Association of surgical timing with postoperative inflammatory biomarkers and clinical outcomes in patients undergoing hematoma evacuation for intracerebral hemorrhage

Background Surgical timing may influence outcomes after spontaneous intracerebral hemorrhage (ICH), but the inflammatory pathways linking delayed surgery to poor recovery remain unclear. Whether postoperative matrix metalloproteinase-9 (MMP-9), C-X-C motif chemokine ligand 10 (CXCL10), and macrophage inflammatory protein-1 alpha (MIP-1α) were associated with complications and 90-day functional outcomes after ICH evacuation was examined. Methods This retrospective cohort study included 234 adults with spontaneous ICH who underwent surgical evacuation within 72 h of symptom onset between January 2022 and December 2024. Patients were classified into three groups according to the onset-to-surgery interval: <12 h, 12–24 h, or >24 h. Postoperative biomarkers were measured within 24 h after surgery. The outcome measures included complications documented during hospitalization and poor functional outcomes at 90 days, defined as a modified Rankin Scale (mRS) score of 3–6. Multivariable logistic regression and counterfactual mediation analyses using parametric g-computation were adjusted for prespecified clinical covariates. Indirect effects and their 95% confidence intervals were estimated using 5,000 nonparametric bootstrap resamples. Results Among the 234 patients, 91 underwent surgery within 12 h, 52 within 12–24 h, and 91 after 24 h. Postoperative CXCL10, MIP-1α, and MMP-9 concentrations increased across later surgical-timing groups (all p < 0.001). The corresponding rates of postoperative complications were 56.0%, 67.3%, and 73.6%, and those of unfavorable 90-day functional outcomes were 45.1%, 51.9%, and 63.7%, respectively. After adjustment, surgery performed >24 h after onset was associated with postoperative complications (OR, 2.19; 95% CI, 1.17–4.08) and unfavorable functional outcomes (OR, 1.88; 95% CI, 1.04–3.40), whereas surgery performed at 12–24 h was not. MIP-1α mediated 21.2 and 24.6% of these respective associations, while MMP-9 mediated 29.3 and 31.0%, respectively. No significant indirect effects were observed for CXCL10 or for surgery performed at 12–24 h. Conclusion Surgery performed more than 24 h after ICH onset was associated with greater postoperative inflammation and higher risks of postoperative complications and unfavorable 90-day functional outcomes. MIP-1α and MMP-9 may partly mediate these associations, although the observational design precludes causal inference.