Inflammatory mediators in intra-abdominal sepsis or injury – a scoping review

Zhengwen Xiao, Crystal Wilson, Helen Lee Robertson, Derek J. Roberts, Chad G. Ball, Craig N. Jenne, Andrew W. Kirkpatrick

Inflammatory and protein mediators (cytokine, chemokine, acute phase proteins) play an important, but still not completely understood, role in the morbidity and mortality of intra-abdominal sepsis/injury. We therefore systematically reviewed preclinical and clinical studies of mediators in intra-abdominal sepsis/injury in order to evaluate their ability to: (1) function as diagnostic/prognostic biomarkers; (2) serve as therapeutic targets; and (3) illuminate the pathogenesis mechanisms of sepsis or injury-related organ dysfunction. We searched MEDLINE, PubMed, EMBASE and the Cochrane Library. Two investigators independently reviewed all identified abstracts and selected articles for full-text review. We included original studies assessing mediators in intra-abdominal sepsis/injury. Among 2437 citations, we selected 182 studies in the scoping review, including 79 preclinical and 103 clinical studies. Serum procalcitonin and C-reactive protein appear to be useful to rule out infection or monitor therapy; however, the diagnostic and prognostic value of mediators for complications/outcomes of sepsis or injury remains to be established. Peritoneal mediator levels are substantially higher than systemic levels after intra-abdominal infection/trauma. Common limitations of current studies included small sample sizes and lack of uniformity in study design and outcome measures. To date, targeted therapies against mediators remain experimental. Whereas preclinical data suggests mediators play a critical role in intra-abdominal sepsis or injury, there is no consensus on the clinical use of mediators in diagnosing or managing intra-abdominal sepsis or injury. Measurement of peritoneal mediators should be further investigated as a more sensitive determinant of intra-abdominal inflammatory response. High-quality clinical trials are needed to better understand the role of inflammatory mediators.