A Study on the Efficacy and Safety of Continuous Renal Replacement Therapy (CVVHDF) Using a Commercial Citrate-containing Replacement Fluid (Prismocitrate 18/0)
Condition: Renal Failure
MeSH terms: Renal Insufficiency
Study type: Interventional

Summary: 
      The investigators aim to examine the efficacy and safety of using a new citrate containing
      commercially available solutions (Prismocitrate 18/0) as the regional citrate anticoagulation
      in continuous renal replacement therapy for critically ill patients.
    

Detailed description: 
      Acute kidney injury is common in critically ill patients, and continuous renal replacement
      therapy is the preferable mode of treatment to remove the metabolic waste while avoiding the
      hemodynamic instability associated with intermittent hemodialysis. Thrombosis frequently
      occurs in the hemofilter which could reduce the circuit lifespan, jeopardize the efficacy of
      renal replacement, result in loss of blood cells and increased transfusion requirement.
      Anticoagulants including conventional heparin and low molecular weight heparin, introduced
      via the arterial port of the circuit, are widely used to reduce clotting within the
      extracorporeal circuit. However, significant amount of heparin is not removed in the circuit
      and will be carried into patient's circulation, which could lead to bleeding complications.
      Regional citrate anticoagulation (RCA) has been used for intermittent haemodialysis since
      1983, and its use has extended to that for continuous renal replacement therapy (CRRT) since
      1987. Citrate is introduced at therapeutic level at the arterial limb of the dialysis
      circuit, where it chelates calcium ions in the blood to prevent clotting within the
      hemofilter. While some calcium-citrate complex is removed in the filter, the residual will be
      circulated to the patient and be metabolized in liver. Patient's systemic ionized calcium
      level remains normal, by hemodilution and also calcium replacement. Therefore, the
      anticoagulant effect from citrate is regional and confined to the extracorporeal circuit. RCA
      has the potential to extend circuit life during renal replacement therapy without systemic
      anticoagulation. In a recent meta-analysis of randomized controlled trials, RCA was as
      efficacious as heparin anticoagulation in term of maintaining circuit function, and RCA was
      associated with decreased risk of bleeding with no significant increase in incidence of
      metabolic alkalosis.(5) Hypocalcemia was more common in patients receiving citrate, but of
      note, no clinical adverse event was reported in the included studies. Although citrate
      anticoagulation had repeatedly been demonstrated to prolong filter life, many hospitals still
      refrained from using it, as a result of limited experience, different patient variety, or
      other reasons.

      The investigators' group has performed a pilot study (HKU/HA HKW IRB No: UW 08-221) to assess
      the efficacy and safety of continuous venous-venous hemodiafiltration(CVVHDF) using a
      commercial citrate containing replacement fluid (Prismocitrate 10/2, Gambro) which contains
      10mmol/l citrate and 2 mmol/l citric acid. 15 subjects were recruited from July 2008 to June
      2011. No serious adverse events were reported, including severe hypocalcemia, hypercalcemia,
      citrate toxicity and severe acid base disturbances. Metabolic acidosis due to renal failure
      were only partially corrected by CRRT with citrate anticoagulation in the initial study
      subjects, the problem was subsequently solved by adding supplemental bicarbonate to the
      dialysate. Since then, all the patients were able to complete the treatment protocols with
      adequate kidney lifespan, correction of metabolic abnormalities and fluid imbalance. However,
      since additional bicarbonate is needed to correct the metabolic acidosis during CRRT, there
      is room for improvement regarding the formulation of the citrate-containing solution to
      reduce acid liberation while increasing the alkali bicarbonate production. Prismocitrate
      18/0, which contains 18mmol/l citrate (one mmol citrate could be metabolized to produce 3
      mmol bicarbonate) and no citric acid, could potentially result in better acid-base control
      during CRRT.
    

Intervention name(s): Prismocitrate 18/0, Prism0cal
Intervention type(s): Device
Intervention description(s): Subjects on continuous hemodiafiltration will ordinarily receive heparin as the anticoagulation. In our study, regional citrate anticoagulation with Prismacitrate is used to replace heparin. Citrate has been shown in study to be safer than heparin with reduced bleeding risk
Other intervention name(s): Prismocitrate 18/0 (replacement solution), Prism0cal (dialysate), Gambro
Intervention MeSH terms: Dialysis Solutions
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care