Therapeutic Temperature Modulation for Fever After Intracerebral Hemorrhage

Background

We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes.

Methods

We performed a retrospective case–control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score.

Results

Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T _max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %).

Conclusions

Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.     

Warfarin and Statins are Associated with Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage

Background and purpose

Despite extensive studies of supratentorial intracerebral hemorrhage (ICH), limited data are available on determinants of hematoma volume in infratentorial ICH. We therefore aimed to identify predictors of infratentorial ICH volume and to evaluate whether location specificity exists when comparing cerebellar to brainstem ICH.

Methods

We undertook a retrospective analysis of 139 consecutive infratentorial ICH cases (95 cerebellar and 44 brainstem ICH) prospectively enrolled in a single-center study of ICH. ICH volume was measured on the CT scan obtained upon presentation to the Emergency Department using an established computer-assisted method. We used linear regression to identify determinants of log-transformed ICH volume and logistic regression to evaluate their role in surgical evacuation.

Results

Median ICH volumes for all infratentorial, cerebellar, and brainstem ICH were nine [interquartile range (IQR), 3–23], ten (IQR, 3–25), and eight (IQR, 3–19) milliliters, respectively. Thirty-six patients were on warfarin treatment, 31 underwent surgical evacuation, and 65 died within 90 days. Warfarin was associated with an increase in ICH volume of 86 % [β = 0.86, standard error (SE) = 0.29, p = 0.003] and statin treatment with a decrease of 69 % (β = ?69, SE = 0.26, p = 0.008). Among cerebellar ICH subjects, those on warfarin were five times more likely to undergo surgical evacuation (OR = 4.80, 95 % confidence interval 1.63–14.16, p = 0.005).

Conclusions

Warfarin exposure increases ICH volume in infratentorial ICH. Further studies will be necessary to confirm the inverse relation observed between statins and ICH volume.     

Factors Considered by Clinicians when Prognosticating Intracerebral Hemorrhage Outcomes

Background

The early subjective clinical judgment of clinicians outperforms formal prognostic scales for accurate determination of outcome after intracerebral hemorrhage (ICH), with the judgment of physicians and nurses having equivalent accuracy. This study assessed specific decisional factors that physicians and nurses incorporate into early predictions of functional outcome.

Methods

This prospective observational study enrolled 121 ICH patients at five US centers. Within 24 h of each patient’s admission, one physician and one nurse on the clinical team were each surveyed to predict the patient’s modified Rankin Scale (mRS) at 3 months and to list up to 10 subjective factors used in prognostication. Factors were coded and compared between (1) physician and nurse and (2) accurate and inaccurate surveys, with accuracy defined as an exact prediction of mRS.

Results

Aside from factors that are components of the ICH or FUNC scores, surveys reported pre-existing comorbidities (40.0%), other clinical or radiographic factors not in clinical scales (43.0%), and non-clinical/radiographic factors (21.9%) as important. Compared to physicians, nurses more frequently listed neurologic examination components (Glasgow Coma Scale motor, 27.3 vs. 5.8%, p < 0.0001; GCS verbal, 12.4 vs. 0.0%, p < 0.0001) and non-clinical/radiographic factors (31.4 vs. 12.4%, p = 0.0005). Physicians more frequently listed neuroimaging factors (ICH location, 33.9 vs. 7.4%, p < 0.0001; intraventricular hemorrhage, 13.2 vs. 2.5%, p = 0.003). There was no difference in listed factors between accurate versus inaccurate surveys.

Conclusions

Clinicians frequently utilize factors outside of the components of clinical scales for prognostication, with physician and nurses focusing on different factors despite having similar accuracy.

     

Predictors of Late Neurological Deterioration After Spontaneous Intracerebral Hemorrhage

Background

Although intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease, little is known about factors leading to neurological deterioration occurring beyond 48 h after hematoma formation. The purpose of this study was to characterize the incidence, consequences, and associative factors of late neurological deterioration (LND) in patients with spontaneous ICH.

