Vol. 24 No. 1 (2020)
ANESTHESIOLOGY & RESUSCITATION

N-terminal pro-B-type natriuretic peptide is a biomarker of myocardial stress in abdominal sepsis and septic shock

PDF (Русский)
  • I. Tyurin,
  • S. Rautbart,
  • D. Protsenko,
  • S. Shurygin,
  • I. Kozlov
I. Tyurin
City Clinical Hospital No. 40, Moscow; Pirogov Russian National Research Medical University, Moscow
S. Rautbart
V.M. Bujanov City Clinical Hospital, Moscow; M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow
D. Protsenko
Pirogov Russian National Research Medical University, Moscow
S. Shurygin
Federal Scientific Center for Physical Culture and Sports, Moscow
I. Kozlov
M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow
Bio
DOI: https://doi.org/10.21688/1681-3472-2020-1-65-77

Published 2020-04-07

Keywords

  • abdominal sepsis,
  • natriuretic peptide,
  • N-terminal pro-B-type natriuretic peptide,
  • septic cardiopathy,
  • septic shock

How to Cite

Tyurin, I., Rautbart, S., Protsenko, D., Shurygin, S., & Kozlov, I. (2020). N-terminal pro-B-type natriuretic peptide is a biomarker of myocardial stress in abdominal sepsis and septic shock. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 24(1), 65–77. https://doi.org/10.21688/1681-3472-2020-1-65-77

Copyright (c) 2020 Tyurin I.N., Rautbart S.A., Protsenko D.N., Shurygin S.N., Kozlov I.A.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Aim. To evaluate the dynamics and prognostic significance of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in patients with severe abdominal sepsis.
Methods. We analysed survey data of 54 patients (28 men and 26 women) aged 64.5 years [56.25–78.00] with abdominal sepsis or septic shock. Disease severity scored according to the Acute Physiology and Chronic Health Evaluation II criteria was 16.3 ± 0.8 and according to the Sequential Organ Failure Assessment (SOFA) was 3 [3–6]. Statistical analysis of these data was performed using correlation analysis, logistic regression and receiver operating characteristic analysis.
Results. Serum NT-proBNP level during the 1st week following admission to the intensive care unit (ICU) exceeded normal values, i.e. 2,570 [116.25–6,559.5] to 4,600 [1,680–18,200] pg/ml. At all disease stages, serum NT-proBNP level correlated with sepsis severity scores (SOFA), procalcitonin (PCT) levels, lactatemia, mean arterial pressure, heart rate and inotropic and vasoactive–inotropic scales (rho = 0.329–0.433; p < 0.02). On ICU days 3–4, serum NT-proBNP level of >5100 pg/ml was associated with increased risk of mortality [65.6%–88.2%; area under the curve (AUC) = 0.806; р < 0.0001]. Similarly, during this interval, elevated serum NT-proBNP level was associated with the use of inotropic drugs (OR = 1.0001, 95% CI = 1.000–1.0002, p < 0.0059). Notably, we found that 76.9%–79.0% of the patients with serum NT-proBNP level of >5250 pg/ml were receiving inotropic drugs including adrenaline, dopamine and dobutamine. We were unable to identify a specific association between serum NT-proBNP level and norepinephrine administration. On ICU days 7 and 8, among patients with serum NT-proBNP level of >3450 pg/ml, we observed a very close relationship between serum NT-proBNP level and PCT (sensitivity = 63.6%, specificity = 66.7%, AUC = 0.708; р = 0.0041).
Conclusion. Serum NT-proBNP level is considerably elevated in patients with abdominal sepsis or septic shock. NT-proBNP level was associated with both traditional indicators of sepsis severity and indicators characterising the state of systemic circulation. Notably, serum NT-proBNP level correlates with cardiac failure and inotropic drug requirement. Although the mechanisms underlying the observed increases in serum NT-proBNP level remain unclear, the present findings indicate that this mediator is clearly a significant biomarker and predictor of adverse outcomes related to abdominal sepsis and septic shock.

