Bastian Volbers

Natural Course of Perihemorrhagic Edema After Intracerebral Hemorrhage

Background and Purpose— There is only limited knowledge on the time course of perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH). We aimed to investigate the chronological PHE course and its relation to in-hospital mortality in a large retrospective ICH cohort. Methods— Patients with supratentorial ICH treated at our institution between 2006 and 2009, who had received at least 3 CT scans in the course of conservative treatment, were included in the present analysis. PHE at Days 1, 2, 3, 4 to 6, 7 to 11, 12 to 16, 17 to 21, and >22 was assessed using a threshold based semiautomatic volumetric algorithm. A chart review was performed to achieve data on duration of stay, ventilation, treatment with external ventricular drains, and in-hospital mortality. Results— Two hundred nineteen patients aged 69.9±10.5 years with deep (n=103) or lobar (n=116) ICH were included in the study. Mean ICH volume was 35.7±31.5 mL. Mean absolute PHE volume significantly increased from initially 32.6±29.9 mL to 63.7±46.7 mL at Days 7 to 11. No significant changes were observed at later time points. ICH volume was strongly correlated with absolute PHE volume (&rgr;=0.8, P<0.001) and inversely correlated with relative PHE (&rgr;=−0.4 to −0.5, P<0.001). Increase in absolute PHE between Days 1 and 3 was significantly predictive for in-hospital mortality (P=0.014, ExpB=1.04). Conclusions— PHE develops early after ICH and doubles within the first 7 to 11 days after the initial bleeding event. This additional mass effect may contribute to secondary clinical deterioration and mortality, especially in larger ICH. Because of its inverse correlation with ICH volume, relative PHE may not be suitable for analyses considering the clinical impact of PHE.

Effects of Continuous Hypertonic Saline Infusion on Perihemorrhagic Edema Evolution

Background and Purpose— Mass effect of hematoma and the associated perihematomal edema are commonly responsible for neurological deterioration after intracerebral hemorrhage. Efficacy of surgical and medical therapy is limited. We studied the effect of early continuous hypertonic saline infusion on development of perihematomal edema after severe spontaneous supratentorial hemorrhage. Methods— Patients with spontaneous lobar and basal ganglia/thalamic bleeding >30 mL (n=26) were treated with early (<72 hours) continuous hypertonic saline infusion (3%) to achieve sodium of 145 to 155 mmol/L and osmolality of 310 to 320 mOsmol/kg. Evolution of absolute edema volume and relative edema volume (ratio absolute edema volume/initial hematoma volume) was assessed on repeated cranial CT and compared to historical patients (n=64) identified on database with hematoma >30 mL. Results— In the treatment group, absolute edema volume was significant smaller between day 8 and day 14 (Pabsolute edema volume= 0.04) and relative edema volume was significant smaller between day 2 and day 14 (Prelative edema volume=0.02). Intracranial pressure crisis (>20 mm Hg for >20 minutes or new anisocoria) occurred less frequently in the treatment group (12 versus 56; P=0.048). In-hospital mortality was 3 (11.5%) in the hypertonic saline group and 16 (25%) in the control group (P=0.078). Side effects theoretically associated with hypertonic saline including cardiac arrhythmia and acute heart and renal failure occurred in both groups to a similar extent. Conclusions— Early and continuous infusion of hypertonic saline in patients with severe spontaneous intracerebral hemorrhage was feasible and safe. The beneficial effect of this treatment regimen on edema evolution and outcome has to be demonstrated in a controlled trial.

