Preadmission statin use does not improve functional outcomes or prevent delayed ischemic events in patients with spontaneous subarachnoid hemorrhage.

STUDY OBJECTIVE: To determine whether preadmission statin use in patients with spontaneous subarachnoid hemorrhage (SAH) is associated with improved functional outcomes and a lower incidence of delayed cerebral ischemic events compared with statin-naive patients with SAH. DESIGN: Prospective cohort study. SETTING: Neurosciences intensive care unit of a tertiary care hospital. PATIENTS: A total of 295 consecutive patients with SAH admitted between March 2006 and May 2013 who had complete medication histories; of these patients, 41 reported taking a statin prior to admission, and 254 were statin naive. INTERVENTION: All patients received clinical management for SAH according to hospital protocol for standard care that included acute statin therapy with enteral pravastatin 40 mg/day on hospital day 1 for up to 21 days. MEASUREMENTS AND MAIN RESULTS: Functional outcomes were assessed by using the modified Rankin Scale (mRS) at 14 days, 28 days, and 3 months. Delayed cerebral ischemia was assessed by using clinical evaluation and computed tomography. Patients taking statins prior to admission were more likely to have a history of diabetes mellitus, hypertension, coronary artery disease, and stroke. No significant difference in favorable neurologic outcome (mRS score 0-3) at 3 months was observed between the preadmission statin group compared with the statin-naive group (56.3% vs 72.4%, p=0.095). In multivariate logistic regression analysis, only age, severity of rupture, and coronary artery disease were less likely to predict a favorable neurologic outcome. No significant difference in the development of delayed cerebral ischemic events was observed between groups (p=0.48). CONCLUSION: Statin use prior to admission did not improve functional outcomes or prevent delayed cerebral ischemic events in patients with SAH. Age, severity of rupture, and coronary artery disease were less likely to predict a favorable neurologic outcome at 3 months after discharge.

Subarachnoid extension of primary intracerebral hemorrhage is associated with fevers.

BACKGROUND: Extension of hemorrhage into the subarachnoid space in primary intracerebral hemorrhage (ICH) has recently been associated with poor outcomes, although the mechanisms underlying that association are uncertain. The objectives of this study are to confirm the association between fever and poor outcomes after ICH, and to determine whether subarachnoid hemorrhage extension (SAHE) is associated with fevers. METHODS: Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. SAHE was identified on imaging by blinded expert reviewers. Patient temperature was recorded hourly, and we defined febrile as any recorded temperature >38 °C within the first 14 days. Regression models were developed to test whether fever was associated with poor outcome and whether the occurrence of SAHE was a predictor of fever. RESULTS: Of the 235 patients studied, 39.7 % had SAHE and 58 % had fever. Fever was associated with higher modified Rankin scores at 3 months (odds ratio, OR 1.8 [1.04-3.12], p = 0.04) after adjustment for ICH score. SAHE was a predictor of fevers (OR 1.82 [95 % confidence interval 1.02-3.24], p = 0.04) after adjustment for ICH score, and remained significant after adjustment for other confounders like pneumonia identified in the univariate analysis. CONCLUSIONS: Our data confirm the deleterious effect of fever on the outcome of patients with ICH and show that SAHE is an independent predictor of fever after ICH. SAHE may provoke dysfunctional thermoregulation similar to what is observed after aneurysmal subarachnoid hemorrhage, creating mechanistic pathway between SAHE and poor functional outcomes.

Intracerebral hemorrhage and delirium symptoms. Length of stay, function, and quality of life in a 114-patient cohort.

