Application of topical citrate acid anticoagulation in patients with severe acute pancreatitis after continuous renal replacement therapy_West China Medical Journal

Authors：

LIU Guiyun ¹ , CAO Lilin ¹ , FAN Hua ² , WANG Lei ¹ ,  WANG Yaning ¹

1. Department of Intensive Care Unit, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, P. R. China;
2. Department of Intensive Care Unit, the Infectious Disease Hospital of Zhangjiakou City, Zhangjiakou, Hebei 075000, P. R. China;

Corresponding?author：

WANG Yaning, Email: wangyaning123@126.com

Keywords：

Severe acute pancreatitis; continuous renal replacement therapy; filter life span; catheter blockage; inflammatory factors

DOI：

10.7507/1002-0179.202309027

Video：

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Objective To investigate the difference of anticoagulant efficacy of heparin and citric acid during continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis, and analyze their effects of on filter life span, length of hospital stay and mortality. Methods Patients with severe acute pancreatitis in Intensive Care Unit of the First Affiliated Hospital of Hebei North University between January 2018 and July 2022 were retrospectively enrolled, and they were divided into heparin group (control group) and citric acid group (research group) according to anticoagulation methods. The differences of anticoagulant catheter blockage during CRRT, filter life span, length of hospital stay, and 90-day mortality between the two groups were analyzed. Results A total of 108 patients were enrolled, including 56 in the research group and 52 in the control group. In pre-CRRT treatment, the balance value of fluid intake and outflow in the research group was significantly lower than that in the control group (P<0.05). The 108 patients received 217 times of CRRT treatment totally, with a median length of treatment of 63 h (range 44-87 h). The severity of catheter blockage in the research group was lower than that in the control group (P=0.003). The filter life span was longer in the research group than that in the control group [42.5 vs. 29.0 h; hazard ratio=1.83, 95% confidence interval (1.23, 2.73), P<0.001]; in the comparison of 90-day mortality, there was no significant difference between the two groups (P>0.05). The mean use of filters in the research group was less than that in the control group (1.93±0.09 vs. 2.17±0.14, P<0.001). The downtime of CRRT due to filter life in the research group was obviously shorter than that in the control group [120 (0, 720) vs. 300 (0, 890) min, P=0.029], while the duration of CRRT in the research group was remarkably better than that in the control group [10.6 (4.9, 27.7) vs. 8.1 (3.6, 25.0) d, P=0.024], and the risk of filter replacement due to special conditons in the research group was lower than that in the control group (46.4% vs. 65.4%, P=0.048). There was no statistically significant difference in the length of intensive care unit hospitalization or total hospitalization between the two groups (P>0.05). Conclusion Both heparin and citric acid could assist the treatment of CRRT, while citric acid might be apt to improve local coagulation and systemic inflammatory response.

Citation： LIU Guiyun, CAO Lilin, FAN Hua, WANG Lei, WANG Yaning. Application of topical citrate acid anticoagulation in patients with severe acute pancreatitis after continuous renal replacement therapy. West China Medical Journal, 2023, 38(11): 1693-1700. doi: 10.7507/1002-0179.202309027 Copy

