Dataset Information

Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.

ABSTRACT: As early as the 1990s, chronic critical illness, a distinct syndrome of persistent high-acuity illness requiring management in the ICU, was reported under a variety of descriptive terms including the "neuropathy of critical illness," "myopathy of critical illness," "ICU-acquired weakness," and most recently "post-intensive care unit syndrome." The widespread implementation of targeted shock resuscitation, improved organ support modalities, and evidence-based protocolized ICU care has resulted in significantly decreased in-hospital mortality within surgical ICUs, specifically by reducing early multiple organ failure deaths. However, a new phenotype of multiple organ failure has now emerged with persistent but manageable organ dysfunction, high resource utilization, and discharge to prolonged care facilities. This new multiple organ failure phenotype is now clinically associated with the rapidly increasing incidence of chronic critical illness in critically ill surgery patients. Although the underlying pathophysiology driving chronic critical illness remains incompletely described, the persistent inflammation, immunosuppression, and catabolism syndrome has been proposed as a mechanistic framework in which to explain the increased incidence of chronic critical illness in surgical ICUs. The purpose of this review is to provide a historic perspective of the epidemiologic evolution of multiple organ failure into persistent inflammation, immunosuppression, and catabolism syndrome; describe the mechanism that drives and sustains chronic critical illness, and review the long-term outcomes of surgical patients who develop chronic critical illness.

SUBMITTER: Efron PA

PROVIDER: S-EPMC6056337 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.

Efron Philip A PA Mohr Alicia M AM Bihorac Azra A Horiguchi Hiroyuki H Hollen McKenzie K MK Segal Mark S MS Baker Henry V HV Leeuwenburgh Christiaan C Moldawer Lyle L LL Moore Frederick A FA Brakenridge Scott C SC

Surgery 20180526 2

As early as the 1990s, chronic critical illness, a distinct syndrome of persistent high-acuity illness requiring management in the ICU, was reported under a variety of descriptive terms including the "neuropathy of critical illness," "myopathy of critical illness," "ICU-acquired weakness," and most recently "post-intensive care unit syndrome." The widespread implementation of targeted shock resuscitation, improved organ support modalities, and evidence-based protocolized ICU care has resulted in ...[more]

PMID: 29807651

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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.

Project description:BackgroundFollowing trauma, persistent inflammation, immunosuppression, and catabolism may characterize delayed recovery or failure to recover. Understanding the metabolic response associated with these adverse outcomes may facilitate earlier identification and intervention. We characterized the metabolic profiles of trauma victims who died or developed chronic critical illness (CCI) and hypothesized that differences would be evident within 1-week postinjury.MethodsVenous blood samples from trauma victims with shock who survived at least 7 days were analyzed using mass spectrometry. Subjects who died or developed CCI (intensive care unit length of stay of ≥14 days with persistent organ dysfunction) were compared with subjects who recovered rapidly (intensive care unit length of stay, ≤7 days) and uninjured controls. We used partial least squares discriminant analysis, t tests, linear mixed effects regression, and pathway enrichment analyses to make broad comparisons and identify differences in metabolite concentrations and pathways.ResultsWe identified 27 patients who died or developed CCI and 33 who recovered rapidly. Subjects were predominantly male (65%) with a median age of 53 years and Injury Severity Score of 36. Healthy controls (n = 48) had similar age and sex distributions. Overall, from the 163 metabolites detected in the samples, 56 metabolites and 21 pathways differed between injury outcome groups, and partial least squares discriminant analysis models distinguished injury outcome groups as early as 1-day postinjury. Differences were observed in tryptophan, phenylalanine, and tyrosine metabolism; metabolites associated with oxidative stress via methionine metabolism; inflammatory mediators including kynurenine, arachidonate, and glucuronic acid; and products of the gut microbiome including indole-3-propionate.ConclusionsThe metabolic profiles in subjects who ultimately die or develop CCI differ from those who have recovered. In particular, we have identified differences in markers of inflammation, oxidative stress, amino acid metabolism, and alterations in the gut microbiome. Targeted metabolomics has the potential to identify important metabolic changes postinjury to improve early diagnosis and targeted intervention.Level of evidencePrognostic/epidemiologic, level III.

