Yang J, Arima H, Wu G, Heeley E, Delcourt C, Zhou J, et al. for the INTERACT Investigators. Prognostic Significance of Perihematomal Edema in Acute Intracerebral Hemorrhage: Pooled Analysis From the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies. Stroke. 2015
The effects of the inflammatory response to intracranial hemorrhage (ICH) include toxicity of blood breakdown products, free radicals and perihematomal edema (PHE). Initial volume and subsequent growth of the hematoma is pivotal to determining outcome in ICH, but perihematomal edema (PHE) also contributes to the risk of death and disability from raised intracranial pressure and possibly hydrocephalus. In past studies, volumetric measurements have been performed to explore whether PHE is an independent predictor of outcome and have shown no statistically significant associations which have been attributed to limited power. The authors of this study investigated the prognostic significance of PHE by analyzing over 1000 patients with acute ICH combining data from INTERACT1 with those of the main phase INTERACT2.
INTERACT1 and INTERACT2 were international, multicenter, prospective, open, blinded endpoint, randomized controlled trials that enrolled 404 and 2839 patients respectively. The patients enrolled were those with spontaneous ICH within 6 hours of onset and elevated systolic blood pressure (SBP, 150-220 mmHg) who were allocated to receive intensive (target SBP <140 mmHg within 1 hour) or guideline-recommended (target SBP <180 mmHg) BP lowering treatment. Patients were included in this analysis if they had 2 CTs available for edema analysis and outcome information. Of the 1138 (87%) patients analyzed, time from ICH onset to baseline CT, baseline hematoma volume, 24-hr hematoma growth, and intraventricular extension were independent predictors of 24-hr PHE growth. Absolute growth in PHE volume was significantly associated with death or dependency (adjusted OR 1.17, 95%CI 1.02-1.33 per 5 mL increase from baseline; p=0.025) at 90 days after adjustment for demographic, clinical and hematoma parameter prognostic factors.
Interestingly, the results show less growth of PHE in the intensive group, suggesting an effect of early intensive BP lowering on PHE. Furthermore the use of mannitol was one of the factors that also independently predicted growth of PHE. The authors recognize that this study is limited in its scope to the first 24 hours as PHE is recognized to expand beyond this time point, reaching a peak in growth after at least several days, and sometimes a few weeks. The results from this study and previous studies should spark further investigation into the factors that can mitigate and promote PHE growth in a patient. The role of MMP-9 has been implicated as a significant factor and correlation between location and PHE growth should also be investigated further. While the use of the INTERACT1 and 2 registry is useful in drawing some limited associations, focus should be placed on dedicated studies that investigate this topic in detail.