High-sensitive troponinT, interleukin-8, and interleukin-6 link with post-surgery risk in infant heart surgery.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0370270 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-6576 (Electronic) Linking ISSN: 00015172 NLM ISO Abbreviation: Acta Anaesthesiol Scand Subsets: MEDLINE

Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Aarhus, Denmark : Universitetsforlaget, 1957-

Interleukin-8*/blood ; Interleukin-6*/blood ; Troponin T*/blood ; Biomarkers*/blood ; Cardiac Surgical Procedures* ; Postoperative Complications*/blood ; Postoperative Complications*/epidemiology ; Acute Kidney Injury*/blood ; Acute Kidney Injury*/etiology ; Cardiopulmonary Bypass*/adverse effects; Humans ; Male ; Female ; Infant ; Double-Blind Method ; Infant, Newborn

Background: This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs.
Methods: Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses.
Results: Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed.
Conclusions: The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.
(© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Comment in: Acta Anaesthesiol Scand. 2024 Aug;68(7):997-998. doi: 10.1111/aas.14431. (PMID: 38666552)

Giacinto O, Satriano U, Nenna A, et al. Inflammatory response and endothelial dysfunction following cardiopulmonary bypass: pathophysiology and pharmacological targets. Recent Patents Inflamm Allergy Drug Discov. 2019;13:158‐173.
Gupta‐Malhotra M, Kern JH, Flynn PA, Schiller MS, Quaegebeur JM, Friedman DM. Cardiac troponin I after cardiopulmonary bypass in infants in comparison with older children. Cardiol Young. 2013;23:431‐435.
Wernovsky G, Wypij D, Jonas RA, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low‐flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995;92:2226‐2235.
Li S, Krawczeski CD, Zappitelli M, et al. Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a prospective multicenter study. Crit Care Med. 2011;39:1493‐1499.
Kapitein B, van Saet AW, Golab HD, et al. Does pharmacotherapy influence the inflammatory responses during cardiopulmonary bypass in children? J Cardiovasc Pharmacol. 2014;64:191‐197.
Kozik DJ, Tweddell JS. Characterizing the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg. 2006;81:S2347‐S2354.
Taggart DP, Hadjinikolas L, Hooper J, et al. Effects of age and ischemic times on biochemical evidence of myocardial injury after pediatric cardiac operations. J Thorac Cardiovasc Surg. 1997;113:728‐735.
Greenberg JH, Parikh CR. Biomarkers for diagnosis and prognosis of AKI in children: one size does not fit all. Pediatr Crit Care Med. 2017;12:1551‐1557.
Nada A, Bonachea EM, Askenazi DJ. Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med. 2017;22:90‐97.
Gorjipour F, Totonchi Z, Gholampour Dehaki M, et al. Serum levels of interleukin‐6, interleukin‐8, interleukin‐10, and tumor necrosis factor‐α, renal function biochemical parameters and clinical outcomes in pediatric cardiopulmonary bypass surgery. Perfusion. 2019;34:651‐659.
Bucholz EM, Whitlock RP, Zappitelli M, et al. Cardiac biomarkers and acute kidney injury after cardiac surgery. Pediatrics. 2015;135:e945‐e956.
Mildh LH, Pettila V, Sairanen HI, Rautiainen PH. Cardiac troponin T levels for risk stratification in pediatric open heart surgery. Ann Thorac Surg. 2006;82:1643‐1648.
de Fontnouvelle CA, Greenberg JH, Thiessen‐Philbrook HR, et al. Interleukin‐8 and tumor necrosis factor predict acute kidney injury after pediatric cardiac surgery. Ann Thorac Surg. 2017;104:2072‐2079.
Gritti MN, Farid P, Manlhiot C, et al. Factors associated with acute kidney injury after cardiopulmonary bypass in children. CJC Pediatr Congenit Heart Dis. 2023;2:20‐29.
Thorlacius EM, Suominen PK, Wahlander H, et al. The effect of Levosimendan versus Milrinone on the occurrence rate of acute kidney injury following congenital heart surgery in infants: a randomized clinical trial. Pediatr Crit Care Med. 2019;20:947‐956.
