Dataset Information

Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.

ABSTRACT:

Objectives

While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.

Design

In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).

Setting

Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.

Patients

Ninety-six adult septic and critically ill nonseptic patients were enrolled.

Interventions

None.

Measurements and main results

Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.

Conclusions

Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.

SUBMITTER: Samuelsen AM

PROVIDER: S-EPMC11208107 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.

Samuelsen Abigail M AM Halstead E Scott ES Lehman Erik B EB McKeone Daniel J DJ Bonavia Anthony S AS Bonavia Anthony S AS

Critical care explorations 20240625 7

<h4>Objectives</h4>While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.<h4>Design</h4>In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Us ...[more]

PMID: 38916619

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Project description:ObjectivesTo determine clinician accuracy in the identification and prediction of multiple organ dysfunction syndrome.DesignProspective cohort study.SettingUniversity of Michigan's C.S. Mott Children's Hospital PICU.PatientsPatients admitted to the PICU with an anticipated PICU length of stay greater than 48 hours.InterventionsNone.Measurements and main resultsFor each patient, the clinical team (attending, fellow, resident/nurse practitioner) was surveyed regarding existing and anticipated organ dysfunction. The primary outcomes were clinicians' accuracy at identifying multiple organ dysfunction syndrome and predicting new or progressive multiple organ dysfunction syndrome, compared to the objective assessment of multiple organ dysfunction syndrome using Proulx criteria. We also measured sensitivity, specificity, negative and positive predictive values, and negative and positive likelihood ratios of clinician assessments. We tested for differences in accuracy by clinician type using chi-square tests. Clinicians rated their confidence in prediction on a 5-point Likert scale. There were 476 eligible PICU admissions, for whom 1,218 surveys were completed. Multiple organ dysfunction syndrome was present in 89 patients (18.7%) at enrollment, and new or progressive multiple organ dysfunction syndrome occurred in 39 (8.2%). Clinicians correctly identified multiple organ dysfunction syndrome with 79.9% accuracy and predicted additional organ dysfunction with 82.6% accuracy. However, the positive and negative likelihood ratios for new or progressive multiple organ dysfunction syndrome prediction were 3.0 and 0.7, respectively, indicating a weak relationship between the clinician prediction and development of new or progressive multiple organ dysfunction syndrome. The positive predictive value of new or progressive multiple organ dysfunction syndrome prediction was just 22.1%. We found no differences in accuracy by clinician type for either identification of multiple organ dysfunction syndrome (80.2% vs 78.2% vs 81.0%; p = 0.57) or prediction of new or progressive multiple organ dysfunction syndrome (84.8% vs 82.8% vs 80.3%; p = 0.26) for attendings, fellows, and residents/nurse practitioners, respectively. There was a weak correlation between the confidence and accuracy of prediction (pairwise correlation coefficient, 0.26; p < 0.001).ConclusionsPICU clinicians correctly identified multiple organ dysfunction syndrome and predicted new or progressive multiple organ dysfunction syndrome with 80% accuracy. However, only 8% of patients developed new or progressive multiple organ dysfunction syndrome, so accuracy was largely due to true negative predictions. The positive predictive value for new or progressive multiple organ dysfunction syndrome prediction was just 22%. Accuracy did not differ by clinician type, but was correlated with self-rated confidence and was higher for negative predictions.

Project description:IntroductionMultiple organ dysfunction (MOD) is a common pathway to morbidity and death in critically ill children. Defining organ dysfunction is challenging, as we lack a complete understanding of the complex pathobiology. Current pediatric organ dysfunction criteria assign the same diagnostic value-the same "weight"- to each organ system. While each organ dysfunction in isolation contributes to the outcome, there are likely complex interactions between multiple failing organs that are not simply additive.ObjectiveDetermine whether certain combinations of organ system dysfunctions have a significant interaction associated with higher risk of morbidity or mortality in critically ill children.MethodsWe conducted a retrospective observational cohort study of critically ill children at two large academic medical centers from 2010 and 2018. Patients were included in the study if they had at least two organ dysfunctions by day 3 of PICU admission based on the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) criteria. Mortality was described as absolute number of deaths and mortality rate. Combinations of two pediatric organ dysfunctions were analyzed with interaction terms as independent variables and mortality or persistent MOD as the dependent variable in logistic regression models.ResultsOverall, 7,897 patients met inclusion criteria and 446 patients (5.6%) died. The organ dysfunction interactions that were significantly associated with the highest absolute number of deaths were cardiovascular + endocrinologic, cardiovascular + neurologic, and cardiovascular + respiratory. Additionally, the interactions associated with the highest mortality rates were liver + cardiovascular, respiratory + hematologic, and respiratory + renal. Among patients with persistent MOD, the most common organ dysfunctions with significant interaction terms were neurologic + respiratory, hematologic + immunologic, and endocrinologic + respiratory. Further analysis using classification and regression trees (CART) demonstrated that the absence of respiratory and liver dysfunction was associated with the lowest likelihood of mortality.Implications and future directionsCertain combinations of organ dysfunctions are associated with a higher risk of persistent MOD or death. Notably, the three most common organ dysfunction interactions were associated with 75% of the mortality in our cohort. Critically ill children with MOD presenting with these combinations of organ dysfunctions warrant further study.

Project description:OBJECTIVES:Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. DESIGN:Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. SETTING:Thirty-five PICUs. PATIENTS:Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. INTERVENTIONS:Randomization to a lower versus higher glucose target group. MEASUREMENTS AND MAIN RESULTS:Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dys function syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). CONCLUSIONS:Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research.

Project description:COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Failure Assessment (SOFA) score is an objective and comprehensive measurement that measures dysfunction severity of six organ systems, i.e., cardiovascular, central nervous system, coagulation, liver, renal, and respiration. Our aim was to identify and characterize distinct subphenotypes of COVID-19 critical illness defined by the post-intubation trajectory of SOFA score. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p = 0.033; intermediate stratum, 29.3% vs. 8.0%, p = 0.002; severe stratum, 53.7% vs. 22.2%, p < 0.001). Pathophysiologic biomarkers associated with progression were distinct at each stratum, including findings suggestive of inflammation in low baseline severity of illness versus hemophagocytic lymphohistiocytosis in higher baseline severity of illness. The findings suggest that there are clear worsening and recovering subphenotypes of COVID-19 respiratory failure after intubation, which are more predictive of outcomes than baseline severity of illness. Distinct progression biomarkers at differential baseline severity of illness suggests a heterogeneous pathobiology in the progression of COVID-19 respiratory failure.

Project description:BackgroundShock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA).MethodsThis was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels.ResultsOf 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651-0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711-852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771-0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799-0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC.ConclusionsThe addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction.

Dataset Information

Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.

Objectives

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.

Similar Datasets

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