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Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage

From the Department of Neurology (S.M.D.), Royal Melbourne Hospital/University of Melbourne, Parkville, Australia; University of Cincinnati Medical Center (J.B.), OH; Department of Neurology (M.H.), University of Heidelberg, Universitätsklinikum Mannheim, Germany; Novo Nordisk (N.C.B., K.B.), Bagsvaerd, Denmark; Washington University School of Medicine (M.N.D.), St. Louis, MO; Departments of Neurology and Neurosurgery (S.A.M.), Columbia University College of Physicians and Surgeons, New York, NY; and University of Heidelberg (T.S.), Germany.

Address correspondence and reprint requests to Dr. S. Davis, Department of Neurology, Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050, Australia; e-mail: Stephen.Davis{at}mh.org.au

Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome.

Methods: To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location.

Results: Overall, 72.9% of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10% increase [95% CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95% CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95% CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95% CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95% CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95% CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95% CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95% CI: 0.92, 0.98; p = 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes.

Conclusions: Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.

Disclosure: Stephen Davis, Joseph Broderick, Michael Diringer, Stephan Mayer, and Thorsten Steiner receive research support, consulting fees, and speaking honoraria from Novo Nordisk. Nikolai Brun is an employee of Novo Nordisk and has equity in excess of $10,000. Kamilla Begtrup is an employee of Novo Nordisk and has equity less than $10,000.

Received October 4, 2005. Accepted in final form January 10, 2006.

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