title: Ethanol causes protein precipitation--new safety issues for catheter locking techniques.
abstract: OBJECTIVE
  The ethanol lock technique has shown great potential to eradicate organisms in biofilms and to treat or prevent central venous catheter related infections. Following instillation of ethanol lock solution, however, the inherent density gradient between blood and ethanol causes gravity induced seepage of ethanol out of the catheter and blood influx into the catheter. Plasma proteins so are exposed to highly concentrated ethanol, which is a classic agent for protein precipitation. We aimed to investigate the precipitating effect of ethanol locks on plasma proteins as a possible cause for reported catheter occlusions.
  
  
  METHODS
  Plasma samples were exposed in-vitro to ethanol (concentrations ranging from 7 to 70 v/v%) and heparin lock solutions. In catheter studies designed to mimic different in-vivo situations, the catheter tip was placed in a plasma reservoir and the material contained within the catheter was analyzed after ethanol lock instillation. The samples underwent standardized investigation for protein precipitation.
  
  
  RESULTS
  Protein precipitation was observed in plasma samples containing ethanol solutions above a concentration of 28%, as well as in material retrieved from vertically positioned femoral catheters and jugular (subclavian) catheters simulating recumbent or head down tilt body positions. Precipitates could not be re-dissolved by dilution with plasma, urokinase or alteplase. Plasma samples containing heparin lock solutions showed no signs of precipitation.
  
  
  CONCLUSIONS
  Our in-vitro results demonstrate that ethanol locks may be associated with plasma protein precipitation in central venous catheters. This phenomenon could be related to occlusion of vascular access devices locked with ethanol, as has been reported. Concerns should be raised regarding possible complications upon injection or spontaneous gravity induced leakage of such irreversibly precipitated protein particles into the systemic circulation. We suggest limiting the maximum advisable concentration of ethanol to 28 v/v% in catheter lock solutions.
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Schilcher
authors.affiliation: Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Axel
authors.initials: A
authors.lastname: Schlagenhauf
authors.affiliation: Institute of Physiology, Medical University of Graz, Graz, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schneditz
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Ribitsch
authors.affiliation: Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Krause
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Joerg H
authors.initials: JH
authors.lastname: Horina
mesh_terms: D000891:Anti-Infective Agents, Local / Q000009:adverse effects* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism*; D055499:Catheter-Related Infections / Q000517:prevention & control*; D062905:Central Venous Catheters / Q000382:microbiology*; D011232:Chemical Precipitation / Q000187:drug effects*; D000431:Ethanol / Q000009:adverse effects* / Q000627:therapeutic use; D018056:Hemorheology; D006801:Humans
chemical_list: D000891:Anti-Infective Agents, Local; D001798:Blood Proteins; D000431:Ethanol