A scoping review in the application of regional citrate anticoagulation in patients undergoing continuous renal replacement therapy
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摘要:目的
基于范围综述的方法，汇总分析局部枸橼酸抗凝(RCA)在连续肾脏替代治疗(CRRT)患者中的应用情况。
方法根据范围综述的研究方法，系统检索中国知网、万方数据库、Cochrane Library、PubMed、Embase等国内外数据库中的CRRT患者应用RCA相关文献，检索时限为建库至2023年8月10日，对纳入文献进行筛选、汇总和分析。
结果本研究最终纳入19篇文献，包括随机对照试验8篇、队列研究8篇、病例对照研究2篇和横断面调查1篇。CRRT的抗凝方式主要包括普通肝素、低分子肝素、凝血酶抑制剂、萘莫司他和RCA等; 相较于其他抗凝方式, RCA具有出血风险较低、滤器寿命更长的优势。RCA应用过程中的钙离子监测目前多采用经验试错法; RCA的主要并发症包括枸橼酸蓄积、酸碱平衡紊乱和离子代谢紊乱等; 对于高出血风险患者、高钙血症患者和脓毒血症患者而言, CRRT过程中选用RCA可能收益更大。
结论RCA已经逐渐成为CRRT患者的首选抗凝方式，其具有延长滤器使用寿命、降低出血风险的优势。未来，研究人员应注重RCA应用过程中的钙离子监测，通过靶向输注系统提高安全性和有效性，并进一步探讨RCA的免疫调节作用及其炎症因子清除率高的相关机制。
Abstract:ObjectiveTo summarize and analyze the application of regional citrate anticoagulation (RCA) in patients undergoing continuous renal replacement therapy (CRRT) using a scoping review methodology.
MethodsFollowing the scoping review methodology, a systematic search was conducted in domestic and international databases, including CNKI, Wanfang Data, Cochrane Library, PubMed, and Embase for literature related to RCA in CRRT patients. The search was limited from the inception of the databases to August 10, 2023. Included studies were screened, summarized, and analyzed.
ResultsA total of 19 articles were included in this study, comprising 8 randomized controlled trials, 8 cohort studies, 2 case-control studies, and 1 cross-sectional survey. Anticoagulation methods for CRRT primarily included unfractionated heparin, low-molecular-weight heparin, thrombin inhibitors, nafamostat, and RCA. Compared to other anticoagulation methods, RCA exhibited advantages in lower bleeding risk and longer filter lifespan. Calcium ion monitoring during RCA application predominantly relies on the empirical trial-and-error approach. Major complications associated with RCA include citrate accumulation, acid-base imbalance, and ion metabolic disorders. For patients with high bleeding risk, hypercalcemia, and sepsis, RCA may confer greater benefits during CRRT.
ConclusionRCA has gradually emerged as a preferred anticoagulation method for CRRT patients, offering advantages in extending filter lifespan and reducing bleeding risk. Future research should focus on calcium ion monitoring during RCA, enhancing safety and efficacy through targeted infusion systems, and further exploring the immunomodulatory effects of RCA and its mechanisms related to high inflammatory factor clearance rates.
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表 1 19篇纳入文献的基本特征
第一作者 发表年份 国家 研究类型 研究对象 样本量 抗凝方式 结局指标 对照组 实验组 对照组 实验组 RATANARAT R[15] 2023 泰国 单中心RCT AKI患者 38 38 ⑦ ① ①②③④ KAEWDOUNGTIEN P[16] 2022 泰国 单中心RCT AKI患者 15 15 ② ① ②⑤ GUO L T[7] 2023 中国 回顾性队列研究 ICU患者 54 59 ③ ① ①⑥ SANSOM B[17] 2022 澳大利亚 回顾性队列研究 ICU患者 1 018次 1 550次 ②③⑥⑦ ① ①⑥ LI P Y[8] 2021 中国 病例对照研究 高乳酸血症患者 46 81 ① ① ①③④⑦ GOULD D W[19] 2022 英国 横断面调查 ICU患者 60 416 8 585 ② ① ②④⑧ XUN K[9] 2021 中国 单中心RCT 出血风险患者 14 17 ⑦ ① ①⑨⑩ ZHAO L J[10] 2019 中国 回顾性队列研究 急性高钠血症出血风险患者 23 41 ⑦ ① ①②⑩ YU Y[11] 2020 中国 回顾性队列研究 严重高钙血症患者 24 9 ③ ① ①⑤⑨ YU Y[12] 2020 中国 病例对照研究 肝衰竭伴出血风险患者 62 41 ⑦ ① ①③④⑦⑨ LI L[13] 2020 中国 回顾性队列研究 高乳酸血症患者 47 80 ③ ① ①②④⑦ HUGUET M[20] 2017 西班牙 回顾性队列研究 ICU患者 27 27 ② ① ①④ MAKINO S[24] 2016 日本 回顾性队列研究 ICU患者 25 76 ② ⑤ ①④ GUTIERREZ-BERNAYS D[18] 2016 澳大利亚 回顾性队列研究 ICU患者 72 94 ② ① ①⑧ WU B Y[14] 2015 中国 单中心RCT ICU患者 15 19 ①③ ①③ ①④ STUCKER F[23] 2015 瑞士 单中心RCT ICU患者 49 54 ② ① ①②④ TRESCHAN T A[21] 2014 德国 单中心RCT 怀疑发生HIT患者 35 35 ⑥ ④ ①④⑦ SCHILDER L[22] 2014 荷兰 多中心RCT ICU患者 73 66 ② ① ①② LEE Y K[25] 2014 韩国 单中心RCT ICU高出血风险患者 28 32 ⑦ ⑤ ①② RCT: 随机对照试验; AKI: 急性肾损伤; ICU: 重症监护病房; HIT: 肝素诱导性血小板减少症。抗凝方式: ①局部枸橼酸抗凝; ②普通肝素; ③低分子肝素; ④阿加曲班; ⑤萘莫司他; ⑥水蛭素类药物; ⑦无。结局指标: ①滤器使用寿命; ②病死率; ③枸橼酸蓄积; ④出血; ⑤ ICU住院时间; ⑥滤器压力; ⑦滤器凝血或导管堵塞; ⑧卫生经济学; ⑨血清总钙与离子钙比值; ⑩其他。 
