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Association between blood caspase-9 concentrations and septic patient prognosis

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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.


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.


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).


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.

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Acute physiology and chronic health evaluation


Activated partial thromboplastin time


Chronic obstructive pulmonary disease

FIO2 :

Fraction of inspired oxygen,


Intensive care unit


International normalized ratio

PaO2 :

Partial pressure of arterial oxygen


Sepsis-related organ failure assessment score


  1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.

    Article  CAS  PubMed  Google Scholar 

  2. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D. Sepsis occurrence in acutely ill patients investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34:344–53.

    Article  PubMed  Google Scholar 

  3. Harjai M, Bogra J, Kohli M, Pant AB. Is suppression of apoptosis a new therapeutic target in sepsis? Anaesth Intensive Care. 2013;41:175–83.

    Article  CAS  PubMed  Google Scholar 

  4. Sygitowicz G, Sitkiewicz D. Molecular mechanisms of organ damage in sepsis: an overview. Braz J Infect Dis. 2020;24:552–60.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Precone V, Stornaiuolo G, Amato A, Brancaccio G, Nardiello S, Gaeta GB. Different changes in mitochondrial apoptotic pathway in lymphocytes and granulocytes in cirrhotic patients with sepsis. Liver Int. 2013;33:834–42.

    Article  CAS  PubMed  Google Scholar 

  6. Delogu G, Famularo G, Tellan G, Marandola M, Antonucci A, Signore M, Marcellini S, Moretti S. Lymphocyte apoptosis, caspase activation and inflammatory response in septic shock. Infection. 2008;36:485–7.

    Article  CAS  PubMed  Google Scholar 

  7. Miliaraki M, Briassoulis P, Ilia S, Polonifi A, Mantzourani M, Briassouli E, Vardas K, Nanas S, Pistiki A, Theodorakopoulou M, Tavladaki T, Spanaki AM, Kondili E, Dimitriou H, Tsiodras S, Georgopoulos D, Armaganidis A, Daikos G, Briassoulis G. Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis. Sci Rep. 2021;11:1049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315:801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. for the Working Group on Sepsis-related Problems of the European Society of Intensive Care Medicine, Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, et al. The Sepsis-related Organ Failure Assessment (SOFA) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22:707–10.

    Article  Google Scholar 

  10. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.

    Article  CAS  PubMed  Google Scholar 

  11. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–45.

    Article  CAS  PubMed  Google Scholar 

  12. Xu P, Zhang WQ, Xie J, Wen YS, Zhang GX, Lu SQ. Shenfu injection prevents sepsis-induced myocardial injury by inhibiting mitochondrial apoptosis. J Ethnopharmacol. 2020;261:113068.

    Article  CAS  PubMed  Google Scholar 

  13. Fan H, Le JW, Zhu JH. Protective effect of N‑Acetylcysteine pretreatment on acute kidney injury in septic rats. J Surg Res. 2020;254:125–34.

    Article  CAS  PubMed  Google Scholar 

  14. Kose A, Parlakpinar H, Ozhan O, Ermis N, Yildiz A, Vardi N, Cigremis Y. Therapeutic effects of dexpanthenol on the cardiovascular and respiratory systems following cecal ligation and puncture-induced sepsis in rats. Biotech Histochem. 2020;95:428–37.

    Article  CAS  PubMed  Google Scholar 

  15. Oberholzer C, Tschoeke SK, Moldawer LL, Oberholzer A. Local thymic caspase‑9 inhibition improves survival during polymicrobial sepsis in mice. J Mol Med. 2006;84:389–95.

    Article  CAS  PubMed  Google Scholar 

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This study was supported by a grant from Instituto de Salud Carlos III (PI-18-00500) (Madrid, Spain) and co-financed with Fondo Europeo de Desarrollo Regional (FEDER).


This study was supported by a grant from Instituto de Salud Carlos III (PI-18-00500) (Madrid, Spain) and co-financed with Fondo Europeo de Desarrollo Regional (FEDER).

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Correspondence to Leonardo Lorente.

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L. Lorente, M.M. Martín, R. Ortiz-López, A. Pérez-Cejas, F. Gómez-Bernal, A. González-Mesa, A. Jiménez and A.F. González-Rivero declare that they have no competing interests.

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This prospective and observational study was conducted with the approval of the Ethics Committee from each hospital. Signed informed consent was obtained from a relative of the patients.

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Lorente, L., Martín, M.M., Ortiz-López, R. et al. Association between blood caspase-9 concentrations and septic patient prognosis. Wien Klin Wochenschr 135, 75–79 (2023).

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