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.


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.


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 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).


(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.


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.


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.


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.


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).


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).


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.


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.


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).


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.


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.


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.


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.


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.


(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).


(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.


(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.


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.


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).


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).


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.


(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.


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).


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.


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.


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.


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) 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.


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.


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.


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.


(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. Animal studies and clinical series have reported that intra- ventricular administration of fibrinolytic agents, including urokinase, streptokinase, and recombinant tissue-type plas- minogen activator (rtPA), in IVH may reduce morbidity and mortality by accelerating blood clearance and clot lysis.206 214 Retrospective analysis of 42 consecutive patients with IVH, 88% attributable to primary ICH, who were treated with intra- ventricular urokinase found death occurred in 21 patients Another prospective study compared 48 patients with IVH (caused by ICH in 40 [83%]) treated with intraventricular rtPA to 49 matched control patients treated with VC alone.207 Mortality was reduced from 30% to 10% in the group treated with rtPA, with 2 patients in the rtPA group diagnosed with ventriculitis. In a small pro- spective trial, 16 patients with IVH and ICH <30 mm3 were randomized to VC or VC plus urokinase.214 Clearance of IVH was faster with urokinase.


In a small pro- spective trial, 16 patients with IVH and ICH <30 mm3 were randomized to VC or VC plus urokinase.214 Clearance of IVH was faster with urokinase. Mortality at 6 months was 14% with urokinase and 44% with VC alone (P=0.22), and there were no significant differences between groups in require- ment for permanent shunts or ventriculitis. Meta-analysis of 4 randomized and 8 observational studies of patients with IVH secondary to spontaneous ICH treated with VC (n=149) or VC with intraventricular fibrinolysis (n=167) found a sig- nificant decrease in mortality from 47% to 23% (pooled Peto OR, 0.32; 95% CI, 0.19 0.52), with the difference occurring principally in patients treated with urokinase.209 There was no difference in complications or need for permanent CSF diver- sion between subjects treated with intraventricular fibrinolytic agents andVC alone. Studies with rtPA have used various dose The largest trial of intraventricular fibrinolysis to date is the CLEAR-IVH trial (Clot Lysis: Evaluating Accelerated Resolution of IVH).184,217,218 CLEAR-IVH included 100 patients (22 placebo, 78 rtPA) with IVH attributable to spon- Overall, bacterial ventriculitis occurred in 3 patients with rtPA (4%) and 2 with placebo (9%). Patients treated with rtPA had significantly lower intracranial pressures, fewer VC obstructions that required replacement, and nonsignificantly shorter duration of VC requirement. There was symptomatic rebleeding in 9 rtPA patients (12%) and 1 patient given placebo (5%; P=0.33). Permanent CSF diversion was required in 14% of placebo and 6% of rtPA patients (P=0.27). Median 30-day modified Rankin scale score was 5 in both groups, and mortality was 19%, with no significant difference between placebo and rtPA. The phase 3 randomized CLEAR III trial is in progress.


The phase 3 randomized CLEAR III trial is in progress. There are now reports of alternative procedures for IVH, such as endoscopic surgical evacuation and ventriculos- A comparison of 48 patients with IVH secondary to ICH and other causes and treated with endoscopic removal of IVH found 17% required permanent CSF diversion com- pared with 50% of 48 historical control patients treated with VC alone. Outcome on the modified Rankin scale was simi- lar. Two randomized trials have been reported comparing endoscopic removal of IVH with VC in patients with IVH secondary to primary ICH <30 mm3 In 1 of the studies, urokinase was also used in both treatment groups.223 Among the 46 patients treated with endoscopy compared with 44 treated with VC, mortality was not significantly different. One study reported improved outcome on the Glasgow Outcome Scale at 2 months with endoscopy but did not report the rate of permanent CSF diversion.223 The other suggested lower rates of permanent CSF diversion after endoscopy.221 Other reported management strategies for IVH include early ventric- endoscopic third ventriculostomy,225 or lumbar drainage.189 In a study comparing 16 patients treated with VC and lumbar drainage for ICH with IVH to 39 histori- cal control patients treated with VC alone, patients managed with VC plus lumbar drainage had a longer median duration of external CSF drainage but were significantly less likely to require permanent CSF diversion.189 IVH: Recommendations Although intraventricular administration of rtPA in IVH appears to have a fairly low complication rate, the efficacy and safety of this treatment are uncer- tain (Class IIb; Level of Evidence B). (Revised from the previous recommendation) The efficacy of endoscopic treatment of IVH is uncertain (Class IIb; Level of Evidence B).


