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Post-operative kinetics of C-reactive protein to distinguish between bacterial infection and systemic inflammation in infants after cardiopulmonary bypass surgery: the early and the late period

Part of: Infectious

Published online by Cambridge University Press:  09 August 2021

Hanna Renk*
Affiliation:
Department of Pediatric Cardiology, Pulmology and Intensive Care Medicine, University Children’s Hospital Tübingen, Tübingen72076, Germany
David Grosse
Affiliation:
Department of Pediatric Cardiology, Pulmology and Intensive Care Medicine, University Children’s Hospital Tübingen, Tübingen72076, Germany
Sarah Schober
Affiliation:
Department of Pediatrics, Hematology/Oncology, University Children’s Hospital Tübingen, Tübingen 72076, Germany
Christian Schlensak
Affiliation:
Department of Thoracic and Cardiovascular Surgery, University Hospital Tübingen, Tübingen 72076, Germany
Michael Hofbeck
Affiliation:
Department of Pediatric Cardiology, Pulmology and Intensive Care Medicine, University Children’s Hospital Tübingen, Tübingen72076, Germany
Felix Neunhoeffer
Affiliation:
Department of Pediatric Cardiology, Pulmology and Intensive Care Medicine, University Children’s Hospital Tübingen, Tübingen72076, Germany
*
Author for correspondence: Dr H. Renk, Department of Pediatric Cardiology, Pulmology and Intensive Care Medicine, University Children’s Hospital Tübingen, Hoppe-Seyler Str. 1, Tübingen 72076, Germany. Fax: +49 7071 29 5127. E-mail: [email protected]

Abstract

Objectives:

Differentiation between post-operative inflammation and bacterial infection remains an important issue in infants following congenital heart surgery. We primarily assessed kinetics and predictive value of C-reactive protein for bacterial infection in the early (days 0–4) and late (days 5–28) period after cardiopulmonary bypass surgery. Secondary objectives were frequency, type, and timing of post-operative infection related to the risk adjustment for congenital heart surgery score.

Methods:

This 3-year single-centre retrospective cohort study in a paediatric cardiac ICU analysed 191 infants accounting for 235 episodes of CPBP surgery. Primary outcome was kinetics of CRP in the first 28 days after CPBP surgery in infected and non-infected patients.

Results:

We observed 22 infectious episodes in the early and 34 in the late post-operative period. CRP kinetics in the early post-operative period did not accurately differentiate between infected and non-infected patients. In the late post-operative period, infected infants displayed significantly higher CRP values with a median of 7.91 (1.64–22.02) and 6.92 mg/dl (1.92–19.65) on days 2 and 3 compared to 4.02 (1.99–15.9) and 3.72 mg/dl (1.08–9.72) in the non-infection group. Combining CRP on days 2 and 3 after suspicion of infection revealed a cut-off of 9.47 mg/L with an acceptable predictive accuracy of 76%.

Conclusions:

