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Procalcitonin and Other Common Biomarkers Do Not Reliably Identify Patients at Risk for Bacterial Infection After Congenital Heart Surgery

D’Souza, Shane1,2; Guhadasan, Rathi DTMH, MSc, MBBS2,3; Jennings, Rebecca MClin Res4; Siner, Sarah BSc4; Paulus, Stéphane MD, FRCPCH2; Thorburn, Kent MMed, MRCP, FCPaed, FRCPCH4; Chesters, Christine BSc4; Downey, Colin BSc5; Baines, Paul MD, PhD, FFICM, MRCP, FRCA4; Lane, Steven BSc, MSc, PhD6; Carrol, Enitan MBChB, MD, FRCPCH, DTMH, PG Cert. Dip.Med.Sci, FHEA2,4

Pediatric Critical Care Medicine: March 2019 - Volume 20 - Issue 3 - p 243-251
doi: 10.1097/PCC.0000000000001826
Cardiac Intensive Care
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Objectives: Following surgery, it is difficult to distinguish a postoperative inflammatory reaction from infection. This study examined the predictive value of the biomarkers; procalcitonin, C-reactive protein, lactate, neutrophils, lymphocytes, platelets, and the biphasic activated partial thromboplastin time waveform in diagnosing bacterial infection following cardiac surgery.

Design: Prospective, observational study.

Setting: A regional, PICU in the United Kingdom.

Patients: Three-hundred sixty-eight children under the age of 16 admitted to the PICU for elective cardiac surgery were enrolled in the study.

Interventions: All biomarker measurements were determined daily until postoperative day 7. Children were assessed for postoperative infection until day 28 and divided into four groups: bacterial infection, culture-negative sepsis, viral infection, and no infection. We used the Kruskal-Wallis test, chi-square test, analysis of variance, and area under the curve in our analysis.

Measurements and Main Results: In total, 71 of 368 children (19%) developed bacterial infection postoperatively, the majority being surgical site infections. In those with bacterial infection, procalcitonin was elevated on postoperative days 1–3 and the last measurement prior to event compared with those without bacterial infection. The most significant difference was the last measurement prior to event; 0.72 ng/mL in the bacterial infection group versus 0.13 ng/mL in the no infection group (for all groups; p < 0.001). Longitudinal profiles of all biomarkers were indistinct in the bacterial infection and nonbacterial infection groups except in those with culture-negative infections who had distinct procalcitonin kinetics on postoperative days 1–4. Children with culture-negative sepsis required longer ventilatory support and PICU stay and were more likely to develop complications than the other groups.

Conclusions: None of the biomarkers studied within 3 days of infection distinguished between infection and postoperative inflammatory reaction. However, procalcitonin kinetics peaked on postoperative day 2 and fell more sharply than C-reactive protein kinetics, which peaked at postoperative day 3. The monitoring of procalcitonin kinetics following cardiac surgery may help guide rational antimicrobial use.

1School of Medicine, University of Liverpool, Liverpool, United Kingdom.

2Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

3Department of Paediatrics, Angkor Hospital for Children, Siem Reap, Cambodia.

4Department of Critical Care, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom.

5Department of Biochemistry, Royal Liverpool and Broadgreen University Hospitals, Liverpool, United Kingdom.

6Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

Mr. D’Souza and Dr. Guhadasan contributed equally as first authors. Drs. Lane and Carrol contributed equally as senior authors.

Drs. Baines and Carrol designed the study and provided oversight. Drs. Guhadasan and Jennings, and Ms. Siner recruited patients and collected data. Mr. D’Souza collected data and helped draft the article. Mr. D’Souza drafted the first version of the article. Dr. Lane performed statistical analysis. Drs. Paulus, Thorburn, and Baines contributed to study management.

Ms. Chesters and Mr. Downey performed laboratory analysis. All authors contributed to drafting the article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/pccmjournal).

Mr. D’Souza disclosed that the study was funded jointly by the National Institute of Health Research (NIHR) Liverpool Biomedical Research Centre in Microbial Diseases and the Alder Hey Charity. Dr. Jennings received support for article research from the NIHR. Dr. Paulus received funding from GlaxoSmithKline (member of Advisory board to determine clinical endpoints for a flu vaccine trial). Dr. Carrol received support for article research from the NIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: hlsdsouz@liverpool.ac.uk

Copyright © 2018 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies