derangements such as hypokalemia. Other potential adverse effects include circulatory overload, pulmonary edema, and a non-anion gap metabolic acidosis. Intravenous mannitol has also been shown to effectively lower ICP [53]. For initial therapy and for patients with evidence of life-threatening or progressive deterioration (including patients with herniation syndromes and those awaiting emergent surgery), we use mannitol 1 g/kg as a bolus via a central intravenous line. For other patients, we use mannitol at a dose of 0.25 to 0.5 g/kg every six hours. The goal of therapy is to force water to exit the brain while maintaining an adequate plasma volume [54]. The plasma osmolal gap should not be allowed to exceed 55 mosmol/kg; higher doses can cause reversible acute kidney injury. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Osmotic therapy and diuresis' and "Complications of mannitol therapy".) The osmolal gap peaks rapidly after mannitol infusion and typically normalizes from diuresis within hours. Therefore, the serum osmolality and electrolytes to calculate the osmolal gap should be drawn prior to subsequent doses to verify renal clearance of the previous dose as well as to monitor, prevent, and correct metabolic derangements and https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 12/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate acute kidney injury. Other potential adverse effects of mannitol therapy include hypotension and intravascular volume depletion [55]. (See "Complications of mannitol therapy" and "Serum osmolal gap".) Surgical approaches for selected patients The role of surgery in patients with acute ICH varies with the site of the bleed. Cerebrospinal fluid drainage for obstructive hydrocephalus Ventricular drainage of cerebrospinal fluid (CSF) with an external ventricular drain can help reduce elevated ICP for selected patients with hydrocephalus, particularly when associated with a decreased level of consciousness [5]. Obstructive hydrocephalus may occur when hemorrhage or mass effect obstructs CSF ventricular outflow. This may commonly be seen with ICH in the following locations: Thalamic hemorrhage (with third ventricle compression) Cerebellar hemorrhage (with fourth ventricle compression) (see 'Cerebellar hemorrhage' below) ICH with intraventricular extension (see "Intraventricular hemorrhage", section on 'External ventricular drain') For patients with neurologic deterioration who develop ventricular enlargement due to a large cerebellar hemorrhage, craniectomy with hematoma evacuation along with CSF drainage is the preferred intervention to treat both hydrocephalus and brainstem compression. In this setting, external drainage alone, without posterior fossa decompression, may create the theoretical risk of upward herniation of the cerebellar mass. (See 'Cerebellar hemorrhage' below.) For other ICH patients, a ventriculostomy catheter may be used with an external ventricular drainage to remove CSF and intraventricular blood to lower and monitor ICP. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Removal of CSF'.) The management of patients with intraventricular hemorrhage is discussed in greater detail separately. (See "Intraventricular hemorrhage", section on 'Management'.) Surgical decompression Cerebellar hemorrhage The indications for evacuation of a cerebellar hematoma depend on the ICH size and location, the time since onset, and the clinical status of the patient [5,56,57]. As examples, patients presenting acutely with a cerebellar hemorrhage greater than 3 3 cm in diameter (volume of at least 14 cm ) and brainstem compression will typically require https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 13/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate urgent surgical decompression of the cerebellum with craniectomy and hematoma evacuation. Some patients with smaller acute cerebellar hematomas may also warrant surgical decompression if they are deteriorating neurologically or have brainstem compression and/or hydrocephalus due to ventricular obstruction. Other patients with small, subacute cerebellar hematomas that do not exert mass effect on the brainstem may be managed medically with close monitoring. These recommendations are in broad agreement with published guidelines. Patients with cerebellar hemorrhage are at risk for rapid deterioration and fatal herniation due to the bony and tentorial confines of the posterior fossa. For patients selected for surgical decompression of a cerebellar hematoma, we suggest craniectomy and hematoma evacuation rather than ventriculostomy without posterior fossa decompression. External drainage