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表 1 19篇纳入文献的基本特征
第一作者 发表年份 国家 研究类型 研究对象 样本量 抗凝方式 结局指标 对照组 实验组 对照组 实验组 RATANARAT R[15] 2023 泰国 单中心RCT AKI患者 38 38 ⑦ ① ①②③④ KAEWDOUNGTIEN P[16] 2022 泰国 单中心RCT AKI患者 15 15 ② ① ②⑤ GUO L T[7] 2023 中国 回顾性队列研究 ICU患者 54 59 ③ ① ①⑥ SANSOM B[17] 2022 澳大利亚 回顾性队列研究 ICU患者 1 018次 1 550次 ②③⑥⑦ ① ①⑥ LI P Y[8] 2021 中国 病例对照研究 高乳酸血症患者 46 81 ① ① ①③④⑦ GOULD D W[19] 2022 英国 横断面调查 ICU患者 60 416 8 585 ② ① ②④⑧ XUN K[9] 2021 中国 单中心RCT 出血风险患者 14 17 ⑦ ① ①⑨⑩ ZHAO L J[10] 2019 中国 回顾性队列研究 急性高钠血症出血风险患者 23 41 ⑦ ① ①②⑩ YU Y[11] 2020 中国 回顾性队列研究 严重高钙血症患者 24 9 ③ ① ①⑤⑨ YU Y[12] 2020 中国 病例对照研究 肝衰竭伴出血风险患者 62 41 ⑦ ① ①③④⑦⑨ LI L[13] 2020 中国 回顾性队列研究 高乳酸血症患者 47 80 ③ ① ①②④⑦ HUGUET M[20] 2017 西班牙 回顾性队列研究 ICU患者 27 27 ② ① ①④ MAKINO S[24] 2016 日本 回顾性队列研究 ICU患者 25 76 ② ⑤ ①④ GUTIERREZ-BERNAYS D[18] 2016 澳大利亚 回顾性队列研究 ICU患者 72 94 ② ① ①⑧ WU B Y[14] 2015 中国 单中心RCT ICU患者 15 19 ①③ ①③ ①④ STUCKER F[23] 2015 瑞士 单中心RCT ICU患者 49 54 ② ① ①②④ TRESCHAN T A[21] 2014 德国 单中心RCT 怀疑发生HIT患者 35 35 ⑥ ④ ①④⑦ SCHILDER L[22] 2014 荷兰 多中心RCT ICU患者 73 66 ② ① ①② LEE Y K[25] 2014 韩国 单中心RCT ICU高出血风险患者 28 32 ⑦ ⑤ ①② RCT: 随机对照试验; AKI: 急性肾损伤; ICU: 重症监护病房; HIT: 肝素诱导性血小板减少症。抗凝方式: ①局部枸橼酸抗凝; ②普通肝素; ③低分子肝素; ④阿加曲班; ⑤萘莫司他; ⑥水蛭素类药物; ⑦无。结局指标: ①滤器使用寿命; ②病死率; ③枸橼酸蓄积; ④出血; ⑤ ICU住院时间; ⑥滤器压力; ⑦滤器凝血或导管堵塞; ⑧卫生经济学; ⑨血清总钙与离子钙比值; ⑩其他。
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[1] BLANKESTIJN P J, VERNOOIJ R W M, HOCKHAM C, et al. Effect of hemodiafiltration or hemodialysis on mortality in kidney failure[J]. N Engl J Med, 2023, 389(8): 700-709. doi: 10.1056/NEJMoa2304820
[2] 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]. J Anesth Analg Crit Care, 2023, 3(1): 7. doi: 10.1186/s44158-023-00091-w
[3] AREPALLY G M, CINES D B. Pathogenesis of heparin-induced thrombocytopenia[J]. Transl Res, 2020, 225: 131-140. doi: 10.1016/j.trsl.2020.04.014
[4] SCHNEIDER A G, JOURNOIS D, RIMMELÉ T. Complications of regional citrate anticoagulation: accumulation or overload?[J]. Crit Care, 2017, 21(1): 281. doi: 10.1186/s13054-017-1880-1
[5] JAMES M, BOUCHARD J, HO J, et al. Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury[J]. Am J Kidney Dis, 2013, 61(5): 673-685. doi: 10.1053/j.ajkd.2013.02.350
[6] PALEVSKY P M, LIU K D, BROPHY P D, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury[J]. Am J Kidney Dis, 2013, 61(5): 649-672. doi: 10.1053/j.ajkd.2013.02.349
[7] GUO L T, HU Y D, ZENG Q J, et al. Factors affecting continuous renal replacement therapy duration in critically ill patients: a retrospective study[J]. Ther Apher Dial, 2023, 27(5): 898-908. doi: 10.1111/1744-9987.14024
[8] LI P Y, ZHANG L, LIN L, et al. Effect of dynamic circuit pressures monitoring on the lifespan of extracorporeal circuit and the efficiency of solute removal during continuous renal replacement therapy[J]. Front Med, 2021, 8: 621921. doi: 10.3389/fmed.2021.621921
