Critical care explorations · 2023
Sustained Perturbation of Metabolism and Metabolic Subphenotypes Are Associated With Mortality and Protein Markers of the Host Response.
СтатьяНазвание и аннотация: Перевод в очереди
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Jennaro Theodore S, Puskarich Michael A, Evans Charles R, Karnovsky Alla, Flott Thomas L, McLellan Laura A, Jones Alan E, Stringer Kathleen A
Аннотация
UNLABELLED: Perturbed host metabolism is increasingly recognized as a pillar of sepsis pathogenesis, yet the dynamic alterations in metabolism and its relationship to other components of the host response remain incompletely understood. We sought to identify the early host-metabolic response in patients with septic shock and to explore biophysiological phenotyping and differences in clinical outcomes among metabolic subgroups.
DESIGN: We measured serum metabolites and proteins reflective of the host-immune and endothelial response in patients with septic shock.
SETTING: We considered patients from the placebo arm of a completed phase II, randomized controlled trial conducted at 16 U.S. medical centers. Serum was collected at baseline (within 24 hr of the identification of septic shock), 24-hour, and 48-hour postenrollment. Linear mixed models were built to assess the early trajectory of protein analytes and metabolites stratified by 28-day mortality status. Unsupervised clustering of baseline metabolomics data was conducted to identify subgroups of patients.
PATIENTS: Patients with vasopressor-dependent septic shock and moderate organ dysfunction that were enrolled in the placebo arm of a clinical trial.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Fifty-one metabolites and 10 protein analytes were measured longitudinally in 72 patients with septic shock. In the 30 patients (41.7%) who died prior to 28 days, systemic concentrations of acylcarnitines and interleukin (IL)-8 were elevated at baseline and persisted at T24 and T48 throughout early resuscitation. Concentrations of pyruvate, IL-6, tumor necrosis factor-α, and angiopoietin-2 decreased at a slower rate in patients who died. Two groups emerged from clustering of baseline metabolites. Group 1 was characterized by higher levels of acylcarnitines, greater organ dysfunction at baseline and postresuscitation (p < 0.05), and greater mortality over 1 year (p < 0.001).
CONCLUSIONS: Among patients with septic shock, nonsurvivors exhibited a more profound and persistent dysregulation in protein analytes attributable to neutrophil activation and disruption of mitochondrial-related metabolism than survivors.
DESIGN: We measured serum metabolites and proteins reflective of the host-immune and endothelial response in patients with septic shock.
SETTING: We considered patients from the placebo arm of a completed phase II, randomized controlled trial conducted at 16 U.S. medical centers. Serum was collected at baseline (within 24 hr of the identification of septic shock), 24-hour, and 48-hour postenrollment. Linear mixed models were built to assess the early trajectory of protein analytes and metabolites stratified by 28-day mortality status. Unsupervised clustering of baseline metabolomics data was conducted to identify subgroups of patients.
PATIENTS: Patients with vasopressor-dependent septic shock and moderate organ dysfunction that were enrolled in the placebo arm of a clinical trial.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Fifty-one metabolites and 10 protein analytes were measured longitudinally in 72 patients with septic shock. In the 30 patients (41.7%) who died prior to 28 days, systemic concentrations of acylcarnitines and interleukin (IL)-8 were elevated at baseline and persisted at T24 and T48 throughout early resuscitation. Concentrations of pyruvate, IL-6, tumor necrosis factor-α, and angiopoietin-2 decreased at a slower rate in patients who died. Two groups emerged from clustering of baseline metabolites. Group 1 was characterized by higher levels of acylcarnitines, greater organ dysfunction at baseline and postresuscitation (p < 0.05), and greater mortality over 1 year (p < 0.001).
CONCLUSIONS: Among patients with septic shock, nonsurvivors exhibited a more profound and persistent dysregulation in protein analytes attributable to neutrophil activation and disruption of mitochondrial-related metabolism than survivors.