alone may create the theoretical risk of upward herniation of the cerebellar mass. Observational evidence suggests that surgical evacuation of hematoma is associated with decreased mortality in patients with cerebellar hemorrhage. In a 2019 meta-analysis with individual patient data from four observational studies including 304 patients with cerebellar hemorrhage, surgical hematoma evacuation was associated with an increased probability of survival at three months compared with conservative treatment (78 versus 61 percent; absolute risk difference [ARD] 18.5 percent, 95% CI 13.8-23.2) [58]. This association was sustained at 12 months. The overall likelihood of a favorable functional outcome was similar for patients who had a hematoma evacuation or conservative treatment (31 versus 36 percent; ARD -3.7 percent, 3 95% CI -8.7 to 1.2). However, for patients with a hematoma volume of 12 cm , the likelihood of a favorable outcome was lower with surgical evacuation (31 versus 62 percent; ARD 35 percent). 3 By contrast, in the subgroup of patients with a hematoma volume of 15 cm , a favorable outcome was more likely with hematoma evacuation than with conservative treatment (75 versus 45 percent). Limitations to this meta-analysis include retrospective design, lack of randomization, small sample size for subgroup analyses, and a high number of patients on oral anticoagulant therapy at baseline, which impacts the generalizability of the findings. Supratentorial hemorrhage Surgical hematoma evacuation for supratentorial ICH is controversial because the potential benefits of hematoma evacuation may be offset by surgical morbidity in many cases. The subset of patients who may benefit from surgical treatment have not been conclusively defined [5]. We reserve surgical therapy for patients with life-threatening mass effect from supratentorial ICH, individualizing treatment decisions based on assessments of prognosis with and without surgical therapy. Limited data suggest that supratentorial hematoma evacuation might reduce mortality for patients who are comatose, have a large hematoma with significant midline shift, or have elevated ICP refractory to medical management [5]. Supratentorial decompression with https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 14/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate hematoma evacuation and/or decompressive hemicraniectomy may reduce mortality but not improve functional outcomes. It should only be considered as a life-saving procedure to treat refractory increases in ICP; even in these instances, decisions should be addressed on an individual basis: Surgery should not be considered for patients who are either fully alert or deeply comatose. Patients with intermediate levels of arousal (obtundation-stupor) are more appropriate candidates. Features that support performing surgery include a recent onset of hemorrhage, ongoing clinical deterioration, and location of the hematoma near the cortical surface. Features in favor of less aggressive therapy include serious concomitant medical problems, advanced age, stable clinical condition, remote onset of hemorrhage, and inaccessibility of the hemorrhage. Open craniotomy with craniectomy is the most widely studied surgical technique in patients with supratentorial ICH. Other methods using craniotomy include endoscopic hemorrhage aspiration, use of fibrinolytic therapy to dissolve the hematoma followed by aspiration, and CT- guided stereotactic aspiration (ie, minimally invasive surgery) [5,59-62]. The role of surgery for patients with supratentorial ICH was evaluated in the International Surgical Trial in IntraCerebral Hemorrhage (STICH) trial. Among 1033 patients with supratentorial ICH, those assigned to early (median time to surgery was 30 hours after hemorrhage onset) surgical hematoma evacuation had similar rates of favorable outcome compared with those assigned initial conservative treatment (24 versus 26 percent; odds ratio [OR] 0.89, 95% CI 0.66-1.19) [63]. There was a trend toward favorable outcome among patients assigned to early surgery who had craniotomy as opposed to alternate techniques, and in those with hematoma located 1 cm or less from the cortical surface. However, substantial cross-over (26 percent of patients initially assigned to conservative medical management underwent surgical evacuation) limits the strength of these results [64-66]. Subsequently, the STICH II trial evaluated the role of early surgery for 601 conscious patients presenting with a supratentorial ICH within 1 cm of the cortical surface. Unfavorable functional outcome at six months was similar in those assigned surgery