Proenkephalin A and Bioactive Adrenomedullin Are Useful for Risk Prognostication in Cardiac Surgery

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2023 Feb 9

PMID 36756642

Authors

Aileen Hill

Deborah Bergmann

Janin Schulte

Rashad Zayat

Gernot Marx

Tim-Philipp Simon

Jana Mossanen

Anne Brucken

Christian Stoppe

Affiliations

Soon will be listed here.

Abstract

Introduction: Various clinical scores have been developed to predict organ dysfunction and mortality in patients undergoing cardiac surgery, but outcome prediction may be inaccurate for some patient groups. Proenkephalin A (penKid) and bioactive adrenomedullin (bio-ADM) have emerged as promising biomarkers correlating with shock and organ dysfunction. This imposes the question of whether they can be used as prognostic biomarkers for risk stratification in the perioperative setting of cardiac surgery.

Methods: Patients undergoing cardiac surgery were prospectively enrolled in this observational study. PenKid and bio-ADM plasma levels, as well as markers evaluating inflammation and organ dysfunction, were measured at five perioperative time points from before the induction of anesthesia to up to 48 h postoperatively. Clinical data regarding organ dysfunction and patient outcomes were recorded during the intensive care unit (ICU)-stay with a special focus on acute kidney injury (AKI).

Results: In 136 patients undergoing cardiac surgery, the bio-ADM levels increased and the penKid levels decreased significantly over time. PenKid was associated with chronic kidney disease (CKD), the incidence of AKI, and renal replacement therapy (RRT). Bio-ADM was associated with lactate and the need for vasopressors. PenKid was useful to predict an ICU-length of stay (LOS)>1 day and added prognostic value to the European System for Cardiac Operative Risk Evaluation Score (EuroSCORE) II when measured after the end of cardiopulmonary bypass and 24 h after cardiac surgery. For bio-ADM, the same was true when measured 24 h after surgery. PenKid also added prognostic value to the EuroSCORE II for the combined outcome "ICU length of stay >1 day and in-hospital mortality."

Conclusion: The combination of preoperative EuroSCORE II and intraoperative measurement of penKid may be more useful to predict a prolonged ICU LOS and increased mortality than EuroSCORE II alone. Bio-ADM correlates with markers of shock. More research is encouraged for early risk stratification and validation of penKid and bio-ADM as a tool involved in clinical decisions, which may enable the early initiation of organ protective strategies.

Citing Articles

Proenkephalin A 119-159 in Perioperative and Intensive Care-A Promising Biomarker or Merely Another Option?.

Walczak-Wieteska P, Zuzda K, Malyszko J, Andruszkiewicz P Diagnostics (Basel). 2024; 14(21).

PMID: 39518330 PMC: 11545452. DOI: 10.3390/diagnostics14212364.

Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery.

Doukas P, Hartmann O, Frankort J, Arlt B, Krabbe H, Jacobs M Sci Rep. 2024; 14(1):12795.

PMID: 38834580 PMC: 11150250. DOI: 10.1038/s41598-024-63412-1.

Plasma proenkephalin and neutrophil gelatinase-associated lipocalin predict mortality in ICU patients with acute kidney injury.

Zhang M, Yang Y, Zhu L, Cui K, Zhang S, Xu Y BMC Nephrol. 2024; 25(1):181.

PMID: 38778257 PMC: 11112877. DOI: 10.1186/s12882-024-03611-0.

References

Donato L, Meeusen J, Lieske J, Bergmann D, Sparwasser A, Jaffe A . Analytical performance of an immunoassay to measure proenkephalin. Clin Biochem. 2018; 58:72-77. DOI: 10.1016/j.clinbiochem.2018.05.010. View

Prins C, De Villiers Jonker I, Botes L, Smit F . Cardiac surgery risk-stratification models. Cardiovasc J Afr. 2012; 23(3):160-4. PMC: 3721858. DOI: 10.5830/CVJA-2011-047. View

Chen Y, Li C . Prognostic value of adrenomedullin in septic patients in the ED. Am J Emerg Med. 2013; 31(7):1017-21. DOI: 10.1016/j.ajem.2013.03.017. View

Morbach C, Marx A, Kaspar M, Guder G, Brenner S, Feldmann C . Prognostic potential of midregional pro-adrenomedullin following decompensation for systolic heart failure: comparison with cardiac natriuretic peptides. Eur J Heart Fail. 2017; 19(9):1166-1175. DOI: 10.1002/ejhf.859. View