1.	Xu C, Liu J, Li Z, et al. Efficacy analysis of continuous blood purification therapy for patients with severe acute pancreatitis and acute kidney injury. Panminerva Med, 2022, 64(4): 593-594.
2.	Shao Y, Li C, Jiang Y, et al. Inhibition of caspase-11-mediated pyroptosis alleviates acute kidney injury associated with severe acute pancreatitis in rats. J Invest Surg, 2023, 36(1): 1-7.
3.	Nassar TI, Qunibi WY. AKI associated with acute pancreatitis. Clin J Am Soc Nephrol, 2019, 14(7): 1106-1115.
4.	Zhu Q, Zou F, Lin J, et al. Effect of continuous renal replacement therapy adjuvant to broad-spectrum enzyme inhibitors on the efficacy and inflammatory cytokines in patients with severe acute pancreatitis. Am J Transl Res, 2021, 13(7): 8067-8075.
5.	Chen ZF, Gui CM, Xie ZH. The effects of continuous renal replacement therapy with different anticoagulation methods on the expression of cytokines in severe acute pancreatitis. Transpl Immunol, 2022, 73: 101603.
6.	Navaneethan SD, Zoungas S, Caramori ML, et al. Diabetes management in chronic kidney disease: synopsis of the kdigo 2022 clinical practice guideline update. Ann Intern Med, 2023, 176(3): 381-387.
7.	Ko?ka A, Kowalik MM, Lango-Maziarz A, et al. Ionic homeostasis, acid-base balance and the risk of citrate accumulation in patients after cardiovascular surgery treated with continuous veno-venous haemofiltration with post-dilution regional citrate anticoagulation. An observational case-control study. Acta Biochim Pol, 2021, 68(4): 695-704.
8.	中華醫學會外科學分會胰腺外科學組. 中國急性胰腺炎診治指南(2021). 中國實用外科雜志, 2021, 41(7): 739-746.
9.	Pakula AM, Skinner RA. Acute kidney injury in the critically ill patient: a current review of the literature. J Intensive Care Med, 2016, 31(5): 319-324.
10.	李曉亮, 肖宏濤, 李延倉, 等. 檸檬酸對行連續性腎臟替代治療的嚴重燒傷并發急性腎損傷患者的影響. 中華燒傷雜志, 2019, 35(8): 568-573.
11.	路永霞. 4% 枸櫞酸鈉與 5% 肝素鈉封管在長期血液透析帶 Cuff 導管患者中的應用效果對比. 吉林醫學, 2022, 43(8): 2291-2292.
12.	劉海燕, 李文龍, 蕭清英, 等. 4% 抗凝血用枸櫞酸鈉不同封管頻次在血液透析病人透析導管封管中的應用. 全科護理, 2021, 23(19): 3244-3247.
13.	Ye X, Wang F, Zeng W, et al. Comparison of empirical high-dose and low-dose of meropenem in critically ill patients with sepsis and septic shock: a randomized controlled study protocol. Medicine (Baltimore), 2020, 99(51): e22829.
14.	薛志剛, 曹鋒, 李昂, 等. 急性胰腺炎診療實踐的調查研究. 中華外科雜志, 2021, 59(8): 672-678.
15.	Yu WK, McNeil JB, Wickersham NE, et al. Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure. Crit Care, 2021, 25(1): 48.
16.	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.
17.	Rogers AR, Jenkins B. Calorie provision from citrate anticoagulation in continuous renal replacement therapy in critical care. J Intensive Care Soc, 2021, 22(3): 183-186.
18.	Martínez-García JJ, León-Sicairos NM, Canizalez-Román A, et al. Fluid balance and acute kidney injury in septic shock. B Med Hosp Infant M, 2017, 74(4): 282-288.
19.	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 trails. Crit Care, 2023, 27(1): 222.
20.	Park MJ, Iyer S, Xue X, et al. HIF1-alpha regulates acinar cell function and response to injury in mouse pancreas. Gastroenterology, 2018, 154(6): 1630-1634. e3.
21.	Kaewdoungtien P, Tachaboon S, Kangsumrith N, et al. Immunomodulation effect of regional citrate anticoagulation in acute kidney injury requiring renal replacement therapy. Blood Purificat, 2023, 52(5): 474-482.
22.	Fisher R, Moore GW, Mitchell MJ, et al. Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receving continuous renal replacement therapy for acute kidney injury: a prospective study. Ann Intensive Care, 2022, 12(1): 29.
23.	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. Chinese Med J-Peking, 2022, 135(20): 2478-2487.
24.	Mori Y, Omori M, Nakao A. Vital but vulnerable: human TRPV6 is a trade-off of powerful Ca²⁺ uptake and susceptibility to epithelial barrier dysfunction. Cell Calcium, 2022, 107: 102652.
25.	Abdel-Fattah M, Johnson D, Constable L, et al. Randomised controlled trial comparing the clinical and cost-effectiveness of various washout policies versus no washout policy in preventing catheter associated complication in adults living with long-term catheters: study protocol for the CATHETER II study. Trials, 2022, 23(1): 630.
26.	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, 2020, 43(4): 234-241.
27.	Raina R, Agrawal N, Kusumi K, et al. A meta-analysis of extracorporeal anticoagulants in pediatric continuous kidney replacement therapy. J Intensive Care Med, 2022, 37(5): 577-594.
28.	Meersch M, Küllmar M, Wempe C, et al. Rgional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial. BMJ Open, 2019, 9(1): e024411.
29.	Zhou H, Mei X, He X, et al. Severity stratification and prognostic prediction of patients with acute pancreatitis at early phase: a retrospective study. Medicine (Baltimore), 2019, 98(16): e15275.
30.	Giani M, Scaravilli V, Stefanini F, et al. Continuous renal replacement therapy in venovenous extracorporeal membrane oxygenation: a retrospective study on regional citrate anticoagulation. ASAIO J, 2020, 66(3): 332-338.