versus conservative treatment (59 versus 62 percent; OR 0.86, 95% CI 0.62-1.2) [67]. However, there was a trend toward reduced mortality among those assigned early surgery (18 versus 24 percent; OR 0.71, 95% CI 0.48-1.06). Limitations in interpreting the results of this study include the clinical and imaging status of the patients selected for treatment (conscious, without intraventricular extension), as well as a high https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 15/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate crossover rate; 21 percent of patients assigned to conservative therapy did undergo surgery [68]. In a systematic review of individual patient data of 15 trials including more than 3000 patients with ICH, surgery was associated with reduced mortality (OR 0.74, 95% CI 0.64-0.86) and a trend toward improved functional outcomes (OR 0.78, 95% CI 0.59-1.02). This benefit appeared highest among those with poorer prognosis on presentation, those who deteriorated after presentation, and those with superficial ICH and no intraventricular extension [67,69]. However, heterogeneity in patient selection, ICH size, and surgical techniques limit generalizability of these results. Salvage therapies Salvage therapies may be used when other therapies to control elevated ICP are insufficient to improve symptoms or reduce ICP. They may be used in conjunction with or in place of other therapies. Hyperventilation causes a rapid lowering of ICP by inducing cerebral vasoconstriction to reduce cerebral blood volume. The effect of hyperventilation on ICP only lasts for a few hours. We generally reserve hyperventilation for the urgent treatment of a patient with acute brain herniation until more definitive therapies can be implemented. This may include deteriorating patients awaiting either urgent surgery or central venous access for osmotherapy. We aim for a target partial pressure of carbon dioxide (PaCO ) goal of 30 to 2 35 mmHg [47]. More aggressive hyperventilation (ie, a PaCO of 26 to 30 mmHg) may 2 result in brain ischemia and worse outcomes [70]. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Hyperventilation'.) Pharmacologic coma acts by reducing cerebral metabolism, which lowers cerebral blood flow and reduces ICP. Barbiturate coma, most often induced with pentobarbital, is of variable benefit for the treatment of elevated ICP from a variety of causes and is associated with a high rate of severe side effects, especially arterial hypotension [71]. Pentobarbital is typically loaded at 5 to 20 mg/kg and infused at 1 to 4 mg/kg per hour. Continuous monitoring with electroencephalography is suggested during high-dose barbiturate treatment, with the dose titrated to a burst-suppression pattern of electrical activity. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Barbiturates'.) Propofol is an alternative sedative agent used to reduce intracranial pressure. Unlike pentobarbital, it has a short half-life and may be more easily titrated or temporarily held to permit arousal for serial neurologic examinations. Propofol is given intravenously to ventilated patients with a loading dose of 1 to 3 mg/kg and continued as an infusion with titration to achieve the desired sedation level, typically at 5 to 50 mcg/kg per minute, with a https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 16/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate maximum dose of 200 mcg/kg per minute [47]. Hypotension is a common adverse effect of propofol infusion; treatment involves intravenous fluids and/or vasopressors to maintain cerebral perfusion pressure. Propofol infusion syndrome is a rare complication associated with high doses (>4 mg/kg per hour or >67 mcg/kg per minute) and prolonged use (>48 hours), though it has been reported with short-term infusions. It is characterized by acute refractory bradycardia, metabolic acidosis, cardiovascular collapse, rhabdomyolysis, hyperlipidemia, renal failure, and hepatomegaly. (See "Sedative-analgesic medications in critically ill adults: Properties, dose regimens, and adverse effects", section on 'Propofol'.) Neuromuscular blockade may be used to reduce ICP in patients who are not responsive to analgesia and sedation alone, as muscle activity can contribute to increased ICP by raising intrathoracic pressure, thereby reducing cerebral venous outflow. Drawbacks of neuromuscular blockade include an increased risk of pneumonia and sepsis. In addition, the ability to evaluate the neurologic status is lost once the patient is paralyzed. (See "Neuromuscular blocking agents in critically ill patients: Use, agent selection, administration, and adverse effects".) Hypothermia can reduce ICP through reduction in cerebral blood flow and metabolism. The benefit for patients with acute ICH has not been demonstrated. Adverse effects include electrolyte abnormalities, pneumonia, coagulopathy, and cardiac arrhythmias. