title: Increased Early Systemic Inflammation in ICU-Acquired Weakness; A Prospective Observational Cohort Study.
abstract: OBJECTIVE
  To investigate whether patients who develop ICU-acquired weakness have a different pattern of systemic inflammatory markers compared with critically ill patients who do not develop ICU-acquired weakness.
  
  
  METHODS
  Prospective observational cohort study.
  
  
  METHODS
  Mixed medical-surgical ICU of a tertiary care hospital in the Netherlands.
  
  
  METHODS
  Newly admitted critically ill patients, greater than or equal to 48 hours on mechanical ventilation with a nonneurologic ICU admission diagnosis, were included.
  
  
  METHODS
  A panel of systemic inflammatory markers and soluble vascular adhesion molecules were measured in plasma samples of day 0, 2, and 4 after ICU admission. ICU-acquired weakness was diagnosed by manual muscle strength testing as soon as patients were awake and attentive.
  
  
  RESULTS
  Ninety-nine of 204 included patients developed ICU-acquired weakness. Principal component regression analysis, adjusted for confounders, showed that principal component 1, mainly loaded with interleukin-6, interleukin-8, interleukin-10, and fractalkine, was significantly higher in patients who developed ICU-acquired weakness (odds ratio, 1.35 [95% CI, 1.18-1.55]). Partial least squares-discriminant analysis also showed that these markers were the most important discriminative markers. Mixed-effects models of these markers showed that ICU-acquired weakness was associated with an independent 1.5- to two-fold increase in these markers.
  
  
  CONCLUSIONS
  Systemic inflammation is increased in patients who develop ICU-acquired weakness compared with patients who do not develop ICU-acquired weakness in the first 4 days after ICU admission. This finding is consistent when adjusted for confounders, like disease severity. A group consisting of interleukin-6, interleukin-8, interleukin-10, and fractalkine was identified to be the most important.
authors.affiliation: 1Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.2Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.3Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.4Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.5Department of Rehabilitation, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Witteveen
authors.forename: Luuk
authors.initials: L
authors.lastname: Wieske
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Marike
authors.initials: M
authors.lastname: van der Schaaf
authors.forename: Ivo N
authors.initials: IN
authors.lastname: van Schaik
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Camiel
authors.initials: C
authors.lastname: Verhamme
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
mesh_terms: D000368:Aged; D015415:Biomarkers; D054428:Chemokine CX3CL1 / Q000378:metabolism; D016638:Critical Illness; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology*; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000502:physiology; D018908:Muscle Weakness / Q000097:blood / Q000276:immunology*; D009426:Netherlands; D011446:Prospective Studies; D012044:Regression Analysis; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology; D062606:Tertiary Care Centers; D013997:Time Factors
chemical_list: D015415:Biomarkers; D054428:Chemokine CX3CL1; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10