Received 22 January 2020. Revised 27 January 2020. Accepted 11 February 2020.

Funding: The study did not have sponsorship.

Conflict of interest: Authors declare no conflict of interest.

Author contributions
Conception and study design: I.N. Tyurin, D.N. Protsenko, I.A. Kozlov
Data collection and analysis: I.N. Tyurin, S.A. Rautbart, S.N. Shurygin
Statistical analysis: I.N. Tyurin, S.A. Rautbart
Drafting the article: I.N. Tyurin, D.N. Protsenko, I.A. Kozlov, S.N. Shurygin
Critical revision of the article: I.N. Tyurin, I.A. Kozlov
Final approval of the version to be published: I.N. Tyurin, S.A. Rautbart, D.N. Protsenko, S.N. Shurygin, I.A. Kozlov

PDF (Русский)

References

  1. Руднов В.А., Молдованов А.В., Астафьева М.Н., Перевалова Е.Ю. Клиническое значение содержания проадреномедуллина в крови у пациентов с сепсисом. Вестник анестезиологии и реаниматологии. 2019;16(5):36-42. [Rudnov V.A., Moldovanov A.V., Astafieva M.N., Perevalova E.Y. The clinical significance of proadrenomedulin level in blood in sepsis patients. Messenger of Anesthesiology and Resuscitation. 2019;16(5):36-42. (In Russ.)] https://doi.org/10.21292/2078-5658-2019-16-5-36-42
  2. Редкин И.В., Лопатин А.Ф., Скрипкин Ю.В., Самойленко В.В., Лихванцев В.В. Определение уровня антитромбина позволяет прогнозировать клинические исходы сепсиса. Вестник анестезиологии и реаниматологии. 2018;15(3):41-46. [Redkin I.V., Lopаtin A.F., Skripkin Y.V., Sаmoylenko V.V., Likhvаntsev V.V. Testing antithrombin level allows predicting a clinical outcome of sepsis. Messenger of Anesthesiology and Resuscitation. 2018;15(3):41-46. (In Russ.)] https://doi.org/10.21292/2078-5658-2018-15-3-41-46
  3. Rubattu S., Volpe M. Natriuretic peptides in the cardiovascular system: multifaceted roles in physiology, pathology and therapeutics. Int J Mol Sci. 2019;20(16):E3991. PMCID: PMC6721730, PMID: 31426320. https://doi.org/10.3390/ijms20163991
  4. Fu S., Ping P., Wang F., Luo L. Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. J Biol Eng. 2018;12:2. PMID: 29344085, PMCID: PMC5766980. https://doi.org/10.1186/s13036-017-0093-0
  5. Savic-Radojevic A., Pljesa-Ercegovac M., Matic M., Simic D., Radovanovic S., Simic T. Novel biomarkers of heart failure. Adv Clin Chem. 2017;79:93-152. PMID: 28212715. https://doi.org/10.1016/bs.acc.2016.09.002
  6. Буржунова М.Г., Гусева О.Г., Рыбаков В.Ю., Козлов И.А. Информативность натрийуретического пептида В-типа у кардиохирургических больных с гиперкреатининемией. Общая реаниматология. 2011;7(6):40-47. [Burzhunova M.G., Guseva O.G., Rybakov V.Y., Krichevsky L.A., Kozlov I.A. The informative value of n-terminal pro-type b natriuretic peptide in cardiac surgical patients with hypercreatininemia. General Reanimatology. 2011;7(6):40-47. (In Russ.)] https://doi.org/10.15360/1813-9779-2011-6-40
  7. Козлов И.А., Буржунова М.Г., Чумаков М.В., Тимербаев В.Х. Периоперационная динамика и клиническая значимость содержания натрийуретического пептида В-типа в крови кардиохирургических больных. Общая реаниматология. 2012;8(4):133-138. [Kozlov I.A., Burzhunova M.G., Chumakov M.V., Timerbayev V.K. The Perioperative Changes in and clinical value of B-type natriuretic peptide levels in the blood of cardiosurgical patients. General Reanimatology. 2012;8(4):133. (In Russ.)] https://doi.org/10.15360/1813-9779-2012-4-133
