Skip to main content
Erschienen in: Wiener klinische Wochenschrift 3-4/2023

19.07.2022 | original article

Association between blood caspase-9 concentrations and septic patient prognosis

verfasst von: Leonardo Lorente, María M. Martín, Raquel Ortiz-López, Antonia Pérez-Cejas, Fuensanta Gómez-Bernal, Adriana González-Mesa, Alejandro Jiménez, Agustín F. González-Rivero

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 3-4/2023

Einloggen, um Zugang zu erhalten

Summary

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.
Literatur
1.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
2.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
3.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
6.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat 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.CrossRef 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.CrossRef
10.
Zurück zum Zitat Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.CrossRefPubMed Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818–29.CrossRefPubMed
11.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
Association between blood caspase-9 concentrations and septic patient prognosis
verfasst von
Leonardo Lorente
María M. Martín
Raquel Ortiz-López
Antonia Pérez-Cejas
Fuensanta Gómez-Bernal
Adriana González-Mesa
Alejandro Jiménez
Agustín F. González-Rivero
Publikationsdatum
19.07.2022
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 3-4/2023
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-022-02059-2

Weitere Artikel der Ausgabe 3-4/2023

Wiener klinische Wochenschrift 3-4/2023 Zur Ausgabe

mitteilungen der gesellschaft der ärzte in wien

Public Health in Österreich