(Revised from the previous recommendation) The efficacy of endoscopic treatment of IVH is uncertain (Class IIb; Level of Evidence B). (New recommendation) Surgical Treatment of ICH (Clot Removal) The role of surgery for most patients with spontaneous ICH remains controversial. The theoretical rationale for hematoma evacuation revolves around the concepts of preventing her- niation, reducing ICP, and decreasing the pathophysiological impact of the hematoma on surrounding tissue by decreas- ing mass effect or the cellular toxicity of blood products. Randomized trials comparing surgery to conservative man- agement have not demonstrated a clear benefit for surgical intervention. Moreover, the generalizability of the results of these trials can be questioned, because patients at risk for her- niation were likely excluded and the largest and most recent studies had high rates of treatment group crossover from con- servative management to surgery. Since the last guidelines, 2 prospective randomized trials and 3 meta-analyses have been completed that compared surgery versus conservative treatment for ICH.226 229 Several other studies have examined minimally invasive approaches compared with craniotomy. Additionally, recent retrospective studies have suggested a possible role for craniectomy in ameliorating increased ICP caused by ICH.230 234 In addition, the current recommendations do not apply to intracranial hemorrhage caused by trauma or underlying structural lesions such as aneurysms and arteriove- nous malformations, because these patients were not included in the described ICH surgery trials.


Additionally, recent retrospective studies have suggested a possible role for craniectomy in ameliorating increased ICP caused by ICH.230 234 In addition, the current recommendations do not apply to intracranial hemorrhage caused by trauma or underlying structural lesions such as aneurysms and arteriove- nous malformations, because these patients were not included in the described ICH surgery trials. Craniotomy for Supratentorial Hemorrhage On the basis of inconclusive evidence from prior trials, STICH was undertaken to determine whether early surgery reduces mortality and improves neurological outcome compared with conservative management for supratentorial ICH when the treating neurosurgeon determined that uncertainty of preferred Hemphill et al Management of Spontaneous ICH 2045 treatment was present.235 In this trial, 1033 patients from 83 centers in 27 countries were randomized to early surgery (<24 hours of randomization) or initial conservative treatment. A favorable outcome on the 8-point extended Glasgow Outcome Scale at 6 months was used as the primary end point. Good outcome was dichotomized, with lower expectations set for those with worse prognosis. Twenty-six percent of the patients in the surgical arm achieved a favorable outcome compared with 24% in the medical arm. STICH found no overall statisti- cally significant difference in mortality or functional outcome between treatment groups. Notably, 26% of patients initially assigned to conservative management ultimately underwent surgery. Subgroup analysis suggested that patients with lobar hemorrhages within 1 cm of the cortical surface might ben- efit from surgery. Additional subgroup analysis suggested that the risk for a poor outcome was increased for patients who presented as comatose (GCS score 8).


Additional subgroup analysis suggested that the risk for a poor outcome was increased for patients who presented as comatose (GCS score 8). On the basis of these observations, the STICH II trial was undertaken.226,236 The STICH II trial addressed the question of whether early surgery would be beneficial for conscious patients with superficial lobar hemorrhage of 10 to 100 mm3 within 1 cm of the cortical surface and without IVH and who were admitted within 48 hours of ictus. Seventy-eight centers in 27 countries participated. The study randomized patients to early surgery (within 12 hours of randomization) plus medical manage- ment or medical management alone. The primary outcome was a prognosis-based dichotomized (favorable or unfavor- able) outcome of the extended Glasgow Outcome Scale. Forty-one percent of patients in the early surgery group had a favorable outcome compared with 38% in the medical arm; this difference was not statistically significant. A nonpre- specified subgroup analysis that included only patients with a poor prognosis (as defined by a specific equation used in STICH) showed that such patients were more likely to have a favorable outcome with early surgery; however, there was no advantage to early surgery for patients in the good prognosis category. A nonsignificant survival advantage was noted for the surgical arm. Twenty-one percent of patients random- ized to initial medical management ultimately underwent surgery, with the most common reason described as patient deterioration. The STICH II authors performed an updated meta-analysis of surgical trials reporting on 3366 patients.228 A significant advantage for surgery was shown when all patients were considered, but there was significant heteroge- neity in the data.


