Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy

Intensive Care Med. 2012 Jan;38(1):20-8. doi: 10.1007/s00134-011-2438-3. Epub 2011 Nov 29.


Purpose: Regional citrate anticoagulation (RCA) is an attractive anticoagulation mode in continuous renal replacement therapy (CRRT) because it restricts the anticoagulatory effect to the extracorporeal circuit. In recent years, several randomized controlled trials have been conducted to investigate its superiority over other anticoagulation modes. Thus, we performed a systematic review of available evidence on the efficacy and safety of RCA.

Methods: A systematic review of randomized controlled trials investigating the efficacy and safety of RCA was performed. PubMed, Current Contents, CINAHL, and EMBASE databases were searched to identify relevance articles. Data on circuit life span, bleeding events, metabolic derangement, and mortality were abstracted. Mean difference was used for continuous variables, and risk ratio was used for binomial variables. The random effects or fixed effect model was used to combine these data according to heterogeneity. The software Review Manager 5.1 was used for the meta-analysis.

Results: Six studies met our inclusion criteria, which involved a total of 658 circuits. In these six studies patients with liver failure or a high risk of bleeding were excluded. The circuit life span in the RCA group was significantly longer than that in the control group, with a mean difference of 23.03 h (95% CI 0.45-45.61 h). RCA was able to reduce the risk of bleeding, with a risk ratio of 0.28 (95% CI 0.15-0.50). Metabolic stability (electrolyte and acid-base stabilities) in performing RCA was comparable to that in other anticoagulation modes, and metabolic derangements (hypernatremia, metabolic alkalosis, and hypocalcemia) could be easily controlled without significant clinical consequences. Two studies compared mortality rate between RCA and control groups, with one reported similar mortality rate and the other reported superiority of RCA over the control group (hazards ratio 0.7).

Conclusions: RCA is effective in maintaining circuit patency and reducing the risk of bleeding, and thus can be recommended for CRRT if and when metabolic monitoring is adequate and the protocol is followed. However, the safety of citrate in patients with liver failure cannot be concluded from current analysis. The metabolic stability can be easily controlled during RCA. Survival benefit from RCA is still controversial due to limited evidence.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Blood Coagulation
  • Citrates / adverse effects
  • Citrates / therapeutic use*
  • Critical Illness / therapy*
  • Female
  • Humans
  • Intensive Care Units
  • Male
  • Randomized Controlled Trials as Topic
  • Renal Replacement Therapy*
  • Treatment Outcome


  • Anticoagulants
  • Citrates