  8. Козлов И.А., Тюрин И.Н., Авдейкин С.Н., Уфимцева И.Ю., Саликов А.В., Карпун Н.А. Биомаркер NTproBNP у больных тяжелой внебольничной пневмонией. Общая реаниматология. 2016;12(3):24-33. [Kozlov I.A., Tyurin I.N., Avdeykin S.N., Ufimtseva I.Y., Salikov A.V., Karpun N.A. Biomarker NTproBNP in patients with severe communityacquired pneumonia. General Reanimatology. 2016;12(3):24-33. (In Russ.)] https://doi.org/10.15360/1813-9779-2016-3-24-33
  9. Kakoullis L., Giannopoulou E., Papachristodoulou E., Pantzaris N., Karamouzos V., Kounis N. G., Koniari I., Velissaris D. The utility of brain natriuretic peptides in septic shock as markers for mortality and cardiac dysfunction: a systematic review. Int J Clin Pract. 2019;73(7):e13374. https://doi.org/10.1111/ijcp.13374
  10. Zhang Y., Khalid S., Jiang L. Diagnostic and predictive performance of biomarkers in patients with sepsis in an intensive care unit. J Int Med Res. 2019;47(1):44-58. https://doi.org/10.1177/0300060518793791
  11. Ehrman R.R., Sullivan A.N., Favot M.J., Sherwin R.L., Reynolds C.A., Abidov A., Levy P.D. Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: a review of the literature. Crit Care. 2018;22(1):112. https://doi.org/10.1186/s13054-018-2043-8
  12. Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.D., Coopersmith C.M., Hotchkiss R.S., Levy M.M., Marshall J.C., Martin G.S., Opal S.M., Rubenfeld G.D., van der Poll T., Vincent J.L., Angus D.C. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801-810. https://doi.org/10.1001/jama.2016.0287
  13. Баутин А.Е., Ксендикова А.В., Белолипецкий С.С., Абуталимова Н.Р., Маричев А.О., Наймушин А.В., Этин В.Л., Радовский А.М., Карпова Л.И., Гребенник В.К., Гордеев М.Л. О возможности использования фармакологических индексов для прогнозирования течения послеоперационного периода кардиохирургических вмешательств. Вестник интенсивной терапии имени А.И. Салтанова. 2019;(2):66-74. [Bautin A.E., Ksendikova A.V., Belolipetskii S.S., Abutalimova N.R., Marichev A.O., Naimushin A.V., Etin V.L., Radovskii A.M., Karpova L.I., Grebennik V.K., Gordeev M.L. About efficiency of the pharmacological scores as a predictors of outcomes after cardiac surgery. Vestnik intensivnoj terapii imeni A.I. Saltanova. 2019;(2):66-74. (In Russ.)] https://doi.org/10.21320/1818-474X-2019-2-66-74
  14. Varpula M., Pulkki K., Karlsson S., Ruokonen E., Pettilä V.; FINNSEPSIS Study Group. Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock. Crit Care Med. 2007;35(5):1277-1283. https://doi.org/10.1097/01.CCM.0000261893.72811.0F
  15. Cheng H., Fan W.Z., Wang S.C., Liu Z.H., Zang H.L., Wang L.Z., Liu H.J., Shen X.H., Liang S.Q. N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study. J Crit Care. 2015;30(3):654.e9-14. PMID: 25575850. https://doi.org/10.1016/j.jcrc.2014.12.008
  16. Wang F., Wu Y., Tang L., Zhu W., Chen F., Xu T., Bo L., Li J., Deng X. Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis. Crit Care. 2012;16(3):R74. PMCID: PMC3580616, PMID: 22559153. https://doi.org/10.1186/cc11331