The STICH II authors performed an updated meta-analysis of surgical trials reporting on 3366 patients.228 A significant advantage for surgery was shown when all patients were considered, but there was significant heteroge- neity in the data. Thus, early hematoma evacuation has not been shown to be beneficial in the 2 largest randomized tri- als, but high crossover rates of patients to surgical interven- tion, narrow patient-based inclusion criteria, and the focus of STICH and STICH II on early surgery leave unclarified whether surgery may benefit specific groups of patients with supratentorial ICH. Craniotomy for Posterior Fossa Hemorrhage Because of the narrow confines of the posterior fossa, dete- rioration can occur quickly in cerebellar hemorrhage caused by obstructive hydrocephalus or local mass effect on the brainstem. Several nonrandomized studies have suggested that patients with cerebellar hemorrhages >3 cm in diameter or patients in whom cerebellar hemorrhage is associated with brainstem compression or hydrocephalus have better out- comes with surgical decompression.237 239 Attempting to con- trol ICP via means other than hematoma evacuation, such as VC insertion alone, is considered insufficient, is not recom- mended, and may actually be harmful, particularly in patients with compressed cisterns.239 In contrast to cerebellar hemor- rhage, evacuation of brainstem hemorrhages may be harm- ful in many cases. Given the broad lack of clinical equipoise for surgical evacuation of cerebellar hemorrhages, especially those >3 cm in diameter occurring in potentially salvageable patients, it is unlikely that a randomized trial could be con- ducted to compare surgery versus conservative treatment. Craniectomy for ICH The potential of DC to improve outcomes for patients with ICH has not been well studied.


Craniectomy for ICH The potential of DC to improve outcomes for patients with ICH has not been well studied. On the basis of the results of the first STICH trial, several authors have suggested that outcomes could potentially be improved with DC for selected patients with high ICP and mass effect related to ICH.232 234,240 Patients in these studies tended to be those in coma (GCS score <8) and those who had significant midline shift, large hematomas, or ICP that did not normalize with medical man- agement. One study of DC without hematoma evacuation matched 12 consecutive patients with supratentorial ICH to control subjects via propensity score.232 Median hematoma , and median preoperative GCS score was 8. Three patients in the study group died compared with 8 in the control group, whereas 9 patients had a study-defined good outcome.Another study on DC without hematoma evac- uation included 5 patients with recalcitrant elevated ICP.234 This small cohort fared better than matched control subjects from the authors institutional prospective ICH database.


Three patients in the study group died compared with 8 in the control group, whereas 9 patients had a study-defined good outcome.Another study on DC without hematoma evac- uation included 5 patients with recalcitrant elevated ICP.234 This small cohort fared better than matched control subjects from the authors institutional prospective ICH database. A retrospective study of DC in addition to hematoma evacu- ation for both putaminal and lobar ICH found that patients with putaminal hemorrhage had greater reduction in midline shift and a trend toward better neurological outcome than matched control subjects.240 A systematic review of studies in which DC was performed in the setting of spontaneous ICH suggested that DC with hematoma evacuation might be safe and might improve outcomes.233 Minimally Invasive Surgical Evacuation of ICH Several recent randomized studies have compared minimally invasive aspiration to standard craniotomies and suggested better outcomes with less invasive approaches.227,231,241 243 A meta-analysis of 12 clinical trials suggested superiority of minimally invasive approaches over craniotomy, but meth- odological issues with this analysis have been raised.229,244 A recent randomized study of 465 patients compared needle aspiration of basal ganglia hemorrhages (25 40 mm3 ) to med- ical management alone. Although there was no significant impact on mortality, 3-month neurological outcome was bet- ter in the aspiration group.227 The Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for ICH Evacuation Trial II (MISTIE II) aimed to determine the safety of minimally invasive surgery plus rtPA in the setting of ICH. This study compared 79 surgical patients with 39 medical patients. The study demonstrated a significant reduc- tion in perihematomal edema in the hematoma evacuation group with a trend toward improved outcomes.231 A random- ized phase 3 clinical trial of minimally invasive hematoma evacuation (MISTIE III) is currently in progress.


