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

ABSTRACT: 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 3-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (?14 days of intensive care unit 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, 19 (13%) died during their hospitalization and 71 (49%) developed CCI. The 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%, p < 0.0001), whereas those with RAP were more often discharged to home or a rehabilitation facility. Six-month mortality was significantly higher in CCI as compared with RAP cohort (37% vs. 2%; p < 0.01). Multivariate logistic regression modeling revealed delayed onset sepsis (>48 hours after admission; odds ratio [OR], 10.93; 95% confidence interval [CI], 4.15-28.82]), interfacility transfer (OR, 3.58; 95% CI, 1.43-8.96), vasopressor-dependent septic shock (OR, 3.75; 95% CI, 1.47-9.54), and Sequential Organ Failure Assessment score of 5 or greater at 72 hours (OR, 5.03; 95% CI, 2.00-12.62) as independent risk factors for the development of CCI. The CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles are consistent with persistent immunosuppression (absolute lymphocyte count and soluble programmed death ligand 1) and catabolism (plasma insulin-like growth factor binding protein 3 and urinary 3-methylhistidine excretion). CONCLUSION: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:Prognostic, level II.

SUBMITTER: Stortz JA

PROVIDER: S-EPMC5780256 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Stortz Julie A JA Mira Juan C JC Raymond Steven L SL Loftus Tyler J TJ Ozrazgat-Baslanti Tezcan T Wang Zhongkai Z Ghita Gabriela L GL Leeuwenburgh Christiaan C Segal Mark S MS Bihorac Azra A Brumback Babette A BA Mohr Alicia M AM Efron Philip A PA Moldawer Lyle L LL Moore Frederick A FA Brakenridge Scott C SC

The journal of trauma and acute care surgery 20180201 2

<h4>Background</h4>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).<h4>Methods</h4>This 3-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients wit ...[more]

PMID: 29251709

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Project description:Background and aimsRisk factors for poor outcomes after critical illness are incompletely understood. While nutritional risk is associated with mortality in critically ill patients, its association with disability, cognitive, and health-related quality of life is unclear in survivors of critical illness. This study's objective was to determine whether greater nutritional risk at ICU admission is associated with greater disability, worse cognition, and worse HRQOL at 3 and 12-month follow-up.MethodsWe enrolled adults (≥18 years of age) with respiratory failure or shock treated in medical and surgical intensive care units from two U.S. centers. We measured nutritional risk using the modified Nutrition Risk in Critically Ill (mNUTRIC) score (range 0-9 [highest risk]) at intensive care unit admission. We measured associations between mNUTRIC scores and discharge destination, disability in basic activities of daily living (ADLs) using the Katz ADL, instrumental ADLs using the Functional Activities Questionnaire (FAQ), global cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), executive function using the Trail Making Test Part B (Trails B), and health-related quality of life using the SF-36, adjusting for sex, education, BMI, baseline frailty, disability, and cognition, severity of illness, days of delirium, coma, and mechanical ventilation.ResultsOf the 821 patients enrolled in the ICU, 636 patients survived to hospital discharge. We assessed outcomes in 448 of 535 survivors (84%) at 3 months and 382 of 476 survivors (80%) at 12 months. Higher mNUTRIC scores predicted greater odds of discharge to an institution (OR 2.0, 95% CI: 1.6 to 2.6; P < 0.01). Higher mNUTRIC scores were associated with a trend towards greater disability in basic activities of daily living (IRR 1.3, 95% CI 1.0 to 1.7) at 3 months that did not reach significance (p = 0.09) with no association demonstrated at 12 months. There were no associations between mNUTRIC scores and FAQ, RBANS, or Trails B scores. mNUTRIC scores were inconsistently associated with SF-36 physical and mental component scale scores.ConclusionsGreater nutritional risk at ICU admission is associated with disability in survivors of critical illness. Future studies should evaluate interventions in those at high nutritional risk as a means to speed recovery.

