Document Detail


The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*.
MedLine Citation:
PMID:  22080637     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 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/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 75th 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 25th percentile (p = .006 and p < .001, respectively).
CONCLUSIONS: Increased kynurenine pathway activation, assessed by plasma kynurenine and kynurenine/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.
Authors:
Jessica R Adams Wilson; Alessandro Morandi; Timothy D Girard; Jennifer L Thompson; Chad S Boomershine; Ayumi K Shintani; E Wesley Ely; Pratik P Pandharipande
Related Documents :
3664917 - Anaesthetic management and non-invasive monitoring for caesarean section in a patient w...
2301257 - Lack of correlation between transient myocardial ischemia and late potentials on the si...
17512787 - Effect of cpap on qt interval dispersion in obstructive sleep apnea patients without hy...
22507327 - Altered immune responses during septicaemia in patients suffering from haematological m...
8997157 - Stroke prevention in non-rheumatic atrial fibrillation.
23647147 - Ictal-onset localization through connectivity analysis of intracranial eeg signals in p...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  40     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-04-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  835-41     Citation Subset:  AIM; IM    
Affiliation:
Vanderbilt University School of Medicine, Nashville, TN, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acute Disease
Aged
Brain Diseases / etiology*
Critical Illness
Female
Humans
Kynurenine / blood,  physiology*
Male
Metabolic Networks and Pathways
Middle Aged
Prospective Studies
Tryptophan / blood,  metabolism*
Grant Support
ID/Acronym/Agency:
AG027472/AG/NIA NIH HHS; AG034257/AG/NIA NIH HHS; K08DK080219/DK/NIDDK NIH HHS; K08DK080219-02S1/DK/NIDDK NIH HHS; KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; R01 AG027472/AG/NIA NIH HHS; TL1 RR024978/RR/NCRR NIH HHS; TL1 TR000447/TR/NCATS NIH HHS; U01GM092691/GM/NIGMS NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 TR000445/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
343-65-7/Kynurenine; 73-22-3/Tryptophan
Comments/Corrections
Comment In:
Crit Care Med. 2012 Mar;40(3):1001-2   [PMID:  22343854 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Family response to critical illness: Postintensive care syndrome-family.
Next Document:  Effects of duty cycle and positive end-expiratory pressure on mucus clearance during mechanical vent...