Methods

Using the Duke University Hospital Neuroscience Intensive Care Unit database from July 2007 to June 2012, a cohort of 149 consecutive patients with spontaneous supratentorial ICH met criteria for analysis. LND was defined as a decrease of two or more points in Glasgow Coma Scale score or death during the period from 48 h to 1 week after ICH symptom onset. Unfavorable outcome was defined as a modified Rankin Scale score of >2 at discharge.

Results

Forty-three subjects (28.9 %) developed LND. Logistic regression models revealed hematoma volume (OR = 1.017, 95 % CI 1.003–1.032, p = 0.019), intraventricular hemorrhage (OR = 2.519, 95 % CI 1.142–5.554, p = 0.022) and serum glucose on admission (OR = 2.614, 95 % CI 1.146–5.965, p = 0.022) as independent predictors of LND. After adjusting for ICH score, LND was independently associated with unfavorable outcome (OR = 4.000, 95 % CI 1.280–12.500, p = 0.017). In 65 subjects with follow-up computed tomography images, an increase in midline shift, as a surrogate for cerebral edema, was independently associated with LND (OR = 3.822, 95 % CI 1.157–12.622, p = 0.028).

Conclusions

LND is a common phenomenon in patients with ICH; further, LND appears to affect outcome. Independent predictors of LND include hematoma volume, intraventricular hemorrhage, and blood glucose on admission. Progression of perihematomal edema may be one mechanism for LND.     

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.     

Brain Iron Metabolism and Brain Injury Following Subarachnoid Hemorrhage: iCeFISH-Pilot (CSF Iron in SAH)

Introduction

Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH.

Methods

Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2–4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data.

Results

A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts.

Conclusions

Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.     

The Impact of Tobacco Smoking on Treatment for Comorbid Depression and Alcohol Misuse

Tobacco use is a major public health concern, and is associated with a number of mental illnesses as well as increased alcohol/other drug (AOD). Research into treatment for individuals experiencing such comorbidities is limited. Participants (n?=?447) were those enrolled in the Depression and Alcohol Integrated and Single-focused Interventions project (Baker et al. 2010), and the Self Help for Alcohol/other drugs and DEpression project (Kay-Lambkin et al. Medical Journal of Australia 195:S44–S50, 2011a, Journal of Medical Internet Research 13(1):e11p11, b), who reported current depression and hazardous alcohol use at entry to the study. Smoking cessation was not targeted in, nor a goal of, treatment. After controlling for socioeconomic variables, tobacco use was not associated with higher levels of depressive symptoms at baseline; however heavy smokers (30+ cigarettes per day) consumed significantly more alcohol at baseline than did non-smokers (13 vs. 9 standard drinks per day). Baseline smoking severity did not impact on depression or alcohol use outcomes over a 12-month period. Reductions in tobacco use between baseline and 3-month follow-up were significantly associated with reductions in depression and alcohol consumption over the same time period. The study results suggest that tobacco use does not interfere with treatment for depression and alcohol use problems, and adds weight to the idea of considering specific treatment for tobacco use in the context of treatment for alcohol/other drug use.     

The relationship between plasma D-dimer levels and outcome of Chinese acute ischemic stroke patients in different stroke subtypes

High-level plasma D-dimer suggests hypercoagulable states. There is a lack of correlation study of plasma D-dimer level and prognosis according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. The goal of this study is to explore the relationship between the plasma D-dimer level and the outcome of acute ischemic stroke patients among different stroke subtypes. We conducted a study of acute ischemic stroke patients admitted to the Department of Neurology in Second Hospital of Lanzhou University within 7 days of symptom onset. They were divided into different groups based on their subtypes according to TOAST criteria. In all the patients the plasma D-dimer levels were detected within 24 h of admission. Clinical neurological assessments were performed in line with National Institutes of Health Stroke Scale (NIHSS) once daily on the day of admission and on the 14th day. The outcome was evaluated by neurological improvement rate. Comparisons were made among the different subtypes based on the level of plasma D-dimer and the outcome. A total of 300 patients with acute ischemic stroke were included, 40 with cardioembolism; 47 with large-artery atherosclerosis; 143 with small-artery occlusion, 5 with other etiology stroke; and 65 with undetermined etiology stroke. The level of plasma D-dimer was negatively related to the outcome (r = ?0.41; P = 0.013). Patients with cardioembolism had the highest level of plasma D-dimer and they suffered the most serious neurological deficit and the worst outcome among the five subtypes, the difference was statistically significant (F = 5.34; P = 0.012); while the lacunar stroke patients had the best outcome with the lowest level of D-dimer. High-level plasma D-dimer of acute period strongly indicates an unfavorable clinical outcome.     

