Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Abstract

Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

Continuous Renal Replacement Therapy and Anticoagulation:

“…21,[31][32][33][34] With some protocols, a citrate solution is infused before the filter in the CRRT circuit in relation to blood flow rate. 32,34,35 With this method, the amount of ionized calcium in the circuit after the filter is monitored routinely; the typical goal is a concentration less than 0.35 mmol/L to ensure that the calcium level is low enough to suppress clotting. 21,31,34 The citrate infusion is then adjusted accordingly.…”

“…32,34,35 With this method, the amount of ionized calcium in the circuit after the filter is monitored routinely; the typical goal is a concentration less than 0.35 mmol/L to ensure that the calcium level is low enough to suppress clotting. 21,31,34 The citrate infusion is then adjusted accordingly. Other methods of citrate administration include using a citrate-containing replacement solution infused before the filter, a method that also requires monitoring the concentration of ionized calcium in the circuit after the filter.…”

“…36 Regardless of the protocol followed for the infusion of citrate, a replacement infusion of calcium is administered at the end of the extracorporeal circuit or via a separate venous access to correct for the calcium that is chelated and also to replace any calcium chelated in the blood or lost into the ultrafiltrate or dialysate. 31,34,37 The calcium infusion must be administered after the filter or into a central catheter to prevent tissue sloughing and necrosis, which can occur with infiltration. 31,38 Generally, because calcium interferes with the action of the citrate, calcium-free dialysate or replacement fluids are often used with citrate anticoagulation.…”

“…1,31,34 Patients with severe liver failure and lactic acidosis may have difficulty with citrate metabolism, leading to an elevated blood level of citrate-chelated calcium. This elevation is a toxic effect of citrate.…”

Acute kidney injury and stroke: unresolved issues

“…No completely satisfying protocols had been established up to the recent implementation of the use of citrate as an anticoagulant agent in this clinical setting. In fact, citrate now represents the gold standard for RRT anticoagulation in AKI, since it allows true regional anticoagulation, i.e., a selective block of the whole hemostatic cascade only in the circuit and not in the patient's blood circulation [20]. This trivalent anion, which is mainly metabolized by the liver, inactivates many enzymatic reactions in the coagulation cascade by chelating ionized calcium, also blunting the activation of platelets and leucocytes in the circuit.…”