Low blood caspase-8 levels in survivor patients of traumatic brain injury

Objective: High concentrations of caspase-8 (main initiator caspase of the extrinsic pathway of apoptosis) have been found in brain tissue of patients with traumatic brain injury (TBI) and in the blood of patients with different diseases. However, blood caspase-8 concentrations in TBI patients have not been reported. Therefore, our aim was to analyze whether blood caspase-8 concentrations are associated with mortality in TBI patients.

Method: Patients with isolated and severe TBI were included. TBI was considered isolated if it showed an Injury Severity Score (ISS) <10 points on non-cranial aspects. TBI was considered severe if it showed a Glasgow Coma Scale (GCS) <9 points. This prospective observational study was conducted in 5 Intensive Care Units. Serum caspase-8 concentrations were measured on day 1 of TBI.

Results: Surviving patients (n=59) had lower age (p=0.004), higher GCS (p=0.001), lower APACHE-II score (p<0.001), lower high-risk-of-death computed tomography (CT) findings (p=0.02), lower intracranial pressure (ICP) (p=0.01), and lower serum caspase-8 concentrations (p<0.001) than non-surviving patients (n=24). An association was found between serum caspase-8 levels and mortality after controlling for CT findings, GCS, and age (OR=1.037; 95% CI=1.013-1.062; p=0.002), and after controlling for CT findings, APACHE-II, and ICP (OR=1.042; 95% CI=1.013-1.071; p=0.004) in multiple logistic regression.

Conclusions: To our knowledge, this is the first series describing blood caspase-8 concentrations in patients with TBI. The association of high blood caspase-8 concentrations with mortality was the main new finding of the study. However, further investigations are needed to validate the preliminary results of our study.