Determinants of External Ventricular Drain Placement and Associated Outcomes in Patients with Spontaneous Intraventricular Hemorrhage

Background

External ventricular drain (EVD) usage in patients with intraventricular hemorrhage (IVH) is variable in current practice and in clinical trials, and its impact on outcome remains controversial. The objective of this study was to identify the clinical predictors of EVD utilization, and associated outcome in adults with spontaneous IVH with or without intracerebral hemorrhage (ICH).

Methods

Retrospective review of 183 consecutive IVH patients admitted to a University Hospital between 2003 and 2010. Clinical and radiographic data were analyzed for associations between EVD placement and mortality, poor outcome, and improvement in Glasgow Coma Scale score (GCS) using multivariate logistic regression models.

Results

Average age was 62 ± 15.6 years, and average ICH and IVH volumes were 35.8 ± 40.9 cc and 19.7 ± 25.3 cc, respectively. Independent predictors of EVD placement within first 5 days of admission were GCS ≤ 8 (OR 11.5; P < 0.001), Graeb score >5 (OR 4.6; P = 0.001), and non-lobar ICH ≤ 30 cc (OR 9.7; P < 0.001). Median GCS increased from 5 (IQR 3–7) 48 h post-EVD (P < 0.001). EVD placement was an independent predictor of reduced mortality (OR 0.31; P = 0.04) and modified Rankin score 0–3 (OR 15.7; P = 0.01) at hospital discharge. In patients with hydrocephalus on presentation, EVD was associated with reduced mortality for patients with GCS > 3 after controlling for ICH and IVH severity (OR 0.02; P = 0.01).

Conclusions

Patients with lower GCS, higher IVH severity, and lower ICH volume are more likely to have an EVD placed. EVD placement is associated with reduced mortality and improved short-term outcomes in patients with IVH after adjusting for known severity factors. EVD use should be protocolized in clinical trials of ICH management where IVH is included.     

A Pilot Study of Darbepoetin Alfa for Prophylactic Neuroprotection in Aortic Surgery

Background

Descending aortic (DA) surgery poses a high risk for spinal and cerebral infarction and routine use of lumbar drains allows for measurement of CSF markers of neurologic injury. Erythropoiesis medications have extensive preclinical data demonstrating neuroprotection. We hypothesized that prophylactic darbepoetin alfa (DARB) given before surgery reduces neurologic injury in patients undergoing DA repair.

Methods and Results

We performed a prospective adaptive dose-finding trial of prophylactic DARB (www.clinicaltrials.gov NCT00647998) that terminated prematurely following publication of an erythropoietin stroke study showing possible harm. Enrollment halted before dose adjustments; nine patients each received 1 mg/kg IV DARB immediately before surgery. A prospective cohort of nine untreated patients was subsequently obtained for comparison. The primary outcome of death or neurologic impairment at discharge occurred in 1/9 (11 %) DARB patients and 3/9 (33 %) controls (p = 0.58). There were no statistical differences in changes of CSF biomarkers from baseline to 48 h comparing DARB patients to controls: S100β, median 214 versus 260 ng/ml (p = 0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58 ng/ml (p = 0.45). In patients with early perioperative neurologic ischemia, there were greater changes in CSF biomarkers, compared to those without ischemia: S100β, median 2301 versus 124 ng/ml (p = 0.04); GFAP, median 31.78 versus 0.31 ng/ml (p = 0.34).

