Citrate Anticoagulation for Continuous Renal Replacement Therapy in the Critically Ill

Abstract

Background: Heparins are used for circuit anticoagulation during continuous renal replacement therapy (CRRT). Because heparins cause systemic anticoagulation, they increase the risk of bleeding. Citrate provides regional anticoagulation. Since citrate is a buffer as well, its use has metabolic consequences. The preferential use of citrate therefore remains controversial. Methods: A synthesis was performed of published studies comparing citrate to heparin for anticoagulation in CRRT with specific regard to feasibility, efficacy and safety. Search of the literature was made to explain the reported superiority of citrate. Results: Citrate provides good metabolic control if and when a well-designed protocol is strictly followed. Randomized studies report similar or longer circuit survival with citrate compared to heparin and less bleeding. The largest randomized trial up to now found that citrate was better tolerated than heparin and improved patient and kidney survival, especially in patients after surgery, with sepsis, a high degree of organ failure or younger age. Both citrate and heparin interfere with inflammation. Conclusion: During critical illness, regional anticoagulation with citrate for CRRT seems superior to heparin anticoagulation concerning tolerance and safety, mainly due to less bleeding. Whether circuit survival is better depends on the modality. In addition, citrate seems to improve patient and kidney survival. This finding needs to be confirmed. Citrate seems to confer a specific benefit in severe organ failure and sepsis. To what extent citrate protects or heparin does harm in the setting of multiple organ failure needs to be unraveled.

Beyond the Randomized Clinical Trial: Citrate for Continuous Renal Replacement Therapy in Clinical Practice

“…Several RCTs and meta-analyses have shown that citrate achieves good circuit patency and is superior to heparin [3,4,5,6,10,11,12,13,14,15]. RCTs are regarded as the ‘gold standard' for establishing causation between a therapy and an outcome.…”

“…A variety of studies using different protocols found diverging circuit survival times [10,11,12,13,14,15]. In most studies, filter life was better when using citrate compared to heparin [11,13,14,15] while others found no difference [10,12]. It is obvious that the efficacy of regional anticoagulation with citrate depends on meticulous attention to detail and adherence to the protocol.…”

Quantification of Systemic Delivery of Substrates for Intermediate Metabolism during Citrate Anticoagulation of Continuous Renal Replacement Therapy

“…RRT might represent a source of metabolic substrates if a systemic dose of citrate is accompanied by a dose of glucose as part of ACD and of lactate as part of the replacement and dialysis fluids. In contrast to lactate, a measurement of citrate is not readily available and has been deemed unnecessary [5,10]. …”

Haemodynamic Impact of a Slower Pump Speed at Start of Continuous Renal Replacement Therapy in Critically Ill Adults with Acute Kidney Injury: A Prospective Before-and-After Study

“…Citrate may be associated with hypotension due to hypocalcaemia [19]. Moreover, haemodynamic instability observed in earlier studies may also be associated with older equipment and protocols which may no longer be reflective of current practice [20,21,22]. …”