In neonates and infants, CRP kinetics is not useful to predict infection in the first 72 hours after CPBP surgery due to the inflammatory response. However, in the late post-operative period, CRP is a valuable adjunctive diagnostic test in conjunction with clinical presentation and microbiological diagnostics.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Seguela, PE, Joram, N, Romefort, B, et al. Procalcitonin as a marker of bacterial infection in children undergoing cardiac surgery with cardiopulmonary bypass. Cardiol Young 2011; 21: 392399.10.1017/S104795111100014XCrossRefGoogle ScholarPubMed
Valera, M, Scolfaro, C, Cappello, N, et al. Nosocomial infections in pediatric cardiac surgery, Italy. Infect Control Hosp Epidemiol 2001; 22: 771775.CrossRefGoogle ScholarPubMed
Sidhu, N, Joffe, AR, Doughty, P, et al. Sepsis after cardiac surgery early in infancy and adverse 4.5-year neurocognitive outcomes. J Am Heart Assoc 2015; 4: e001954.10.1161/JAHA.115.001954CrossRefGoogle Scholar
Alten, JA, Rahman, A, Zaccagni, HJ, et al. The epidemiology of healthcare-associated infections in pediatric cardiac intensive care units. Pediatr Infect Dis J 2018; 37: 768772.10.1097/INF.0000000000001884CrossRefGoogle ScholarPubMed
Mastropietro, CW, Barrett, R, Davalos, MC, et al. Cumulative corticosteroid exposure and infection risk after complex pediatric cardiac surgery. Ann Thorac Surg 2013; 95: 21332139.CrossRefGoogle ScholarPubMed
Tarnok, A, Schneider, P. Pediatric cardiac surgery with cardiopulmonary bypass: pathways contributing to transient systemic immune suppression. Int Congr Ser 2001; 16: 2432.Google ScholarPubMed
Shi, SS, Shi, CC, Zhao, ZY, et al. Effect of open heart surgery with cardiopulmonary bypass on peripheral blood lymphocyte apoptosis in children. Pediatr Cardiol 2009; 30: 153159.CrossRefGoogle ScholarPubMed
Habermehl, P, Knuf, M, Kampmann, C, et al. Changes in lymphocyte subsets after cardiac surgery in children. Eur J Pediatr 2003; 162: 1521.CrossRefGoogle ScholarPubMed
Yamaguchi, T, Murakami, A, Fukahara, K, et al. Changes in T-cell receptor subsets after cardiac surgery in children. Surg Today 2000; 30: 875878.CrossRefGoogle ScholarPubMed
Millar, JE, Fanning, JP, McDonald, CI, et al. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Crit Care 2016; 20: 387.CrossRefGoogle ScholarPubMed
Paparella, D, Yau, TM, Young, E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002; 21: 232244.10.1016/S1010-7940(01)01099-5CrossRefGoogle ScholarPubMed
Tacconelli, E, De Angelis, G, Cataldo, MA, et al. Antibiotic usage and risk of colonization and infection with antibiotic-resistant bacteria: a hospital population-based study. Antimicrob Agents Chemother 2009; 53: 42644269.10.1128/AAC.00431-09CrossRefGoogle ScholarPubMed
Bhalodi, AA, van Engelen, TSR, Virk, HS, et al. Impact of antimicrobial therapy on the gut microbiome. J Antimicrob Chemother 2019; 74: i6i15.CrossRefGoogle ScholarPubMed
Davidson, J, Tong, S, Hauck, A, et al. Kinetics of procalcitonin and C-reactive protein and the relationship to postoperative infection in young infants undergoing cardiovascular surgery. Pediatr Res 2013; 74: 413419.10.1038/pr.2013.124CrossRefGoogle ScholarPubMed
Haponiuk, I, Jaworski, R, Paczkowski, K, et al. Postoperative kinetics of common inflammatory biomarkers after congenital heart defect procedures with extracorporeal circulation in children. Kardiol Pol 2018; 76: 968973.10.5603/KP.a2018.0038CrossRefGoogle ScholarPubMed
McMaster, P, Park, DY, Shann, F, et al. Procalcitonin versus C-reactive protein and immature-to-total neutrophil ratio as markers of infection after cardiopulmonary bypass in children. Pediatr Crit Care Med 2009; 10: 217221.CrossRefGoogle ScholarPubMed
Bobillo-Perez, S, Rodríguez-Fanjul, J, Jordan Garcia, I. Is procalcitonin useful in pediatric critical care patients? Biomark Insights 2018, 13:1177271918792244.CrossRefGoogle Scholar