[9] XUN K, QIU H, JIA M, et al. Treatment effect of regional sodium citrate anticoagulation in elderly patients with high-risk bleeding receiving continuous renal replacement therapy[J]. Clin Appl Thromb Hemost, 2021, 27: 1-6.
[10] ZHAO L J, MA F, YU Y, et al. Regional citrate anticoagulation versus No-anticoagulation for continuous venovenous hemofiltration in acute severe hypernatremia patients with increased bleeding risk: a retrospective cohort study[J]. Blood Purif, 2020, 49(1/2): 44-54.
[11] YU Y, BAI M, WEI Z, et al. Regional citrate anticoagulation versus low molecular weight heparin anticoagulation for continuous venovenous hemofiltration in patients with severe hypercalcemia: a retrospective cohort study[J]. Ren Fail, 2020, 42(1): 748-758. doi: 10.1080/0886022X.2020.1795879
[12] 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[J]. PLoS One, 2020, 15(5): e0232516. doi: 10.1371/journal.pone.0232516
[13] LI L, BAI M, YU Y, et al. Regional citrate anticoagulation vs no-anticoagulation for CRRT in hyperlactatemia patients with increased bleeding risk: a retrospective cohort study[J]. Semin Dial, 2020: 209-217.
[14] WU B Y, ZHANG K Y, XU B, et al. Randomized controlled trial to evaluate regional citrate anticoagulation plus low-dose of dalteparin in continuous veno-venous hemofiltration[J]. Blood Purif, 2015, 39(4): 306-312. doi: 10.1159/000381662
[15] RATANARAT R, PHAIRATWET P, KHANSOMPOP S, et al. Customized citrate anticoagulation versus No anticoagulant in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a prospective randomized controlled trial[J]. Blood Purif, 2023, 52(5): 455-463. doi: 10.1159/000529076
[16] KAEWDOUNGTIEN P, TACHABOON S, KANGSUMRITH N, et al. Immunomodulation effect of regional citrate anticoagulation in acute kidney injury requiring renal replacement therapy[J]. Blood Purif, 2023, 52(5): 474-482. doi: 10.1159/000529350
[17] SANSOM B, UDY A, SRIRAM S, et al. Circuit haemodynamics during non-citrate and regional citrate continuous renal replacement, and impact of blood flow on filter life[J]. Int J Artif Organs, 2022, 45(12): 988-996. doi: 10.1177/03913988221118585
[18] GUTIERREZ-BERNAYS D, OSTWALD M, ANSTEY C, et al. Transition from heparin to citrate anticoagulation for continuous renal replacement therapy: safety, efficiency, and cost[J]. Ther Apher Dial, 2016, 20(1): 53-59. doi: 10.1111/1744-9987.12331
[19] GOULD D W, DOIDGE J, SADIQUE M Z, et al. Erratum: Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study[J]. Health Technol Assess, 2022, 26(13): 85-86. doi: 10.3310/ZXHI9396-c202204
[20] HUGUET M, RODAS L, BLASCO M, et al. Clinical impact of regional citrate anticoagulation in continuous renal replacement therapy in critically ill patients[J]. Int J Artif Organs, 2017, 40(12): 676-682. doi: 10.5301/ijao.5000633
[21] TRESCHAN T A, SCHAEFER M S, GEIB J, et al. Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial[J]. Crit Care, 2014, 18(5): 588. doi: 10.1186/s13054-014-0588-8
[22] SCHILDER L, NURMOHAMED S A, BOSCH F H, et al. Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial[J]. Crit Care, 2014, 18(4): 472. doi: 10.1186/s13054-014-0472-6
[23] STUCKER F, PONTE B, TATAW J, et al. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial[J]. Crit Care, 2015, 19(1): 91. doi: 10.1186/s13054-015-0822-z
[24] MAKINO S, EGI M, KITA H, et al. Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy[J]. Int J Artif Organs, 2016, 39(1): 16-21. doi: 10.5301/ijao.5000465
