Hellenic Journal of Surgery

, Volume 90, Issue 5, pp 232–238 | Cite as

Pilot Trial Evaluating Mid-Regional Pro-Atrial Natriuretic Peptide as a Marker of Sepsis after Abdominal Surgery

  • L KousoulasEmail author
  • Jm Fink
  • T Glatz
  • C LäβLe
  • IJ Bohlmann
  • S Fichtner-Feigl
  • S Utzolino
Original Article



Mid-regional pro-atrial natriuretic peptide (MR pro-ANP) has been shown to be a diagnostic marker for sepsis. The objective of this pilot study was to evaluate the potential of MR pro-ANP in the diagnosis of postoperative sepsis.


We enrolled 18 patients with postoperative sepsis, 19 patients who underwent major abdominal surgery without sepsis and 9 healthy individuals as control subjects. MR pro-ANP, interleukin-6 (IL-6) and procalcitonin (PCT) were measured on the day of inclusion in the study, and at days 3, 7 and 10.


The mean levels of MR pro-ANP were significantly higher in patients with postoperative sepsis than in patients without sepsis (two-way ANOVA p <0.0001). The best cut-off level for MR pro-ANP was determined to be 162.5 pmol/l, with a sensitivity of 100% and specificity of 68%. On the day of inclusion in the study, MR pro-ANP detected postoperative sepsis equally as well as PCT (Youden test P = 0.17). MR pro-ANP levels in patients with postoperative sepsis remained significantly elevated for 10 days, regardless of the clinical state, whereas falling levels of IL-6 and PCT indicated improvement of sepsis. The overall correlation of MR pro-ANP with IL-6 and PCT was therefore low (Pearson´s r 0.15 and 0.36, respectively).


MR pro-ANP may contribute to the diagnosis of postoperative sepsis, as its level can differentiate between elevation of other inflammatory markers due to abdominal surgery alone or postoperative sepsis.