RATIONALE: The prognostic significance of delirium symptoms in intensive care unit (ICU) patients with focal neurologic injury is unclear. OBJECTIVES: To determine the relationship between delirium symptoms and subsequent functional outcomes and quality of life (QOL) after intracerebral hemorrhage. METHODS: We prospectively enrolled 114 patients. Delirium symptoms were routinely assessed twice daily using the Confusion Assessment Method for the ICU by trained nurses. Functional outcomes were recorded with modified Rankin Scale (scored from 0 [no symptoms] to 6 [dead]), and QOL outcomes with Neuro-QOL at 28 days, 3 months, and 12 months. MEASUREMENTS AND MAIN RESULTS: Thirty-one (27%) patients had delirium symptoms ("ever delirious"), 67 (59%) were never delirious, and the remainder (14%) had persistent coma. Delirium symptoms were nearly always hypoactive, were detected mean 6 days after intracerebral hemorrhage presentation, and were associated with longer ICU length of stay (mean 3.5 d longer in ever vs. never delirious patients; 95% confidence interval, 1.5-8.3; P = 0.004) after correction for age, admit National Institutes of Health (NIH) Stroke Scale, and any benzodiazepine exposure. Delirium symptoms were associated with increased odds of poor outcome at 28 days (odds ratio, 8.7; 95% confidence interval, 1.4-52.5; P = 0.018) after correction for admission NIH Stroke Scale and age, and with worse QOL in the domains of applied cognition-executive function and fatigue after correcting for the NIH Stroke Scale, age, benzodiazepine exposure, and time of follow-up. CONCLUSIONS: After focal neurologic injury, delirium symptoms were common despite low rates of infection and sedation exposure, and were predictive of subsequent worse functional outcomes and lower QOL.

Predictors of 30-day readmission after intracerebral hemorrhage: a single-center approach for identifying potentially modifiable associations with readmission.

OBJECTIVE: To determine whether patient's demographics or severity of illness predict hospital readmission within 30 days following spontaneous intracerebral hemorrhage, to identify readmission associations that may be modifiable at the single-center level, and to determine the impact of readmission on outcomes. DESIGN: We collected demographic, clinical, and hospital course data for consecutive patients with spontaneous intracerebral hemorrhage enrolled in an observational study. Readmission within 30 days was determined retrospectively by an automated query with manual confirmation. We identified the reason for readmission and tested for associations between readmission and functional outcomes using modified Rankin Scale (a validated functional outcome measure from 0, no symptoms, to 6, death) scores before intracerebral hemorrhage and at 14 days, 28 days, and 3 months after intracerebral hemorrhage. SETTING: Neurologic ICU of a tertiary care hospital. PATIENTS: Critically ill patients with spontaneous intracerebral hemorrhage. INTERVENTIONS: Patients received standard critical care management for intracerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Of 246 patients (mean age, 65 yr; 51% female), 193 patients (78%) survived to discharge. Of these, 22 patients (11%) were readmitted at a median of 9 days (interquartile range, 4-15 d). The most common readmission diagnoses were infections after discharge (n = 10) and vascular events (n = 6). Age, history of stroke and hypertension, severity of neurologic deficit at admission, Acute Physiology and Chronic Health Evaluation score, ICU and hospital length of stay, ventilator-free days, days febrile, and surgical procedures were not predictors of readmission. History of coronary artery disease was associated with readmission (p = 0.03). Readmitted patients had similar modified Rankin Scale and severity of neurologic deficit at 14 days but higher (worse) modified Rankin Scale scores at 3 months (median [interquartile range], 5 [3-6] vs 3 [1-4]; p = 0.01). CONCLUSIONS: Severity of illness and hospital complications were not associated with 30-day readmission. The most common indication for readmission was infection after discharge, and readmission was associated with worse functional outcomes at 3 months. Preventing readmission after intracerebral hemorrhage may depend primarily on optimizing care after discharge and may improve functional outcomes at 3 months.

Infarct volume predicts delayed recovery in patients with subarachnoid hemorrhage and severe neurological deficits.

BACKGROUND: Recovery is common after subarachnoid hemorrhage (SAH), even in patients who are severely disabled at hospital discharge. Little is known about predictors of late recovery in such patients, even though such knowledge may influence treatment decisions. We hypothesized that cerebral infarction volume would be associated with 3 months outcomes in patients who are severely disabled at 14 days. METHODS: We prospectively identified consecutive aneurysmal SAH patients, documented the development of cerebral infarction, and ascertained the modified Rankin Scale (mRS) at 14 days and 3 months. We included patients with mRS 4 or 5 and NIH Stroke Scale (NIHSS) at least 8 on hospital day 14 (i.e., severe neurologic impairment) and calculated infarct volume in a semi-automated fashion using CT imaging. We explored outcome determinants with ordinal regression. RESULTS: At 14 days, 66 patients were severely disabled, 65 (98.5 %) of whom had mRS of 5; the median NIHSS was 21 [14-24]. At 3 months, 20 (32.8 %) of the 61 patients with known outcomes were independent. Larger infarction volumes were associated with death (20.4 vs. 0.85 mL, P = 0.02). In ordinal regression, increased infarct volume was associated with the worse mRS after correction for WFNS grade, age, and withdrawal of life support (OR 1.01 per mL of infarct, 95 % CI 1.01-1.03, P = 0.01). CONCLUSIONS: After SAH, even with severe neurological injury at 14 days, good recovery is frequent and is associated with lower infarction volume. These data may help clinicians inform surrogate decision makers as they plan the future care of such severely disabled patients.

