Optimizing Safety and Efficacy in Pediatric Continuous Renal Replacement: The Promise of Diluted Regional Citrate Anticoagulation Free

Dear Editor,

We read with great interest the systematic review by Sethi et al. [1] evaluating diluted regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) in pediatric patients. This work underscores critical advancements in refining RCA protocols to enhance safety while maintaining efficacy in vulnerable pediatric populations. The authors’ emphasis on mitigating metabolic and electrolyte complications through a modified diluted citrate protocol aligns with emerging evidence supporting the use of lower concentration citrate solutions. We commend their findings and propose further considerations to optimize RCA implementation in pediatric CRRT.

The review highlights two key limitations of traditional citrate formulations: 4% trisodium citrate (TSC) and ACD-A solutions. While effective for anticoagulation, 4% TSC introduces hypertonic sodium and bicarbonate loads, predisposing patients to hypernatremia and metabolic alkalosis. Similarly, ACD-A, though less toxic than TSC, contains supraphysiologic glucose and citrate concentrations not tailored for CRRT. Both formulations necessitate laborious adjustments to dialysate/replacement fluids, complicated clinical workflows and increasing risks of iatrogenic derangements. These challenges mirror findings from Davenport et al. [2], where concentrated citrate protocols correlated with higher rates of metabolic alkalosis.

Sethi et al. demonstrate that diluted citrate protocols (e.g., 0.5% TSC) reduce complications while preserving circuit longevity – a critical balance in pediatric CRRT. Their single-center experience (n = 16) showed prolonged filter life and fewer clotting events, reinforcing prior adult data [3]. Notably, diluted citrate minimizes sodium and alkali burdens, simplifying fluid management. This aligns with the physiological rationale for using commercial, ready-to-use citrate-buffered replacement fluids, which integrate anticoagulant and buffer functions. For instance, solutions containing 12–18 mmol/L citrate (e.g., Regiocit^®, PrismoCitrate^®) have demonstrated safety in adults [4, 5], reducing manual compounding errors and infection risks while standardizing delivery.

We advocate for broader adoption of pediatric-specific, low-concentration citrate formulations in CRRT. Key advantages include:

• 1.

  Metabolic stability: lower citrate loads decrease bicarbonate generation, mitigating alkalosis [6].

• 2.

  Reduced monitoring burden: simplified protocols minimize frequent electrolyte adjustments [7].

• 3.

  Operational efficiency: premixed solutions expedite CRRT initiation, crucial in critical care [8].

However, challenges persist. As Sethi et al. [1] note, citrate accumulation remains a concern in liver dysfunction or shock. Close monitoring of ionized calcium (iCa) and total-to-iCa ratios (tCa:iCa >2.5 signals toxicity) is essential. Emerging technologies like real-time iCa sensors [9] could further enhance safety.

In conclusion, the work by Sethi et al. [1] validates diluted RCA as a safer, effective alternative to heparin and concentrated citrate in pediatric CRRT. Future efforts should prioritize standardized, commercial citrate-buffered fluids designed for pediatric physiology. Collaborative trials comparing diluted citrate protocols across diverse populations will help establish evidence-based guidelines, ultimately improving outcomes for critically ill children with AKI.