Hyponatremia Is an Independent Predictor of In-Hospital Mortality in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Hyponatremia is the most frequent electrolyte disturbance in critical care. Across various disciplines, hyponatremia is associated with increased mortality and longer hospital stay, yet in intracerebral hemorrhage (ICH) no data are available. This the first study that investigated the prevalence and clinical associations of hyponatremia in patients with ICH. Methods— This observational study included all consecutive spontaneous ICH patients (n=464) admitted during a 5-year period to the Department of Neurology. Patient characteristics, in-hospital measures, mortality, and functional outcome (90 days and 1 year) were analyzed to determine the effects of hyponatremia (Na <135 mEq/L). Multivariable regression analyses were calculated for factors associated with hyponatremia and predictors of in-hospital mortality. Results— The prevalence of hyponatremia on hospital admission was 15.6% (n=66). Normonatremia was achieved and maintained in almost all hyponatremia patients <48 hours. In-hospital mortality was roughly doubled in hyponatremia compared with nonhyponatremia patients (40.9%; n=27 versus 21.1%; n=75), translating into a 2.5-fold increased odds ratio (P<0.001). Multivariable analyses identified hyponatremia as an independent predictor of in-hospital mortality (odds ratio, 2.2; 95% confidence interval, 1.05–4.62; P=0.037). Within 90 days after ICH, hyponatremia patients surviving hospital stay were also at greater risk of death (odds ratio, 4.8; 95% confidence interval, 2.1–10.6; P<0.001); thereafter, mortality rates were similar. Conclusions— Hyponatremia was identified as an independent predictor of in-hospital mortality with a fairly high prevalence in spontaneous ICH patients. The presence of hyponatremia at hospital admission is related to an increased short-term mortality in patients surviving acute care, possibly reflecting a preexisting condition that is linked to worse outcome due to greater comorbidity. Correction of hyponatremia does not seem to compensate its influence on mortality, which strongly warrants future research.

Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage

Background and Purpose— The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH). Methods— Patients with intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; n=32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; n=22). CT scans on Days 1 to 4, 7±1 and 10±1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months. Results— The overall effect of IVF dosage was not significantly different between the 2 groups (F=1.3, P=0.25). The course of IVH volume in the third and fourth ventricles was similar with high- and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4±4.2 mL versus 8.8±8.1 mL; P=0.01) and 10 (1.4±2.8 mL versus 4.9±65.8 mL; P=0.005). Total clot half-life was 78±43 hours in the low-dose and 56±25 hours in the high-dose group (P=0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months. Conclusions— Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).

Semi-automatic volumetric assessment of perihemorrhagic edema with computed tomography.

Background and purpose:  Magnetic resonance imaging (MRI) shows perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH) with high contrast, but the procedure is often difficult or not available for clinical use. The aim of the present study was to establish and validate an observer independent method for quantification of PHE on computed tomography (CT) by comparing with simultaneously performed MRI.

Single versus bilateral external ventricular drainage for intraventricular fibrinolysis in severe ventricular haemorrhage

Background: Intraventricular fibrinolysis (IVF) through bilateral external ventricular drains (EVD) may provide better access of the thrombolytic agent to the intraventricular clot, potentially influencing clot clearance and outcome. Methods: Patients with spontaneous ganglionic intracerebral haemorrhage (ICH)<40 cm3 and intraventricular haemorrhage (IVH) with acute hydrocephalus have been treated with IVF. The decision for placement of one or two EVDs has been left to the discretion of the treating physician. CT volumetry, the effects on cerebrospinal fluid (CSF) circulation and outcome at 3 months have been analysed for patients with one (group I, n = 13) or two EVDs (group II, n = 14). Results: No difference was found in clot resolution between the two groups (clot half life 2.1 (SD 1.2) vs 2.4 (1.3) days). A separate analysis of the third and fourth ventricle clearance was similar (1.6 (0.6) versus 1.8 (0.8) days), indicating no difference in reconstitution of CSF circulation. A trend towards a longer EVD duration and higher infection rate was found in the bilateral EVD group. No difference was found in outcome at 3 months. Conclusions: Our results do not support the use of bilateral EVDs for IVF in patients with severe IVH.

Comparison of Conventional CTA and Volume Perfusion CTA in Evaluation of Cerebral Arterial Vasculature in Acute Stroke

BACKGROUND AND PURPOSE: CTA-like datasets can be reconstructed from whole-brain VPCTA. The aim of our study was to compare VPCTA with CTA for detection of intracranial stenosis and occlusion in stroke patients. Omitting CTA from stroke CT could reduce radiation dose. MATERIALS AND METHODS: One hundred sixty-three patients were included in this retrospective analysis. Inclusion criterion was suspected stroke within 4.5 hours after onset of symptoms. All examinations were performed on a 128-section multidetector CT scanner. Axial, coronal, and sagittal maximum intensity projections were reconstructed from CTA and from peak arterial phase of VPCTA. Images were scored for quality and presence of intracranial stenosis >50% or occlusion. For statistical analysis, the Wilcoxon signed-rank test and Fisher exact test were used, with a 2-tailed P value of .05 or less for statistical significance. RESULTS: Average image quality was superior in CTA (P < .05). However, image quality dichotomized for diagnostic significance was without difference between CTA and VPCTA (P > .05). Comparative statistical analysis revealed no significant difference for detection of intracranial stenosis and occlusion between CTA and VPCTA (P > .05). Substitution of intracranial CTA by VPCTA would lower radiation dose by 0.5 mSv. CONCLUSIONS: VPCTA is suited to assess the intracranial vasculature in patients with stroke and might have the potential to decrease radiation dose by substituting for intracranial CTA in stroke CT. Additional studies are necessary to further evaluate potential benefits of the dynamic nature of VPCTA.