Surveillance neuroimaging and neurologic examinations affect care for intracerebral hemorrhage.

OBJECTIVE: We tested the hypothesis that surveillance neuroimaging and neurologic examinations identified changes requiring emergent surgical interventions in patients with intracerebral hemorrhage (ICH). METHODS: Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. Patients were managed in a neuroscience intensive care unit with a protocol that included serial neuroimaging at 6, 24, and 48 hours, and hourly neurologic examinations using the Glasgow Coma Scale and NIH Stroke Scale. We evaluated all cases of craniotomy and ventriculostomy to determine whether the procedure was part of the initial management plan or occurred subsequently. For those that occurred subsequently, we determined whether worsening on neurologic examination or worsened neuroimaging findings initiated the process leading to intervention. RESULTS: There were 88 surgical interventions in 84 (35%) of the 239 patients studied, including ventriculostomy in 52 (59%), craniotomy in 21 (24%), and both in 11 (13%). Of the 88 interventions, 24 (27%) occurred subsequently and distinctly from initial management, a median of 15.9 hours (8.9-27.0 hours) after symptom onset. Thirteen (54%) were instigated by findings on neurologic examination and 11 (46%) by neuroimaging. Demographics, severity of hemorrhage, and hemorrhage location were not associated with delayed intervention. CONCLUSIONS: More than 25% of surgical interventions performed after ICH were prompted by delayed imaging or clinical findings. Serial neurologic examinations and neuroimaging are important and effective surveillance techniques for monitoring patients with ICH.

Delayed intraventricular hemorrhage is common and worsens outcomes in intracerebral hemorrhage.

OBJECTIVE: To evaluate the incidence, characteristics, and clinical consequences of delayed intraventricular hemorrhage (dIVH). METHODS: Patients with primary intracerebral hemorrhage (ICH) were enrolled into a prospective registry between December 2006 and February 2012. Patients were managed, and serial neuroimaging obtained, per a structured protocol. Initial and delayed IVH were identified on imaging, along with ICH volumes, with outcomes blinded. Multivariate models were developed to test whether the occurrence of dIVH was a predictor of functional outcomes independent of known predictors, including the ICH score elements and ICH growth. RESULTS: A total of 216 patients were studied, and 104 (48%) had IVH on initial imaging. Of the 112 with no IVH, 23 (21%) subsequently developed IVH. Emergent surgical intervention, mostly ventriculostomy placement, was required after discovery of dIVH in 10 (43%) of these 23. In multivariate models adjusting for all elements of the ICH score and hematoma growth, dIVH was an independent predictor of death at 14 days (p = 0.015) and higher modified Rankin Scale scores at 3 months (all p = 0.037). The effect of dIVH remained significant in a secondary analysis that adjusted for all other variables significant in the univariate analysis. CONCLUSIONS: Similar to hematoma expansion dIVH is independently associated with death and poor outcomes. Because IVH is easily detected by serial neuroimaging and often requires emergent surgical intervention, monitoring for dIVH is recommended.

