Association between blood caspase-9 concentrations and septic patient prognosis

Abstract

Background: There are few data on caspase‑9 (intrinsic apoptosis pathway initiating caspase) in septic patients. Higher serum caspase‑9 levels in septic patients than in healthy subjects have been found. However, there are no data on the prognosis of septic patients and blood caspase‑9 concentrations. Therefore, the objective of this study was to analyze the potential association between blood caspase‑9 concentrations and prognosis in septic patients.

Methods: Three Spanish hospitals participated in the recruitment of septic patients admitted to intensive care units in this observational and prospective study. Serum caspase‑9 concentrations were determined at the time of sepsis diagnosis. The 30-day mortality was the outcome variable.

Results: Higher Acute Phisiology and Chronic Health Evaluation(APACHE)-II (p < 0.001), Sepsis-related Organ Failure Assessment score (SOFA) (p < 0.001), serum lactic acid levels (p = 0.001), serum caspase‑9 levels (p < 0.001), age (p < 0.001), International normalized ratio (INR) (p = 0.001), rate of septic shock (p = 0.001), Activated partial thromboplastin time (aPTT) (p = 0.03), rate of diabetes mellitus (p = 0.04), and lower platelet counts (p = 0.01) were found in non-surviving (n = 80) than in surviving patients (n = 134). Multiple logistic regression analysis showed an association between serum caspase‑9 concentrations and mortality (Odds Ratio (OR) = 1.985; 95% Confidence Interval (CI) = 1.359-2.900; p < 0.001) regardless of age, SOFA, lactic acid and septic shock and history of diabetes mellitus. No significant differences were found when we compared area under ROC curves of serum caspase‑9 with SOFA (p = 0.92) and with lactic acid (p = 0.59).

Conclusions: The main novel finding of our study was the association between blood caspase‑9 concentrations and septic patient prognosis. However, our study showed some limitations (for example, the absence of data in respect to execution of Surviving Sepsis Campaign bundles); thus, more research could be interesting to confirm our preliminary findings.

Keywords: Apoptosis; Evolution; Mortality; Outcome; Sepsis.