The study demonstrated a significant reduc- tion in perihematomal edema in the hematoma evacuation group with a trend toward improved outcomes.231 A random- ized phase 3 clinical trial of minimally invasive hematoma evacuation (MISTIE III) is currently in progress. Timing of Surgery Timing of surgery for ICH remains controversial. Randomized prospective trials to date have reported on a wide time frame for surgery that ranges from 4 to 96 hours after symptom Subgroup analyses of patients in STICH II suggested a trend toward better outcome for patients operated on before 21 hours from ictus.226 An individual patient meta- analysis of 2186 patients from 8 trials of surgery for ICH found that surgery improved outcome if performed within 8 hours of Ultra-early craniotomy (within 4 hours from ictus) was associated with an increased risk of rebleeding in a study that involved 24 patients.248 Surgical Treatment of ICH: Recommendations Patients with cerebellar hemorrhage who are dete- riorating neurologically or who have brainstem compression and/or hydrocephalus from ventricu- lar obstruction should undergo surgical removal of the hemorrhage as soon as possible (Class I; Level of Evidence B). Initial treatment of these patients with ventricular drainage rather than surgical evacuation is not recommended (Class III; Level of Evidence C). (Unchanged from the previous guideline) For most patients with supratentorial ICH, the usefulness of surgery is not well established (Class IIb; Level of Evidence A). (Revised from the previous guideline) Specific exceptions and potential subgroup considerations are outlined below in recommenda- tions 3 through 6. A policy of early hematoma evacuation is not clearly beneficial compared with hematoma evacu- ation when patients deteriorate (Class IIb; Level of Evidence A). (New recommendation) Supratentorial hematoma evacuation in deteriorating patients might be considered as a life-saving measure (Class IIb; Level of Evidence C).


(New recommendation) Supratentorial hematoma evacuation in deteriorating patients might be considered as a life-saving measure (Class IIb; Level of Evidence C). (New recommendation) DC with or without hematoma evacuation might reduce mortality for patients with supratentorial ICH who are in a coma, have large hematomas with significant midline shift, or have elevated ICP refrac- tory to medical management (Class IIb; Level of Evidence C). (New recommendation) The effectiveness of minimally invasive clot evacuation with stereotactic or endoscopic aspiration with or with- out thrombolytic usage is uncertain (Class IIb; Level of Evidence B). (Revised from the previous guideline) Outcome Prediction and Withdrawal of Technological Support Observational and epidemiological studies have identified a wide range of factors associated with outcome after acute ICH; identification of these factors led to the development of models to predict mortality and functional outcome. These prediction models include individual patient characteristics such as score on the GCS or NIHSS, age, hematoma volume and location, and the presence and amount of IVH.26,30,249 256 None of these prediction models, however, account for the impact of care limitations such as do-not-attempt-resuscitation (DNAR) orders or the withdrawal of technological support. Most patients who die of ICH do so during the initial acute hospitalization, and these deaths usually occur in the setting of withdrawal of support because of presumed poor Palliative care is an important aspect of care for patients with severe ICH and their families whether or not withdrawal of support is being pursued, and this is discussed in substantially more detail in the recently released American Heart Association scientific statement on Palliative and End- of-Life Care in Stroke.


Most patients who die of ICH do so during the initial acute hospitalization, and these deaths usually occur in the setting of withdrawal of support because of presumed poor Palliative care is an important aspect of care for patients with severe ICH and their families whether or not withdrawal of support is being pursued, and this is discussed in substantially more detail in the recently released American Heart Association scientific statement on Palliative and End- of-Life Care in Stroke. 259 Several studies, however, have identified withdrawal of medical support and other early care limitations, such as DNAR orders within the first day of hospi- talization, as independent predictors of outcome.260 262 By defi- nition, a DNAR order means that there should be no attempt at resuscitation should a cardiopulmonary arrest occur. In practi- cal use, however, DNAR orders are a proxy for overall lack of aggressive care when administered early after ICH, and the overall aggressiveness of ICH care at a hospital is associated with patient outcomes, even after controlling for specific indi- The decision to limit care early after ICH may therefore result in self-fulfilling prophecies of poor outcome, and studies show that current outcome predic- tion models are overly pessimistic because of the failure to account for these care limitations.264,265 Prognostication early after ICH is often desired by physicians, patients, and families, but existing prognostic models are biased by limitation-of-care decisions. Providers should therefore be cautious about offering precise prog- noses early after ICH, especially if the purpose of prog- nostication is to consider withdrawal of support or DNAR Aggressive, guideline-concordant therapy is thus recommended for patients with ICH who do not have advanced directives specifying that such care should not be undertaken.