Leukoaraiosis on magnetic resonance imaging correlates with worse outcomes after spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is associated with dementia, ischemic stroke, and intracerebral hemorrhage (ICH), but there are few data on how LA might impact outcomes after acute ICH. We tested the hypothesis that the severity of LA on magnetic resonance imaging is related to worse functional outcomes after spontaneous ICH. METHODS: We prospectively identified patients with spontaneous acute ICH. LA was identified on magnetic resonance imaging and its severity was graded using the Fazekas method to include a score for the deep white matter and periventricular regions. Outcomes were obtained at 14 days, 28 days, and 3 months with the modified Rankin Scale (mRS; a validated scale from 0 [no symptoms] to 6 [dead]) and analyzed with multivariate logistic regression. RESULTS: Higher Fazekas total (periventricular plus deep white matter) score correlated with higher mRS score at 14 days (P=0.02) and 3 months (P=0.02). This relationship was driven by the periventricular score, for which higher score (more severe disease) correlated with higher National Institute of Health Stroke Scale at 14 days (P=0.03), and higher mRS score at 14 days (P<0.001), 28 days (P=0.004), and 3 months (P=0.005). A higher (more severe) Fazekas periventricular score was associated with dependence or death at 3 months (odds ratio, 1.8 per point; 95% confidence interval, 1.02-3.1; P=0.04) after correction for the ICH score. CONCLUSIONS: Increased LA is an independent predictor of worse functional outcomes in patients after spontaneous ICH. The pathophysiology associating LA with worse outcomes requires further study. These data may improve prognostication and selection for clinical trials.

Subarachnoid extension of primary intracerebral hemorrhage is associated with poor outcomes.

BACKGROUND AND PURPOSE: Extension of hemorrhage into the subarachnoid space is observed in primary intracerebral hemorrhage (ICH), yet the phenomenon has undergone limited study and is of unknown significance. The objective of this study is to evaluate the incidence, characteristics, and clinical consequences of subarachnoid hemorrhage extension (SAHE) in ICH on functional outcomes. METHODS: Patients with primary ICH were enrolled into a prospective registry between December 2006 and June 2012. Patients were managed and serial neuroimaging was obtained per a structured protocol. Presence of any subarachnoid blood on imaging was identified as SAHE by expert reviewers blinded to outcomes. Regression models were developed to test whether the occurrence of SAHE was an independent predictor of functional outcomes as measured with the modified Rankin Scale. RESULTS: Of 234 patients with ICH, 93 (39.7%) had SAHE. Interrater agreement for SAHE was excellent (kappa=0.991). SAHE was associated with lobar hemorrhage location (65% of SAHE vs 19% of non-SAHE cases; P<0.001) and larger hematoma volumes (median 23.8 vs 6.7; P<0.001). Fever (69.9% vs 51.1%; P=0.005) and seizures (8.6% vs 2.8%; P=0.07) were more common in patients with SAHE. SAHE was a predictor of death by day 14 (odds ratio, 4.45; 95% confidence interval, 1.88-10.53; P=0.001) and of higher (worse) modified Rankin Scale scores at 28 days (odds ratio, 1.76 per mRS point; 95% confidence interval, 1.01-3.05; P=0.012) after adjustment for ICH score. CONCLUSIONS: SAHE is associated with worse modified Rankin Scale independent of traditional ICH severity measures. Underlying mechanisms and potential treatments of SAHE require further study.

Coagulopathy disproportionately predisposes to lobar intracerebral hemorrhage.

BACKGROUND: Anticoagulation increases the risk of intracerebral hemorrhage (ICH), yet whether different underlying disease processes are equally affected is unknown. We tested the hypothesis that coagulopathy, measured by admission international normalized ratio (INR), disproportionately increases the risk for lobar hemorrhages. METHODS: Patients with primary ICH were enrolled into a registry between December 2006 and February 2012 with prospective data acquisition and systematic follow up. Logistic regression was used to test whether lobar versus deep ICH location was independently associated with INR, and then whether INR had an influence on mortality. Spearman's correlation coefficient was used to test for an association between INR and hematoma volume separately in the lobar and deep ICH groups. RESULTS: 221 patients were studied. Patients with lobar ICH were older (71 vs. 62 years old, p < 0.001) and more likely to have prior ICH (10 vs. 0 %, p < 0.001). INR >1.4 was observed on admission more frequently in lobar versus deep ICH (19 vs. 8 %, p = 0.02). Lobar ICH location was independently associated with INR >1.4 (OR: 2.51, 95 % CI: 1.03-6.14, p = 0.043). ICH volume correlated with INR in lobar ICH (p = 0.009), but not deep ICH (p = 0.8). Death at 1 month was independently associated with INR >1.4 (OR: 7.6, 95 % CI: 2.4-24.1, p = 0.001) after correction for the ICH Score. CONCLUSIONS: Abnormal coagulation occurs disproportionally in lobar versus deep ICH, and is associated with larger ICH volumes and higher mortality. These findings suggest a unique risk interaction between coagulopathy and underlying brain pathology due to cerebral amyloid angiopathy.