  17. Ozcan N., Ozcan A., Kaymak C., Basar H., Kotanoglu M., Kose B. Comparison of prognostic value of N-terminal pro-brain natriuretic peptide in septic and non-septic intensive care patients. Arch Med Sci. 2017;13(2):418-425. PMCID: PMC5332440, PMID: 28261297. https://doi.org/10.5114/aoms.2015.54196
  18. Chua G, Kang-Hoe L. Marked elevations in N-terminal brain natriuretic peptide levels in septic shock. Crit Care. 2004;8(4):R248-250. PMCID: PMC522851, PMID: 15312225. https://doi.org/10.1186/cc2889
  19. Almog Y., Novack V., Megralishvili R., Kobal S., Barski L., King D., Zahger D. Plasma level of N terminal pro-brain natriuretic peptide as a prognostic marker in critically ill patients. Anesth Analg. 2006;102(6):1809-1815. PMID: 16717330. https://doi.org/10.1213/01.ane.0000217202.55909.5d
  20. Shah K.B., Nolan M.M., Rao K., Wang D.J., Christenson R.H., Shanholtz C.B., Mehra M.R., Gottlieb S.S. The characteristics and prognostic importance of NT-ProBNP concentrations in critically ill patients. Am J Med. 2007;120(12):1071-1077. PMID: 18060928. https://doi.org/10.1016/j.amjmed.2007.07.032
  21. Christenson R.H. What is the value of B-type natriuretic peptide testing for diagnosis, prognosis or monitoring of critically ill adult patients in intensive care? Clin Chem Lab Med. 2008;46(11):1524-1532. PMID: 18847367. https://doi.org/10.1515/CCLM.2008.294
  22. Wang J., Ji W., Xu Z., Pan Т. Clinical significance of plasma levels of brain natriuretic peptide and cardiac troponin T in patients with sepsis. Exp Ther Med. 2016;11(1):154-156. PMID: 26889232, PMCID: PMC4726858. https://doi.org/10.3892/etm.2015.2863
  23. Guaricci A.I., Santoro F., Paoletti Perini A., Ioffredo L., Trivedi C., Pontone G., Di Biase M., Brunetti N.D. Correlations between NT-proBNP, outcome and haemodynamics in patients with septic shock. Acta Cardiol. 2015;70(5):545-552. https://doi.org/10.2143/AC.70.5.3110515
  24. Khoury J., Arow M., Elias A., Makhoul B.F., Berger G., Kaplan M., Mashiach T., Ismael-Badarneh R., Aronson D., Azzam Z.S. The prognostic value of brain natriuretic peptide (BNP) in non-cardiac patients with sepsis, ultra-long follow-up. J Crit Care. 2017;42:117-122. PMID: 28719839. https://doi.org/10.1016/j.jcrc.2017.07.009
  25. Harada E., Nakagawa O., Yoshimura M., Harada M., Nakagawa M., Mizuno Y., Shimasaki Y., Nakayama M., Yasue H., Kuwahara K., Saito Y., Nakao K. Effect of interleukin-1 beta on cardiac hypertrophy and production of natriuretic peptides in rat cardiocyte culture. J Mol Cell Cardiol. 1999;31(11):1997-2006. PMID: 10591026. https://doi.org/10.1006/jmcc.1999.1030
  26. Tanaka T., Kanda T., Takahashi T., Saegusa S, Moriya J., Kurabayashi M. Interleukin-6-induced reciprocal expression of SERCA and natriuretic peptides mRNA in cultured rat ventricular myocytes. J Int Med Res. 2004;32(1):57-61. PMID: 14997707. https://doi.org/10.1177/147323000403200109
  27. Ma K.K., Banas K., de Bold A.J. Determinants of inducible brain natriuretic peptide promoter activity. Regul Pept. 2005;128(3):169-176. PMID: 15837525. https://doi.org/10.1016/j.regpep.2004.12.025