[25] LEE Y K, LEE H W, CHOI K H, et al. Ability of nafamostat mesilate to prolong filter patency during continuous renal replacement therapy in patients at high risk of bleeding: a randomized controlled study[J]. PLoS One, 2014, 9(10): e108737. doi: 10.1371/journal.pone.0108737
[26] TRAKARNVANICH T, SIRIVONGRANGSON P, TRONGTRAKUL K, et al. The effect of citrate in cardiovascular system and clot circuit in critically ill patients requiring continuous renal replacement therapy[J]. J Artif Organs, 2023, 26(1): 53-64. doi: 10.1007/s10047-022-01329-0
[27] WEI T 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[J]. Chin Med J, 2022, 135(20): 2478-2487. doi: 10.1097/CM9.0000000000002369
[28] SHENG R M, ZHAO W B, HUANG L H, et al. A target-oriented algorithm for maintaining serum calcium stability automatically in regional citrate anticoagulation[J]. Int J Artif Organs, 2021, 44(8): 551-559. doi: 10.1177/0391398820982620
[29] 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[J]. Crit Care, 2019, 23(1): 22. doi: 10.1186/s13054-019-2317-9
[30] HONORE P M, RIMMELÉ T. Total-to-ionized calcium ratio, taken alone, is no longer valid to diagnose citrate accumulation!What additional parameters should we consider to strengthen the utility of this ratio[J]. J Crit Care, 2020, 59: 172-175. doi: 10.1016/j.jcrc.2020.06.009
[31] HONORE P M, MUGISHA A, DAVID C, et al. In severe liver disease, citrate can be used safely: the question remains-by which mechanism[J]. Crit Care, 2020, 24(1): 63. doi: 10.1186/s13054-020-2801-2
[32] ANANTHARAMAN S, CHIONH C Y. Correcting hyponatremia by fluid sodium modulation in continuous renal replacement therapy with regional citrate anticoagulation[J]. Semin Dial, 2022, 35(2): 198-203. doi: 10.1111/sdi.13054
[33] KHADZHYNOV D, DAHLINGER A, SCHELTER C, et al. Hyperlactatemia, lactate kinetics and prediction of citrate accumulation in critically ill patients undergoing continuous renal replacement therapy with regional citrate anticoagulation[J]. Crit Care Med, 2017, 45(9): e941-e946. doi: 10.1097/CCM.0000000000002501
[34] MORABITO S, PISTOLESI V, TRITAPEPE L, et al. Regional citrate anticoagulation for RRTs in critically ill patients with AKI[J]. Clin J Am Soc Nephrol, 2014, 9(12): 2173-2188. doi: 10.2215/CJN.01280214
[35] BIANCHI N A, ALTARELLI M, ECKERT P, et al. Complications of regional citrate anticoagulation for continuous renal replacement therapy: an observational study[J]. Blood Purif, 2020, 49(5): 567-575. doi: 10.1159/000506253
[36] SIGWALT F, BOUTELEUX A, DAMBRICOURT F, et al. Clinical complications of continuous renal replacement therapy[J]. Contrib Nephrol, 2018, 194: 109-117.
[37] JACOBS R, VERBRUGGHE W, DAMS K, et al. Regional citrate anticoagulation in continuous renal replacement therapy: is metabolic fear the enemy of logic A systematic review and meta-analysis of randomised controlled trials[J]. Life, 2023, 13(5): 1198. doi: 10.3390/life13051198
[38] ZHOU Z F, LIU C, YANG Y 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[J]. Crit Care, 2023, 27(1): 222. doi: 10.1186/s13054-023-04519-1
[39] MARGRAF A, LIU C, KVLLMAR M, et al. Analysis of leukocyte recruitment in continuous veno-venous hemofiltration with regional citrate vs. systemic heparin anticoagulation[J]. Cells, 2022, 11(11): 1815. doi: 10.3390/cells11111815
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