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Meta-analysis links perihematomal edema growth to poor outcomes in intracerebral hemorrhage patientsBrain swelling linked to worse outcomes in hemorrhage patients

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Key Takeaway
Note that early perihematomal edema growth associates with higher odds of death or dependence at 90 days.

This meta-analysis evaluated the relationship between changes in absolute perihematomal edema volume and clinical outcomes in patients with intracerebral hemorrhage. The study population included 1523 participants who had a diagnostic CT within 72 hours and a repeat CT within 14 days. These individuals were not treated with surgery or therapy that could affect perihematomal edema. The primary outcome was death or dependence, defined as a modified Rankin Scale score of 3 to 6, assessed at 90 plus or minus 14 days after intracerebral hemorrhage onset.

The analysis reported a positive association between absolute perihematomal edema growth and the primary outcome. Specifically, an unadjusted odds ratio of 1.04 per mL increase in edema volume within the first 24 plus or minus 12 hours was observed. The adjusted odds ratio for this early period was also 1.04 per mL increase with a 95% confidence interval of 1.01 to 1.06 and a p-value less than 0.01. Growth in the first 72 plus or minus 12 hours showed a similar pattern with an adjusted odds ratio of 1.02 per 1 mL increase and a 95% confidence interval of 1.01 to 1.04.

The study did not report adverse events, discontinuations, or specific tolerability data. Funding sources and potential conflicts of interest were not reported. The authors did not provide a specific certainty note or causality note regarding the findings. Practice relevance was not explicitly detailed in the source material. Clinicians should interpret these pooled estimates as associations rather than causal effects given the observational nature of the underlying data.

This meta-analysis looked at 1,523 participants with intracerebral hemorrhage. Researchers examined changes in the volume of swelling around the bleed on CT scans taken within 72 hours and again within 14 days. These patients were not treated with surgery or other therapies that could affect the swelling.

The study found a link between increased swelling and worse outcomes. Specifically, greater growth in swelling volume during the first 24 hours was associated with higher odds of death or dependence at 90 days. The same pattern held true for swelling growth measured over the first 72 hours.

The results suggest that early swelling is connected to the risk of poor outcomes. However, this study does not prove that the swelling causes the bad outcomes. It also does not report on safety issues or specific treatments. Readers should understand that this is observational data showing an association, not a cause-and-effect relationship.

What this means for you:
Early brain swelling after a bleed is linked to higher risk of death or disability.

Study Details

Study typeMeta analysis
Sample sizen = 1,523
EvidenceLevel 1
PublishedMay 2026
View Original Abstract ↓
BACKGROUND: Perihematomal edema (PHE) after intracerebral hemorrhage (ICH) is a biomarker of secondary brain injury. We aimed to determine the direction, strength, and temporality of the association between PHE and functional outcome after ICH onset. METHODS: We did a systematic review to identify cohort studies or trials that used brain computed tomography (CT) imaging to diagnose ICH, and measured functional outcome. We sought individual participant data if they had a diagnostic CT within 72 hours, a repeat CT within 14 days of the diagnostic scan, and were not treated with surgery or therapy that could affect PHE. We did a 2-stage individual participant data meta-analysis. The primary analysis was the association between the change in absolute PHE volume between the diagnostic CT and repeat CT and the primary outcome of death or dependence (modified Rankin Scale score, 3-6) at 90±14 days after ICH onset. We quantified the association between change in absolute PHE volume at 2 repeat CT time points (24±12 and 72±12 hours) and outcome, both unadjusted and adjusted for age, sex, ICH volume on the diagnostic CT, and intraventricular extension using multivariable logistic regression. RESULTS: From 12 969 studies, 38 were eligible, of which 12 studies (with 1 unpublished cohort and the VISTA [Virtual International Stroke Trials Archive]-ICH databank) provided data. We included 1523 participants, of whom 1347 participants (516 [38%] participants female; median age, 66 [interquartile range, 55-75] years) had repeat CT at 24±12 hours, and 495 (195 [39%] participants female; median age, 66 [interquartile range, 55-74] years) had repeat CT at 72±12 hours. 319 participants contributed to both analyses. Death or dependence was associated with absolute PHE growth both in the first 24±12 hours (unadjusted odds ratio, 1.04 per mL increase [95% CI, 1.01-1.06]; <0.01; adjusted odds ratio, 1.04 per mL increase [95% CI, 1.01-1.06]; <0.01) and in the first 72±12 hours (unadjusted odds ratio, 1.03 per mL [95% CI, 1.01-1.04]; <0.01; adjusted odds ratio, 1.02 [95% CI, 1.01-1.04] per 1 mL increase; <0.01). CONCLUSIONS: PHE growth within 24 and 72 hours of ICH onset is independently associated with death or dependence after ICH.
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