title: Trisodium citrate induced protein precipitation in haemodialysis catheters might cause pulmonary embolism.
abstract: BACKGROUND
  The locking anticoagulant plays a decisive role in the patency of central venous catheters (CVCs) used for haemodialysis. During injection, the hydraulic effects inevitably cause lock solution to spill into the systemic circulation. Density differences between whole blood (WB) and the lock solution cause further gravity-induced seepage of lock solution. This is followed by an influx of WB into the catheter, also described for trisodium citrate, which is a common agent for serum protein precipitation. Embolic complications from haemodialysis catheters locked with hypertonic trisodium citrate have been reported. We aimed to investigate protein precipitation in trisodium citrate locked catheters as a possible cause of pulmonary embolisms.
  
  
  METHODS
  In vitro, WB and trisodium citrate (concentrations ranging from 4.7 to 46.7%) mixtures in a ratio of 1:4 were used to assess protein precipitation. Additionally, WB/trisodium citrate mixture was pumped through a 20-μm mesh filter, simulating pulmonary vessels, and filtrate pressure was measured. In vivo, listed filling volumes of haemodialysis catheters locked with trisodium citrate 4% (n=10), 10% (n=10), 20% (n=10) or 46.7% (n=10) were aspirated and then analysed for protein precipitation.
  
  
  RESULTS
  In vitro, protein precipitation capable of causing filter occlusion was observed in test solutions containing trisodium citrate above a concentration of 12%. In vivo, protein precipitation was detected in all samples from the CVCs filled with trisodium citrate 46.7% (n=10) and 20% (n=10). In contrast, there were no signs of precipitation in samples from the catheters filled with trisodium citrate 4% (n=10) or 10% (n=10).
  
  
  CONCLUSIONS
  Our in vitro results demonstrate that protein precipitates inside haemodialysis catheters when trisodium citrate is used above the concentrations of 12%. Precipitated protein may have contributed to the pathophysiology of reported embolisms from haemodialysis catheters filled with hypertonic trisodium citrate. Based on our findings, we suggest that trisodium citrate lock solution up to the concentration of 10% can be used safely.
authors.affiliation: Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. gernot.schilcher@medunigraz.at
authors.forename: Gernot
authors.initials: G
authors.lastname: Schilcher
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.forename: Joerg H
authors.initials: JH
authors.lastname: Horina
authors.forename: Werner
authors.initials: W
authors.lastname: Ribitsch
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Rosenkranz
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.forename: Hans-Dietrich
authors.initials: HD
authors.lastname: Polaschegg
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects*; D002408:Catheters, Indwelling / Q000009:adverse effects*; D011232:Chemical Precipitation; D002951:Citrates / Q000009:adverse effects*; D006801:Humans; D011379:Prognosis; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011655:Pulmonary Embolism / Q000209:etiology*; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000628:therapy
chemical_list: D000925:Anticoagulants; D002951:Citrates; D011506:Proteins; C514290:trisodium citrate