Skip to main content

Association between apoptosis and mortality in severe septic patients


The apoptotic process, in which cells are actively eliminated by a programmed pathway, is increased in sepsis. Extrinsic and intrinsic apoptotic death cell pathways activate caspase-3, which leads to cell apoptosis. Cytokeratin 18 (CK-18), a protein present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptotic death. The novel objectives of this study were to determine whether there are associations between serum caspase-3 levels, serum CK-18 levels and mortality in septic patients.


A prospective, multicenter, observational study in six Spanish ICUs, including 216 patients with severe sepsis. We collected blood samples at the severe sepsis diagnosis moment to determine serum levels of caspase-3 (to assess the main executor of apoptosis) and CCCK18 (to assess the apoptosis level). The endpoint was 30-day mortality.


We found that nonsurvivor (n = 76) in comparison with survivor (n = 140) septic patients showed higher serum levels of caspase-3 (0.41 ng/ml (0.14 to 0.52) vs. 0.11 ng/ml (0.10 to 0.25); P < 0.001) and CCCK18 (448 (310 to 723) vs. 319 (236 to 445); P < 0.001). Multiple logistic regression showed that serum caspase-3 levels >0.25 ng/ml were associated with mortality at 30 days (odds ratio = 6.51; 95% confidence interval = 3.32 to 12.77; P < 0.001), controlling for SOFA score and age. Kaplan-Meier survival analysis showed a higher risk of death in septic patients with serum caspase-3 levels >0.25 ng/ml than in patients with lower levels (hazard ratio = 3.80; 95% CI = 2.35 to 6.15; P < 0.001). We found a positive association between serum levels of caspase-3 and CCCK-18 (ρ = 0.32; P < 0.001).


The novel findings of our study were that there is an association between serum caspase-3 levels, serum CK-18 levels and mortality in septic patients. There has been reported decreased apoptosis and increased survival in septic rats with the administration of caspase inhibitors; thus, it may be interesting to explore those agents in septic patients.


Funded by Grant FIS-PI-14-00220 from Instituto de Salud Carlos III (Madrid, Spain) and co-financed by Fondo Europeo de Desarrollo Regional (FEDER).

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lorente, L., Martín, M., González-Rivero, A. et al. Association between apoptosis and mortality in severe septic patients. Crit Care 19 (Suppl 1), P53 (2015).

Download citation

  • Published:

  • DOI:


  • Severe Sepsis
  • Septic Patient
  • Apoptotic Death
  • Death Cell Pathway
  • Sofa Score