In children undergoing surgery with the use of CPB, there are many uncertainties in the early postoperative days regarding infection status and appropriate antibiotic use. Although the recommendations for perioperative antibiotic prophylaxis in cardiac surgery are well known, several authors have reported that in many centers, especially pediatric ones, the antibiotic prophylaxis is commonly extended for more than 24–48 h in fear of possible infection that could complicate the postoperative course (Jaworski et al., 2019; Alphonso et al., 2007). The situation is even more complex in patients whose sternum is left open for several days after the surgery.
Therefore, clinicians need reliable tools to guide their decisions on antibiotic use in the early postoperative period to avoid their overuse without increasing the risk of infectious complications. One option is to monitor the concentrations of inflammatory markers. However, this requires precise knowledge of their kinetics in a specific group of patients, especially when interference with additional factors (such as, e.g., the use of CPB) may be significant. Currently, the most widely used acute phase marker is CRP, a short pentraxin produced during a systemic inflammatory response (Doni et al., 2017). However, due to its kinetics (slow rise and long time to normalization), it is of limited value in postoperative monitoring, and studies have shown that PCT performs better in this setting (Farias et al., 2021).
Recently, many authors described PTX3 as a potential biomarker of the acute phase in various clinical settings. Serum PTX3 levels were shown to correlate with progression of autoimmune diseases (childhood-onset systemic lupus erythematosus (Quismorio Jr. & Quismorio, 2018), juvenile idiopathic arthritis, atopic dermatitis (Marseglia et al., 2012)), degenerative disorders, arteritis (Hajishengallis & Russell, 2015), and a variety of cardiovascular diseases (Cieślik & Hrycek, 2012; Inoue et al., 2012), as well as acute pancreatitis (Gluszek et al., 2020) and appendicitis (Ates et al., 2020). Studies conducted in neonates revealed that PTX3 is a good biomarker of early-onset sepsis (Densen & Ram, 2015; Baumert et al., 2021). It has also been shown that PTX3 may play a role in tissue repair in various models of non-infectious tissue damage, such as excisional skin wounds, chemically induced liver, and lung injury or arterial thrombosis (Doni et al., 2017).
Normal plasma PTX3 levels in healthy individuals are ≤ 2 ng/ml; slightly higher concentrations are observed in females than in males; levels also increase with age (Ristagno et al., 2019; Garlanda et al., 2018; Peri et al., 2000; Yamasaki et al., 2009). However, normal plasma PTX3 concentrations in children have not been determined so far. The main characteristic of PTX3 is that it rises faster than CRP (peak levels after 6–8 h and 24–48 h post stimulation, respectively) (Ristagno et al., 2019; Garlanda et al., 2018). Patients with acute myocardial infarction show an early peak in PTX3 levels observed within 6–8 h of symptom onset to values 3–5 times the normal range. Baseline PTX3 levels are reached within 3 days after stimulation (Daigo et al., 2014; Peri et al., 2000; Helseth et al., 2014).
To the best of our knowledge, there are currently no studies on the kinetics of PTX3 in patients undergoing cardiac surgery with the use of CPB, especially in children. Cardiac surgery with CPB induces a non-specific acute inflammatory response, and the contact of cellular and humoral blood components with the synthetic material of CPB provokes SIRS. This causes activation of leukocytes and endothelial cells, leading to massive cytokine release.
In this study, we investigated the kinetics of PTX3 in children in the early period after surgery for congenital heart disease with the use of CPB. PTX3 concentrations were compared to other commonly used biomarkers, namely CRP and PCT. We observed that the peak value of PTX3 was reached within 24 h after the operation with CPB, with the mean peak value of 72.4 ng/ml (and a maximum value as high as 193.4 ng/ml). This was significantly higher than the expected reference range. In all but two patients (90.5%), PTX3 decreased on POD 2 in comparison to POD 1 and in this aspect, it was similar to the changes in PCT; however, the proportion of this reduction seemed to be different. The reduction in PCT was rather little, while the mean PTX3 concentration on POD 2 was only 30% of that on POD 1. Moreover, on POD 3, the PTX3 concentrations were in the reference range, while PCT remained elevated. Therefore, the kinetics of PTX3 appear more favorable than other acute phase markers in pediatric cardiac surgery patients in the early postoperative period; however, our results concern children without postoperative infections. The rapid decrease of PTX3 on POD 2 could be a positive prognostic factor for an uneventful postoperative course in terms of infection. However, larger clinical studies should be performed to verify these observations. In our opinion, it is very important because this is the time when antibiotics prophylaxis ends, and physicians have to decide whether to start empirical antibiotic treatment or not. This decision is twice as difficult because the CRP value on POD 2 is almost always higher than on POD 1. It is not uncommon to see high body temperature or even fever with tachycardia on POD 2 associated with SIRS in this group of patients. However, it is worth emphasizing that the decision on empirical antibiotic therapy in patients after CPB should not be based solely on CRP, PTX3, or PCT values.
Our study has some limitations. Firstly, it included a small number of patients. Secondly, we could not perform advanced pharmacokinetic analysis due to the limited number of blood samples that could be taken from children due to ethical concerns related to the pediatric population. Additionally, there are far more complex procedures in pediatric cardiac surgery than in our selected patient group; therefore, our results cannot be simply extrapolated to all groups of pediatric patients.
We demonstrated that PTX3 concentrations were significantly higher in the early postoperative days in children after congenital heart surgery with CPB, with maximum values at 24 h after the procedure. Under normal circumstances, PTX3 rises and falls quickly in contrast to CRP and PCT, and a second PTX3 rise in the early postoperative period may be abnormal; however, this needs further investigations. A single assessment of any biomarker in the early postoperative period in these patients may lead to overdiagnosis of infections and overuse of antibiotics. Patient status can be more reliably monitored using the dynamics of biomarker concentrations on consecutive postoperative days. Multicentre prospective clinical studies should be performed to confirm our observations.