatment targeted to an SBP level <140 mmHg to improve their chances of achieving better functional recovery should they survive the condition. There are fewer data avail- able pertaining to the safety and effectiveness of such treatment in patients with very high BP (sustained SBP >220 mmHg) on presentation, large and more severe ICH, and those requiring surgical decompression. Because the speed and degree of BP reduction will vary according to the agent and method of deliv- ery (bolus versus infusion) and clinical features, the choice of agent should take into account the practicability, pharmaco- logical profile, potential side effects, and cost. BP: Recommendations For ICH patients presenting with SBP between 150 and 220 mmHg and without contraindication to acute BP treatment, acute lowering of SBP to 140 mmHg is safe (Class I; Level of Evidence A) and can be effective for improving functional outcome (Class IIa; Level of Evidence B). (Revised from the previous guideline) For ICH patients presenting with SBP >220 mmHg, it may be reasonable to consider aggressive reduc- tion of BP with a continuous intravenous infusion and frequent BP monitoring (Class IIb; Level of Evidence C). (New recommendation) Inpatient Management and Prevention of Secondary Brain Injury General Monitoring Patients with ICH are frequently medically and neurologically unstable, particularly within the first few days after onset. Care of ICH patients in a dedicated neuroscience intensive care unit is associated with a lower mortality rate.136 Many patients in the INTERACT2 study were cared for in a dedi- cated stroke unit rather than an intensive care unit.134 Frequent vital sign checks, neurological assessments, and continuous cardiopulmonary monitoring including a cycled automated BP cuff, electrocardiographic telemetry, and pulse oximetry probe should be standard. Continuous intra-arterial BP moni- toring should be considered in patients receiving intravenous vasoactive medications. Nursing Care The specific nursing care required for ICH patients in inten- sive care units may include (1) surveillance and monitoring of ICP, cerebral perfusion pressure (CPP), and hemody- namic function; (2) titration and implementation of protocols for management of ICP, BP, mechanical ventilation, fever, and serum glucose; and (3) prevention of complications of immobility through positioning, airway maintenance, and mobilization within physiological tolerance. The consensus document from the Brain Attack Coalition on comprehensive stroke centers delineates these as specific areas of monitor- ing and complication prevention in which nurses should This document also recommends that nurses be trained in detailed assessment of neurological function, including standardized scales such as the NIHSS, GCS, and the Glasgow Outcome Scale. In a Canadian study of 49 hospitals that included ICH patients, a higher proportion of registered nurses at the hos- pital and better nurse-physician communication were inde- pendently associated with lower 30-day mortality even after adjustment for disease severity, comorbidities, and hospital Hemphill et al Management of Spontaneous ICH 2041 In a Swedish study of 86 hospitals, stroke unit care was associated with a lower risk of death or institu- tional living after 3 months in patients with ICH (OR, 0.60; General Monitoring and Nursing Care: Recommendation Initial monitoring and management of ICH patients should take place in an intensive care unit or dedi- cated stroke unit with physician and nursing neu- roscience acute care expertise (Class I; Level of Evidence B). (Revised from the previous guideline) Glucose Management High blood glucose on admission predicts an increased risk of mortality and poor outcome in patients with ICH, indepen- dent of the presence of diabetes mellitus.140 144 A randomized trial showing improved outcomes with tight glucose control (range, 80 110 mg/dL) using insulin infusions in mainly surgical critical care patients141 has increased the use of this therapy. However, more recent studies have demonstrated an increased incidence of systemic and cerebral hypoglycemic events and possibly even an increased risk of mortality in patients treated with this regimen.145 148 A cluster randomized trial of a set of interventions (managing glucose, fever, and swallowing dysfunction in stroke units) found improved out- comes in a mixed cohort of ischemic and hemorrhagic stroke At present, the optimal management of hypergly- cemia in ICH and the target glucose level remains to be clari- fied. Hypoglycemia should be avoided. Glucose Management: Recommendation Glucose should be monitored. Both hyperglyce- mia and hypoglycemia should be avoided (Class I; Level of Evidence C). (Revised from the previous guideline) Temperature Management Fever worsens outcome in experimental models of brain Fever is common after ICH, especially in patients with intraventricular hemorrhage. In patients surviving the first 72 hours after hospital admission, the duration of fever is related to outcome and appears to be an independent prog- nostic factor in these patients.152 Fever may also be associated with hematoma growth, although a cause-effect relation- ship is unclear.153 Although these data provide a rationale for treatment of fever in ICH patients, maintenance of nor- mothermia has not been clearly demonstrated as beneficial Preliminary animal and human studies have suggested that therapeutic cooling may reduce perihemato- However, treatment with mild hypothermia should be considered investigational in ICH at this time.157 Temperature Management: Recommendation IIb; Level of Evidence C). (New recommendation) Seizures and Antiseizure Drugs The frequency of clinical seizures early (within 1 week) after ICH is as high as 16%, with the majority occurring at or near Cortical involvement of ICH is the most impor- tant risk factor for early seizures.158 160 In a large single-center study, prophylactic antiseizure drugs significantly reduced the number of clinical seizures after lobar ICH.161 Prospective and population-based studies, however, have shown no asso- ciation between clinical seizures and neurological outcome or Studies of continuous electroencephalography (EEG) report electrographic seizures in 28% to 31% of select cohorts of ICH patients, despite most having received prophylactic The clinical impact of subclini- cal seizures detected on EEG is unclear. Most studies suggest that prophylactic antiseizure drugs (primarily phenytoin) are associated with increased death and disability in ICH,165 167 although a recent study found no association between antiseizure drugs and out- come in those who survived beyond 5 days after ICH, which highlights the possible influence of confounding in A small randomized trial of 1-month prophylactic treatment with valproic acid showed no reduc- tion in incident seizures over 1-year follow-up (19.5% in the treatment group, 22.2% in the placebo group; P=0.8).168 Prophylactic anticonvulsant medication has thus not been demonstrated to be beneficial. Clinical seizures or electrographic seizures in patients with a change in mental status should be treated with antisei- zure drugs. Continuous EEG monitoring should be considered in ICH patients with depressed mental status that is dispropor- tionate to the degree of brain injury. Epilepsy occurs in up to 10% of young patients (18 50 years) with ICH; the risk of poststroke epilepsy may be less in older patients.169,170 Risk factors for epilepsy include stroke severity, cortical location of the hematoma, and delayed initial seizures.169,170 There are no data to sug- gest that early use of antiseizure drugs will prevent lesion- related epilepsy. Seizures and Antiseizure Drugs: Recommendations Clinical seizures should be treated with antiseizure drugs (Class I; Level of Evidence A). (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; Level of Evidence C). (Unchanged from the previous guideline) Continuous EEG monitoring is probably indicated in ICH patients with depressed mental status that is out of proportion to the degree of brain injury (Class IIa; Level of Evidence C). (Revised from the previous guideline) Prophylactic antiseizure medication is not recom- mended (Class III; Level of Evidence B). (Unchanged from the previous guideline) Management of Medical Complications The frequency of medical complications after acute stroke is high, although there is substantially more information reported for ischemic stroke than ICH. In a trial of the safety and tolerability of NXY-059 (CHANT [Cerebral Hematoma and NXY Treatment]) in patients with sponta- neous ICH, at least 1 adverse event was reported in 88% of the placebo-treated patients, 40% of which were serious (ie, resulted in prolonged hospitalization, were immediately life threatening, or were fatal). The most common compli- cations were pneumonia (5.6%), aspiration (2.6%), respira- tory failure/distress (2%), PE (1.3%), and sepsis (1.7%).171 Approximately 50% of deaths after stroke are attributed to medical complications, usually after 7 days of hospitaliza- tion. Stroke patients who experience medical complications while in the hospital have increased mortality up to 4 years after the initial event. Dysphagia and aspiration are major risk factors for the development of pneumonia. Dysphagia is defined by swal- lowing impairment of the upper digestive tract and includes impairments in swallowing efficiency and safety, with delays in the timing of movements, reduced range of movements, and frank aspiration. Aspiration in this population is a sign of severe dysphagia and refers to abnormal entry of fluid, particulate exogenous substances, or endogenous secretions into the airways. In a retrospective study that included 90 Japanese ICH patients, 68% could not tolerate oral feed- In another German study of 208 ICH patients, 25% of patients required percutaneous endoscopic gastrostomy.173 In this study, GCS, occlusive hydrocephalus, mechanical venti- lation, and sepsis were independent risk factors for dyspha- gia and percutaneous endoscopic gastrostomy placement. In a prospective multicenter study, use of a formal screen- ing protocol for dysphagia (eg, water swallow test) for all patients admitted with ischemic stroke was associated with a significantly reduced risk of pneumonia compared with no The pneu- monia rate of sites with a formal dysphagia screen was 2.4% versus 5.4% of those without a screen, a 3% absolute risk reduction. Serious cardiac events and cardiac death after stroke may be