| The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness. | |
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MedLine Citation:
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PMID: 22080637 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVES:: Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. DESIGN, SETTING, AND PATIENTS:: This was a nested prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. MEASUREMENTS AND MAIN RESULTS:: Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the intensive care unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine-to-tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75 percentile of our population had an average of 1.8 (95% confidence interval, 0.6-3.1) and 2.1 (95% confidence interval, 1.0-3.2) fewer delirium/coma-free days than those patients with values at the 25 percentile (p = .006 and p < .001, respectively). CONCLUSIONS:: Increased kynurenine pathway activation, assessed by plasma kynurenine and kynurenine-to-tryptophan ratio, was associated with fewer days alive and without acute brain dysfunction in intensive care unit patients. Future studies are warranted to clarify this relationship and investigate potential therapeutic interventions. |
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Authors:
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Jessica R Adams Wilson; Alessandro Morandi; Timothy D Girard; Jennifer L Thompson; Chad S Boomershine; Ayumi K Shintani; E Wesley Ely; Pratik P Pandharipande |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-10 |
Journal Detail:
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Title: Critical care medicine Volume: - ISSN: 1530-0293 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the Vanderbilt University School of Medicine (JRAD), Nashville, TN; Department of Medicine (AM, TDG, EWE), Division of Allergy, Pulmonary, and Critical Care Medicine, Center for Health Service Research, and Center for Quality of Aging (AM), Vanderbilt University School of Medicine, Nashville, TN; Department of Biostatistics (JLT, AKS), Department of Medicine (CSB), Division of Rheumatology and Immunology, Vanderbilt University School of Medicine Anesthesia Service (PPP), Tennessee Valley Health Care System (Nashville); Department of Anesthesiology, Division of Critical Care Medicine, Vanderbilt Medical Center and the Geriatric Research (EWE, TDG), Education and Clinical Center (GRECC) Service, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN. |
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