Blood Pressure Management Is Only Part of the Story in Intracerebral Hemorrhage

hemorrhagic stroke
hemorrhagic stroke
A joint medical and surgical approach may ensure the best outcome.

Adnan Qureshi, MD, and his colleagues at the University of Minnesota recently published the anticipated Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage (ATACH2)1 trial in the New England Journal of Medicine, examining the effects of rapidly lowering blood pressure in patients suffering from acute intracerebral hemorrhage (ICH).

This large, open-label, multicenter trial recruited 1000 patients randomized within 4.5 hours to intensive blood pressure management with a goal systolic blood pressure (SBP) of less than 140 mmHg or standard guideline care for 24 hours. The primary outcome of death or disability (modified Rankin scale score of 4-6) at 3 months was not statistically significant between groups. The trial stopped recruiting prematurely, citing futility prior to reaching the intended target of 1280 participants.

The trial concluded that acute intensive blood pressure management to SBP less than 140 mmHg was not beneficial in terms of functional outcomes at 3 months compared to current standard guidelines, and serves to demystify some of the confusion surrounding the acute management of blood pressure in ICH. A narrow interpretation of the results would conclude that intensive acute blood pressure management is likely not warranted in most cases of ICH. However, when we consider the immensely complex and dynamic cascades of secondary brain injury, this view becomes overly simplistic.

The primary mechanism of damage is thought to occur from hematoma expansion and edema resulting in deformation of neuronal and glial cell membranes leading to cell death.2,3 Patients are at highest risk for hematoma expansion within the first 6 hours of presentation, likely due to continued acute hypertension and/or coagulation defects, and are at risk for expansion up to 20 hours post bleed.3,4

After the initial bleed, continuing damage occurs from a variety of processes including vascular autoregulatory dysfunction, microangiopathic coagulopathy and reactive oxygen species from exposure of vascular collagen and metalloproteinases, excitotoxicity from calcium and glutamate, direct neurotoxicity from exposure to free iron, and increased inflammatory response with cytokine release, leukocyte infiltration and microglial activation.5,6 Trial data supports the idea that larger areas of hematoma expansion and peri-hematomal edema have a negative effect on outcomes.7

Several trials have explored therapeutic strategies to reduce the primary brain injury resulting from hematoma expansion and peri-hematomal edema by addressing coagulopathy and hypertension. Studies examining early infusion with recombinant factor VII showed reduced hematoma growth, but failed to show improvement in functional outcomes in phase 3 efficacy trials.8,9 Similarly, pilot studies examining the effect of intensive blood pressure lowering in acute ICH have shown reduced hematoma growth, but this was not clearly translated into better functional outcomes,10,11 including the current ATACH2 trial. As such, current guidelines lay out vague recommendations regarding these interventions.12