Time Course of Procalcitonin Concentration Following Birth and Surgery

Introduction: Procalcitonin plasma concentration (PCT) has been suggested as a biomarker for acute infection (usually bacterial). Concentrations increase rapidly within 4-6 hours of infection [1]. However PCT also increases following events such as birth and surgery without any known infection [2, 3]. It is important to understand the time course of PCT following these events in non-infected patients to provide a reference range so that acute infection can be identified.

Aim: To describe the time course of PCT following birth and surgery.

Methods: PCT measurements from non-infected pre-term and term neonates following birth [4], and non-infected neonates and infants following cardiothoracic surgery [5] were provided by other researchers. Some patients had their chest closed at the end of the initial surgery (immediate chest closure), whilst others had a period with the chest remaining open with a subsequent surgery (delayed chest closure). A one compartment turnover model with first order elimination was used to describe PCT input and output. The PCT volume of distribution was fixed at 15L/70kg. The time course of the birth and surgical effects were described by one compartment distribution with an infusion input and first order elimination. Event stimulus concentrations, CBE and CSE, changed PCT production. Baseline PCT concentration was calculated by PCT production rate (RateIN) / PCT clearance (CL), and RateIN was assumed to increase with birth and surgical events. Linear pharmacodynamic models specific for birth, initial surgery, open chest period and delayed surgical chest closure linked stimulus to PCT change. Covariates included postmenstrual age (empirical sigmoid emax) and theory based allometric size using total body weight. Models were developed using NONMEM 7.5.1.

Results:1537 PCT concentrations were measured in 351 patients. Population parameter estimates were PCT CL 11.7 L/day/70kg, PCT RateIN 0.11 mcg/day, elimination half life (Tel) of birth effect stimulus 4.8 h, Tel of surgical effect stimulus 20.6 h. The initial surgery and open chest period could be linked to changes in PCT concentration, however an effect of the delayed chest closure surgery on PCT could not be identified. The birth effect slope for stimulation of PCT was 1010, 4 times larger than that of the initial surgical effect (251) and 100 times that of the open chest period (10).

Conclusion: The birth event increases the PCT concentration to a much larger extent than the surgical events do. However, the surgical effect stimulus lasts four times longer than the birth effect stimulus. This provides more information about the time course of PCT following non-infectious events and may help identify patients with increased PCT concentrations associated with infection.

References

  1. Dandona, P., et al., Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab, 1994. 79(6): p. 1605-8.
  2. Chiesa, C., et al., C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta, 2011. 412(11-12): p. 1053-9.
  3. Li, X., et al., Diagnostic Value of Procalcitonin on Early Postoperative Infection After Pediatric Cardiac Surgery. Pediatr Crit Care Med, 2017. 18(5): p. 420-428.
  4. Fukuzumi, N., et al., Age-specific percentile-based reference curve of serum procalcitonin concentrations in Japanese preterm infants. Scientific reports, 2016. 6(1): p. 1-6.
  5. Davidson, J., 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(4): p. 413-9.

A Bokor

  • University of Auckland