title: Critical illness polyneuropathy in ICU patients is related to reduced motor nerve excitability caused by reduced sodium permeability.
abstract: BACKGROUND
  Reduced motor and sensory nerve amplitudes in critical illness polyneuropathy (CIP) are characteristic features described in electrophysiological studies and due to dysfunction of voltage-gated sodium channels. Yet, faulty membrane depolarization as reported in various tissues of critically ill patients may cause reduced membrane excitability as well. The aim of this study was to compare the pathophysiological differences in motor nerve membrane polarization and voltage-gated sodium channel function between CIP patients and critically ill patients not developing CIP during their ICU stay (ICU controls).
  
  
  METHODS
  ICU patients underwent electrophysiological nerve conduction studies and were categorized as either ICU controls or CIP patients. Subsequently, excitability parameters were recorded as current-threshold relationship, stimulus-response behavior, threshold electrotonus, and recovery of excitability from the abductor pollicis brevis following median nerve stimulation.
  
  
  RESULTS
  Twenty-six critically ill patients were enrolled and categorized as 12 ICU controls and 14 CIP patients. When compared to 31 healthy subjects, the ICU controls exhibited signs of membrane depolarization as shown by reduced superexcitability (p = 0.003), depolarized threshold electrotonus (p = 0.007), increased current-threshold relationship (p = 0.03), and slightly prolonged strength-duration time constant. In contrast, the CIP patients displayed a significantly reduced strength-duration time constant (p < 0.0001), which indicates an increased inactivation of voltage-gated sodium channels.
  
  
  CONCLUSIONS
  Abnormal motor nerve membrane depolarization is a general finding in critically ill patients whereas voltage-gated sodium channel dysfunction is a characteristic of CIP patients.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. susanne.koch@charite.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Koch
authors.affiliation: Klinik für diagnostische und interventionelle Radiologie und Nuklearmedizin, Klinikum Esslingen GmbH, Hirschlandstraße 97, 73730, Esslingen a.N, Germany.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bierbrauer
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Haas
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Wolter
authors.affiliation: Neurology, Universitätsklinikum Jena, Jena, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Grosskreutz
authors.affiliation: Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Jena, Germany.
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Spies
authors.affiliation: Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Jena, Germany.|Heart Center Brandenburg and Medical School Brandenburg (MHB), Bernau, Germany.|Berlin Institute of Health (BIH), Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fielitz
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Berlin Institute of Health (BIH), Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Weber-Carstens
keywords: Critical illness myopathy; Critical illness polyneuropathy; Intensive care unit acquired weakness; Motor nerve excitability; Sepsis