Regional citrate anticoagulation for continuous renal replacement therapy in newborns

**Background:** Regional citrate anticoagulation (RCA) is the preferred anticoagulation modality for continuous renal replacement therapy (CRRT) in adults, but its use in neonates is limited due to concerns about immature liver metabolism and citrate accumulation (CA). Neonatal CRRT presents unique challenges including slow blood flow increasing clotting risk, high bleeding risk, and small blood volume. This study aimed to evaluate the safety and efficacy of RCA-CRRT exclusively in neonates.

**Methods:** This retrospective observational study was conducted at the Children's Hospital of Chongqing Medical University from September 2015 to January 2021. Twenty-three neonates (age <28 days, irrespective of gestational age) who underwent 57 sessions of RCA-CRRT were included. CRRT was performed using the PlasautoΣ blood purification device with AEF-03 filters (26 ml capacity) as continuous veno-venous hemodiafiltration. The initial blood flow rate (BFR) was 3-5 ml/kg/min, with 4% sodium citrate infused to achieve an in vitro ionized calcium target of 0.2-0.4 mmol/L and 10% calcium gluconate to maintain in vivo ionized calcium at 1.0-1.35 mmol/L. Blood gas analysis was performed every 30 minutes initially, then every 4-6 hours. Citrate accumulation was defined as total-to-ionized calcium ratio (T/iCa) >2.5. Statistical analyses used t-tests, Mann-Whitney U tests, and chi-squared tests as appropriate, with P<0.05 considered significant.

**Key Results:** The mean patient age was 10.1±6.9 days, mean weight 3.0±0.7 kg (range 0.95-4 kg), and mean corrected gestational age 268±24 days. The mean filter lifespan was 31.54±19.58 hours (range 3.3-72.5 hours). Mean in vitro ionized calcium during RCA-CRRT was 0.37±0.08 mmol/L, with 61.8% of 207 measurements below 0.4 mmol/L. In-hospital mortality was 39.1% (9/23), with no deaths directly attributed to CRRT. After treatment, creatinine decreased significantly (92.96±51.58 vs. 73.90±27.20 mmol/L, P=0.032), pH improved (7.37±0.14 vs. 7.44±0.11, P=0.001), and bicarbonate increased (25.70±6.27 vs. 29.66±4.95 mmol/L, P=0.000). The incidence of acidosis (pH <7.35) decreased from 22 to 10 sessions (P=0.025). T/iCa increased from 2.00±0.36 to 2.19±0.40 (P=0.056), and the incidence of T/iCa >2.5 rose from 11.4% to 14.3% (P=0.477), neither statistically significant. In the CA group (n=5 sessions) vs. NCA group (n=30 sessions), body weight was significantly higher (3.64±0.32 vs. 2.95±0.41 kg, P=0.033) and BFR/BW was significantly lower (3.08±0.08 vs. 4.07±0.71 ml/kg/min, P=0.027). No significant differences were found in age, corrected gestational age, PRISM-III score, liver function tests, or coagulation parameters between groups. The incidence of CA post-treatment (14.3%) was lower than the 25% reported in a prior neonatal/infant study.

**Clinical Implications:** RCA-CRRT appears safe and effective for neonatal CRRT, achieving adequate filter lifespan (mean 31.54 hours) comparable to heparin-based regimens while avoiding systemic anticoagulation in a population at high bleeding risk (43.8% of sessions had prolonged prothrombin time, 82.5% had prolonged aPTT). The lack of significant correlation between CA and gestational age suggests that even premature neonates can metabolize citrate adequately. The main factors limiting filter lifespan were inadequate in vitro ionized calcium control (50% of short filter runs) and catheter malfunction (45.5%). The study is limited by its retrospective design, small sample size, and missing data (22 of 57 sessions lacked post-treatment T/iCa measurements). Larger prospective studies are needed to confirm these findings and establish optimal RCA-CRRT protocols for neonates.