Aryafar, A, Di Marzio, A, Guillard, O, et al. Procalcitonin concentration measured within the first days of cardiac surgery is predictive of postoperative infections in neonates: a case-control study. Pediatr Cardiol 2019; 40: 12891295.CrossRefGoogle ScholarPubMed
D’Souza, S, Guhadasan, R, Jennings, R, et al. Procalcitonin and other common biomarkers do not reliably identify patients at risk for bacterial infection after congenital heart surgery. Pediatr Crit Care Med 2019; 20: 243251.CrossRefGoogle Scholar
Skrak, P, Kovacikova, L, Kunovsky, P. Procalcitonin, neopterin and C-reactive protein after pediatric cardiac surgery with cardiopulmonary bypass. Bratisl Lek Listy 2007; 108: 501505.Google ScholarPubMed
Pérez, SB, Rodríguez-Fanjul, J, García, IJ, et al. Procalcitonin is a better biomarker than C-reactive protein in newborns undergoing cardiac surgery: the PROKINECA study. Biomark Insights 2016; 11: 123129.10.4137/BMI.S40658CrossRefGoogle ScholarPubMed
Franz, AR, Bauer, K, Schalk, A, et al. Measurement of interleukin 8 in combination with C-reactive protein reduced unnecessary antibiotic therapy in newborn infants: a multicenter, randomized, controlled trial. Pediatrics 2004; 114: 18.10.1542/peds.114.1.1CrossRefGoogle ScholarPubMed
Kollmann, TR, Kampmann, B, Mazmanian, SK, et al. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity 2017; 46: 350363.CrossRefGoogle Scholar
Levy, I, Ovadia, B, Erez, E, et al. Nosocomial infections after cardiac surgery in infants and children: incidence and risk factors. J Hosp Infect 2003; 53: 111116.CrossRefGoogle ScholarPubMed
Boehne, M, Sasse, M, Karch, A, et al. Systemic inflammatory response syndrome after pediatric congenital heart surgery: incidence, risk factors, and clinical outcome. J Card Surg 2017; 32: 116125.CrossRefGoogle ScholarPubMed
Boralessa, H, de Beer, FC, Manchie, A, et al. C-reactive protein in patients undergoing cardiac surgery. Anaesthesia 1986; 41: 1115.CrossRefGoogle ScholarPubMed
Jenkins, KJ, Gauvreau, K, Newburger, JW, et al. Consensus-based method for risk adjustment for surgery for congenital heart disease. J Thorac Cardiovasc Surg 2002; 123: 110118.10.1067/mtc.2002.119064CrossRefGoogle ScholarPubMed
Goldstein, B, Giroir, B, Randolph, A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6: 28.10.1097/01.PCC.0000149131.72248.E6CrossRefGoogle Scholar
CDC. National healthcare safety network (NHSN) surveillance system: definition of healthcare-associated infections (HAI). Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual_current.pdf Google Scholar
Surveillance of hospital-acquired infections (version 2017) of the German Institute of public health, the Robert Koch Institute (RKI). Available from: https://www.nrz-hygiene.de/fileadmin/nrz/module/KISS_Definitionen_E-book_Neuauflage_06_2017.pdf Google Scholar
Li, X, Wang, X, Li, S, et al. Diagnostic value of procalcitonin on early postoperative infection after pediatric cardiac surgery. Pediatr Crit Care Med 2017; 18: 420428.10.1097/PCC.0000000000001118CrossRefGoogle ScholarPubMed
Shaath, GA, Jijeh, A, Faruqui, F, et al. Ventilator-associated pneumonia in children after cardiac surgery. Pediatr Cardiol 2014; 35: 627631.CrossRefGoogle ScholarPubMed
Hasija, S, Makhija, N, Kiran, U, et al. Nosocomial infections in infants and children after cardiac surgery. Indian J Thorac Cardiovasc Surg 2008; 24: 233239.10.1007/s12055-008-0052-yCrossRefGoogle Scholar
Arkader, R, Troster, EJ, Abellan, DM, et al. Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients. J Cardiothorac Vasc Anesth. 2004; 18: 160165.10.1053/j.jvca.2004.01.021CrossRefGoogle ScholarPubMed
Kolamunnage-Dona, R, Williamson, PR. Time-dependent efficacy of longitudinal biomarker for clinical endpoint. Stat Methods Med Res 2018; 27: 19091924.CrossRefGoogle ScholarPubMed
Brown, JVE, Meader, N, Cleminson, J, et al. C-reactive protein for diagnosing late-onset infection in newborn infants. Cochrane Database Syst Rev 2019; 1: 16.Google ScholarPubMed
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