Skip to main content
Log in

Prognostic value of troponins in sepsis: a meta-analysis

  • Systematic Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Rationale

The role of biomarkers such as troponin in risk stratification of sepsis is still debated. The aim of this meta-analysis is to assess the relation between troponin elevation in sepsis and mortality.

Methods

All observational studies from Embase, Medline and those manually searched up to September 2010 were included. Studies identified were those which reported on patients with a diagnosis of sepsis and if a 2 × 2 table could be constructed based on troponins and death. We pooled the relative risk (RR) and odds-ratio (OR) using the inverse variance method in studies that conducted univariate and multivariable (adjusted) analysis.

Main results

Thirteen studies encompassing 1,227 patients were included. The prevalence of elevated troponin was 61 % ([95 %] CI 58–64 %). Elevated troponin was significantly associated with all-cause mortality (RR 1.91; CI 1.63–2.24), with homogeneity across studies. In adjusted analysis (four studies comprising 791 patients) according to prognostic scores, elevated troponin was associated with an increased risk of death (OR 1.92; CI 1.35–2.74). The area under the ROC curve was 0.68 (CI 0.63–0.71). Pooled sensitivity and specificity were 77 % (CI 61–88) and 47 % (CI 30–64) with heterogeneity across studies. It corresponded to positive and negative likelihood ratios of 1.50 (95 % CI: 1.20–1.90) and 0.49 (CI 0.38–0.64), respectively.

Conclusions

Elevated troponin identifies a subset of patients with sepsis at higher risk of death. Further studies are needed to define the precise role of troponins and their optimal cut-offs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, Ognibene FP (1990) Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 113:227–242

    Article  CAS  PubMed  Google Scholar 

  2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310

    Article  CAS  PubMed  Google Scholar 

  3. Grocott-Mason RM, Shah AM (1998) Cardiac dysfunction in sepsis: new theories and clinical implications. Intensive Care Med 24:286–295

    Article  CAS  PubMed  Google Scholar 

  4. Khan IA, Tun A, Wattanasauwan N, Win MT, Hla TA, Hussain A, Vasavada BC, Sacchi TJ (1999) Elevation of serum cardiac troponin I in non cardiac and cardiac diseases other than acute coronary syndromes. Am J Emerg Med 17:225–229

    Google Scholar 

  5. Markou N, Gregorakos L, Myrianthefs P (2011) Increased blood troponin levels in ICU patients. Curr Opin Crit Care 17:454–463

    Article  PubMed  Google Scholar 

  6. Brivet FG, Jacobs FM, Colin P, Prat D, Grigoriu B (2006) Cardiac troponin level is not an independent predictor of mortality in septic patients requiring medical intensive care unit admission. Crit Care 10:404

    Article  PubMed  Google Scholar 

  7. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  PubMed  Google Scholar 

  8. Levy M, Fink MP, Marshall JC, Abraham JC, Abraham E, Angus D, Cook D, Cohen D, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definitions conference. Intensive Care Med 29(4):530–538

    PubMed  Google Scholar 

  9. 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 (1992) Crit Care 20:864–874

    Google Scholar 

  10. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  11. Cucherat M, Boissel JP, Leizorovicz A, Haugh MC (1997) EasyMA: a program for the meta-analysis of clinical trials. Comput Methods Programs Biomed 53:187–190

    Article  CAS  PubMed  Google Scholar 

  12. Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240:1285–1293

    Article  CAS  PubMed  Google Scholar 

  13. Arends LR, Hamza TH, van Houwelingen JC, Heijenbrok-Kal MH, Hunink MG, Stijnen T (2008) Bivariate random effects meta-analysis of ROC curves. Med Decis Making 28:621–638

    Article  CAS  PubMed  Google Scholar 

  14. Irwig L, Tosteson AN, Gatsonis C, Lau J, Colditz G, Chalmers TC, Mosteller F (1994) Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med 120:667–676

    Article  CAS  PubMed  Google Scholar 

  15. Walter SD (2002) Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 15(21):1237–1256

    Article  Google Scholar 

  16. Gatsonis C, Paliwal P (2006) Meta-analysis of diagnostic and screening test accuracy evaluations: methodologic primer. AJR Am J Roentgenol 187:271–281

    Article  PubMed  Google Scholar 

  17. STATA. Data analysis and statistical software. Copyright StataCorp. College Station, TX

  18. Baker WL, White CM, Cappelleri JC, Kluger J, Coleman CI (2009) Understanding heterogeneity in meta- analysis: the role of meta-regression. Int J Clin Pract 63:1426–1434

    Article  CAS  PubMed  Google Scholar 

  19. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  Google Scholar 

  20. Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58:882–893

    Article  PubMed  Google Scholar 

  21. Spies C, Haude V, Fitzner R, Schroder K, Overbeck M, Runkel N, Schaffartzik W (1998) Serum cardiac troponin T as a prognostic marker in early sepsis. Chest 113:1055–1063

    Article  CAS  PubMed  Google Scholar 

  22. Fernandes CJ Jr, Akamine N, Knobel E (1999) Cardiac troponin: a new serum marker of myocardial injury in sepsis. Intensive Care Med 25:1165–1168