caused by acute myocardial infarction (MI), heart failure, ventricular arrhythmias including ventricular tachycardia/ fibrillation, and cardiac arrest. Concurrent stroke and MI are not uncommon. Recent data from the prospective Austrian Stroke Unit Registry, which included 4984 ICH patients, found that 0.3% of patients had an MI over a median duration These patients not only experienced higher in- hospital mortality but also had greater complications, includ- ing pneumonia and progressive stroke. History of prior MI and severity of deficits on admission are associated with the occurrence of MI. In a meta-analysis of 65996 stroke patients with a mean follow-up of 3.5 years,176 the annual risk of MI was 2.2 %. For ICH patients, an elevated troponin level >0.4 ng/mL was found in 15% within 24 hours of admission and was associated with increased in-hospital mortality.21 In another study of 49 patients with supratentorial ICH, exclud- ing those who died within 12 hours or were moribund, 20% had elevated troponin levels, although this was not associated Heart failure can occur as the result of myocardial isch- emia, infarction, stress-induced cardiomyopathy, or uncon- trolled hypertension in the setting of acute ICH. Neurogenic pulmonary edema is an increase in interstitial and alveolar fluid in the setting of an acute central nervous system injury well documented in subarachnoid hemorrhage but prevalent in ICH as well.178 Neurogenic pulmonary edema presents abruptly and progresses quickly after the neurological insult. Radiographically, it is indistinguishable from cardiogenic pulmonary edema. Resolution usually occurs within several days. Intubation with mechanical ventilator support is often required for airway protection and maximum oxygen delivery. ICH patients may be at risk for acute respiratory distress syn- drome from multiple different origins179 ; however, at present, ways to prevent this have not been studied. When ICH patients develop acute respiratory distress syndrome, it is reasonable to use ventilation strategies used in non-neurological patients (such as low-tidal-volume ventilation)180 ; however, attention should be paid to avoid ICP elevations or inadequate cerebral oxygen delivery. Other medical complications in ICH patients include acute kidney injury, hyponatremia, gastrointestinal bleeding, impaired nutritional status, urinary tract infections, and post- stroke depression. Acute nephropathy (defined in a study by Oleinik et al181 as a rise in creatinine of at least 25% or 0.5 mg/ dL to a level of at least 1.5 mg/dL) occurred in 41 of 539 ICH patients (8%) admitted to a single institution over a 5-year period and was no more frequent in those who underwent which suggests that kidney injury was a result of overall medical status rather than this particular pro- cedure. Screening and monitoring are keys to detecting these events. Management at this time is focused on prevention and targeting these complications as they arise. Because of lim- ited information regarding ICH-specific issues related to ven- tilator-associated events, acute respiratory distress syndrome management, and acute kidney injury, these should be consid- ered areas for future study. The identification of preventive or treatment strategies for other medical complications will also require further studies focused on ICH patients. Management of Medical Complications: Recommendations A formal screening procedure for dysphagia should be performed in all patients before the initiation of oral intake to reduce the risk of pneumonia (Class I; Level of Evidence B). (New recommendation) Systematic screening for myocardial ischemia or infarction with electrocardiogram and cardiac enzyme testing after ICH is reasonable (Class IIa; Level of Evidence C). (New recommendation) Procedures/Surgery ICP Monitoring and Treatment Limited data exist regarding the frequency of elevated ICP and its management in patients with ICH.182 185 A recently reported Hemphill et al Management of Spontaneous ICH 2043 cohort study of 243 consecutive ICH patients described ICP episode of intracranial hypertension (defined as an ICP >20 In a randomized trial of intraventricular thrombol- ysis in 100 patients with intraventricular hemorrhage (IVH) and ICH smaller than 30 mm3 , ICP was >20 mmHg at the time of ventricular catheter (VC) insertion in 14 patients.184 Overall, however, ICP was not frequently elevated during monitoring and VC drainage in these patients. There is evidence for dif- ferential pressure gradients in at least some cases of ICH, so that ICP may be elevated in and around the hematoma but not distant from it.186 Because the usual causes of elevated ICP are hydrocephalus from IVH or mass effect from the hematoma (or surrounding edema), patients with small hematomas and limited IVH usually will not require treatment to lower ICP. Increased ICP also may be more common in younger patients and those with supratentorial ICH.185 Hydrocephalus is associ- ated with worsened outcome in acute ICH.187 189 patients with follow-up data who were randomized into the international Surgical Trial for Intracerebral Haemorrhage (STICH), 377 had IVH, and 208 of these had hydrocephalus (23% of all patients, 55% of those with IVH).190 ICP is measured by use of