Application progress of regional citrate anticoagulant technology in blood purification_West China Medical Journal

Authors：

HUANG Yimei ^1,2 ,  ZHANG Ling ¹

1. Department of Nephrology and Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Nephrology, the First People’s Hospital of Liangshan Yi Autonomous Prefecture, Xichang, Sichuan 615000, P. R. China;

Corresponding?author：

ZHANG Ling, Email: zhangling_crrt@163.com

Keywords：

Citric acid; anticoagulation; blood purification

DOI：

10.7507/1002-0179.202404124

Video：

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Abstract Full text Figures/Tables Video References Cited by

In recent years, Regional citrate anticoagulation (RCA) technology has been widely used not only in adult blood purification, but also in children’s blood purification, and its advantages in patients with high bleeding risk, active bleeding and heparin-induced thrombocytopenia have been repeatedly confirmed. Therefore, this article reviews and analyzes the application of RCA in different blood purification modes at home and abroad in recent years. It is found that its anticoagulation is not only safe and effective, but also can prolong the life of filter and reduce bleeding complications, which is suitable for the practice of blood purification.

Citation： HUANG Yimei, ZHANG Ling. Application progress of regional citrate anticoagulant technology in blood purification. West China Medical Journal, 2024, 39(6): 980-984. doi: 10.7507/1002-0179.202404124 Copy