Conclusions

There were no significant effects of prophylactic DARB on clinical outcome or CSF markers of neurologic injury in this pilot study, although all point estimates favored treatment. DA repair is a promising model of prophylactic neuroprotection.     

The Effect of a Neurocritical Care Service without a Dedicated Neuro-ICU on Quality of Care in Intracerebral Hemorrhage

Background

Introduction of neurocritical care services to dedicated neuro-ICUs is associated with improved quality of care. The impact of a neurocritical care service without a dedicated neuro-ICU has not been studied.

Methods

We retrospectively identified all patients admitted to our institution with intracerebral hemorrhage (ICH) in two 12-month periods: immediately before the arrival of the first neurointensivist (“before”) and after the neurocritical care service was established (“after”). There was no nursing team, ICU housestaff/physician extender team, or physical unit dedicated to the care of patients with critical neurologic illness during either period. Using an uncontrolled before-after design, we compared clinical outcomes and performance on quality metrics between groups.

Results

We included 74 patients with primary supratentorial ICH. Mortality, length of stay (LOS), proportion of patients with modified Rankin Score 0–3, and destination on discharge did not differ between groups when adjusted for confounders. Time to first two consecutive systolic blood pressure (SBP) measurements <180 mmHg was shorter in the “after” cohort (mean 4.5 vs. 3.2 h, p = 0.001). Area under the curve measurement for change in SBP from baseline over the first 24 h after ED arrival demonstrated greater, sustained SBP reduction in the “after” cohort (mean ?187.9 vs. ?720.9, p = 0.04). A higher proportion of patients were fed without passing a dysphagia screen in the “before” group (45 vs. 0 %, p < 0.001).

Conclusions

Introduction of a neurocritical service without a neuro-ICU at our institution was associated with a trend toward longer ICU LOS and improvement in some key metrics of quality of care for patients with ICH.     

Cerebral Vasospasm and Delayed Cerebral Ischemia in Intraventricular Hemorrhage

Background

Intracerebral hemorrhage (ICH) with intraventricular extension (IVH) is a devastating disease with a particular high mortality. In some aspects, IVH may resemble subarachnoid hemorrhage. The incidence and role of cerebral vasospasm in ICH with IVH are poorly understood. Here, we aimed to analyze the incidence and relationship of cerebral vasospasm to clinical characteristics, in-hospital mortality, and functional outcome at 3 months in patients suffering ICH with IVH.

Methods

Patients with ICH and IVH treated on a neurological intensive care unit were prospectively enrolled in a single-center observational study. Vasospasm was defined using established ultrasound criteria. Delayed cerebral ischemia (DCI) was defined as a new hypodensity on follow-up cranial CT. Functional outcome at 3 months was assessed using the modified Rankin Scale.

Results

129 patients with ICH and IVH were screened for the study. 62 patients entered the final analysis. The incidence of significant vasospasm was 37 %. A strong trend was found for the association between all cerebral vasospasm and DCI (P = 0.046). Early (up to 48 h) vasospasm was significantly associated with a DCI (P = 0.033). Overall mortality and outcome after 3 months did not differ between the groups.

Conclusion

Cerebral vasospasm seems to be a frequent complication after ICH with IVH and might be associated with DCI. Larger studies are warranted to confirm this hypothesis.     

Predictors of 30-Day Readmission After Subarachnoid Hemorrhage

Background

Readmission within 30 days is increasingly evaluated as a measure of quality of care. There are few data on the rates of readmission after subarachnoid hemorrhage (SAH).

Objective

We sought to determine the predictors of 30-day readmission in patients with SAH.

Methods

We prospectively identified 283 patients with SAH admitted between 2006 and 2012. Readmission was determined by means of an automated query with confirmation in the electronic medical record.

