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Background <p>Regional citrate anticoagulation (RCA) is the most widespread technique which allows to perform extracorporeal treatments, avoiding the complications of systemic anticoagulation. Due to limited citrate clearance, RCA may be applied only to low extracorporeal blood flows (i.e., BF &lt; 200&#xa0;ml/min). In this proof of concept study, we developed an innovative RCA technique based on Ion Exchange Resin (i-ER) technology capable of regionally anticoagulating BF up to 500&#xa0;mL/min.</p> Methods <p>Six healthy swine (41.0 ± 3.1&#xa0;kg) were sedated, mechanically ventilated, and connected to a prototype extracorporeal circuit for continuous renal replacement therapy featuring a citrate-removal stage based on absorbent materials and replacement fluids. Blood flow was 500&#xa0;ml/min. Sodium citrate was continuously infused at the circuit inlet (5&#xa0;mmol/L). Heparin was continuously infused. Citrate concentration and Kaolin Heparinase thromboelastography (KH-TEG) were measured on arterial blood, extracorporeal blood downstream the citrate infusion port, and downstream the citrate-removal stage. Samples were collected at baseline, 2, 8, 15, 30, 45, 60, 90, and 120&#xa0;min for citrate and at baseline, 2, 30, 60, and 120&#xa0;min for KH–TEG. Calcium chloride was infused to maintain systemic ionized calcium within the physiological range. The experiment lasted 2&#xa0;h.</p> Results <p>During the whole experiment, KH–TEG in the artery showed normal coagulation: reaction time (R) was 8.30[6.80–10.10] min, with Maximum Amplitude (MA) of 71.70[67.90–77.00] mm, while in the extracorporeal circuit, KH–TEG showed no sign of clot formation R &gt; 60&#xa0;min, MA = 0&#xa0;mm. Citrate concentrations in blood samples were stable within 30&#xa0;min, then slowly increased. The efficacy of the citrate-removal dropped from 93.8 ± 3.4% to 48.3 ± 1.5% at the beginning (2&#xa0;min) and at the end (2&#xa0;h), respectively (<i>p</i> &lt; 0.001), due to loss of efficiency of the iERs.</p> Conclusions <p>This study demonstrates that iER-based RCA is a feasible and effective technique for regional anticoagulation of extracorporeal blood flow up to 500&#xa0;mL/min for 60&#xa0;min without significant complications.</p>

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Citrate regional anticoagulation of 500 ml/min of extracorporeal blood flow: an experimental study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月24日

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  • Sebastiano Maria Colombo,
  • Luigi Vivona,
  • Michele Battistin,
  • Vittorio Scaravilli,
  • Alessandro Galli,
  • Chiara Anzanello,
  • Elisa Cipriani,
  • Francesca Gori,
  • Serena Todaro,
  • Carlo Valsecchi,
  • Daniele Dondossola,
  • Anna Paola Marcello,
  • Andrea Carlin,
  • Antonio Pesenti,
  • Giacomo Grasselli,
  • Alberto Zanella

摘要

Background

Regional citrate anticoagulation (RCA) is the most widespread technique which allows to perform extracorporeal treatments, avoiding the complications of systemic anticoagulation. Due to limited citrate clearance, RCA may be applied only to low extracorporeal blood flows (i.e., BF < 200 ml/min). In this proof of concept study, we developed an innovative RCA technique based on Ion Exchange Resin (i-ER) technology capable of regionally anticoagulating BF up to 500 mL/min.

Methods

Six healthy swine (41.0 ± 3.1 kg) were sedated, mechanically ventilated, and connected to a prototype extracorporeal circuit for continuous renal replacement therapy featuring a citrate-removal stage based on absorbent materials and replacement fluids. Blood flow was 500 ml/min. Sodium citrate was continuously infused at the circuit inlet (5 mmol/L). Heparin was continuously infused. Citrate concentration and Kaolin Heparinase thromboelastography (KH-TEG) were measured on arterial blood, extracorporeal blood downstream the citrate infusion port, and downstream the citrate-removal stage. Samples were collected at baseline, 2, 8, 15, 30, 45, 60, 90, and 120 min for citrate and at baseline, 2, 30, 60, and 120 min for KH–TEG. Calcium chloride was infused to maintain systemic ionized calcium within the physiological range. The experiment lasted 2 h.

Results

During the whole experiment, KH–TEG in the artery showed normal coagulation: reaction time (R) was 8.30[6.80–10.10] min, with Maximum Amplitude (MA) of 71.70[67.90–77.00] mm, while in the extracorporeal circuit, KH–TEG showed no sign of clot formation R > 60 min, MA = 0 mm. Citrate concentrations in blood samples were stable within 30 min, then slowly increased. The efficacy of the citrate-removal dropped from 93.8 ± 3.4% to 48.3 ± 1.5% at the beginning (2 min) and at the end (2 h), respectively (p < 0.001), due to loss of efficiency of the iERs.

Conclusions

This study demonstrates that iER-based RCA is a feasible and effective technique for regional anticoagulation of extracorporeal blood flow up to 500 mL/min for 60 min without significant complications.