1. Xu C, Liu J, Li Z, et al. Efficacy analysis of continuous blood purification therapy for patients with severe acute pancreatitis and acute kidney injury. Panminerva Med, 2022, 64(4): 593-594.
2. Shao Y, Li C, Jiang Y, et al. Inhibition of caspase-11-mediated pyroptosis alleviates acute kidney injury associated with severe acute pancreatitis in rats. J Invest Surg, 2023, 36(1): 1-7.
3. Nassar TI, Qunibi WY. AKI associated with acute pancreatitis. Clin J Am Soc Nephrol, 2019, 14(7): 1106-1115.
4. Zhu Q, Zou F, Lin J, et al. Effect of continuous renal replacement therapy adjuvant to broad-spectrum enzyme inhibitors on the efficacy and inflammatory cytokines in patients with severe acute pancreatitis. Am J Transl Res, 2021, 13(7): 8067-8075.
5. Chen ZF, Gui CM, Xie ZH. The effects of continuous renal replacement therapy with different anticoagulation methods on the expression of cytokines in severe acute pancreatitis. Transpl Immunol, 2022, 73: 101603.
6. Navaneethan SD, Zoungas S, Caramori ML, et al. Diabetes management in chronic kidney disease: synopsis of the kdigo 2022 clinical practice guideline update. Ann Intern Med, 2023, 176(3): 381-387.
7. Ko?ka A, Kowalik MM, Lango-Maziarz A, et al. Ionic homeostasis, acid-base balance and the risk of citrate accumulation in patients after cardiovascular surgery treated with continuous veno-venous haemofiltration with post-dilution regional citrate anticoagulation. An observational case-control study. Acta Biochim Pol, 2021, 68(4): 695-704.
8. 中華醫學會外科學分會胰腺外科學組. 中國急性胰腺炎診治指南(2021). 中國實用外科雜志, 2021, 41(7): 739-746.
9. Pakula AM, Skinner RA. Acute kidney injury in the critically ill patient: a current review of the literature. J Intensive Care Med, 2016, 31(5): 319-324.
10. 李曉亮, 肖宏濤, 李延倉, 等. 檸檬酸對行連續性腎臟替代治療的嚴重燒傷并發急性腎損傷患者的影響. 中華燒傷雜志, 2019, 35(8): 568-573.
11. 路永霞. 4% 枸櫞酸鈉與 5% 肝素鈉封管在長期血液透析帶 Cuff 導管患者中的應用效果對比. 吉林醫學, 2022, 43(8): 2291-2292.
12. 劉海燕, 李文龍, 蕭清英, 等. 4% 抗凝血用枸櫞酸鈉不同封管頻次在血液透析病人透析導管封管中的應用. 全科護理, 2021, 23(19): 3244-3247.
13. Ye X, Wang F, Zeng W, et al. Comparison of empirical high-dose and low-dose of meropenem in critically ill patients with sepsis and septic shock: a randomized controlled study protocol. Medicine (Baltimore), 2020, 99(51): e22829.
14. 薛志剛, 曹鋒, 李昂, 等. 急性胰腺炎診療實踐的調查研究. 中華外科雜志, 2021, 59(8): 672-678.
15. Yu WK, McNeil JB, Wickersham NE, et al. Angiopoietin-2 outperforms other endothelial biomarkers associated with severe acute kidney injury in patients with severe sepsis and respiratory failure. Crit Care, 2021, 25(1): 48.
16. 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.
17. Rogers AR, Jenkins B. Calorie provision from citrate anticoagulation in continuous renal replacement therapy in critical care. J Intensive Care Soc, 2021, 22(3): 183-186.
18. Martínez-García JJ, León-Sicairos NM, Canizalez-Román A, et al. Fluid balance and acute kidney injury in septic shock. B Med Hosp Infant M, 2017, 74(4): 282-288.
19. 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 trails. Crit Care, 2023, 27(1): 222.
20. Park MJ, Iyer S, Xue X, et al. HIF1-alpha regulates acinar cell function and response to injury in mouse pancreas. Gastroenterology, 2018, 154(6): 1630-1634. e3.
21. Kaewdoungtien P, Tachaboon S, Kangsumrith N, et al. Immunomodulation effect of regional citrate anticoagulation in acute kidney injury requiring renal replacement therapy. Blood Purificat, 2023, 52(5): 474-482.
22. Fisher R, Moore GW, Mitchell MJ, et al. Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receving continuous renal replacement therapy for acute kidney injury: a prospective study. Ann Intensive Care, 2022, 12(1): 29.
23. 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. Chinese Med J-Peking, 2022, 135(20): 2478-2487.
24. Mori Y, Omori M, Nakao A. Vital but vulnerable: human TRPV6 is a trade-off of powerful Ca²⁺ uptake and susceptibility to epithelial barrier dysfunction. Cell Calcium, 2022, 107: 102652.
25. Abdel-Fattah M, Johnson D, Constable L, et al. Randomised controlled trial comparing the clinical and cost-effectiveness of various washout policies versus no washout policy in preventing catheter associated complication in adults living with long-term catheters: study protocol for the CATHETER II study. Trials, 2022, 23(1): 630.
26. 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, 2020, 43(4): 234-241.
27. Raina R, Agrawal N, Kusumi K, et al. A meta-analysis of extracorporeal anticoagulants in pediatric continuous kidney replacement therapy. J Intensive Care Med, 2022, 37(5): 577-594.
28. Meersch M, Küllmar M, Wempe C, et al. Rgional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial. BMJ Open, 2019, 9(1): e024411.
29. Zhou H, Mei X, He X, et al. Severity stratification and prognostic prediction of patients with acute pancreatitis at early phase: a retrospective study. Medicine (Baltimore), 2019, 98(16): e15275.
30. Giani M, Scaravilli V, Stefanini F, et al. Continuous renal replacement therapy in venovenous extracorporeal membrane oxygenation: a retrospective study on regional citrate anticoagulation. ASAIO J, 2020, 66(3): 332-338.

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