title: Calcium flux in continuous venovenous haemodiafiltration with heparin and citrate anticoagulation.
abstract: BACKGROUND
  Calcium chelation with citrate is an effective alternative to heparin for anticoagulation of the extracorporeal circuit during continuous venovenous haemodiafiltration (CVVHD-F). Calcium release occurs upon citrate metabolism; however, ultrafiltration of citrate-bound and free ions also occurs.
  
  
  OBJECTIVE
  To quantify calcium loss and improve understanding of calcium homeostasis in CVVHD-F.
  
  
  METHODS
  Calcium loss was prospectively quantified from heparinised and citrated circuits in consecutive intensive care patients requiring CVVHD-F. CVVHD-F prescription and anticoagulation choice was by the treating intensivist using commercial solutions (Gambro, Lundia, Sweden). Sample sets comprising arterial, prefilter and postfilter blood and an effluent sample were analysed for ionised total calcium (iCa(2+)) and magnesium levels. Flow rates were then used to calculate calcium flux. Citrate dose (predilution rate) and calcium replacement followed unit protocols to maintain a circuit iCa(2+) concentration of 0.3-0.5 mmol/L and an arterial iCa(2+) concentration of 0.8-1.1 mmol/L.
  
  
  RESULTS
  26 heparinised circuits and 22 citrated circuits in 13 patients were included; 334 sample sets were tested. For target extracorporeal blood flows of 200 mL/min, mean predilution Prismocitrate 10/2 flows were 1660 mL/h, delivering 2.42 mmol citrate per litre of blood. For heparin, mean predilution flows of Hemosol B0 were 2058mL/h. Mean calcium loss was 4.01 mmol/h from citrate anticoagulated circuits versus a gain of 0.24mmol/h from heparinised circuits (P < 0.001). Despite calcium replacement, citrate patients experienced a mean calcium loss of 1.12 mmol/h (SD, 0.70; 95% CI 1.0-1.22mmol/h; P < 0.001). Calculated effective diffusion volume (Q(E)) for calcium was closer to total blood water volume in heparin circuits and closer to plasma water volume in citrate circuits.
  
  
  CONCLUSIONS
  Despite supplementation to maintain arterial iCa(2+) levels, citrate anticoagulation results in a net calcium deficit. An equation for estimating required citrate dose may allow revision of citrate dosing protocols.
authors.affiliation: Launceston General Hospital, Launceston, TAS, Australia. mbrain@tassie.net.au.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brain
authors.forename: Scott
authors.initials: S
authors.lastname: Parkes
authors.forename: Peter
authors.initials: P
authors.lastname: Fowler
authors.forename: Iain
authors.initials: I
authors.lastname: Robertson
authors.forename: Andrew
authors.initials: A
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism*; D019343:Citric Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016638:Critical Illness / Q000628:therapy*; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D017583:Hemodiafiltration / Q000009:adverse effects / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D006996:Hypocalcemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D004338:Drug Combinations; D019343:Citric Acid; D006493:Heparin; D002118:Calcium