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Therapeutic hypothermia'.) SEIZURE MANAGEMENT Patients with acute ICH are at risk for early seizures (within one to two weeks of ICH) and late (post-stroke) seizures. Early seizures may be self-limited, attributed to transient neurochemical changes associated with the acute ICH. By contrast, late seizures are felt to be due to structural changes from gliosis and are likelier to become recurrent, as poststroke epilepsy ( 2 unprovoked seizures occurring after the acute phase) [72]. For patients with acute ICH who have a seizure, immediate intravenous antiseizure medication treatment should be initiated to reduce the risk of a recurrent seizure [5]. (See "Evaluation and management of the first seizure in adults".) The optimal duration of antiseizure medication therapy for patients with ICH and a seizure is uncertain. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 17/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate For patients who have an early seizure (<14 days from ICH onset), we typically continue treatment for several days and then wean when patients are clinically stable if seizures do not recur. For patients who have a late seizure (>14 days from ICH onset), we typically continue long-term seizure therapy. (See "Overview of the management of epilepsy in adults", section on 'Poststroke seizures'.) The choice of the initial antiseizure medication is guided by medical comorbidities, drug interactions, side effect drug profile, and contraindications ( table 8). (See "Initial treatment of epilepsy in adults".) For patients with acute ICH who do not have a seizure, we do not start antiseizure medication prophylaxis, in agreement with guidelines from the American Heart Association [5]. Early seizures are more common than poststroke epilepsy [73]. In various studies, the risk of seizure within two weeks of acute ICH was 8 to 15 percent but may be up to approximately 30 percent when including patients with electrographic (nonconvulsive) seizures captured by routine continuous electroencephalogram (EEG) monitoring [73-75]. The incidence of poststroke epilepsy at one year was 2.6 to 4 percent in cohort studies but may be higher with longer follow- up [73,74,76]. Antiseizure medications may reduce the rate of early seizures in patients with lobar ICH but have not been shown to improve functional outcome or reduce the rate of poststroke epilepsy [74,77]. In a small trial of 50 patients with ICH, patients were assigned to prophylactic use of levetiracetam or placebo within 24 hours of ICH onset [78]. The rate of electrographic seizures within the first 72 hours was lower among the levetiracetam group (16 versus 43 percent). However, the seizure rate at 1 and 12 months and the functional outcomes were similar between groups. In a 2019 systematic review and meta-analysis evaluating antiseizure medication prophylaxis, antiseizure medication prophylaxis was not associated with a reduction in disability, mortality, or incident seizures [79]. The one trial included in the meta-analysis found that seizure prophylaxis with valproate starting immediately after ICH and continued for one month reduced the rate of early seizures but did not reduce incident seizures at one year [80]. Some other studies have found that prophylactic antiseizure medications were associated with worse outcome in patients with acute ICH [81,82]. PREVENTION AND MANAGEMENT OF MEDICAL COMPLICATIONS https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 18/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Patients with acute ICH are at risk for medical complications due to comorbid medical conditions as well as from immobility related to the neurologic injury. These complications may prolong hospitalization, delay recovery, and increase the risk of in-hospital and long-term mortality [83,84]. (See "Complications of stroke: An overview".) Specific interventions to prevent or manage common medical complications for patients with acute ICH include [85,86]: Prevention of aspiration Dysphagia is a common complication of ICH and a major risk factor for aspiration pneumonia. Patients with acute ICH at risk for aspiration should be given no oral nutrition (initial nil per os [NPO] status) until swallowing function is evaluated. For patients unable to take oral nutrition due to dysphagia from acute ICH, we give enteral