  28. Hanford D.S., Thuerauf D.J., Murray S.F., Glembotski C.C. Brain natriuretic peptide is induced by alpha 1-adrenergic agonists as a primary response gene in cultured rat cardiac myocytes. J Biol Chem. 1994;269(42):26227-26233. PMID: 7929338.
  29. Di Somma S., Pittoni V., Raffa S., Magrini L., Gagliano G., Marino R., Nobili V., Torrisi MR. IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytes in vitro and its plasma levels correlate with B-type natriuretic peptide in non-overloaded acute heart failure patients. Eur Heart J Acute Cardiovasc Care. 2017;6(5):450-461. PMID: 24585936. https://doi.org/10.1177/2048872613499282
  30. Vila G., Resl M., Stelzeneder D., Struck J., Maier C., Riedl M., Hülsmann M., Pacher R., Luger A., Clodi M. Plasma NT-proBNP increases in response to LPS administration in healthy men. J Appl Physiol. 2008;105(6):1741-1745. PMID: 18845786. https://doi.org/10.1152/japplphysiol.90442.2008
  31. Jeong H.S., Lee T.H., Bang C.H., Kim J.H., Hong S.J. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock: A comparative retrospective study. Medicine (Baltimore). 2018;97(13):e0263. PMID: 29595686, PMCID: PMC5895365. https://doi.org/10.1097/MD.0000000000010263
  32. Tartavoulle T., Fowler L. Cardiogenic shock in the septic patient: early identification and evidence-based management. Crit Care Nurs Clin North Am. 2018;30(3):379-387. https://doi.org/10.1016/j.cnc.2018.05.006
  33. Walley K.R. Sepsis-induced myocardial dysfunction and mammalian target of rapamycin signalling pathways. Can J Cardiol. 2019;35(7):809-812. https://doi.org/10.1016/j.cjca.2019.04.003
  34. Козлов И.А., Тюрин И.Н., Раутбарт С.А. Ранние гемодинамические предикторы летального исхода абдоминального сепсиса. Вестник анестезиологии и реаниматологии. 2018;15(2):6-15. [Kozlov I.A., Tyurin I.N., Rаutbаrt S.А. Early hemodynamic predictors of lethal outcomes of abdominal sepsis. Messenger of Anesthesiology and Resuscitation. 2018;15(2):6-15. (In Russ.)] https://doi.org/10.21292/2078-5658-2018-15-2-6-15
  35. Omar S., Ali A., Atiya Y., Mathivha R.L., Dulhunty J.M. Changes in B-type natriuretic peptide and related hemodynamic parameters following a fluid challenge in critically ill patients with severe sepsis or septic shock. Indian J Crit Care Med. 2017;21(3):117-121. https://doi.org/10.4103/ijccm.IJCCM_318_16
  36. Landesberg G., Levin P.D., Gilon D., Goodman S., Georgieva M., Weissman C., Jaffe A.S., Sprung C.L., Barak V. Myocardial dysfunction in severe sepsis and septic shock: no correlation with inflammatory cytokines in real-life clinical setting. Chest. 2015;148(1):93-102. https://doi.org/10.1378/chest.14-2259
  37. Rolando G., Espinoza E.D., Avid E., Welsh S., Pozo J.D., Vazquez A.R., Arzani Y., Masevicius F.D., Dubin A. Prognostic value of ventricular diastolic dysfunction in patients with severe sepsis and septic shock. Rev Bras Ter Intensiva. 2015;27(4):333-339. PMID: 26761470, PMCID: PMC4738818. https://doi.org/10.5935/0103-507X.20150057
  38. Díez J. Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy. Eur J Heart Fail. 2017;19(2):167-176. PMID: 27766748, PMCID: PMC5297869. https://doi.org/10.1002/ejhf.656