    Article  PubMed  Google Scholar 

  23. Turner A, Tsamitros M, Bellomo R (1999) Myocardial cell injury in septic shock. Crit Care Med 27:1775–1780

    Article  CAS  PubMed  Google Scholar 

  24. ver Elst KM, Spapen HD, Nguyen DN, Garbar C, Huyghens LP, Gorus FK (2000) Cardiac troponins I and T are biological markers of left ventricular dysfunction in septic shock. Clin Chem 46:650–657

    CAS  PubMed  Google Scholar 

  25. Ammann P, Fehr T, Minder EI, Gunter C, Bertel O (2001) Elevation of troponin I in sepsis and septic shock. Intensive Care Med 27:965–969

    Article  CAS  PubMed  Google Scholar 

  26. Mehta NJ, Khan IA, Gupta V, Jani K, Gowda RM, Smith PR (2004) Cardiac troponin I predicts myocardial dysfunction and adverse outcome in septic shock. Int J Cardiol 95:13–17

    Article  PubMed  Google Scholar 

  27. John J, Awab A, Norman D, Dernaika T, Kinasewitz GT (2007) Activated protein C improves survival in severe sepsis patients with elevated troponin. Intensive Care Med 33:2122–2128

    Article  CAS  PubMed  Google Scholar 

  28. Issa VS, Taniguchi LU, Park M, Cruz LM, Bocchi EA, Velasco IT, Soriano F (2008) Positive end-expiratory pressure and renal function influence B-type natriuretic peptide in patients with severe sepsis and septic shock. Arq Bras Cardiol 91:107–112

    Article  PubMed  Google Scholar 

  29. Choon-ngarm T, Partpisanu P (2008) Serum cardiac troponin-T as a prognostic marker in septic shock. J Med Assoc Thai 91:1818–1821

    PubMed  Google Scholar 

  30. Yucel T, Memis D, Karamanlioglu B, Sut N, Yuksel M (2008) The prognostic value of atrial and brain natriuretic peptides, troponin I and C-reactive protein in patients with sepsis. Exp Clin Cardiol 13:183–188

    CAS  PubMed  Google Scholar 

  31. Kang EW, Na HJ, Hong SM, Shin SK, Kang SW, Choi KH, Lee HY, Han DS, Han SH (2009) Prognostic value of elevated cardiac troponin I in ESRD patients with sepsis. Nephrol Dial Transplant 24:1568–1573

    Article  CAS  PubMed  Google Scholar 

  32. John J, Woodward DB, Wang Y, Yan SB, Fisher D, Kinasewitz GT, Heiselman D (2010) Troponin-I as a prognosticator of mortality in severe sepsis patients. J Crit Care 25:270–275

    Article  CAS  PubMed  Google Scholar 

  33. Guest TM, Ramanathan AV, Tuteur PG, Schechtman KB, Ladenson JH, Jaffe AS (1995) Myocardial injury in critically ill patients. A frequently unrecognized complication. JAMA 273:1945–1949

    Article  CAS  PubMed  Google Scholar 

  34. Gurkan F, Alkaya A, Ece A et al (2004) Cardiac troponin-I as a marker of myocardial dysfunction in children with septic shock. Swiss Med Wkly 134:593–596

    CAS  PubMed  Google Scholar 

  35. Hirsch R, Landt Y, Porter S et al (1997) Cardiac troponin I in pediatrics:normal values and potential use in the assessment of cardiac injury. J Pediatr 130:872–877

    Article  CAS  PubMed  Google Scholar 

  36. Singh S, Evans TW (2006) Organ dysfunction during sepsis. Intensive Care Med 32:349–360

    Article  CAS  PubMed  Google Scholar 

  37. Maeder M, Fehr T, Rickli H, Ammann P (2006) Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest 129:1349–1366

    Article  CAS  PubMed  Google Scholar 

  38. Altmann DR, Korte W, Maeder MT, Fehr T, Haager P, Rickli H, Kleger GR, Rodriguez R, Ammann P (2010) Elevated cardiac troponin I in sepsis and septic shock: no evidence for thrombus associated myocardial necrosis. PLoS One 5

  39. Wu AHB (2001) Increased troponin in patients with sepsis and septic shock: myocardial necrosis or reversible myocardial depression? Intensive Care Med 27:959–961

    Article  CAS  PubMed  Google Scholar 

  40. Dinnes J, Deeks J, Kirby J, Roderick P (2005) A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess 9:1–113

    CAS  Google Scholar 

Download references

Acknowledgments

For help with editing in English, and other valuable advice, the authors thank Dr. Michael Cotton of the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. We are grateful to FG Brivet for the additional data from his study. Grants, funding, financial support: none declared.

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Christophe Lega.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 111 kb)

Supplementary material 2 (DOC 59 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bessière, F., Khenifer, S., Dubourg, J. et al. Prognostic value of troponins in sepsis: a meta-analysis. Intensive Care Med 39, 1181–1189 (2013). https://doi.org/10.1007/s00134-013-2902-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-013-2902-3

Keywords

Navigation