nutrition and maintain the head of the bed positioned up at 30 to 45 degrees, whenever possible. (See "Complications of stroke: An overview", section on 'Dysphagia' and "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Preventing aspiration'.) Prevention of venous thromboembolism Patients hospitalized with an acute illness are at risk for venous thromboembolism and those with acute ICH are also at risk due to immobility. Intermittent pneumatic compression should be started on the first day of hospital admission for patients with ICH and impaired mobility [5]. We add chemical prophylaxis for most patients one to four days after ICH stability is documented. An exception would be some patients with elevated intracranial pressure being evaluated for urgent surgery for whom chemical prophylaxis may be temporarily withheld. In a 2022 meta-analysis of 28 studies that included nearly 3700 patients with acute ICH, chemical prophylaxis was associated with a lower rate of deep venous thrombosis than controls (3.4 versus 14.7 percent) [87]. Treatment was typically started within four days of ICH onset and continued for 10 to 14 days. The rate of hematoma expansion was similar between groups (2.4 versus 2.8 percent). (See "Prevention and treatment of venous thromboembolism in patients with acute stroke", section on 'Approach in intracerebral hemorrhage' and "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".) Prevention of pressure-induced skin injury Patients with impaired mobility are at risk for pressure-induced skin injuries, including ulcers. Strategies to reduce skin injury include cushioned bed surfaces, frequent repositioning, and proper skin care. (See "Prevention of pressure-induced skin and soft tissue injury".) Isotonic fluid replacement Isotonic fluids, such as normal saline, should be used for maintenance and replacement fluids in the acute setting. Hypotonic fluids are https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 19/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate contraindicated in the first several days after ICH as they may exacerbate cerebral edema and intracranial pressure. We also avoid hypervolemia as it may worsen cerebral edema. (See 'Intracranial pressure management' above and "Maintenance and replacement fluid therapy in adults".) Fever management Fever is common in acute ICH and may frequently be due to systemic infections such as aspiration pneumonia. Central (noninfectious) fever may also occur in acute ICH and has been associated with large hemorrhages and those with intraventricular extension [88]. Fever has been associated with poor outcomes in patients with ICH [89]. Sources of fever should be investigated and treated, and fevers should be treated with antipyretic medications. We do not use prophylactic antibiotics as they have not been shown to improve clinical outcomes [90]. (See "Initial assessment and management of acute stroke", section on 'Fever'.) Management of hyperglycemia and hypoglycemia Hyperglycemia after stroke is associated with adverse outcomes. We treat hyperglycemia in agreement with guidelines [5]. (See "Initial assessment and management of acute stroke", section on 'Hyperglycemia' and "Glycemic control in critically ill adult and pediatric patients".) Hypoglycemia should be avoided as it may cause neurologic deficits acutely and lead to permanent neurologic injury if uncorrected. (See "Initial assessment and management of acute stroke", section on 'Hypoglycemia' and "Glycemic control in critically ill adult and pediatric patients", section on 'Our approach'.) Avoiding routine gastric acid suppression Patients with acute ICH are at high risk of aspiration pneumonia due to dysphagia. We avoid routine use of agents to suppress gastric acid (ie, proton pump inhibitors, histamine-2 receptor antagonists) because they are associated with an increased risk of hospital-acquired pneumonia, Clostridioides di cile infection, and other enteric infections. We reserve gastrointestinal (GI) stress ulcer prophylaxis for high-risk patients, such as those on mechanical ventilation or with a history of recent GI bleeding. (See "Complications of stroke: An overview", section on 'Gastrointestinal bleeding' and "Stress ulcers in the intensive care unit: Diagnosis, management, and prevention", section on 'High-risk patients'.) EARLY PROGNOSIS The main determinants of functional outcome and mortality in the first 90 days after acute ICH include clinical risk factors and specific features seen on neuroimaging. The long-term prognosis https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 20/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate among survivors of ICH is discussed separately. (See "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Long-term prognosis'.) Functional outcome may be assessed at different times after the ICH and using varying performance thresholds or clinical scoring tools. The modified Rankin Scale (mRS) is frequently used ( table 9). In several trials, patients with ICH achieving a score of 0 to 3 have been described as having a good functional outcome; poor outcome included those scoring 4 to 6. Mortality rates In various studies, the 30-day mortality rate from ICH ranged from 32 to 52 percent [91-98]; one-half of these deaths occurred within the first two days [94,99,100]. Some evidence suggests that the mortality rate has decreased since the early 2000s, possibly because of better supportive care and secondary prevention [101]. However, this mortality reduction may be partially attributed to an increased proportion of survivors with disability [102]. Mortality rates differ by clinical features and underlying etiology. Mortality among patients with lobar ICH, most commonly associated with cerebral amyloid angiopathy, has been reported from 10 to 30 percent, varying with patient comorbidities and ICH size [103,104]. Several studies suggest that hemorrhage due to vascular malformations is associated with lower mortality than other causes of ICH [105-108]. (See 'Clinical risk factors' below and 'Imaging risk factors' below.) [92,109] Risk factors for poor outcomes Several risk factors have been associated with poor functional outcome and mortality in patients with acute ICH. They include clinical risk factors and imaging features associated with the ICH. Clinical risk factors Increasing age Advanced age is associated with a reduced likelihood of good functional outcome and an elevated risk of early mortality among patients with acute ICH [110,111]. Severe impairment on baseline exam or early neurologic deterioration Patients with baseline functional impairment and those with more severe impairment from the ICH on initial clinical examination, as measured by the Glasgow Coma Scale (GCS) score, have elevated mortality rates [99,111]. (See 'Clinical prediction scores' below.) Early neurologic deterioration within 48 hours after ICH onset is common and is associated with a poor prognosis. Potential mechanisms include hemorrhage enlargement, development of hydrocephalus, perilesional edema, and the inflammatory response to the hemorrhage [112-114]. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 21/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Early withdrawal of support The early use of "do not attempt resuscitation" (DNAR) orders, along with decisions to limit aggressive treatments and/or withdraw medical care may negatively influence outcome in patients with ICH and may even invalidate some prognostic models that do not control for this variable [9,11,115-118]. (See 'Initial aggressive care' above.) Preceding antithrombotic use In the setting of an acute ICH, patients with preceding use of anticoagulants or antiplatelet agents appear to have larger initial hematoma volumes or greater hemorrhage enlargement leading to worse outcomes [119-121]. Patients on oral anticoagulant therapy have a mortality rate of 38 to 73 percent after ICH [119,122-124]. These rates appear to be three to four times higher than in those not on anticoagulation therapy [119,122]. This increased risk may be mitigated but not eliminated by rapid reversal of anticoagulation [125]. (See "Reversal of anticoagulation in intracranial hemorrhage".) Patients with direct oral anticoagulant (DOAC)-associated ICH may have better outcomes than those with warfarin-associated ICH. In some small observational studies, patients with DOAC-associated ICH were found to have smaller ICH volumes and better clinical outcomes than those with warfarin-associated ICH [126,127]; other studies failed to show this difference [128,129]. However, in a large registry-based cohort study including nearly 20,000 patients with anticoagulation-associated ICH, the risk of in-hospital mortality or discharge to hospice was lower in those taking a DOAC than those taking warfarin (38 versus 43 percent) [124]. Additionally, the rate of disability or dependence at discharge was lower and the rate of discharge to home was higher for patients with DOAC-associated ICH than those with warfarin-associated ICH and similar to those taking no anticoagulation at the time of the ICH. Antiplatelet use is associated with hematoma enlargement and worse prognosis after ICH in some [120,122,130-132] but not all [24,123,133-136] studies. A 2010 systematic review of 25 