devices inserted into the brain parenchyma or cerebral ventricles. Fiber optic technology can be used in both types of devices. A VC inserted into the lat- eral ventricle allows for drainage of cerebrospinal fluid (CSF), which can help reduce ICP. A parenchymal ICP device is inserted into the brain parenchyma and allows for monitoring of ICP, but not CSF drainage. The absence of published stud- ies showing that management of elevated ICP has an effect on ICH outcome makes the decision whether to monitor and treat elevated ICP unclear in patients with ICH. Risks associated with ICP monitors include infection and intracranial hemor- rhage. The risk of hemorrhage or infection is thought to be higher with VC than with parenchymal catheters, although data on these rates are not derived from patients with ICH but principally from those with traumatic brain injury or aneurys- mal subarachnoid hemorrhage. In a 1997 series of 108 intrapa- renchymal devices, the rate of infection was 2.9% and the rate of intracranial hemorrhage was 2.1% (15.3% in patients with Two of 22 patients (9%) patients in the pla- cebo arm of a trial of intraventricular thrombolysis developed ventriculitis, but these patients had multiple intrathecal injec- tions, which could potentially increase the risk of infection.184 Before insertion of a monitoring device, the patient s coagula- tion status should be evaluated. Prior use of antiplatelet agents may justify platelet transfusion before the procedure, and the use of warfarin may require reversal of coagulopathy before placement. The decision to use a VC or a parenchymal cath- eter device should be based on whether there is a need to drain CSF to treat hydrocephalus or elevated ICP. Because of limited data regarding indications for monitor- ing and treatment of ICP in ICH, management principles for elevated ICP are usually generalized from those for traumatic brain injury, in which current guidelines recommend place- ment of an ICP monitor in patients with a GCS score of 3 to 8 and maintenance of an ICP <20 mmHg and a CPP of 50 to 70 mmHg, depending on the status of cerebral autoregula- Data from small, retrospectively analyzed cohorts of ICH patients suggest that rising ICP and declining CPP are associated with mortality.184,195,196 In 1 study of multimodality monitoring in 18 ICH patients, CPP <70 to 80 mmHg was associated with brain tissue hypoxia and poor outcome.195 Thus, ICP monitoring and subsequent treatment might be considered in ICH patients with a GCS score of 8 that is presumed related to hematoma mass effect, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus. Methods of treating elevated ICP are generally borrowed from traumatic brain injury guidelines as well. Basic princi- ples include elevation of the head of the bed to 30 , the use of mild sedation, and avoidance of collar-endotracheal tube ties that might constrict cervical veins.197 Mannitol or hypertonic saline may be used to treat acute ICP elevations, and hypertonic saline may be more effective.198 In patients with CSF outflow obstruction caused by hydrocephalus or a trapped ventricle, CSF drainage should be considered. Hematoma evacuation and decompressive craniectomy (DC) are options for treating ele- vated ICP and are discussed in the section on SurgicalTreatment of ICH. Salvage therapies might include barbiturate coma or mild hypothermia. Corticosteroids should not be used, because they are not effective in ICH and increase complications.199 Small case series have described the use of brain tissue oxygen and cerebral microdialysis monitoring in patients with Because of the small numbers of patients and limited data, no recommendation can be made regarding the use of these technologies at this time. ICP Monitoring and Treatment: Recommendations Ventricular drainage as treatment for hydrocephalus is reasonable, especially in patients with decreased level of consciousness (Class IIa; Level of Evidence B). (Revised from the previous guideline) Patients with a GCS score of 8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus might be consid- ered for ICP monitoring and treatment. A CPP of 50 to 70 mmHg may be reasonable to maintain depend- ing on the status of cerebral autoregulation (Class IIb; Level of Evidence C). (Unchanged from the previ- ous guideline) Corticosteroids should not be administered for treat- ment of elevated ICP in ICH (Class III; Level of Evidence B). (New recommendation) Intraventricular Hemorrhage IVH occurs in 45% of patients with spontaneous ICH and is an independent factor associated with poor outcome.190,202,203 Pooled analysis of 13 studies found IVH in association with ICH increased the risk of death from 20% without to 51% IVH can be primary, confined to the ventricles, or secondary, originating as an extension of an ICH. Most IVH is secondary and related to hypertensive hemorrhages involving the basal ganglia and thalamus.202,205 Although the insertion of a VC should theoretically aid in drainage of blood and CSF from the ventricles, VC use alone may be ineffec- tive because of difficulty maintaining catheter patency and the slow removal of intraventricular blood.188 Thus, there has been recent interest in the use of thrombolytic agents as adjuncts to VC use in the setting of IVH. 