Wagner K, Wachter U, Vogt J, Scheuerle A, McCook O, Weber S . Adrenomedullin binding improves catecholamine responsiveness and kidney function in resuscitated murine septic shock. Intensive Care Med Exp. 2015; 1(1):21. PMC: 4796991. DOI: 10.1186/2197-425X-1-2. View

Mehta R, Kellum J, Shah S, Molitoris B, Ronco C, Warnock D . Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007; 11(2):R31. PMC: 2206446. DOI: 10.1186/cc5713. View

Hill A, Nesterova E, Lomivorotov V, Efremov S, Goetzenich A, Benstoem C . Current Evidence about Nutrition Support in Cardiac Surgery Patients-What Do We Know?. Nutrients. 2018; 10(5). PMC: 5986477. DOI: 10.3390/nu10050597. View

Marino R, Struck J, Hartmann O, Maisel A, Rehfeldt M, Magrini L . Diagnostic and short-term prognostic utility of plasma pro-enkephalin (pro-ENK) for acute kidney injury in patients admitted with sepsis in the emergency department. J Nephrol. 2014; 28(6):717-24. DOI: 10.1007/s40620-014-0163-z. View

Parikh C, Moledina D, Coca S, Thiessen-Philbrook H, Garg A . Application of new acute kidney injury biomarkers in human randomized controlled trials. Kidney Int. 2016; 89(6):1372-9. PMC: 4869991. DOI: 10.1016/j.kint.2016.02.027. View

10.

Lundberg O, Bergenzaun L, Ryden J, Rosenqvist M, Melander O, Chew M . Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients. Crit Care. 2016; 20(1):178. PMC: 4899903. DOI: 10.1186/s13054-016-1361-y. View

11.

Hall R . Identification of inflammatory mediators and their modulation by strategies for the management of the systemic inflammatory response during cardiac surgery. J Cardiothorac Vasc Anesth. 2013; 27(5):983-1033. DOI: 10.1053/j.jvca.2012.09.013. View

12.

Struck J, Hein F, Karasch S, Bergmann A . Epitope specificity of anti-Adrenomedullin antibodies determines efficacy of mortality reduction in a cecal ligation and puncture mouse model. Intensive Care Med Exp. 2015; 1(1):22. PMC: 4796695. DOI: 10.1186/2197-425X-1-3. View

13.

Vincent J, Moreno R, Takala J, Willatts S, de Mendonca A, Bruining H . The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996; 22(7):707-10. DOI: 10.1007/BF01709751. View

14.

Ng L, Sandhu J, Narayan H, Quinn P, Squire I, Davies J . Proenkephalin and prognosis after acute myocardial infarction. J Am Coll Cardiol. 2013; 63(3):280-9. DOI: 10.1016/j.jacc.2013.09.037. View

15.

Arbit B, Marston N, Shah K, Lee E, Aramin H, Clopton P . Prognostic Usefulness of Proenkephalin in Stable Ambulatory Patients With Heart Failure. Am J Cardiol. 2016; 117(8):1310-4. DOI: 10.1016/j.amjcard.2016.01.042. View

16.

Ad N, Holmes S, Patel J, Pritchard G, Shuman D, Halpin L . Comparison of EuroSCORE II, Original EuroSCORE, and The Society of Thoracic Surgeons Risk Score in Cardiac Surgery Patients. Ann Thorac Surg. 2016; 102(2):573-9. DOI: 10.1016/j.athoracsur.2016.01.105. View

17.

Nashef S, Roques F, Sharples L, Nilsson J, Smith C, Goldstone A . EuroSCORE II. Eur J Cardiothorac Surg. 2012; 41(4):734-44. DOI: 10.1093/ejcts/ezs043. View

18.

Sullivan P, Wallach J, Ioannidis J . Meta-Analysis Comparing Established Risk Prediction Models (EuroSCORE II, STS Score, and ACEF Score) for Perioperative Mortality During Cardiac Surgery. Am J Cardiol. 2016; 118(10):1574-1582. DOI: 10.1016/j.amjcard.2016.08.024. View

19.

Hill A, Heyland D, Rossaint R, Arora R, Engelman D, Day A . Longitudinal Outcomes in Octogenarian Critically Ill Patients with a Focus on Frailty and Cardiac Surgery. J Clin Med. 2020; 10(1). PMC: 7793078. DOI: 10.3390/jcm10010012. View

20.

Self W, Storrow A, Hartmann O, Barrett T, Fermann G, Maisel A . Plasma bioactive adrenomedullin as a prognostic biomarker in acute heart failure. Am J Emerg Med. 2015; 34(2):257-62. PMC: 4753125. DOI: 10.1016/j.ajem.2015.10.033. View