1.	Khwaja A. KDIGO clinical practice guideline for acute kidney injury. Nephron Clin Pract, 2012, 120(4): c179-c184.
2.	陳香美. 血液凈化標準操作規程(2021 版). 人民衛生出版社, 2021: 150-154.
3.	Mehta RL, McDonald BR, Aguilar MM, et al. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int, 1990, 38(5): 976-981.
4.	Zarbock A, Küllmar M, Kindgen-Milles D, et al. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial. JAMA, 2020, 324(16): 1629-1639.
5.	Liu C, Mao Z, Kang H, et al. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crit Care, 2016, 20(1): 144.
6.	Li L, Bai M, Zhang W, et al. Regional citrate anticoagulation versus low molecular weight heparin for CRRT in hyperlactatemia patients: a retrospective case-control study. Int J Artif Organs, 2022, 45(4): 343-350.
7.	James M, Bouchard J, Ho J, et al. Canadian society of nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis, 2013, 61(5): 673-685.
8.	Fiaccadori E, Pistolesi V, Mariano F, et al. Regional citrate anticoagulation for renal replacement therapies in patients with acute kidney injury: a position statement of the Work Group “Renal Replacement Therapies in Critically Ill Patients” of the Italian Society of Nephrology. Nephrol, 2015, 28(2): 151-164.
9.	楊向紅, 孫仁華, 趙鳴雁, 等. 重癥新型冠狀病毒肺炎患者血液凈化治療流程的專家建議. 中華醫學雜志, 2020, 100(16): 1217-1222.
10.	中華醫學會腎臟病學分會專家組. 連續性腎臟替代治療的抗凝管理指南. 中華腎臟病雜志, 2022, 38(11): 1016-1024.
11.	Bunchman TE, Maxvold NJ, Barnett J, et al. Pediatric hemofiltration: normocarb dialysate solution with citrate anticoagulation. Pediatr Nephrol, 2002, 17(3): 150-154.
12.	Soltysiak J, Warzywoda A, Kociński B, et al. Citrate anticoagulation for continuous renal replacement therapy in small children. Pediatr Nephrol, 2014, 29(3): 469-475.
13.	Rico MP, Fernández Sarmiento J, Rojas Velasquez AM, et al. Regional citrate anticoagulation for continuous renal replacement therapy in children. Pediatr Nephrol, 2017, 32(4): 703-711.
14.	S?k G, Demirbuga A, Annayev A, et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill children. Int J Artif Organs. Int J Artif Organs, 2020, 43(4): 234-241.
15.	Di Mario F, Regolisti G, Maggiore U, et al. Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions. Nephrol Dial Transplant, 2022, 37(12): 2505-2513.
16.	兒童危重癥連續性血液凈化應用共識工作組. 連續性血液凈化在兒童危重癥應用的專家共識. 中華兒科雜志, 2021, 59(5): 352-360.
17.	Buturovic J, Gubensek J, Cerne D, et al. Standard citrate versus sequential citrate/anticoagulant-free anticoagulation during hemodialysis: a randomized trial. Artif Organs, 2008, 32(1): 77-81.
18.	Lin T, Song L, Huang R, et al. Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies. BMC Nephrology, 2019, 20(1): 472.
19.	Tang X, Chen D, Zhang L, et al. Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial. J Zhejiang Univ Sci B, 2022, 23(11): 931-942.
20.	Yuan F, Li Z, Li X, et al. Application of regional citrate anticoagulation in membrane therapeutic plasma exchange. Int Urol Nephrol, 2020, 52(12): 2379-2384.
21.	Jiao J, Yu Y, Wei S, et al. Heparin anticoagulation versus regional citrate anticoagulation for membrane therapeutic plasma exchange in patients with increased bleeding risk. Ren Fail, 2023, 45(1): 2210691.
22.	Xinping Z, Jie H, Zhenya Y, et al. Citrate anticoagulation in plasma exchange followed by continuous renal replacement therapy in critically ill children. Int J Artif Organs, 2024, 47(2): 85-95.
23.	Teh SP, Ho QY, Kee YST, et al. Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis. J Clin Apher, 2023, 38(1): 16-23.
24.	王婷立, 張凌, 陳志文, 等. 枸櫞酸抗凝在持續緩慢低效血液透析中的應用. 中華內科雜志, 2014, 53(12): 953-956.
25.	Pourcine F, Vong LVP, Chelly J, et al. Sustained low-efficiency dialysis with regional citrate anticoagulation for patients with liver impairment in intensive care unit: a single center experience. Ther Apher Dial, 2021, 25(2): 211-217.
