Dataset Information

Chronic Critical Illness Patients Fail to Respond to Current Evidence-Based Intensive Care Nutrition Secondarily to Persistent Inflammation, Immunosuppression, and Catabolic Syndrome.

ABSTRACT:

Background

Sepsis-induced multiple-organ failure (MOF) has plagued surgical intensive care units (ICUs) for decades. Early nutrition (principally enteral) improves hospital outcomes of high-risk ICU patients. The purpose of this study is to document how the growing epidemic of chronic critical illness (CCI) patients responds to adequate evidence-based ICU nutrition.

Methods

This retrospective post hoc subgroup analysis of an ongoing sepsis database identified 56 CCI patients who received early, adequate nutrition per an established surgical ICU protocol compared with 112 matched rapid-recovery (RAP) patients.

Results

The matched CCI and RAP groups had similar baseline characteristics. Serial biomarkers showed that CCI patients remained persistently inflamed with ongoing stress metabolism and that despite receiving evidence-based protocol nutrition, they had persistent catabolism and immunosuppression with more secondary infections. More CCI patients were discharged to poor nonhome destinations (ie, skilled nursing facilities, long-term acute care, hospice) (81% vs 29%, P < 0.05). At 12-month follow-up, CCI patients had worse functional status by Zubrod score (3.17 vs 1.62, P < 0.001) and Short Physical Battery Testing (4.78 vs 8.59, P < 0.02), worse health-related quality of life by EQ-5D-3L descriptive measures (9.07 vs 7.45, P < 0.003), and lower survival (67% vs 92%, P < 0.05).

Conclusions

Despite early, adequate, evidence-based ICU nutrition, septic surgical ICU patients who develop CCI exhibit persistent inflammation, immunosuppression, and catabolism with unacceptable long-term morbidity and mortality. Although current evidence-based ICU nutrition may improve short-term ICU outcomes, novel adjuncts are needed to improve long-term outcomes for CCI patients.

SUBMITTER: Rosenthal MD

PROVIDER: S-EPMC7415498 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14.Complicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings.Genomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS.Epidemiologic study, level III.