Anemia and transfusion after aneurysmal subarachnoid hemorrhage.

Anemia is common in patients with aneurysmal subarachnoid hemorrhage (SAH), but these patients have constituted only a small fraction of those studied in large trials of anemia and transfusion. Unlike other critically ill patients, those with SAH face a well-defined risk of vasospasm and cerebral ischemia in the weeks after their hemorrhage. The risk of ongoing ischemia may make them less able to tolerate anemia and more likely to benefit from blood transfusion. The available data show that anemia is associated with poor outcomes after SAH but that blood transfusion does not consistently improve physiological markers, and it may be associated with poor outcomes. Most of these data are observational in nature, although 1 recent study demonstrated the safety and feasibility of maintaining relatively high transfusion thresholds in patients with SAH. Larger, randomized trials are needed to determine at what levels of anemia patients with SAH might benefit from transfusion, the optimal timing of transfusion, and how to identify those patients who are most likely to benefit.

Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage.

BACKGROUND: In patients with acute intracerebral hemorrhage (ICH), reduced platelet activity on admission predicts hemorrhage growth and poor outcomes. We tested the hypotheses that platelet transfusion improves measured platelet activity. Further, we hypothesized that earlier treatment in patients at high risk for hemorrhage growth and poor outcome would reduce follow-up hemorrhage size and poor clinical outcomes. METHODS: We prospectively identified consecutive patients with ICH who had reduced platelet activity on admission and received a platelet transfusion. We defined high-risk patients as per a previous publication, reduced platelet activity, or known anti-platelet therapy (APT) and the diagnostic CT within 12 h of symptom onset. Platelet activity was measured with the VerifyNow-ASA (Accumetrics, CA), ICH volumes on CT with computerized quantitative techniques, and functional outcomes with the modified Rankin Scale (mRS) at 3 months. RESULTS: Forty-five patients received a platelet transfusion with an increase in platelet activity from 472 ± 50 (consistent with an aspirin effect) to 561 ± 92 aspirin reaction units (consistent with no aspirin effect, P < 0.001). For high-risk patients, platelet transfusion within 12 h of symptom onset, as opposed to >12 h, was associated with smaller follow-up hemorrhage size (8.4 [3-17.4] vs. 13.8 [12.3-62.5] ml, P = 0.04) and increased odds of independence (mRS < 4) at 3 months (11 of 20 vs. 0 of 7, P = 0.01). There were similar results for patients with known APT. CONCLUSIONS: In patients at high risk for hemorrhage growth and poor outcome, early platelet transfusion improved platelet activity assay results and was associated with smaller final hemorrhage size and more independence at 3 months.

Aspirin use or reduced platelet activity predicts craniotomy after intracerebral hemorrhage.

BACKGROUND: Craniotomy is potentially life-saving in selected patients with intracerebral hemorrhage (ICH). Aside from specific scenarios (cerebellar hemorrhage with hydrocephalus, midline shift from an accessible lesion, etc.) the indications for surgical decompression are controversial. Based on the earlier work that aspirin and reduced platelet activity are associated with larger hemorrhage size and hemorrhage growth, we tested the hypothesis that aspirin or reduced platelet activity would be associated with increased odds of craniotomy, likely through hemorrhage growth. METHODS: We prospectively identified patients with spontaneous ICH and routinely measured platelet activity on admission. Patients were prospectively tracked, and outcomes were obtained with the modified Rankin Scale (mRS). RESULTS: There were 187 patients in the sample. Craniotomy (N = 32, 17%) was associated with a higher initial ICH volume (37.9 [20-63] vs. 12 [5-24] ml, P < 0.001) and location (P = 0.005). In multivariate logistic regression, after controlling for ICH volume and location, any known aspirin use (OR 3.4, 95% CI 1.1-10.4, P = 0.03), platelet activity ≤550 aspirin reaction units (OR 3.1, 95% CI 1.05-9.3, P = 0.04), or an elevated PFA-EPI closure time (OR 3.2, 95% CI 1.02-10.3, P = 0.04) were associated with increased odds of craniotomy. Craniotomy was not associated with mRS at 14 days, 28 days, or 3 months. CONCLUSIONS: After correction for ICH volume and location, aspirin use or reduced platelet activity was associated with similar increased odds for craniotomy.