cohort studies concluded that prior antiplatelet use was associated with increased mortality (odds ratio [OR] 1.3) but not poor functional outcome after ICH [137]. In a 2021 large observational study of more than 13,000 patients with ICH, the 90-day mortality rate was 44 percent among both ICH patients taking anticoagulants and those taking antiplatelets compared with 26 percent among those not taking antithrombic medications at the time of the ICH [138]. A good functional outcome at 90-days was achieved by 27 percent of patients taking anticoagulants and 25 percent of those taking antiplatelets compared with 40 percent of those on no antithrombotic therapy. Patients taking antithrombotic medications were older and had more comorbidities. https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 22/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Combination antithrombotic therapy has been associated with a worse prognosis and larger initial ICH volume than single-agent therapy. In a pooled analysis of three German observational studies including 3545 patients with ICH, a favorable functional outcome at three months was less frequent in those taking warfarin and an antiplatelet compared with those taking warfarin alone (24 versus 32 percent) [139]. Similarly, the rates of achieving a favorable outcome were numerically lower for patients taking a DOAC and antiplatelet compared with those taking a DOAC alone (21 versus 33 percent), although this difference was not statistically significant. In addition, patients taking an antiplatelet agent and warfarin or a DOAC had larger initial ICH volumes than those taking either anticoagulant alone (warfarin and antiplatelet OR 1.8, 95% CI 1.2-2.7; DOAC and antiplatelet OR 3.75, 95% CI 1.13-12.44). There was a trend toward larger ICH volumes in those on dual- versus single-antiplatelet therapy. Other laboratory markers Multiple laboratory test results have been associated with poor outcome in patients with acute ICH. Several studies have identified that an elevated admission blood glucose may be associated with a poor outcome [85,91,140-145]. Additionally, elevated C-reactive protein levels, lower serum levels of low-density lipoprotein cholesterol (LDL-C), and lower total cholesterol have been linked to a risk of neurologic deterioration and mortality in patients with acute ICH [146,147]. Imaging risk factors Initial ICH volume The ICH volume on initial head computed tomography (CT) scan at admission may be a particularly important prognostic indicator [99,107,111,148]. In a study of 188 patients, the initial ICH volume was associated with 30-day mortality rate. Among patients with a GCS score 9, the probability of death by 30 days was 19 percent when the ICH volume was 30 mL and 75 percent when the ICH volume was 60 mL [99]. The method for calculating ICH volume from head CT is discussed separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Estimating hemorrhage volume'.) ICH location Patients with ICH located in the infratentorial brainstem or cerebellar regions have worse prognosis than those with supratentorial ICH [149]. Intraventricular extension Intraventricular and subarachnoid extension of ICH may be present on initial evaluation or occur subsequently. Data from a number of studies suggest that extension of blood into the ventricles and/or subarachnoid space is an independent predictor of poor outcome in patients with spontaneous ICH [107,150-156]. One of the largest of these reports evaluated 406 patients with ICH, 45 percent of whom had https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 23/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate intraventricular extension of hemorrhage [154]. After controlling for age and ICH volume, a poor outcome at discharge (defined as an mRS score of 4 to 6 ( table 9)) was significantly more likely in patients with intraventricular hemorrhage than in those without intraventricular hemorrhage (OR 2.25, 95% CI 1.40-3.64). Intraventricular hemorrhage is discussed in detail separately. (See "Intraventricular hemorrhage".) Hematoma shape and features ICH shape irregularity and heterogeneity on head CT and the spot sign on CT angiography suggest ongoing bleeding or risk of hematoma expansion and have been associated with poor functional outcome ( image 1 and image 2) [157]. These are discussed separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Predicting hemorrhage expansion'.) Hematoma growth Hematoma growth, particularly within the first 24 hours, is also an independent predictor of mortality and poor outcome [112,157,158]. In a meta-analysis of 218 patients with spontaneous ICH who had a head CT scan within three hours of onset and follow-up head CT within 24 hours, for each 10 percent increase in hematoma volume, patients were 5 percent more likely to die (hazard ratio 1.05, 95% CI 1.03-1.08) and 16 percent less likely to have a good outcome as measured by the modified Rankin scale (cumulative OR 0.84, 95% CI 0.75-0.92) [25]. Risk factors for hematoma enlargement (eg, contrast extravasation or "spot sign" on CT angiography, hemorrhage volume on baseline imaging, antithrombotic therapy) are discussed separately. