Advances in Therapeutic Approaches for Spontaneous Intracerebral Hemorrhage

Abstract

Spontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse outcomes. Therapeutic interventions in acute ICH have continued to emerge with focus on arresting hemorrhage expansion, clot volume reduction of both intraventricular and parenchymal hematomas, and targeting perihematomal edema and inflammation. Large randomized controlled trials addressing the effectiveness of rapid blood pressure lowering, hemostatic therapy with platelet transfusion, and other clotting complexes and hematoma volume reduction using minimally invasive techniques have impacted clinical guidelines. We review the recent evolution in the management of acute spontaneous ICH, discussing which interventions have been shown to be safe and which may potentially improve outcomes.

Keywords: Fibrinolysis; Intracerebral hemorrhage; Intraventricular hemorrhage; Outcomes; Stroke.

Fig. 1

Associations of categorized systolic blood pressure summary measures and clinical outcomes from the pooled INTERACT2 and the ATACH-II trials. These assessments of the systolic blood pressure (SBP) summary measures (mean achieved and standard deviation (variability) over first 24 h, and magnitude of change in SBP over first hour after treatment initiation) as categories show that generally lower categories of achieved SBP (left) seemed to be associated with better outcomes, down to 120–130 mmHg, although not significant in the categorical analysis (top), that lower variability (middle) was associated with weak evidence for associations with adverse outcomes, significant for death (bottom), and that U-shaped associations were apparent for increasing magnitude of decrease in SBP over the first 24 h (right). Reprinted from Moullaali et al. [6], Blood pressure control and clinical outcomes in acute intracerebral hemorrhage: a preplanned pooled analysis of individual participant data, Lancet Neurol. 2019;18:857–864 by permission of Elsevier

Fig. 2

Hematoma reduction and probability of a good outcome from the MISTIE III trial. Cubic spline regression analyses (blue line) and linear spline regression analyses (black line) showing the relationship of hematoma reduction (EOT ICH Volume) to the probability of having a good outcome, mRS 0 to 3, at 1 year. Outcome is dichotomized as 1 or 0 (green dots at 1 = mRS 0 to 3, red dots at 0 = mRS 4 to 6). Further reduction beyond the 15 mL threshold (OR 0.09, P = 0.002) increased the chance of having a good outcome by 10% for each additional milliliter of hematoma removed (green shading showing statistically significant area of curve). Volume reductions to > 15 mL threshold did not significantly impact the likelihood of achieving a good outcome. Reprinted from Awad et al. [56], Surgical performance determines functional outcome benefit in the Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure, Neurosurgery 2019;84:1157–1168, by permission of the Congress of Neurological Surgeons

Fig. 3

Kaplan-Meier survival estimates from day of randomization to observed day of death from the CLEAR III trial. Estimated survival probabilities were higher throughout 180 days of follow-up with alteplase compared with saline (p = 0·006). Shading shows 95% CI. Reprinted from Hanley et al. [75], The Lancet, 389, Thrombolytic removal of intraventricular hemorrhage in treatment of severe stroke: results of the randomized, multicenter, multi-region, placebo-controlled CLEAR III trial, 603–611, Copyright 2017, with permission from Elsevier