The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study.

ABSTRACT

Background: Ischaemic intestines could be a driver of critical illness through an inflammatory response. We have previously published reports on a biomarker for intestinal injury, plasma Intestinal Fatty Acid Binding Protein (IFABP), and inflammatory biomarkers after out-of-hospital cardiac arrest (OHCA). In this post-hoc study we explored the potential indirect effects of intestinal injury mediated through the inflammatory response on organ dysfunction and mortality. Methods: We measured IFABP and twenty-one inflammatory biomarkers in 50 patients at admission to intensive care unit after OHCA. First, we stratified patients on median IFABP and compared biomarkers between "low" and "high" IFABP. Second, by causal mediation analysis, we assessed effects of IFABP through the two most important inflammatory biomarkers, interleukin (IL)-6 and terminal complement complex (TCC), on day two circulatory variables, Sequential Organ Failure Assessment (SOFA)-score, and 30-day mortality. Results: Cytokines and complement activation were higher in the high IFABP group. In mediation analysis, patients on the 75th percentile of IFABP, compared to the 25th percentile, had 53% (95% CI, 33-74; p < 0.001) higher risk of dying, where 13 (95% CI, 3-23; p = 0.01) percentage points were mediated through an indirect effect of IL-6. Similarly, the indirect effect of IFABP through IL-6 on SOFA-score was significant, but smaller than potential other effects. Effects through IL-6 on circulatory variables, and all effects through TCC, were not statistically significant and/or small. Conclusion: Effects of intestinal injury mediated through inflammation on organ dysfunction and mortality were limited. Small, but significant, effects through IL-6 were noted.Trial registration ClinicalTrials.gov NCT02648061.