Evaluation of the efficacy and associated complications of regional citrate anticoagulation in neonates: experience from a fourth level neonatal intensive care unit

Eur J Pediatr. 2023 Nov;182(11):4897-4908. doi: 10.1007/s00431-023-05162-2. Epub 2023 Aug 19.


Continuous kidney replacement therapy (CKRT) use has increased in recent years, but anticoagulation is a challenge for neonates. Regional citrate anticoagulation (RCA) is rarely preferred in neonates because of citrate accumulation (CA) and metabolic complications. We aimed to demonstrate the efficacy and safety of RCA in neonates. We retrospectively analyzed the medical records of 11 neonates treated with RCA-CKRT between 2018 and 2023. The initial dose of RCA was 2.1-3 mmol/l, and then, its dose was increased according to the level of ionized calcium (iCa+2) in the circuit and patients. The total/iCa+2 ratio after-treatment > 2.5 was indicated as CA. We evaluated to citrate dose, CA, circuit lifespan, and dialysis effectivity. The median gestational age was 39 (36.4-41.5) weeks, the median body weight (BW) was 3200 (2400-4000) grams, and the mean postnatal age was 4 (2-24) days. The most common indication for CKRT was hyperammonemia (73%). All neonates had metabolic acidosis and hypocalcemia during CKRT. Other common metabolic complications were hypophosphatemia (90%), hypokalemia (81%), and hypomagnesemia (63%). High dialysate rates with a median of 5765 ml/h/1.73 m2 allowed for a rapid decrease in ammonia levels to normal. Four patients (36.3%) had CA, and seven (63.7%) did not (non-citrate accumulation, NCA). Mean BW, median postnatal age, biochemical parameters, coagulation tests, and ammonia levels were similar between the CA and NCA groups. Low pH, low HCO3, high lactate, and SNAPPE-II scores could be associated with a higher T/iCa ratio.

Conclusion: RCA was an efficient and safe anticoagulation for neonates requiring CKRT. Metabolic complications may occur, but they could be managed with adequate supplementation.

What is known: • Continuous kidney replacement therapy (CKRT) has become popular in recent years due to its successful treatment of fluid overload, electrolyte imbalance, metabolic acidosis, multi-organ failure, and hyperleucinemia/hyperammonemia associated with inborn errors of metabolism. • The need for anticoagulation is the major difficulty in neonatal CKRT. In adult and pediatric patients, regional citrate anticoagulation has been shown to be effective.

What is new: • RCA is an effective and safe anticoagulation method for neonates who require CKRT. • Electrolyte imbalances and metabolic acidosis could be managed with adequate supplementation and appropriate treatment parameters such as citrate dose, blood flow rate, and dialysate flow rate.

Keywords: Citrate accumulation; Continuous kidney replacement therapy; Infant; Neonate; Regional citrate anticoagulation.

MeSH terms

  • Acidosis* / chemically induced
  • Acidosis* / drug therapy
  • Ammonia
  • Anticoagulants / adverse effects
  • Child
  • Citrates / adverse effects
  • Citric Acid / adverse effects
  • Dialysis Solutions
  • Electrolytes
  • Humans
  • Hyperammonemia*
  • Infant
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Retrospective Studies


  • Citric Acid
  • Anticoagulants
  • Ammonia
  • Citrates
  • Dialysis Solutions
  • Electrolytes