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Predicting hemorrhage expansion'.) Other factors Other imaging such as extensive white matter lesions on CT or magnetic resonance imaging (MRI) have been associated with poor outcome and mortality after ICH in various studies [159-161]. Some studies have found that a significant number of patients with ICH have acute ischemic lesions on diffusion-weighted MRI sequence that are not contiguous to the hematoma [162]. The implication for these findings for prognosis is as yet undefined, although one study found that the presence of these lesions was associated with increased odds of death and disability [163]. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Mechanisms of brain injury'.) https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 24/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate Clinical prediction scores Multiple clinical scores have been developed to help approximate the risk of 30-day mortality or likelihood of good functional recovery for patients with acute ICH. These clinical scoring systems can be used in the acute setting to assist clinicians, patients, and caregivers gauge the expected severity of the ICH. They should be used along with overall clinical judgement, incorporating patient values and preferences to guide treatment decisions or limitations of care in the acute settings. Patients with acute ICH should be offered full treatment, and new limitations of care should be delayed at least until the second hospital day for most patients. (See 'Initial aggressive care' above.) ICH score A simple six-point clinical and radiographic grading scale called the ICH score has been devised to predict 30-day mortality after ICH [149]. This scale incorporates several clinical components that may be independent predictors of outcome ( table 10). The ICH score is determined by adding the score from each component as follows: GCS ( - - - table 7) score at presentation 3 to 4 (= 2 points) 5 to 12 (= 1 point) 13 to 15 (= 0 points) ICH volume on initial imaging - 3 30 cm (= 1 point) 3 <30 cm (= 0 points) Intraventricular extension of ICH - Present (= 1 point) Absent (= 0 points) Infratentorial origin of ICH - Yes (= 1 point) No (= 0 points) Age - - 80 (= 1 point) <80 (= 0 points) Thirty-day mortality rates increased steadily with ICH score. The mortality rates were: ICH score 1 (13 percent) ICH score 2 (26 percent) https://www.uptodate.com/contents/spontaneous-intracerebral-hemorrhage-acute-treatment-and-prognosis/print 25/79 7/5/23, 12:24 PM Spontaneous intracerebral hemorrhage: Acute treatment and prognosis - UpToDate ICH score 3 (72 percent) ICH score 4 (97 percent) ICH score 5 (100 percent) No patient with an ICH score of 0 died, and none had a score of 6 in the initial cohort. The ICH score has been validated by multiple analyses [164-166]. A modified ICH score using the National Institutes of Health Stroke Scale (NIHSS) score ( table 11) in place of the GCS score performed similar to the original ICH score for mortality prediction but was a better predictor of outcome in one study [164]. FUNC score The FUNC score ( table 12) rates prognosis for good functional (neurologic) outcome at 90 days using an 11-point scale [167]. Components include age, ICH volume, ICH location, GCS score, and history of prior cognitive impairment. The proportion of patients who achieved functional independence increased steadily with FUNC score [167]. In the study cohort, functional independence rates were: FUNC scores 0 to 4 (none) FUNC scores 5 to 7 (13 percent) FUNC score 8 (42 percent) FUNC scores 9 to 10 (66 percent) FUNC score 11 (82 percent) These results have also been independently validated [168]. One study found that GCS score at presentation alone is a useful predictor of 30-day mortality [169]. However, the GCS score is insufficient for clinical prognostication after ICH because some patients with acute ICH and reversible causes to stupor may have a low GCS score at admission but still achieve a good functional outcome. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".) INFORMATION FOR PATIENTS