Results

Overall, 21 (8 %) patients were readmitted for infection (n = 8), headache (n = 5), hydrocephalus (n = 4), cardiovascular causes (n = 2), medication-related complications (n = 1), and cerebral ischemia (n = 1). Readmission was associated with longer intensive care unit (ICU) length of stay (LOS) (15.4 [13.4–19.3] vs. 12.2 [8.2–18.5] days, P = 0.02), hospital LOS (22.2 [17.4–23.0] vs. 16.8 [12.0–24.1] days, P = 0.01), and placement of an external ventricular drain (EVD, OR 3.9, 95 % CI 1.3–12.0, P = 0.01). Readmission was not associated with admission neurologic grade, NIH Stroke scale at 14 days, modified Rankin scale at 3 months, history of cardiovascular disease, or radiographic cerebral infarction (P > 0.1).

Conclusions

Demographics, severity of neurologic injury, radiographic cerebral infarction, and outcomes were not associated with readmission after SAH. Markers of a more complicated hospital course (ICU and hospital LOS, EVD placement) were associated with 30-day readmission. Most readmissions were for infections acquired after discharge. Readmission within 30 days is difficult to predict, and, since the most common reason was infection acquired after discharge, it may be difficult to prevent without an integrated health system and coordinated care.     

A Critical Analysis of Intra-arterial Thrombolytic Doses in Acute Ischemic Stroke Treatment

Background

Intra-arterial thrombolytics (IAT) such as Alteplase, Tenecteplase, and Reteplase are currently used in patients with acute ischemic stroke in varying doses. We evaluated the relationship of IA thrombolytic dose with angiographic recanalization, intracerebral hemorrhage (ICH) rates, and clinical outcomes at three comprehensive stroke centers.

Methods

We stratified patients who underwent endovascular treatment into tertiles based on intra-arterial thrombolytic dose administered: lower tertile (range 1.5–5 mg), middle tertile (range 6–10 mg), and upper tertile (range 10.3–68.5 mg) of rt-PA equivalent. The rates of angiographic recanalization, ICH, and favorable clinical outcomes (discharge modified Rankin score [mRS] = 0–2) were ascertained and compared within the three tertiles. Logistic regression analyses were performed to determine the association between IA thrombolytic dosages and angiographic recanalization, ICH, and favorable clinical outcomes after adjusting for potential confounders.

Results

A total of 197 patients were treated with IAT; mean age ±SD was 65.6 ± 16 years; 105 (53.3 %) were women. Ninety-one (46.2 %) patients received both IVT and IAT. IA rt-PA equivalent dose was not different between the patients with and without ICH [mean (mg) ± SD, 9.8 ± 6.1 versus 9.8 ± 9.5, p = 0.9]. We did not find any relation between increasing doses of IAT (from 2 to 69 mg rt-PA equivalent) and symptomatic or asymptomatic ICH: (p = 0.1630) and (p = 0.6702), respectively. Multivariate analysis demonstrated that IAT dose was not associated with ICH (OR 1.0, 95 % CI 0.97–1.07, p = 0.3919) or favorable outcome (OR, 1.00, 95 % CI 0.95–1.06, p = 0.7375). In a subset analysis of IVT patients, total doses ranged from 48.2 to 149 mg and were not associated with either symptomatic (p = 0.23) or asymptomatic (p = 0.24) ICHs.

Conclusion

Our study demonstrates that IAT in doses up to 69 mg is safe without any evidence of dose-related ICHs even in those patients who had received IVT.     

Is Early DNR a Self-Fulfilling Prophecy for Patients with Spontaneous Intracerebral Hemorrhage?

Background

To investigate differences in outcome of patients with intracerebral hemorrhage (ICH) based on institution of do-not-resuscitate (DNR) order within first 24 h of admission.

Methods

A prospective registry of patients presenting with ICH from Jan 2006 to Dec 2008 was created. Patients with and without DNR orders instituted within 24 h of admission were classified as cases and controls respectively and were matched based on age and stroke severity. Demographics, intracerebral volume of hematoma, intraventricular extension of hemorrhage (IVH), invasive treatments, and outcomes at discharge were collected. All patients were followed up at least for 1 year, to determine mortality outcomes.