26.	張凌, 李佩蕓, 魏甜甜, 等. 簡化枸櫞酸抗凝技術在持續緩慢低效血液透析中的臨床應用. 華西醫學, 2018, 33(7): 838-842.
27.	張海鋼, 吳京蘭, 黃鐳, 等. 局部枸櫞酸抗凝在重癥中毒患者血液灌流治療中的應用研究. 中國血液凈化, 2018, 17(4): 217-221.
28.	普亞軍, 張凌, 王芳, 等. 局部枸櫞酸抗凝在血液灌流聯合連續性腎臟替代治療中的應用觀察. 華西醫學, 2023, 38(8): 1174-1180.
29.	Schulthei? C, Saugel B, Phillip V, et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care, 2012, 16(4): R162.
30.	Zhang W, Bai M, Yu Y, et al. Safety and efficacy of regional citrate anticoagulation for continuous renal replacement therapy in liver failure patients: a systematic review and meta-analysis. Crit Care, 2019, 23(1): 22.
31.	Bai M, Yu Y, Zhao L, et al. Regional citrate anticoagulation versus no anticoagulation for CKRT in patients with liver failure with increased bleeding risk. Clin J Am Soc Nephrol, 2023, 19(2): 151-160.
32.	Yu Y, Bai M, Ma F, et al. Regional citrate anticoagulation versus no-anticoagulation for continuous venovenous hemofiltration in patients with liver failure and increased bleeding risk: a retrospective case-control study. PLoS One, 2020, 15(5): e0232516.
33.	Peng B, Lu J, Guo H, et al. Regional citrate anticoagulation for replacement therapy in patients with liver failure: a systematic review and meta-analysis. Front Nutr, 2023, 10: 1031796.
34.	Pistolesi V, Morabito S, Pota V, et al. Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission. J Anesth Analg Crit Care, 2023, 3(1): 7.
35.	莊峰, 俞雯艷, 馬帥, 等. 一種“二階段補鈣模型”在 RCA-CVVH 中的臨床應用. 中國血液凈化, 2018, 17(7): 461-465.
36.	席春生, 劉同存, 劉飛, 等. 在線下調透析液碳酸氫鹽濃度預防局部枸櫞酸鈉抗凝血液透析患者代謝性堿中毒. 中國血液凈化, 2023, 22(4): 269-272.
37.	Gupta M, Wadhwa NK, Bukovsky R, et al. Regional citrate anticoagulation for continuous venovenous hemodiafiltration using calcium-containing dialysate. Am J Kidney Dis, 2004, 43(1): 67-73.
38.	Zhang L, Liao Y, Xiang J, et al. Simplified regional citrate anticoagulation using a calcium-containing replacement solution for continuous venovenous hemofiltration. J Artif Organs, 2013, 16(2): 185-192.
39.	席春生, 劉同存, 蔡蕊蓮, 等. 含鈣透析液和置換液局部枸櫞酸抗凝連續靜脈靜脈血液透析濾過臨床觀察. 中國血液凈化, 2022, 21(8): 576-579.
40.	Wei T, Tang X, Zhang L, et al. Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial. Chin Med J (Engl), 135(20): 2478-2487.
41.	Rhee H, Berenger B, Mehta RL, et al. Regional citrate anticoagulation for continuous kidney replacement therapy with calcium-containing solutions: a cohort study. Am J Kidney Dis, 2021, 78(4): 550-559. e1.
42.	Liu SY, Xu SY, Yin L, et al. Emergency medical doctor branch of the chinese medical doctor association. Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus. Mil Med Res, 2023, 10(1): 23.
43.	Hadid T, Kafri Z, Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Rev, 2021, 47: 100761.
44.	Shankaranarayanan D, Muthukumar T, Barbar T, et al. Anticoagulation strategies and filter life in COVID-19 patients receiving continuous renal replacement therapy: a single-center experience. Clin J Am Soc Nephrol, 2020, 16(1): 124-126.
45.	Zhou Z, Liu C, Yang Y, et al. Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Crit Care, 2023, 27(1): 222.
46.	Abdel Azim ABE, ElSaid TW, El Said HW, et al. A randomized controlled clinical trial of 4% sodium citrate versus heparin as locking solution for temporary dialysis catheters among hemodialysis patients. Clin Nephrol, 2018, 90(5): 341-349.
47.	Mai H, Zhao Y, Salerno S, et al. Citrate versus heparin lock for prevention of hemodialysis catheter-related complications: updated systematic review and meta-analysis of randomized controlled trials. Int Urol Nephrol, 2019, 51(6): 1019-1033.
48.	Quenot JP, Helms J, Bourredjem A, et al. Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial. Ann Intensive Care, 2019, 9(1): 75.
49.	Huang HM, Jiang X, Meng LB, et al. Reducing catheter-associated complications using 4% sodium citrate versus sodium heparin as a catheter lock solution. J Int Med Res, 2019, 47(9): 4204-4214.

