Biomarker Evidence Of The Persistent Inflammation, Immunosuppression And Catabolism Syndrome (PICS) In Chronic Critical Illness (CCI) After Surgical Sepsis
*Dijoia B Darden, *Scott C Brakenridge, Philip A Efron, *Gabriela Ghita, *Brittany P Fenner, *Lauren S Kelly, *Alicia M Mohr, *Lyle M Moldawer, Frederick A Moore
University of Florida, Gainesville, FL
Objective: While deaths after surgical ICU sepsis have decreased and most survivors rapidly recover (RAP), over 1/3rd develop CCI with dismal outcomes. Our goal was to analyze serial blood biomarkers to validate PICS in the pathobiology of CCI.
Methods: PICS biomarkers over 14 days from 124 CCI and 225 RAP sepsis survivors were analyzed to determine associations and prediction models for 1) CCI ( >14 ICU days with organ dysfunction) and 2) dismal 1-year outcomes (Zubrod 4/5 score). Clinical prediction models were first created using PIRO variables (predisposition, insult, response and organ dysfunction). Biomarkers were then added to determine if they strengthened predictions.
Results: CCI (versus RAP) and Zubrod 4/5 (versus Zubrod 0-3) patient cohorts had greater elevations in biomarkers of inflammation (IL-6, IL-8, IP-10, MCP1), immunosuppression (IL-10, sPDL-1), stress metabolism (CRP, GLP-1), and angiogenesis (Ang-2, VEGF, Flt1, SDF) at most time-points (Figure). Clinical models successfully predicted CCI on day 4 (AUC= 0.89) and Zubrod 4/5 on day 7 (AUC=0.80). IL-10 and IP-10 on day 4 only modestly improved prediction of CCI (AUC=0.90). However, IL-10, IL-6, IL-8, MCP-1, IP-10, Ang-2, GLP-1, sPDL-1 and SDF on day 7 significantly improved the prediction of Zubrod 4/5 status (AUC=0.88).
Conclusions: Persistent elevations of PICS biomarkers in the CCI and Zubrod 4/5 cohorts and their improved prediction of Zubrod 4/5 validate that PICS plays a role in CCI pathobiology. 
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