Results

Of a total of 245 subjects, 18 % had DNR order instituted within 24 h of admission. After matching, a total of 69 controls were available for 44 cases. There was no difference in demographics, IVH extension, volume of hemorrhage, and length of stay among cases and controls. Higher proportions of controls had surgical evacuation of the hematoma (p = 0.0125) and mechanical ventilation (p = 0.0001). There was no significant difference in functional outcome and survival rates among cases and controls at the end of 1 week, 1 month, and 1 year.

Conclusions

DNR institution and restriction of resuscitation was not associated with poor outcome or difference in survival within 1 year after ICH. This indicates an early DNR probably does not lead to a self-fulfilling prophecy in this population, and might be explained by our practice, were DNR orders do not impact the level of supportive medical care we provide.     

A Comparative Study of Fractional Anisotropy Measures and ICH Score in Predicting Functional Outcomes After Intracerebral Hemorrhage

Background

Improved prognostication during the acute phase of intracerebral hemorrhage (ICH) could influence goals of care. We investigated the utility of diffusion tensor imaging (DTI)-derived data obtained during the acute phase of ICH in predicting outcome, compared with the ICH score.

Methods

We measured fractional anisotropy (FA) values in 5 slices below the level of the lesion on the affected and unaffected corticospinal tracts (CST) and in the cerebral peduncles (CPs) in 32 patients with supratentorial ICH who had DTI MRI within 4 days after ictus. We calculated the FA ratio (rFA = FA_{affected side}/FA_{unaffected side}), and examined the value of the ICH score and rFA in predicting functional outcome assessed by modified Ranking Scale (mRS) at follow-up, using ROC analyses.

Results

The rFA values at the CPs level, but not the 5 slices below the lesion, were significantly lower in the group with poor functional outcome (defined as mRS > 2) than in those with good functional outcome (0.96 ± 0.14 vs. 0.99 ± 0.08, p = 0.025). The ICH score had greater areas under ROC curve in predicting functional outcome compared to the mean rFA (AUC 0.74 vs. 0.44; p = 0.01 for mRS > 2; and 0.84 vs. 0.40; p < 0.001 for mRS > 3).

Conclusions

The prognostic value of the ICH score surpassed that of DTI-derived data during the acute phase of ICH in this cohort of patients. Prospective and larger studies are needed to validate our findings and to assess the prognostic role of various DTI-derived measures at different times following ICH.     

Perihematomal Edema Expansion Rates and Patient Outcomes in Deep and Lobar Intracerebral Hemorrhage

Background

Perihematomal edema (PHE) expansion rate may predict functional outcome following spontaneous intracerebral hemorrhage (ICH). We hypothesized that the effect of PHE expansion rate on outcome is greater for deep versus lobar ICH.

Methods

Subjects (n = 115) were retrospectively identified from a prospective ICH cohort enrolled from 2000 to 2013. Inclusion criteria were age ≥ 18 years, spontaneous supratentorial ICH, and known onset time. Exclusion criteria were primary intraventricular hemorrhage (IVH), trauma, subsequent surgery, or warfarin-related ICH. ICH and PHE volumes were measured from CT scans and used to calculate expansion rates. Logistic regression assessed the association between PHE expansion rates and 90-day mortality or poor functional outcome (modified Rankin Scale > 2). Odds ratios are per 0.04 mL/h.

Results

PHE expansion rate from baseline to 24 h (PHE24) was associated with mortality for deep (p = 0.03, OR 1.13[1.02–1.26]) and lobar ICH (p = 0.02, OR 1.03[1.00–1.06]) in unadjusted regression and in models adjusted for age (deep p = 0.02, OR 1.15[1.02–1.28]; lobar p = 0.03, OR 1.03[1.00–1.06]), Glasgow Coma Scale (deep p = 0.03, OR 1.13[1.01–1.27]; lobar p = 0.02, OR 1.03[1.01–1.06]), or time to baseline CT (deep p = 0.046, OR 1.12[1.00–1.25]; lobar p = 0.047, OR 1.03[1.00–1.06]). PHE expansion rate from baseline to 72 h (PHE72) was associated with mRS > 2 for deep ICH in models that were unadjusted (p = 0.02, OR 4.04[1.25–13.04]) or adjusted for ICH volume (p = 0.02, OR 4.3[1.25–14.98]), age (p = 0.03, OR 5.4[1.21–24.11]), GCS (p = 0.02, OR 4.19[1.2–14.55]), or time to first CT (p = 0.03, OR 4.02[1.19–13.56]).