Prognostic significance of third ventricle blood volume in intracerebral haemorrhage with severe ventricular involvement

Background and purpose Intraventricular haemorrhage (IVH) is an independent predictor of poor outcome in spontaneous intracerebral haemorrhage (ICH). Larger IVH volume and increasing number of affected ventricles have been associated with worse prognosis, however, little is known about the prognostic value of blood volume in the different parts of the ventricular system. Therefore, the correlation of IVH volume in the third, fourth and lateral ventricles with outcome in patients with ICH and severe IVH, treated with intraventricular fibrinolysis (IVF), was investigated. Methods Patients with ICH <40 ml, severe IVH and acute hydrocephalus were treated with IVF. The course of IVH volume for each ventricle was measured by CT based volumetry. Outcome at 90 days was assessed by a telephone follow-up survey and correlated with initial IVH volume. Results 50 patients aged 62.5±10.3 years with spontaneous ICH (12.5±10.8 ml) and severe IVH (33.5±25 ml) were included. Clearance of the third and fourth ventricle from blood occurred after 3±1.9 days. Initial IVH volume in the third ventricle (3.8±3.3 ml) was predictive for poor outcome (OR 2.6 per ml, p=0.02). Correlation between larger IVH volume in the fourth ventricle and poor outcome showed a trend towards significance (p=0.07). Total IVH volume and lateral ventricle IVH volume were not correlated with outcome. Conclusion Despite rapid clot removal, initial IVH volume in the third ventricle was a strong and independent negative predictor. This is possibly explained by irreversible damage of brainstem structures by the initial mass effect of IVH.

Impact of Hypothermia Initiation and Duration on Perihemorrhagic Edema Evolution After Intracerebral Hemorrhage

Background and Purpose— Intracerebral hemorrhage (ICH) causes high morbidity and mortality. Recently, perihemorrhagic edema (PHE) has been suggested as an important prognostic factor. Therapeutic hypothermia may be a promising therapeutic option to treat PHE. However, no data exist about the optimal timing and duration of therapeutic hypothermia in ICH. We examined the impact of therapeutic hypothermia timing and duration on PHE evolution. Methods— In this retrospective, single-center, case–control study, we identified patients with ICH treated with mild endovascular hypothermia (target temperature 35°C) from our institutional database. Patients were grouped according to hypothermia initiation (early: days 1–2 and late: days 4–5 after admission) and hypothermia duration (short: 4–8 days and long: 9–15 days). Patients with ICH matched for ICH volume, age, ICH localization, and intraventricular hemorrhage were identified as controls. Relative PHE, temperature, and intracranial pressure course were analyzed. Clinical outcome on day 90 was assessed using the modified Rankin scale (0–3=favorable and 4–6=poor). Results— Thirty-three patients with ICH treated with hypothermia and 37 control patients were included. Early hypothermia initiation led to relative PHE decrease between admission and day 3, whereas median relative PHE increased in control patients (−0.05 [interquartile range, −0.4 to 0.07] and 0.07 [interquartile range, −0.07 to 0.26], respectively; P=0.007) and patients with late hypothermia initiation (0.22 [interquartile range 0.12–0.27]; P=0.037). After day 3, relative PHE increased in all groups without difference. Outcome was not different between patients treated with hypothermia and controls. Conclusions— Early hypothermia initiation after ICH onset seems to have an important impact on PHE evolution, whereas our data suggest only limited impact later than day 3 after onset.

Sex differences in perihemorrhagic edema evolution after spontaneous intracerebral hemorrhage

Background and purpose: Clinical data on sex differences in perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH) are lacking.