Project description:BackgroundGlucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin secretion, cellular glucose uptake, and has immune-regulatory functions. Glucagon-like peptide-1 is markedly altered after trauma and sepsis, but the implications remain unclear.Study designWe performed an analysis of a prospective, longitudinal cohort study of critically ill surgical patients with sepsis. Patient characteristics and clinical data were collected, as well as peripheral blood sampling for biomarker analysis, out to 28 days after sepsis onset. We prospectively adjudicated sepsis diagnosis, severity, clinical outcomes, and 6-month follow-up.ResultsThe cohort included 157 septic surgical patients with significant physiologic derangement (Maximum Sequential Organ Failure Assessment [SOFA] score 8, interquartile range [IQR] 4 to 11), a high rate of multiple organ failure (50.3%), and septic shock (24.2%). Despite high disease severity, both early death (<14 days; n = 4, 2.9%) and overall inpatient mortality were low (n = 12, 7.6%). However, post-discharge 6-month mortality was nearly 3-fold higher (19.7%). Both GLP-1 and interleukin [IL]-6 levels were significantly elevated for 21 days (p ≤ 0.01) in patients who developed chronic critical illness (CCI) compared with patients with a rapid recovery. Elevated GLP-1 at 24 hours was a significant independent predictor for the development of CCI after controlling for IL-6 and glucose levels (p = 0.027), and at day 14 for death or severe functional disability at 6 months (WHO/Zubrod score 4-5, p = 0.014).ConclusionsElevated GLP-1 within 24 hours of sepsis is a predictor of early death or persistent organ dysfunction. Among early survivors, persistently elevated GLP-1 levels at day 14 are strongly predictive of death or severe functional disability at 6 months. Persistently elevated GLP-1 levels may be a marker of a nonresolving catabolic state that is associated with muscle wasting and dismal outcomes after sepsis and chronic critical illness.

Project description:ObjectiveTo analyze serial biomarkers of the persistent inflammation, immunosuppression, and catabolism syndrome (PICS) to gain insight into the pathobiology of chronic critical illness (CCI) after surgical sepsis.BackgroundAlthough early deaths after surgical intensive care unit sepsis have decreased and most survivors rapidly recover (RAP), one third develop the adverse clinical trajectory of CCI. However, the underlying pathobiology of its dismal long-term outcomes remains unclear.MethodsPICS biomarkers over 14 days from 124 CCI and 225 RAP sepsis survivors were analyzed to determine associations and prediction models for (1) CCI (≥14 intensive care unit days with organ dysfunction) and (2) dismal 1-year outcomes (Zubrod 4/5 performance scores). Clinical prediction models were created using PIRO variables (predisposition, insult, response, and organ dysfunction). Biomarkers were then added to determine if they strengthened predictions.ResultsCCI (vs RAP) and Zubrod 4/5 (vs Zubrod 0-3) cohorts had greater elevations in biomarkers of inflammation (interleukin [IL]-6, IL-8, interferon gamma-induced protein [IP-10], monocyte chemoattractant protein 1), immunosuppression (IL-10, soluble programmed death ligand-1), stress metabolism (C-reactive protein, glucagon-like peptide 1), and angiogenesis (angiopoietin-2, vascular endothelial growth factor, vascular endothelial growth factor receptor-1, stromal cell-derived factor) at most time-points. Clinical models predicted CCI on day 4 (area under the receiver operating characteristics curve [AUC] = 0.89) and 1 year Zubrod 4/5 on day 7 (AUC = 0.80). IL-10 and IP-10 on day 4 minimally improved prediction of CCI (AUC = 0.90). However, IL-10, IL-6, IL-8, monocyte chemoattractant protein 1, IP-10, angiopoietin-2, glucagon-like peptide 1, soluble programmed death ligand-1, and stromal cell-derived factor on day 7 considerably improved the prediction of Zubrod 4/5 status (AUC = 0.88).ConclusionsPersistent 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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Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients.

Publications

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

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