THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Anticoagulation for Continuous Renal Replacement Therapy

Abstract

Continuous renal replacement therapy (CRRT) has emerged as the preferred dialysis modality for critically ill patients with acute kidney injury, particularly those with hemodynamic instability. Anticoagulation is necessary for effective delivery of CRRT, but this requirement can also present challenges, as many critically ill patients with sepsis and inflammation already have a higher risk of bleeding as well as clotting. Without anticoagulation, CRRT filter and circuit survival are diminished, and therapy becomes less helpful. Heparins are presently the most commonly used anticoagulants worldwide for CRRT. They are widely available and can be easily monitored, but disadvantages include risks of hemorrhage, heparin resistance, and heparin-induced thrombocytopenia (HIT). Because of the potential side effects of heparin, alternative methods of anticoagulation have been investigated, including regional heparin/protamine, low molecular weight heparins, heparinoids, thrombin antagonists (hirudin and argatroban), regional citrate, and platelet inhibiting agents (prostacyclin and nafamostat). Each of these techniques has unique advantages and disadvantages, and anticoagulation for CRRT should be adapted to the patient's characteristics and institution's experience. Of the alternative methods, citrate anticoagulation is gaining wider acceptance with the development of simplified and safer protocols.

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

“…However, a high incidence of hemorrhagic complications has been documented in patients undergoing RRT in the intensive care unit (ICU), with wide variability (5%-30%) related to differences in patient populations and anticoagulation protocols (4)(5)(6)(7). Thus, the choice of the anticoagulant strategy, possibly limited to the extracorporeal circuit (i.e., regional anticoagulation), represents a key issue for safe and effective RRT in AKI.…”

Continuous Renal Replacement Therapy and Anticoagulation:

“…When anticoagulation is used, the ideal method yields inhibition of platelet activity and thrombotic activity in the circuit, can be easily titrated and reversed, and minimizes complications such as bleeding and other side effects. 1 Although anticoagulation does increase the chance of bleeding, changing the circuit often because of clotting is costly. Therefore, some type of anticoagulation is commonly used.…”

“…Heparin potentiates antithrombin III, resulting in inhibition of thrombin and factor Xa. 1,4,20 Level of…”

“…1,4,6 Heparin has a half-life of 90 minutes, which can be increased up to 3 hours in patients with renal insufficiency. 1,4,6,20 Heparin is inexpensive and easy to monitor, and its effects can be reversed with protamine. Studies 21,22 have indicated that the incidence of bleeding is greater with heparin administration than with other types of anticoagulation.…”

“…Contraindications for the use of heparin include patient characteristics such as an intolerance to heparin, development of heparin-induced thrombocytopenia, and an increased chance of bleeding. 1,3,4 Heparin is usually administered as a bolus followed by a continuous intravenous infusion into the arterial side of the CRRT circuit. Various protocols exist for the administration.…”