DISCUSSION
critically ill
CRITICAL ILLNESS, CRITICALLY ILL
This study investigated the course of several GI biomarkers during the first 5 days of pediatric critical illness and its association with ENA. Whereas leptin and citrulline did not change over time, we found that plasma CCK and I-FABP2 concentrations decreased significantly, and glucagon concentrations increased significantly during the first 5 days of PICU stay. None of the GI biomarkers were longitudinally associated with the amount of EN provided. Moreover, except for lower CCK levels in patients with FIS on day 3, GI biomarker concentrations did not differ between patients with or without FIS. For now, we thus conclude that these biomarkers could not be used as a predictor for ENA during the first 5 days of their PICU stay.We have studied the course of biomarkers of 3 pathophysiological pathways deemed involved in FI, that is, GI motility, enterocyte damage, and enterocyte function.In our study, CCK concentrations were lower on day 5 compared to day 3 (Fig. Our results regarding glucagon correspond to a study in critically ill adults that had also found normal glucagon concentrations upon admission, followed by an increase during ICU stay (Fig. The I-FABP2 concentrations on admission in our study are higher than reference concentrations in healthy children (The range of leptin concentrations was in line with ranges found in critically ill adults (Regarding citrulline, a study in children undergoing heart surgery found a decrease in citrulline concentrations post-surgery (PYY concentrations increased significantly during the first 5 days of PICU stay (Figure 1, Supplemental Digital Content 3, Despite the variation in the biomarker concentrations, both intra-individually and inter-individually, none of the biomarkers was associated with ENA as a proxy of FI (Table The studied biomarkers are all part of complex pathways and are affected by multiple physiological, pathophysiological, and iatrogenic processes. For example, a study in critically ill adults found a correlation between glucagon and severity of illness (Our study has several strengths, of which the longitudinal aspect is unique in this patient population. Secondly, we have investigated multiple GI biomarkers involved in different pathways in an attempt to capture the various aspects of FI. However, our study also has some limitations that need to be addressed. Most importantly, several details regarding GI symptoms and reasons for withholding or not providing EN according to the protocol (eg, fluid restrictions and fasting for procedures) were lacking. Hence, we could not use the proposed definition of FI of Eveleens et al (