BACKGROUND: Contraindications to regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) have recently been challenged. We aimed to assess the safety of the generalization of RCA to all CRRT sessions. METHODS: We reviewed all CRRT sessions performed in our ICU during two periods (P1:2018-2019 and P2:2020-2022). RCA was considered as contraindicated in situations at risk of citrate accumulation (lactate >
4 mmol/L and/or prothrombin time <
40 %) during P1 but not P2. We reviewed CRRT modality, filter lifespan, and therapy-associated complications including citrate accumulation, electrolyte and acid/base disturbances, and blood transfusion requirements. CRRT efficacy was assessed by serum creatinine and urea kinetics across circuits' lifespan. RESULTS: We studied 1877 circuits in 467 (P1:245, P2:222) patients. The proportion of patients with risk factors for citrate accumulation was similar between both periods (P1:35 %, P2:32 % p = 0.61). During P2, RCA was used in more circuits (93 vs 66 %, p <
0.001) and filter lifespan was longer (44 vs 32 h, p <
0.001). CRRT efficacy was similar between the two periods. Although risk factors for citrate accumulation were present at first circuit initiation in more RCA circuits during P2 (25 vs 11 %, p = 0.002), the rate of citrate accumulation remained similar (0.3 vs 0.4 %, p = 0.72). There was no increase in the rates of electrolyte disturbances or significant bleeding. There was, however, a higher rate of metabolic acidoses during P2 (13 vs. 9 %, p = 0.01). CONCLUSION: In an experienced team, generalization of RCA to nearly all patients requiring CRRT extended median filter lifespan without increasing the rate of significant complications.