1. Khwaja A. KDIGO clinical practice guideline for acute kidney injury. Nephron Clin Pract, 2012, 120(4): c179-c184.
2. 陳香美. 血液凈化標準操作規程(2021 版). 人民衛生出版社, 2021: 150-154.
3. Mehta RL, McDonald BR, Aguilar MM, et al. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int, 1990, 38(5): 976-981.
4. Zarbock A, Küllmar M, Kindgen-Milles D, et al. Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial. JAMA, 2020, 324(16): 1629-1639.
5. Liu C, Mao Z, Kang H, et al. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crit Care, 2016, 20(1): 144.
6. Li L, Bai M, Zhang W, et al. Regional citrate anticoagulation versus low molecular weight heparin for CRRT in hyperlactatemia patients: a retrospective case-control study. Int J Artif Organs, 2022, 45(4): 343-350.
7. James M, Bouchard J, Ho J, et al. Canadian society of nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis, 2013, 61(5): 673-685.
8. Fiaccadori E, Pistolesi V, Mariano F, et al. Regional citrate anticoagulation for renal replacement therapies in patients with acute kidney injury: a position statement of the Work Group “Renal Replacement Therapies in Critically Ill Patients” of the Italian Society of Nephrology. Nephrol, 2015, 28(2): 151-164.
9. 楊向紅, 孫仁華, 趙鳴雁, 等. 重癥新型冠狀病毒肺炎患者血液凈化治療流程的專家建議. 中華醫學雜志, 2020, 100(16): 1217-1222.
10. 中華醫學會腎臟病學分會專家組. 連續性腎臟替代治療的抗凝管理指南. 中華腎臟病雜志, 2022, 38(11): 1016-1024.
11. Bunchman TE, Maxvold NJ, Barnett J, et al. Pediatric hemofiltration: normocarb dialysate solution with citrate anticoagulation. Pediatr Nephrol, 2002, 17(3): 150-154.
12. Soltysiak J, Warzywoda A, Kociński B, et al. Citrate anticoagulation for continuous renal replacement therapy in small children. Pediatr Nephrol, 2014, 29(3): 469-475.
13. Rico MP, Fernández Sarmiento J, Rojas Velasquez AM, et al. Regional citrate anticoagulation for continuous renal replacement therapy in children. Pediatr Nephrol, 2017, 32(4): 703-711.
14. S?k G, Demirbuga A, Annayev A, et al. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill children. Int J Artif Organs. Int J Artif Organs, 2020, 43(4): 234-241.
15. Di Mario F, Regolisti G, Maggiore U, et al. Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions. Nephrol Dial Transplant, 2022, 37(12): 2505-2513.
16. 兒童危重癥連續性血液凈化應用共識工作組. 連續性血液凈化在兒童危重癥應用的專家共識. 中華兒科雜志, 2021, 59(5): 352-360.
17. Buturovic J, Gubensek J, Cerne D, et al. Standard citrate versus sequential citrate/anticoagulant-free anticoagulation during hemodialysis: a randomized trial. Artif Organs, 2008, 32(1): 77-81.
18. Lin T, Song L, Huang R, et al. Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: a prospective randomized study of three anticoagulation strategies. BMC Nephrology, 2019, 20(1): 472.
19. Tang X, Chen D, Zhang L, et al. Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial. J Zhejiang Univ Sci B, 2022, 23(11): 931-942.
20. Yuan F, Li Z, Li X, et al. Application of regional citrate anticoagulation in membrane therapeutic plasma exchange. Int Urol Nephrol, 2020, 52(12): 2379-2384.
21. Jiao J, Yu Y, Wei S, et al. Heparin anticoagulation versus regional citrate anticoagulation for membrane therapeutic plasma exchange in patients with increased bleeding risk. Ren Fail, 2023, 45(1): 2210691.
22. Xinping Z, Jie H, Zhenya Y, et al. Citrate anticoagulation in plasma exchange followed by continuous renal replacement therapy in critically ill children. Int J Artif Organs, 2024, 47(2): 85-95.
23. Teh SP, Ho QY, Kee YST, et al. Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis. J Clin Apher, 2023, 38(1): 16-23.
24. 王婷立, 張凌, 陳志文, 等. 枸櫞酸抗凝在持續緩慢低效血液透析中的應用. 中華內科雜志, 2014, 53(12): 953-956.
25. Pourcine F, Vong LVP, Chelly J, et al. Sustained low-efficiency dialysis with regional citrate anticoagulation for patients with liver impairment in intensive care unit: a single center experience. Ther Apher Dial, 2021, 25(2): 211-217.
26. 張凌, 李佩蕓, 魏甜甜, 等. 簡化枸櫞酸抗凝技術在持續緩慢低效血液透析中的臨床應用. 華西醫學, 2018, 33(7): 838-842.
27. 張海鋼, 吳京蘭, 黃鐳, 等. 局部枸櫞酸抗凝在重癥中毒患者血液灌流治療中的應用研究. 中國血液凈化, 2018, 17(4): 217-221.