Key words

Sepsis markers mid-regional pro-atrial natriuretic peptide (MR pro-ANP) abdominal surgery postoperative sepsis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303–10.CrossRefGoogle Scholar
  2. 2.
    Gerlach H, Toussaint S. Sepsis therapy—Why change-management of sepsis can lower its lethality. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS 2006;41:614–24.CrossRefGoogle Scholar
  3. 3.
    Vogel TR, Dombrovskiy VY, Carson JL, et al. Postoperative sepsis in the United States. Ann Surg 2010;252:1065–71.CrossRefGoogle Scholar
  4. 4.
    Adamzik M, Eggmann M, Frey UH, et al. Comparison of thromboelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critically ill adults. Crit Care 2010;14:R178.CrossRefGoogle Scholar
  5. 5.
    Nakao K, Ogawa Y, Suga S, et al. Molecular biology and biochemistry of the natriuretic peptide system. I: Natriuretic peptides. J Hypertens 1992;10:907–12.Google Scholar
  6. 6.
    de Bold AJ. Atrial natriuretic factor: A hormone produced by the heart. Science 1985;230(4727):767–70.CrossRefGoogle Scholar
  7. 7.
    Witthaut R, Busch C, Fraunberger P, et al. Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: Impact of interleukin-6 and sepsisassociated left ventricular dysfunction. Intensive Care Med 2003;29:1696–702.CrossRefGoogle Scholar
  8. 8.
    Ghosh N, Haddad H. Atrial natriuretic peptides in heart failure: Pathophysiological significance, diagnostic and prognostic value. Canadian journal of physiology and pharmacology. 2011;89:587–91.CrossRefGoogle Scholar
  9. 9.
    Ognibene FP, Parker MM, Natanson C, et al. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock. Chest 1988;93:903–10.Google Scholar
  10. 10.
    Price S, Anning PB, Mitchell JA, et al. Myocardial dysfunction in sepsis: Mechanisms and therapeutic implications. Eur Heart J 1999;20:715–24.CrossRefGoogle Scholar
  11. 11.
    Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993;328:1471–7.CrossRefGoogle Scholar
  12. 12.
    Hall C, Rouleau JL, Moye L, et al. N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction. Circulation 1994;89:1934–42.Google Scholar
  13. 13.
    Hartemink KJ, Groeneveld AB, de Groot MC, et al. Alphaatrial natriuretic peptide, cyclic guanosine monophosphate, and endothelin in plasma as markers of myocardial depression in human septic shock. Crit Care Med 2001;29:80–7.CrossRefGoogle Scholar
  14. 14.
    Ala-Kopsala M, Magga J, Peuhkurinen K, et al. Molecular heterogeneity has a major impact on the measurement of circulating N-terminal fragments of A-and B-type natriuretic peptides. Clin Chem 2004;50:1576–88.CrossRefGoogle Scholar
  15. 15.
    Morgenthaler NG, Struck J, Christ-Crain M, et al. Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: An observational study. Crit Care 2005;9:R37–45.CrossRefGoogle Scholar
  16. 16.
    Morgenthaler NG, Struck J, Thomas B, et al. Immunoluminometric assay for the midregion of pro-atrial natriuretic peptide in human plasma. Clin Chem 2004;50:234–6.CrossRefGoogle Scholar
  17. 17.
    Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315:801–10.CrossRefGoogle Scholar
  18. 18.
    Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock: For the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:775–87.CrossRefGoogle Scholar
  19. 19.
    Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis: For the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:762–74.CrossRefGoogle Scholar
  20. 20.
    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.CrossRefGoogle Scholar
  21. 21.
    Knaus WA, Draper EA, Wagner DP, et al. APACHE II: A severity of disease classification system. Crit Care Med 1985;13:818–29.CrossRefGoogle Scholar
  22. 22.
    Fried E, Weissman C, Sprung C. Postoperative sepsis. Curr Opin Crit Care 2011;17:396–401.CrossRefGoogle Scholar
  23. 23.
    Biffl WL, Moore EE, Moore FA, et al. Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation? Ann Surg 1996;224:647–64.Google Scholar
  24. 24.
    Mokart D, Merlin M, Sannini A, et al. Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS): Early markers of postoperative sepsis after major surgery. Br J Anaesth 2005;94:767–73.CrossRefGoogle Scholar
  25. 25.
    Tschaikowsky K, Hedwig-Geissing M, Braun GG, et al. Predictive value of procalcitonin, interleukin-6, and C-reactive protein for survival in postoperative patients with severe sepsis. J Crit Care 2011;26:54–64.CrossRefGoogle Scholar
  26. 26.
    Durila M, Bronsky J, Harustiak T, et al. Early diagnostic markers of sepsis after oesophagectomy (including thromboelastography). BMC Anesthesiology 2012;12:12.CrossRefGoogle Scholar
  27. 27.
    Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: A systematic review and meta-analysis. Crit Care Med 2006;34:1996–2003.CrossRefGoogle Scholar
  28. 28.
    Jung B, Molinari N, Nasri M, et al. Procalcitonin biomarker kinetics fails to predict treatment response in perioperative abdominal infection with septic shock. Crit Care 2013;17.Google Scholar
  29. 29.
    Kumar A, Haery C, Parrillo JE. Myocardial dysfunction in septic shock. Crit Care Clin 2000;16:251–87.CrossRefGoogle Scholar
  30. 30.
    Brueckmann M, Huhle G, Lang S, et al. Prognostic value of plasma N-terminal pro-brain natriuretic peptide in patients with severe sepsis. Circulation 2005;112:527–34.CrossRefGoogle Scholar
  31. 31.
    Parrillo JE, Burch C, Shelhamer JH, et al. A circulating myocardial depressant substance in humans with septic shock. Septic shock patients with a reduced ejection fraction have a circulating factor that depresses in vitro myocardial cell performance. J Clin Invest 1985;76:1539–53.Google Scholar
  32. 32.
    Pathan N, Hemingway CA, Alizadeh AA, et al. Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet 2004;363(9404):203–9.CrossRefGoogle Scholar
  33. 33.
    Witthaut R. Science review: natriuretic peptides in critical illness. Crit Care 2004;8:342–9.CrossRefGoogle Scholar

Copyright information

© Hellenic Surgical Society and Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • L Kousoulas
    • 1
    Email author
  • Jm Fink
    • 1
  • T Glatz
    • 1
  • C LäβLe
    • 1
  • IJ Bohlmann
    • 1
  • S Fichtner-Feigl
    • 1
  • S Utzolino
    • 1
  1. 1.Department of General and Visceral Surgery, Medical Center, University of Freiburg, Faculty of MedicineUniversity of FreiburgFreiburgGermany

Personalised recommendations