Providers should therefore be cautious about offering precise prog- noses early after ICH, especially if the purpose of prog- nostication is to consider withdrawal of support or DNAR Aggressive, guideline-concordant therapy is thus recommended for patients with ICH who do not have advanced directives specifying that such care should not be undertaken. Outcome Prediction and Withdrawal of Technological Support: Recommendation Aggressive care early after ICH onset and postpone- ment of new DNAR orders until at least the second full day of hospitalization is probably recommended (Class IIa; Level of Evidence B). Patients with preex- isting DNAR orders are not included in this recom- mendation. Current prognostic models for individual patients early after ICH are biased by failure to account for the influence of withdrawal of support and early DNAR orders. DNAR status should not limit appropriate medical and surgical interventions unless otherwise explicitly indicated (Class III; Level of Evidence C).


DNAR status should not limit appropriate medical and surgical interventions unless otherwise explicitly indicated (Class III; Level of Evidence C). (Revised from the previous guideline) Prevention of Recurrent ICH Patients with ICH are at high risk of a recurrent event and of other major vascular disease.267 The cumulative risk of Hemphill et al Management of Spontaneous ICH 2047 ICH recurrence is 1% to 5% per year.267 269 In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), the hazard ratio (HR) for ICH recurrence among subjects with prior ICH relative to a first ICH in subjects with prior isch- Although the risk of ICH recurrence is highest in the first year after the ini- tial event, the ongoing risk extends for years, particularly in patients with lobar ICH.269,270 Risk Factors Hypertension, older age, and location of the initial hemor- rhage (deep versus lobar) are important risk factors for ICH High BP is associated with an increase in the recurrence of both deep and lobar hemorrhages.271 Increased risk in the elderly is attributed to a higher prevalence of cere- bral amyloid angiopathy (CAA) and increased use of anti- thrombotic medications with accumulating comorbidities.272 CAA is a recognized risk factor for recurrent ICH, particularly in lobar locations.271 Carriers of the apolipoprotein E 2 or patients with previous ICH before the present- and patients with a greater number of microbleeds (particularly microbleeds in lobar brain locations) on gradient echo MRI appear to be at higher risk for ICH recurrence.272,275 In whites, most of the initial and recurrent hemorrhages tend to be lobar, whereas deep hemorrhages (both initial and recur- rent) are more common in Asians.269,276 A history of ischemic stroke, particularly of the small-vessel lacunar type, which shares a common pathogenesis with ICH, might also be a pre- dictor of ICH recurrence.277,278 BP Management Among the preceding risk factors, only BP and the use of anti- thrombotic agents are modifiable.


(Revised from the previous guideline) Prevention of Recurrent ICH Patients with ICH are at high risk of a recurrent event and of other major vascular disease.267 The cumulative risk of Hemphill et al Management of Spontaneous ICH 2047 ICH recurrence is 1% to 5% per year.267 269 In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), the hazard ratio (HR) for ICH recurrence among subjects with prior ICH relative to a first ICH in subjects with prior isch- Although the risk of ICH recurrence is highest in the first year after the ini- tial event, the ongoing risk extends for years, particularly in patients with lobar ICH.269,270 Risk Factors Hypertension, older age, and location of the initial hemor- rhage (deep versus lobar) are important risk factors for ICH High BP is associated with an increase in the recurrence of both deep and lobar hemorrhages.271 Increased risk in the elderly is attributed to a higher prevalence of cere- bral amyloid angiopathy (CAA) and increased use of anti- thrombotic medications with accumulating comorbidities.272 CAA is a recognized risk factor for recurrent ICH, particularly in lobar locations.271 Carriers of the apolipoprotein E 2 or patients with previous ICH before the present- and patients with a greater number of microbleeds (particularly microbleeds in lobar brain locations) on gradient echo MRI appear to be at higher risk for ICH recurrence.272,275 In whites, most of the initial and recurrent hemorrhages tend to be lobar, whereas deep hemorrhages (both initial and recur- rent) are more common in Asians.269,276 A history of ischemic stroke, particularly of the small-vessel lacunar type, which shares a common pathogenesis with ICH, might also be a pre- dictor of ICH recurrence.277,278 BP Management Among the preceding risk factors, only BP and the use of anti- thrombotic agents are modifiable. In PROGRESS, treatment with perindopril (4 mg daily) and indapamide reduced base- line BP by an average of 12 mmHg systolic and 5 mmHg dia- stolic and lowered the risks of first and recurrent ICH (adjusted respectively), as well as other vascular events.267,273,279 In that trial, the lowest risk of stroke recurrence was seen among patients with the lowest follow-up BP levels (median, 112 mmHg systolic and 72 mmHg diastolic) 280 ; those with prior ICH derived the greatest benefit, and the size of the benefit was directly related to the degree of BP lowering, with no clear evidence of a lower threshold below which the benefit attenuated or even reversed, as is seen for ischemic stroke or coronary artery disease.