28. 普亞軍, 張凌, 王芳, 等. 局部枸櫞酸抗凝在血液灌流聯合連續性腎臟替代治療中的應用觀察. 華西醫學, 2023, 38(8): 1174-1180.
29. Schulthei? C, Saugel B, Phillip V, et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care, 2012, 16(4): R162.
30. Zhang W, Bai M, Yu Y, et al. Safety and efficacy of regional citrate anticoagulation for continuous renal replacement therapy in liver failure patients: a systematic review and meta-analysis. Crit Care, 2019, 23(1): 22.
31. Bai M, Yu Y, Zhao L, et al. Regional citrate anticoagulation versus no anticoagulation for CKRT in patients with liver failure with increased bleeding risk. Clin J Am Soc Nephrol, 2023, 19(2): 151-160.
32. Yu Y, Bai M, Ma F, et al. Regional citrate anticoagulation versus no-anticoagulation for continuous venovenous hemofiltration in patients with liver failure and increased bleeding risk: a retrospective case-control study. PLoS One, 2020, 15(5): e0232516.
33. Peng B, Lu J, Guo H, et al. Regional citrate anticoagulation for replacement therapy in patients with liver failure: a systematic review and meta-analysis. Front Nutr, 2023, 10: 1031796.
34. Pistolesi V, Morabito S, Pota V, et al. Regional citrate anticoagulation (RCA) in critically ill patients undergoing renal replacement therapy (RRT): expert opinion from the SIAARTI-SIN joint commission. J Anesth Analg Crit Care, 2023, 3(1): 7.
35. 莊峰, 俞雯艷, 馬帥, 等. 一種“二階段補鈣模型”在 RCA-CVVH 中的臨床應用. 中國血液凈化, 2018, 17(7): 461-465.
36. 席春生, 劉同存, 劉飛, 等. 在線下調透析液碳酸氫鹽濃度預防局部枸櫞酸鈉抗凝血液透析患者代謝性堿中毒. 中國血液凈化, 2023, 22(4): 269-272.
37. Gupta M, Wadhwa NK, Bukovsky R, et al. Regional citrate anticoagulation for continuous venovenous hemodiafiltration using calcium-containing dialysate. Am J Kidney Dis, 2004, 43(1): 67-73.
38. Zhang L, Liao Y, Xiang J, et al. Simplified regional citrate anticoagulation using a calcium-containing replacement solution for continuous venovenous hemofiltration. J Artif Organs, 2013, 16(2): 185-192.
39. 席春生, 劉同存, 蔡蕊蓮, 等. 含鈣透析液和置換液局部枸櫞酸抗凝連續靜脈靜脈血液透析濾過臨床觀察. 中國血液凈化, 2022, 21(8): 576-579.
40. Wei T, Tang X, Zhang L, et al. Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial. Chin Med J (Engl), 135(20): 2478-2487.
41. Rhee H, Berenger B, Mehta RL, et al. Regional citrate anticoagulation for continuous kidney replacement therapy with calcium-containing solutions: a cohort study. Am J Kidney Dis, 2021, 78(4): 550-559. e1.
42. Liu SY, Xu SY, Yin L, et al. Emergency medical doctor branch of the chinese medical doctor association. Management of regional citrate anticoagulation for continuous renal replacement therapy: guideline recommendations from Chinese emergency medical doctor consensus. Mil Med Res, 2023, 10(1): 23.
43. Hadid T, Kafri Z, Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Rev, 2021, 47: 100761.
44. Shankaranarayanan D, Muthukumar T, Barbar T, et al. Anticoagulation strategies and filter life in COVID-19 patients receiving continuous renal replacement therapy: a single-center experience. Clin J Am Soc Nephrol, 2020, 16(1): 124-126.
45. Zhou Z, Liu C, Yang Y, et al. Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Crit Care, 2023, 27(1): 222.
46. Abdel Azim ABE, ElSaid TW, El Said HW, et al. A randomized controlled clinical trial of 4% sodium citrate versus heparin as locking solution for temporary dialysis catheters among hemodialysis patients. Clin Nephrol, 2018, 90(5): 341-349.
47. Mai H, Zhao Y, Salerno S, et al. Citrate versus heparin lock for prevention of hemodialysis catheter-related complications: updated systematic review and meta-analysis of randomized controlled trials. Int Urol Nephrol, 2019, 51(6): 1019-1033.
48. Quenot JP, Helms J, Bourredjem A, et al. Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial. Ann Intensive Care, 2019, 9(1): 75.
49. Huang HM, Jiang X, Meng LB, et al. Reducing catheter-associated complications using 4% sodium citrate versus sodium heparin as a catheter lock solution. J Int Med Res, 2019, 47(9): 4204-4214.

West China Medical Journal

Application progress of regional citrate anticoagulant technology in blood purification

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