title: Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study.
abstract: BACKGROUND
  Regional citrate anticoagulation (RCA) for continuous renal replacement therapy is widely used in intensive care units (ICUs). However, concern exists about the safety of citrate in patients with liver failure (LF). The aim of this study was to evaluate safety and efficacy of RCA in ICU patients with varying degrees of impaired liver function.
  
  
  METHODS
  In a multicenter, prospective, observational study, 133 patients who were treated with RCA and continuous venovenous hemodialysis (RCA-CVVHD) were included. Endpoints for safety were severe acidosis or alkalosis (pH ≤7.2 or ≥7.55, respectively) and severe hypo- or hypercalcemia (ionized calcium ≤0.9 or ≥1.5 mmol/L, respectively) of any cause. The endpoint for efficacy was filter lifetime. For analysis, patients were stratified into three predefined liver function or LF groups according to their baseline serum bilirubin level (normal liver function ≤2 mg/dl, mild LF >2 to ≤7 mg/dl, severe LF >7 mg/dl).
  
  
  RESULTS
  We included 48 patients with normal liver function, 43 with mild LF, and 42 with severe LF. LF was predominantly due to ischemia (39 %) or multiple organ dysfunction syndrome (27 %). The frequency of safety endpoints in the three patient strata did not differ: severe alkalosis (normal liver function 2 %, mild LF 0 %, severe LF 5 %; p = 0.41), severe acidosis (normal liver function 13 %, mild LF 16 %, severe LF 14 %; p = 0.95), severe hypocalcemia (normal liver function 8 %, mild LF 14 %, severe LF 12 %; p = 0.70), and severe hypercalcemia (0 % in all strata). Only three patients showed signs of impaired citrate metabolism. Overall filter patency was 49 % at 72 h. After censoring for stop of the treatment due to non-clotting causes, estimated 72-h filter survival was 96 %.
  
  
  CONCLUSIONS
  RCA-CVVHD can be safely used in patients with LF. The technique yields excellent filter patency and thus can be recommended as first-line anticoagulation for the majority of ICU patients.
  
  
  BACKGROUND
  ISRCTN Registry identifier: ISRCTN92716512 . Date assigned: 4 December 2008.
authors.affiliation: Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. torsten.slowinski@charite.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Slowinski
authors.affiliation: Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. stanislao.morgera@charite.de.
authors.forename: Stanislao
authors.initials: S
authors.lastname: Morgera
authors.affiliation: Divison of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria. michael.joannidis@i-med.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Joannidis
authors.affiliation: Department of Visceral and Transplant Surgery, University Hospital Charité, CVK, Berlin, Germany. thomas.henneberg@charite.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henneberg
authors.affiliation: Surgical Intensive Care, University Hospital Zurich, Zurich, Switzerland. reto.stocker@hirslanden.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Stocker
authors.affiliation: Department of Anesthesiology, Oslo University Hospital, Oslo, Norway. ehj@ous-hf.no.
authors.forename: Elin
authors.initials: E
authors.lastname: Helset
authors.affiliation: Department of Acute Medicine, Oslo University Hospital, Oslo, Norway. kide@uus.no.
authors.forename: Kirsti
authors.initials: K
authors.lastname: Andersson
authors.affiliation: Department of Anesthesiology, Leipzig University Hospital, Leipzig, Germany. markus.wehner@kh-mtl.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Wehner
authors.affiliation: Clinical Research, Fresenius Medical Care, Bad Homburg, Germany. justyna.kozik-jaromin@fmc-ag.com.
authors.forename: Justyna
authors.initials: J
authors.lastname: Kozik-Jaromin
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Heinrich-Heine-University, Duesseldorf, Germany. brett@uni-duesseldorf.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brett
authors.affiliation: Divison of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria. julia.hasslacher@i-med.ac.at.
authors.forename: Julia
authors.initials: J
authors.lastname: Hasslacher
authors.affiliation: Surgical Intensive Care, University Hospital Zurich, Zurich, Switzerland. john.stover@fresenius-kabi.com.
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
authors.affiliation: Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. harm.peters@charite.de.
authors.forename: Harm
authors.initials: H
authors.lastname: Peters
authors.affiliation: Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. hans-h.neumayer@charite.de.
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Neumayer
authors.affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Heinrich-Heine-University, Duesseldorf, Germany. kindgen-milles@med.uni-duesseldorf.de.
authors.forename: Detlef
authors.initials: D
authors.lastname: Kindgen-Milles
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000139:chemically induced; D000368:Aged; D000471:Alkalosis / Q000139:chemically induced; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D019343:Citric Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D007362:Intensive Care Units; D017093:Liver Failure / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D019343:Citric Acid