Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Background and Purpose—: Acute leukocytosis is a well-established response to intracerebral hemorrhage (ICH). Leukocytes, because of their interaction with platelets and coagulation factors, may in turn play a role in hemostasis. We investigated whether admission leukocytosis was associated with reduced bleeding after acute ICH. Methods—: Consecutive patients with primary ICH were prospectively collected from 1994 to 2015 and retrospectively analyzed. We included subjects with a follow-up computed tomographic scan available and automated complete white blood cell count performed within 48 hours from onset. Baseline and follow-up hematoma volumes were calculated with semiautomated software, and hematoma expansion was defined as volume increase >30% or 6 mL. The association between white blood cell count and ICH expansion was investigated with multivariate logistic regression. Results—: A total of 1302 subjects met eligibility criteria (median age, 75 years; 55.8% men), of whom 207 (15.9%) experienced hematoma expansion. Higher leukocyte count on admission was associated with reduced risk of hematoma expansion (odds ratio for 1000 cells increase, 0.91; 95% confidence interval, 0.86–0.96; P =0.001). The risk of hematoma expansion was inversely associated with neutrophil count (odds ratio, 0.90; 95% confidence interval, 0.85–0.96; P =0.001) and directly associated with monocyte count (odds ratio, 2.71; 95% confidence interval, 1.08–6.83; P =0.034). There was no association between lymphocyte count and ICH expansion (odds ratio, 0.96; 95% confidence interval, 0.79–1.17; P =0.718). Conclusions—: Higher admission white blood cell count is associated with lower risk of hematoma expansion. This highlights a potential role of the inflammatory response in modulating the coagulation cascade after acute ICH.

Objective: To validate various noncontrast CT (NCCT) predictors of hematoma expansion in a large international cohort of ICH patients and investigate whether intensive blood pressure (BP) treatment reduces ICH growth and improves outcome in patients with these markers. Methods: We analyzed patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized controlled trial. Participants were assigned to intensive (systolic BP <140 mm Hg) vs standard (systolic BP 33% and unfavorable outcome was defined as modified Rankin Scale score >3 at 90 days. Logistic regression was used to identify predictors of ICH expansion and explore the association between NCCT signs and clinical benefit from intensive BP treatment. Results: A total of 989 patients were included (mean age 62 years, 61.9% male), of whom 186/869 experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable outcome. NCCT markers independently predicted ICH expansion (all p < 0.01) with overall accuracy ranging from 61% to 78% and good interrater reliability (k > 0.6 for all markers). There was no evidence of an interaction between NCCT markers and benefit from intensive BP reduction (all p for interaction >0.10). Conclusions: NCCT signs reliably identify ICH patients at high risk of hematoma growth. However, we found no evidence that patients with these markers specifically benefit from intensive BP reduction. Clinicaltrials.gov identifier: NCT01176565.

Objective To provide precise estimates of the association between non-contrast CT (NCCT) markers, hematoma expansion (HE) and functional outcome in patients presenting with intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. Methods We searched PubMed for English-written observational studies or randomized controlled trials reporting data on NCCT markers of HE and outcome in spontaneous ICH including at least 50 subjects. The outcomes of interest were HE (hematoma growth >33%, >33% and/or >6 mL, >33% and/or >12.5 mL), poor functional outcome (modified Rankin Scale 3–6 or 4–6) at discharge or at 90 days, and mortality. We pooled data in random-effects models and extracted cumulative odds ratio (OR) for each NCCT marker. Results We included 25 eligible studies (n = 10,650). The following markers were associated with increased risk of HE and poor outcome respectively: black hole sign (OR = 3.70, 95% confidence interval [CI] = 1.42–9.64 and OR = 5.26, 95% CI = 1.75–15.76), swirl sign (OR = 3.33, 95% CI = 2.42–4.60 and OR = 3.70; 95% CI = 2.47–5.55), heterogeneous density (OR = 2.74; 95% CI = 1.71–4.39 and OR = 2.80; 95% CI = 1.78–4.39), blend sign (OR = 3.49; 95% CI = 2.20–5.55 and OR = 2.21; 95% CI 1.16–4.18), hypodensities (OR = 3.47; 95% CI = 2.18–5.50 and OR = 2.94; 95% CI = 2.28–3.78), irregular shape (OR = 2.01, 95% CI = 1.27–3.19 and OR = 3.43; 95% CI = 2.33–5.03) and island sign (OR = 7.87, 95% CI = 2.17–28.47 and OR = 6.05, 95% CI = 4.44–8.24). Conclusion Our results suggest that multiple NCCT ICH shape and density features, with different effect size, are important markers for HE and clinical outcome, and may provide useful information for future randomized controlled trials.