Thorlacius EM, Wåhlander H, Ojala T, et al. Levosimendan versus milrinone for inotropic support in pediatric cardiac surgery: results from a randomized trial. J Cardiothorac Vasc Anesth. 2020;34:2072‐2080.
Thorlacius EM, Vistnes M, Ojala T, et al. Levosimendan versus milrinone and release of myocardial biomarkers after pediatric cardiac surgery: post hoc analysis of clinical trial data. Pediatr Crit Care Med. 2021;22:e402‐e409.
Section 2: AKI definition. Kidney Int Suppl. 2012;2:19‐36.
Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Pediatr Crit Care Med. 2009;4:1832‐1843.
Sutherland SM, Byrnes JJ, Kothari M, et al. AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions. Pediatr Crit Care Med. 2015;10:554‐561.
Ross RD. The Ross classification for heart failure in children after 25 years: a review and an age‐stratified revision. Pediatr Cardiol. 2012;33:1295‐1300.
Gaies MG, Gurney JG, Yen AH, et al. Vasoactive‐inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med. 2010;11:234‐238.
Christmann M, Wipf A, Dave H, et al. Risk factor analysis for a complicated postoperative course after neonatal arterial switch operation: the role of troponin T. Congenit Heart Dis. 2018;13:594‐601.
Liu KD, Altmann C, Smits G, et al. Serum interleukin‐6 and interleukin‐8 are early biomarkers of acute kidney injury and predict prolonged mechanical ventilation in children undergoing cardiac surgery: a case‐control study. Crit Care. 2009;13:R104.
Reed CR, McCoy CC, Nag U, et al. Proteomic analysis of infants undergoing cardiopulmonary bypass using contemporary ontological tools. J Surg Res. 2020;246:83‐92.
Rathgeber SL, Chakrabarti A, Kapravelou E, et al. Association of preoperative diuretic use with early acute kidney injury in infants with biventricular hearts following cardiac surgery. J Am Heart Assoc. 2021;10:e020519.
Fridén V, Starnberg K, Muslimovic A, et al. Clearance of cardiac troponin T with and without kidney function. Clin Biochem. 2017;50:468‐474.
Singbartl K, Formeck CL, Kellum JA. Kidney‐immune system crosstalk in AKI. Semin Nephrol. 2019;39:96‐106.
Mikłaszewska M, Korohoda P, Zachwieja K, et al. Serum interleukin 6 levels as an early marker of acute kidney injury on children after cardiac surgery. Adv Clin Exp Med. 2013;22:377‐386.
Allan CK, Newburger JW, McGrath E, et al. The relationship between inflammatory activation and clinical outcome after infant cardiopulmonary bypass. Anesth Analg. 2010;111:1244‐1251.
Pérez‐Navero JL, de la Torre‐Aguilar MJ, Ibarra de la Rosa I, et al. Cardiac biomarkers of low cardiac output syndrome in the postoperative period after congenital heart disease surgery in children. Rev Esp Cardiol (English Ed). 2017;70:267‐274.
Januzzi JL Jr, Mahler SA, Christenson RH, et al. Recommendations for institutions transitioning to high‐sensitivity troponin testing: JACC scientific expert panel. J Am Coll Cardiol. 2019;73:1059‐1077.
Su JA, Kumar SR, Mahmoud H, et al. Postoperative serum troponin trends in infants undergoing cardiac surgery. Semin Thorac Cardiovasc Surg. 2019;31:244‐251.
Carmona F, Manso PH, Vicente WV, Castro M, Carlotti AP. Risk stratification in neonates and infants submitted to cardiac surgery with cardiopulmonary bypass: a multimarker approach combining inflammatory mediators, N‐terminal pro‐B‐type natriuretic peptide and troponin I. Cytokine. 2008;42:317‐324.

the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement; The Scandinavian Society of Anesthesia and Intensive Care stipendiate in 2017

Keywords: acute kidney injury; biomarkers; cardiac surgery; congenital heart defects; infants; outcomes assessments; pediatric intensive care unit

0 (Interleukin-8)
0 (Interleukin-6)
0 (Troponin T)
0 (Biomarkers)
0 (CXCL8 protein, human)

Date Created: 20240326 Date Completed: 20240619 Latest Revision: 20240925

20240926

10.1111/aas.14405

38531618