Several Cytokines and Protein C Levels with the Apache II Scoring System for Evaluation of Patients with Sepsis

Abstract

Objective: We investigated whether determination IL-6, IL-8, IL-1beta and TNF-alpha at baseline, total protein C (PC) levels at time of admission and 48 hours after initiation could complement the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system to identify patients with sepsis, severe sepsis or septic shock for clinical outcome. Material and Methods: The study was carried out prospectively. 60 consecutive patients with sepsis, severe sepsis or septic shock were included. Blood samples were obtained at baseline and 48 hours after initiation. Cytokines and PC levels in plasma were measured with an enzyme-linked immunoabsorbent assay (ELISA). APACHE II score was calculated on admission. Results: Baseline IL-6 levels and PC levels 48 hours after initiation were predictive of increased mortality (p=0.016, p=0.044 respectively). Baseline IL-6, IL-8 and TNF-alpha baseline levels correlate with the severity of physiologic insult, as determined by the APACHE II score. However, our multiple logistic regression analysis of these did not reveal any predictive value in combination with the APACHE II score. Conclusion: Determination of baseline IL-6 and PC 48 hours after initiation were of predictive value for prognostic evaluation of septic patients, but did not significantly increase predictive power of the APACHE scoring system to identify patients with sepsis for fatal clinical outcome.

Keywords

• Interleukin 6, Interleukin 8, Interleukin 1-beta, Tumor necrosis factor-alpha, Protein C, Sepsis, APACHE II

Several Cytokines and Protein C Levels with the Apache II Scoring System for Evaluation of Patients with Sepsis

Abstract

References

1. Members of the American College of Chest Physicians/Society of Critical Care Medicine consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-74. [CrossRef]
2. Satran R, Almog Y. The coagulopathy of sepsis: pathophysiology and management. IMAJ 2003;5:516-20.
3. Knaus WA, Draper EA Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med 1985;13:818-29. [CrossRef]
4. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, et al. The APACHE III prognostic system. Risk predic- tion of hospital mortality for critically ill hospitalized adults. Chest 1991;100:1619-36. [CrossRef]
5. Oda S, Hiroyuki H, Shiga H, Nakanishi K, Matsuda K, Nakamua M. Sequential measurement of IL-6 blood levels in patients with sys- temic inflammatory response syndrome (SIRS)/sepsis. Cytokine 2005;29:169-75. [CrossRef]
6. Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, et al. Persistant elevation of inflammatory cytokines predicts a poor outcome in ARDS:plasma IL-1β and IL-6 levels are con- sistent and efficient predictors of outcome over time. Chest 1995;107:1062-73. [CrossRef]
7. Damas P, Canivet JL, Groote DD, Vrindts Y, Albert A, Franchimont P, et al. Sepsis and serum cytokine concentrations. Crit Care Med 1997;25:405-12. [CrossRef]
8. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Defi- nitions Conference Intensive Care Med 2003;29:530-8.

9. Terregino CA, Lopez BL, Karras DJ, Killian AJ, Arnold GK. Endog- enous Mediators in Emergency Department patients with pre- sumed sepsis: are levels associated with progression to severe sepsis and death? Ann Emerg Med 2000;35:26-34. [CrossRef]
10. Bellomo R. The cytokine network in the critically ill. Anesth Inten- sive Care 1992;20:288-301.
11. Pober JS, Cotran RS. Cytokines and endothelial cell biology. Physiol Rev 1990;70:427-51.
12. Gårdlund B, Sjölin J, Nilsson A, Roll M, Wickerts CJ, Wretlind B. Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity. J Infect Dis 1995;172:296-301. [CrossRef]
13. Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, et al. Dynamic evolution of coagulopathy in the first day of severe sepsis: Relationship with mortality and organ failure.Crit Care Med 2005;33:341-8. [CrossRef]
14. Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abou- hamze A, Pribble JP, et al. Plasma cytokine measurments aug- ment prognostic scores as indicators of outcome in patients with severe sepsis. Shock 2005;23:488-93.
15. Presterl E, Staudinger T, Pettermann M, Lassnigg A, Burgmann H, Winkler S, et al. Cytokine profile and correlation to the APACHE III and MPM II scores in patients with sepsis. Am J Respir Crit Care Med 1997;156:825-32.
16. Groenoveld ABJ, Tacx AN, Bossink AWJ, van Mierlo GJ, Hack CE. Circulating inflamatory mediators predict shock and mor- tality in febrile patients with microbial infection. Clin Immunol 2003;106;106-15. [CrossRef]
17. Uras N, Karadag A, Tonbul A, Mete E, Kara S, Karabel M, et al. Serum Interleukin-6 Levels in differential Diagnosis of Sepsis and Transient Tachypnea of Newborn. Trakya Univ Tıp Fak Derg 2010;27:257-60.
18. Philippe J, Offner F, Declerck PJ, Leraux-Roels G, Vogelaers D, Baele G, et al. Fibrinolysis and coagulation in patients with infec- tious disease and sepsis. Thromb Haemost 1991;65:291-5.
19. Lorente JA, Garcia-Frade LJ, Landin L, de Pablo R, Torrado C, Renes E, et al. Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 1993;103:1536-42. [CrossRef]
20. Carvalho AC, Freeman NJ. How coagulation defects alter out- come in sepsis: survival may depend on reversing procoagulant conditions. J Crit Illness 1994;9:51-75.
21. Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, et al. Septic shock, multiple organ failure and disseminated intravas- cular coagulation: compare patterns of antithrombin III, protein C and protein S deficiencies. Chest 1992;101:816-23. [CrossRef]
22. Fisher CJ, Yan SB. Protein C levels as a prognostic indica- tor of outcome in sepsis and related diseases. Crit Care Med 2000;28:49-56. [CrossRef]
23. Macias WL, Nelson DR. Severe protein deficiency predicts early death in severe sepsis. Crit Care Med 2004;32:223-8. [CrossRef]
24. Levi M, Ten Cate H, van der Poll T. Endothelium: interface between coagulation and inflammation. Crit Care Med 2002;30:S230-4. [CrossRef]
25. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez- odriquez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Eng J Med 2001;344:699-709. [CrossRef]