title: Muscle and nerve inflammation in intensive care unit-acquired weakness: a systematic translational review.
abstract: BACKGROUND
  Intensive care unit-acquired weakness (ICU-AW) is an important complication of critical illness. The main risk factors, sepsis and the systemic inflammatory response syndrome, suggest an inflammatory pathogenesis. In this systematic translational review we summarize current knowledge on inflammation in muscle and nerve tissue in animal models of ICU-AW and in critically ill patients with ICU-AW.
  
  
  METHODS
  We conducted a systematic search in the databases of MEDLINE, EMBASE and Web of Science using predefined search and selection criteria. From the included studies we extracted data on study characteristics and on inflammation in muscle and nerve tissue.
  
  
  RESULTS
  The literature search yielded 349 unique articles, of which 12 animal studies and 20 human studies fulfilled the in- and exclusion criteria. All studies had important shortcomings in methodological quality. In the animal studies, inflammation of muscle tissue was found, represented by cellular infiltration and increased local levels of various inflammatory mediators. In human studies, high levels of various inflammatory mediators were found in muscle and nerve tissue of ICU-AW patients.
  
  
  CONCLUSIONS
  This systematic translational review suggests a role for local inflammation in ICU-AW, but the available evidence is limited and studies have severe methodological limitations.
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L∙E∙I∙C∙A), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: e.witteveen@amc.nl.
authors.forename: Esther
authors.initials: E
authors.lastname: Witteveen
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L∙E∙I∙C∙A), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Neurology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: l.wieske@amc.nl.
authors.forename: Luuk
authors.initials: L
authors.lastname: Wieske
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: c.verhamme@amc.nl.
authors.forename: Camiel
authors.initials: C
authors.lastname: Verhamme
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Laboratory of Experimental Intensive Care and Anesthesiology (L∙E∙I∙C∙A), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: marcus.j.schultz@gmail.com.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: i.n.vanschaik@amc.nl.
authors.forename: Ivo N
authors.initials: IN
authors.lastname: van Schaik
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. Electronic address: j.horn@amc.nl.
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
mesh_terms: D000818:Animals; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data*; D018908:Muscle Weakness / Q000453:epidemiology*; D009220:Myositis / Q000453:epidemiology*; D020078:Neurogenic Inflammation / Q000453:epidemiology*
keywords: Critical illness myopathy; Critical illness polyneuropathy; Inflammation; Inflammatory mediators; Intensive care unit-acquired weakness; Systematic review