Regional citrate anticoagulation for continuous renal replacement therapy in newborns and infants: Focus on citrate accumulation

Abstract

Continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA) in newborns and infants is challenging and accumulation of citrate can occur.There are only a few studies reporting the detailed data on RCA. We aimed to analyze RCA-CRRT at our institution with focus on citrate accumulation. Critically ill newborns and infants up to 11 kg of body weight (BW), treated with RCA-CRRT in the 2011-2016 period were included in this retrospective observational study.Prismaflex(R) and Multifiltrate-CiCa(R) dialysis monitors were used with either automated or manual RCA. Data was collected regarding the circuit lifetime, parameters of RCA, markers of citrate accumulation (total/ionized calcium ratio > 2.5), and metabolic complications. We included 10 children with mean age of 2.6 ± 3.8 months and BW of 4.6 ± 2.7 kg. In-hospital mortality was 60%. RCA-CRRT parameters were: blood flow 46 ± 9 mL/min (12 ± 5 mL/min/kg BW), citrate dose 2.8 ± 0.6 mmol/L of blood resulting in estimated citrate load to the patient of 1.7 ± 0.8 mmol/h/kg BW. In total, 57 dialysis circuits were used with mean filter lifetime of 39 ± 29 h. Citrate accumulation (total/ionized calcium ratio > 2.5) was observed in 7/10 patients and in 14/57 (25%) of circuits; those circuits were performed in children with lower age and BW, had higher relative blood flow and citrate load, while citrate dose was similar. When citrate load to the patient was used to predict citrate accumulation, AUC under the ROC curve was 0.78 and 1.7 mmol/h/kg BW was considered the optimal cutoff value (sensitivity 71% and specificity 72%). CRRT with RCA using equipment, developed for adult population, is feasible in newborns and infants. Signs of citrate accumulation developed relatively often. To prevent it, we suggest avoiding citrate loads above 1.7 mmol/h/kg BW, which can best be achieved by keeping the blood flow below 9 mL/min/kg BW. K E Y W O R D Scitrate accumulation, continuous renal replacement therapy, infants, newborns, regional citrate anticoagulation 498 | PERSIC Et al.

Regional citrate anticoagulation for continuous renal replacement therapy in newborns

“…In this study, there was no significant difference in the incidence of CA before and after the treatment. After RCA-CRRT, the incidence of CA was 14.3%, which was significantly lower than that reported by Persic et al in their study on neonatal and infant RCA-CRRT (25%) ( 14 ). Compared with the NCA group, in the CA group, the body weight was significantly higher and the BFR/BW value was significantly lower, and the molers of citrate per CiFR/BW value was lower but without statistical significance.…”

Anticoagulation strategies in continuous kidney replacement therapy — does one size fit all?

“…Due to smaller vascular access and relatively small blood flows used in neonates, the risk of filter clotting is higher, therefore the need for anticoagulation is equally higher. Contrary to earlier beliefs, recent studies have demonstrated safety and efficacy of RCA in this population [ 12 , 13 ]. In addition, depending on the local expertise and drug availability, standard UFH, LMWH, RCA or argatroban can be safely used in this population.…”

Analysis of the extracorporeal anticoagulation effect of modified citrate infusion during continuous renal replacement therapy in critically ill patients

“…The application of local citrate anticoagulation in CRRT for critically ill patients has received significant attention in recent years because of its unique advantages. Citrate anticoagulation acts by modulating the level of ionized calcium in blood, thus intervening in the coagulation process [14]. After pumping citrate through the arterial end of the CRRT tubing, the ionized calcium in blood binds to citrate radicals to form calcium citrate; this reduces the ionized calcium concentrations in the extracorporeal blood, and affects the conversion of prothrombin to thrombin.…”

“…Citrate also affects other coagulation links to maintain the post-filter calcium ion concentration at 0.25-0.35 mmol/L for optimal anticoagulation effect in the extracorporeal circulation [5]. After entering the body, citrate participates in the tricarboxylic acid cycle in the liver, muscle tissue, and renal cortex and is quickly metabolized to bicarbonate radical ions without leaving any residue [4,14]. Supplementation with sufficient ionized calcium to maintain the blood concentration at 1.00-1.20 mmol/L before the blood returns to the body through the venous end restores the coagulation process in the body to normal.…”