Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients

ABSTRACTBackgroundA growing number of patients survive sepsis but remain chronically critically ill. We sought to define clinical outcomes and incidence of chronic critical illness (CCI) after sepsis and to determine whether selected biomarkers of inflammation, immunosuppression, and catabolism differ between these patients and those that rapidly recover (RAP).MethodsThis three-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (≥14 days of ICU resource utilization with persistent organ dysfunction). Patient clinical demographics, outcomes, and serial serum/urine samples were collected for plasma protein and urinary metabolite analyses.ResultsOf 145 sepsis patients enrolled, nineteen (13%) died during their hospitalization and 71 (49%) developed CCI. CCI patients were significantly older (mean 63±15 vs 58 ±13 years, p=0.006), and more likely to be discharged to long-term acute care facilities (32% vs 3%, p48 hours after admission; O.R. 10.93, 95% C.I. [4.15-28.82]), inter-facility transfer (O.R. 3.58, [1.43-8.96]), vasopressor-dependent septic shock (O.R. 3.75, [1.47-9.54]), and SOFA score ≥5 at 72 hours (O.R. 5.03, [2.00-12.62]) as independent risk factors for the development of CCI. CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles consistent with persistent immunosuppression (absolute lymphocyte count and sPDL-1) and catabolism (plasma IGFBP3 and urinary 3-methylhistidine excretion).ConclusionsThe development of CCI has become the predominant clinical trajectory in critically-ill surgical patients with sepsis. These patients exhibit biomarker profiles consistent with an immunocatabolic phenotype of persistent inflammation, immunosuppression, and catabolism.Level of EvidenceLevel II, prognostic Background A growing number of patients survive sepsis but remain chronically critically ill. We sought to define clinical outcomes and incidence of chronic critical illness (CCI) after sepsis and to determine whether selected biomarkers of inflammation, immunosuppression, and catabolism differ between these patients and those that rapidly recover (RAP). Methods This three-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (≥14 days of ICU resource utilization with persistent organ dysfunction). Patient clinical demographics, outcomes, and serial serum/urine samples were collected for plasma protein and urinary metabolite analyses. Results Of 145 sepsis patients enrolled, nineteen (13%) died during their hospitalization and 71 (49%) developed CCI. CCI patients were significantly older (mean 63±15 vs 58 ±13 years, p=0.006), and more likely to be discharged to long-term acute care facilities (32% vs 3%, p48 hours after admission; O.R. 10.93, 95% C.I. [4.15-28.82]), inter-facility transfer (O.R. 3.58, [1.43-8.96]), vasopressor-dependent septic shock (O.R. 3.75, [1.47-9.54]), and SOFA score ≥5 at 72 hours (O.R. 5.03, [2.00-12.62]) as independent risk factors for the development of CCI. CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles consistent with persistent immunosuppression (absolute lymphocyte count and sPDL-1) and catabolism (plasma IGFBP3 and urinary 3-methylhistidine excretion). Conclusions The development of CCI has become the predominant clinical trajectory in critically-ill surgical patients with sepsis. These patients exhibit biomarker profiles consistent with an immunocatabolic phenotype of persistent inflammation, immunosuppression, and catabolism. Level of Evidence Level II, prognostic Correspondence should be directed to: Scott Brakenridge, M.D., Department of Surgery, University of Florida College of Medicine, PO Box 100019, Gainesville, Florida 32610-0019, Phone: 352-272-5670, FAX: 352-273-5683, Email: scott.brakenridge@surgery.ufl.edu Supported, in part, by National Institute of General Medical Sciences grants: R01 GM-040586 and R01 GM-104481 (LM), R01 GM-113945 (PE), and P50 GM-111152 (FM, SB, LM, PE, BB, MS, AB) awarded by the National Institute of General Medical Sciences (NIGMS). In addition, this work was supported, in part, by a postgraduate training grant T32 GM-008721 (JS, JM, TL) in burns, trauma, and perioperative injury by NIGMS. All authors report no conflict of interest. © 2017 Lippincott Williams & Wilkins, Inc.

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