Lack of Early Improvement Predicts Poor Outcome Following Acute Intracerebral Hemorrhage

Objectives: There are limited data as to what degree of early neurologic change best relates to outcome in acute intracerebral hemorrhage. We aimed to derive and validate a threshold for early postintracerebral hemorrhage change that best predicts 90-day outcomes. Design: Derivation: retrospective analysis of collated clinical stroke trial data (Virtual International Stroke Trials Archive). Validation: retrospective analysis of a prospective multicenter cohort study (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT]). Setting: Neurocritical and ICUs. Patients: Patients with acute intracerebral hemorrhage presenting less than 6 hours. Derivation: 552 patients; validation: 275 patients. Interventions: None. Measurements and Main Results: We generated a receiver operating characteristic curve for the association between 24-hour National Institutes of Health Stroke Scale change and clinical outcome. The primary outcome was a modified Rankin Scale score of 4–6 at 90 days; secondary outcomes were other modified Rankin Scale score ranges (modified Rankin Scale, 2–6, 3–6, 5–6, 6). We employed Youden's J Index to select optimal cut points and calculated sensitivity, specificity, and predictive values. We determined independent predictors via multivariable logistic regression. The derived definitions were validated in the PREDICT cohort. Twenty-four–hour National Institutes of Health Stroke Scale change was strongly associated with 90-day outcome with an area under the receiver operating characteristic curve of 0.75. Youden's method showed an optimum cut point at –0.5, corresponding to National Institutes of Health Stroke Scale change of greater than or equal to 0 (a lack of clinical improvement), which was seen in 46%. Early neurologic change accurately predicted poor outcome when defined as greater than or equal to 0 (sensitivity, 65%; specificity, 73%; positive predictive value, 70%; adjusted odds ratio, 5.05 [CI, 3.25–7.85]) or greater than or equal to 4 (sensitivity, 19%; specificity, 98%; positive predictive value, 91%; adjusted odds ratio, 12.24 [CI, 4.08–36.66]). All definitions reproduced well in the validation cohort. Conclusions: Lack of clinical improvement at 24 hours robustly predicted poor outcome and showed good discrimination for individual patients who would do poorly. These findings are useful for prognostication and may also present as a potential early surrogate outcome for future intracerebral hemorrhage treatment trials. † Deceased. Data collection took place at varying sites. Primary analysis was conducted at the University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada. Drs. Yogendrakumar, Smith, and Dowlatshahi were responsible for study concept, design, and statistical analysis. Drs. Yogendrakumar and Dowlatshahi were responsible for drafting the article. All authors participated in acquisition of data (Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign [PREDICT] and Virtual International Stroke Trials Archive) and in critical revisions of the article for intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). Dr. Demchuk's institution received funding from Canadian Stroke Consortium and NovoNordisk Canada, and he disclosed off-label product use of recombinant factor VIIa (administered for intracerebral hemorrhage in a limited fashion within the PREDICT study). Dr. Aviv received support for article research from the Canadian Institutes of Health Research. Dr. Lyden's institution received funding from the National Institute of Health (National Institute of Neurological Disorders and Stroke), and he received funding from expert testimony. Dr. Hill disclosed that the PREDICT study was supported by a grant from the Canadian Stroke Consortium. Dr. Dowlatshahi was funded by a uOttawa Department of Medicine Clinician-Scientist Research Chair award and a Heart & Stroke Foundation of Canada New Investigator Award. Dr. Dowlatshahi received funding from Bayer Canada, BMS/Pfizer, and Boerhinger Ingleheim. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: vyogendrakumar@toh.on.ca Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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