Conclusions

PHE72 was associated with poor functional outcomes after deep ICH, whereas PHE24 was associated with mortality for deep and lobar ICH.

     

Monitoring Biomarkers of Cellular Injury and Death in Acute Brain Injury

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.     

Mild Prolonged Hypothermia for Large Intracerebral Hemorrhage

Background

Perihemorrhagic edema (PHE) develops after intracerebral hemorrhage (ICH). It can worsen the clinical situation by its additional mass effect. Therapeutic hypothermia (TH) might be an effective method to control PHE, but has not been sufficiently studied in ICH patients.

Methods

We report data on n = 25 consecutive patients with large supratentorial ICH (volume > 25 ml) who were treated by mild TH of 35 °C for 8–10 days. Body temperature was controlled by endovascular cooling catheters. We followed the clinical course during hospital stay and measured volumes of ICH and PHE in regularly performed serial cranial computed tomography. Outcome was assessed after 3 and 12 months. These data were compared to a historical group of n = 25 patients with large ICH.

Results

While PHE continuously increased in the historical control group up to day 10, PHE volumes in the hypothermia group remained stable. There was a significant difference from day 3 after symptom onset. Shivering (36 %) and pneumonia (96 %) were the most frequent complications during TH. Mortality rate was 8.3 % in TH versus 16.7 % in the control group after 3 months and 28 versus 44 % after 1 year.

Conclusions

These data support the promising results of our first case series on TH in large ICH. TH prevents the development of PHE and its complications. Side effects of TH appeared often, but could be treated sufficiently. Therefore, TH might represent a new therapy for PHE after large ICH, but has to be further tested in randomized trials.     

No Exacerbation of Perihematomal Edema with Intraventricular Tissue Plasminogen Activator in Patients with Spontaneous Intraventricular Hemorrhage

Introduction

In severe spontaneous intraventricular hemorrhage (IVH), intraventricular (IVR) administration of tissue plasminogen activator (rtPA) clears blood from the ventricles more rapidly than with external ventricular drainage (EVD) alone. However, experimental studies suggest tPA may be neurotoxic in compromised brain tissue and may exacerbate perihematomal edema.

Methods

We used computerized volumetrics to assess change in intracerebral hemorrhage (ICH), IVH, ventricular, and perihematomal edema (PHE) volumes at 2–4 (T1) and 5–9 (T2) days following diagnostic CT scans (T0) of 24 patients (12 tPA-treated; 12 controls) with IVH requiring EVD. Controls from a hospital registry were matched by IVH and ICH volume to tPA-treated patients who came from a multicenter trial involving 52 patients with IVH.

Results

There were no significant differences between matched pairs in admission ICH and IVH volumes. IVR tPA resulted in more rapid clearance of IVH as determined by T2–T0 decrease in median IVH volume (tPA: ?18.7 cc, iqr 14.9; control:?6.9 cc, iqr 6.4; P = 0.002). Median ratios of PHE to ICH volume were not significantly different in control versus tPA-treated patients at T1 and T2 [control:tPA = 0.55:0.56 (T1); P = 0.84 and 0.81:0.71 (T2); P = 1.00]. Total ventricular volume was significantly larger in the control group at T2 (mean: 57.57 ± 10.32 vs. tPA: 24.80 ± 2.67 cc; P = 0.01). Bacterial ventriculitis was more frequent in the control group (5 vs. 1 episodes; P = 0.06) as was shunt dependence (4 vs. 0 cases; P = 0.03).

Conclusions

For case matched large IVH with small ICH volume, IVR tPA enhances lysis of intraventricular blood clots and has no significant impact on PHE.