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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: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:Rationale: A small but growing number of hospitals are experimenting with emergency department-embedded critical care units (CCUs) in an effort to improve the quality of care for critically ill patients with sepsis and acute respiratory failure (ARF).Objectives: To evaluate the potential impact of an emergency department-embedded CCU at the Hospital of the University of Pennsylvania among patients with sepsis and ARF admitted from the emergency department to a medical ward or intensive care unit (ICU) from January 2016 to December 2017.Methods: The exposure was eligibility for admission to the emergency department-embedded CCU, which was defined as meeting a clinical definition for sepsis or ARF and admission to the emergency department during the intervention period on a weekday. The primary outcome was hospital length of stay (LOS); secondary outcomes included total emergency department plus ICU LOS, hospital survival, direct admission to the ICU, and unplanned ICU admission. Primary interrupted time series analyses were performed using ordinary least squares regression comparing monthly means. Secondary retrospective cohort and before-after analyses used multivariable Cox proportional hazard and logistic regression.Results: In the baseline and intervention periods, 3,897 patients met the inclusion criteria for sepsis and 1,865 patients met the criteria for ARF. Among patients admitted with sepsis, opening of the emergency department-embedded CCU was not associated with hospital LOS (β = -1.82 d; 95% confidence interval [CI], -4.50 to 0.87; P = 0.17 for the first month after emergency department-embedded CCU opening compared with baseline; β = -0.26 d; 95% CI, -0.58 to 0.06; P = 0.10 for subsequent months). Among patients admitted with ARF, the emergency department-embedded CCU was not associated with a significant change in hospital LOS for the first month after emergency department-embedded CCU opening (β = -3.25 d; 95% CI, -7.86 to 1.36; P = 0.15) but was associated with a 0.64 d/mo shorter hospital LOS for subsequent months (β = -0.64 d; 95% CI, -1.12 to -0.17; P = 0.01). This result persisted among higher acuity patients requiring ventilatory support but was not supported by alternative analytic approaches. Among patients admitted with sepsis who did not require mechanical ventilation or vasopressors in the emergency department, the emergency department-embedded CCU was associated with an initial 9.9% reduction in direct ICU admissions in the first month (β = -0.099; 95% CI, -0.153 to -0.044; P = 0.002), followed by a 1.1% per month increase back toward baseline in subsequent months (β = 0.011; 95% CI, 0.003-0.019; P = 0.009). This relationship was supported by alternative analytic approaches and was not seen in ARF. No associations with emergency department plus ICU LOS, hospital survival, or unplanned ICU admission were observed among patients with sepsis or ARF.Conclusions: The emergency department-embedded CCU was not associated with clinical outcomes among patients admitted with sepsis or ARF. Among less sick patients with sepsis, the emergency department-embedded CCU was initially associated with reduced rates of direct ICU admission from the emergency department. Additional research is necessary to further evaluate the impact and utility of the emergency department-embedded CCU model.

Dataset Information

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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