Project description:PurposePatients with persistent critical illness may account for up to half of all intensive care unit (ICU) bed-days. It is unknown if there is hospital variation in the development of persistent critical illness and if hospital performance affects the incidence of persistent critical illness.MethodsThis is a retrospective analysis of Veterans admitted to the Veterans Administration (VA) ICUs from 2015 to 2017. Hospital performance was defined by the risk- and reliability-adjusted 30-day mortality. Persistent critical illness was defined as an ICU length of stay of at least 11 days. We used 2-level multilevel logistic regression models to assess variation in risk- and reliability-adjusted probabilities in the development of persistent critical illness.ResultsIn the analysis of 100 hospitals which encompassed 153,512 hospitalizations, 4.9% (N = 7640/153,512) developed persistent critical illness. There was variation in the development of persistent critical illness despite controlling for patient characteristics (intraclass correlation: 0.067, 95% CI 0.049-0.091). Hospitals with higher risk- and reliability-adjusted 30-day mortality had higher probabilities of developing persistent critical illness (predicted probability: 0.057, 95% CI 0.051-0.063, p < 0.01) compared to those with lower risk- and reliability-adjusted 30-day mortality (predicted probability: 0.046, 95% CI 0.041-0.051, p < 0.01). The median odds ratio was 1.4 (95% CI 1.33-1.49) implying that, for two patients with the same physiology on admission at two different VA hospitals, the patient admitted to the hospital with higher adjusted mortality would have 40% greater odds of developing persistent critical illness.ConclusionHospitals with higher risk- and reliability-adjusted 30-day mortality have a higher probability of developing persistent critical illness. Understanding the drivers of this variation may identify modifiable factors contributing to the development of persistent critical illness.

Project description:BACKGROUND:Many sepsis survivors develop chronic critical illness (CCI) and are assumed to be immunosuppressed, but there is limited clinical evidence to support this. We sought to determine whether the incidence of secondary infections and immunosuppressive biomarker profiles of patients with CCI differ from those with rapid recovery (RAP) after sepsis. METHODS:This prospective observational study evaluated 88 critically ill patients with sepsis and 20 healthy controls. Cohorts were defined based on clinical trajectory (early death, RAP, or CCI), whereas immunosuppression was clinically determined by the presence of a postsepsis secondary infection. Serial blood samples were collected for absolute lymphocyte counts (ALCs), monocytic human leukocyte antigen-DR (mHLA-DR) expression, and plasma-soluble programmed death-ligand 1 (sPD-L1) concentrations. RESULTS:Of the 88 patients with sepsis, 3 (3%) died within 14 days of sepsis onset, 50 (57%) experienced RAP, and 35 (40%) developed CCI. Compared with RAP patients, CCI patients exhibited a higher incidence and overall number of infections adjusted for hospital length of stay. ALC and mHLA-DR levels were dramatically reduced at the time of sepsis diagnosis when compared with healthy controls, whereas sPD-L1 concentrations were significantly elevated. There were no differences between RAP and CCI patients in ALC, sPD-L1, or mHLA-DR at the time of diagnosis or within 24?h after sepsis diagnosis. However, in contrast to the RAP group, CCI patients failed to exhibit any trend toward restoration of normal values of ALC, HLA-DR, and sPD-L1. CONCLUSIONS:Septic patients demonstrate clinical and biological evidence to suggest they are immunosuppressed at the time of sepsis diagnosis. Those who develop CCI have a greater incidence of secondary infections and persistently aberrant markers of impaired host immunity, although measurements at the time of sepsis onset did not distinguish between subjects with RAP and CCI.

Project description:To identify actionable processes of care, quality indicators, or performance measures and their evidence base relevant to patients with persistent or chronic critical illness and their family members including themes relating to patient/family experience. Data Sources:Two authors independently searched electronic, systemic review, and trial registration databases (inception to November 2016). Study Selection:We included studies with an ICU length of stay of greater than or equal to 7 days as an inclusion criterion and reported actionable processes of care; quality improvement indicators, measures, or tools; or patient/family experience. We excluded case series/reports of less than 10 patients. Data Extraction:Paired authors independently extracted data and performed risk of bias assessment. Data Synthesis:We screened 13,130 references identifying 114 primary studies and 102 relevant reviews. Primary studies reported data on 24,252 participants; median (interquartile range) sample size of 70 (32-182). We identified 42 distinct actionable processes of care, the most commonly investigated related to categories of 1) weaning methods (21 studies; 27 reviews); 2) rehabilitation, mobilization, and physiotherapy (20 studies; 40 reviews); and 3) provision of information, prognosis, and family communication (14 studies; 11 reviews). Processes with limited evidence were generally more patient-centered categories such as communication, promotion of sleep, symptom management, or family support. Of the 21 randomized controlled trials, only two were considered at low risk of bias across all six domains, whereas just two cohort studies and one qualitative study were considered of high quality. Conclusions:We identified 42 distinct actionable processes of care relevant to patients with persistent or chronic critical illness and their families, with most frequently studied processes relating to weaning, rehabilitation/mobilization, and family communication. Qualitative studies highlighted the need to address psychologic needs and distressing symptoms as well as enabling patient communication. Our findings are informative for clinicians and decision-makers when planning high-quality patient and family-focused care.

Dataset Information

Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.

Publications

Persistent inflammation, immunosuppression, and catabolism and the development of chronic critical illness after surgery.

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