In PROGRESS, treatment with perindopril (4 mg daily) and indapamide reduced base- line BP by an average of 12 mmHg systolic and 5 mmHg dia- stolic and lowered the risks of first and recurrent ICH (adjusted respectively), as well as other vascular events.267,273,279 In that trial, the lowest risk of stroke recurrence was seen among patients with the lowest follow-up BP levels (median, 112 mmHg systolic and 72 mmHg diastolic) 280 ; those with prior ICH derived the greatest benefit, and the size of the benefit was directly related to the degree of BP lowering, with no clear evidence of a lower threshold below which the benefit attenuated or even reversed, as is seen for ischemic stroke or coronary artery disease. Results of the Secondary Prevention of Small Subcortical Strokes (SPS3) study have shown that the greatest benefit of more intensive BP lowering is on the prevention of ICH in patients with established small-vessel stroke disease and that lowering target SBP to <130 mmHg significantly reduced the risk of ICH (risk reduction, 60%; which suggests that ICH patients should have their BP lowered to or beyond the targets currently rec- ommended in other high-risk groups (<130 mmHg systolic and 80 mmHg diastolic in the presence of diabetes mellitus, heart failure, or chronic kidney disease).282 Other factors, such as BP variability, the presence of obstructive sleep apnea,283,284 obesity, and other lifestyle modifications, should also be considered despite the lack of systematic data regarding their effect on ICH recurrence. Frequent alcohol use (>2 drinks per and illicit drug use have been linked to elevated BP and and should be avoided in ICH patients. Tobacco use is also associated with increased ICH risk287 291 and should be discontinued. The optimal timing for initiating BP lowering after ICH to prevent recurrence is unknown.


The optimal timing for initiating BP lowering after ICH to prevent recurrence is unknown. In INTERACT2, rapid reduction of SBP to <140 mmHg within a few hours was safe, which indicates that such treatment can be safely initiated as soon as possible after ICH onset.134 Management of Antithrombotic Drugs The rising use of anticoagulant agents in an aging population is associated with increased risk of ICH and its recurrence.292 There is a marked paucity of prospective population-based data on the risk of ICH recurrence and mortality after reini- tiation of warfarin. In a cohort of 284 consecutive patients with warfarin-related ICH in the Registry of the Canadian Stroke Network, mortality rates were lower in those who restarted warfarin in the hospital: 31.9% versus 54.4% at 30 the rates of bleeding events were not increased.293 In a ret- rospective cohort study of 2869 ICH patients, of whom 234 had warfarin-associated ICH, the HR for recurrent ICH with resumption of warfarin was 5.6 (95% CI, 1.8 17.2) during a In another study of 48 patients with warfarin-associated ICH, of 23 patients who began taking warfarin again, 1 had a recurrent ICH and 2 subsequently had traumatic intracranial hemorrhage, whereas none who did not restart warfarin had recurrent intracranial bleeding.


In a cohort of 284 consecutive patients with warfarin-related ICH in the Registry of the Canadian Stroke Network, mortality rates were lower in those who restarted warfarin in the hospital: 31.9% versus 54.4% at 30 the rates of bleeding events were not increased.293 In a ret- rospective cohort study of 2869 ICH patients, of whom 234 had warfarin-associated ICH, the HR for recurrent ICH with resumption of warfarin was 5.6 (95% CI, 1.8 17.2) during a In another study of 48 patients with warfarin-associated ICH, of 23 patients who began taking warfarin again, 1 had a recurrent ICH and 2 subsequently had traumatic intracranial hemorrhage, whereas none who did not restart warfarin had recurrent intracranial bleeding. However, 5 patients in the nonrestarted group devel- oped thromboembolism (2 with stroke) compared with none in the group who restarted warfarin.295 Using a Markov deci- sion model and estimates for 1-year risk of ICH recurrence of 15% after lobar ICH versus 2.1% for deep ICH, Eckman found that withholding anticoagulation improved quality-adjusted life-year expectancy by 1.9 quality-adjusted life-years after lobar ICH and 0.3 quality-adjusted life-years after deep ICH, which led to the conclusion that anticoagula- tion should be avoided after lobar ICH but can be considered in patients with deep hemorrhage if the risk of thromboem- bolism is particularly high. CAA is an important cause of warfarin-associated lobar ICH in the elderly. The presence of microbleeds might increase the risk of ICH recurrence in warfarin users, although there are no prospective data.