Timing of initiation of renal replacement therapy for severe acute pancreatitis_West China Medical Journal

Authors：

LI Mingxia ¹ ,  ZHAO Shuangping ^1,2,3

1. Department of Critical Care Medicine, Xiangya Hospital Central South University, Changsha, Hunan 410008, P. R. China;
2. National Clinical Research Center for Geriatric Disorders, Changsha, Hunan 410008, P. R. China;
3. Hunan Provincial Clinical Research Center of Intensive Care Medicine, Changsha, Hunan 410008, P. R. China;

Corresponding author：

ZHAO Shuangping, Email: zhshping@csu.edu.cn

Keywords：

Severe acute pancreatitis; renal replacement therapy; timing of initiation

DOI：

10.7507/1002-0179.202205156

Video：

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Abstract Full text Figures/Tables Video References Cited by

Severe acute pancreatitis (SAP) is a serious acute inflammatory disease with complex pathogenesis, rapid progression, high mortality, extensive treatment, and heavy socioeconomic burden, which is often complicated by systemic multiple organ dysfunction. Renal replacement therapy (RRT) is essential for removing inflammatory mediators, cytokines or other toxins, as well as stabilizing the internal environment. Therefore, RRT is utilized as an organ support technology in the clinical management of SAP. Currently, there is no consensus regarding when and under what circumstances RRT can be employed in patients with SAP. In this paper, the pathogenesis of SAP and the indications and timing of initiation of RRT will be discussed.

Citation： LI Mingxia, ZHAO Shuangping. Timing of initiation of renal replacement therapy for severe acute pancreatitis. West China Medical Journal, 2022, 37(7): 979-983. doi: 10.7507/1002-0179.202205156 Copy

1.	Mederos MA, Reber HA, Girgis MD. Acute pancreatitis: a review. JAMA, 2021, 325(4): 382-390.
2.	Forsmark ChE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med, 2017, 376(6): 598-599.
3.	Gapp J, Hall AG, Walters RW, et al. Trends and outcomes of hospitalizations related to acute pancreatitis: epidemiology from 2001 to 2014 in the United States. Pancreas, 2019, 48(4): 548-554.
4.	Trikudanathan G, Wolbrink DRJ, van Santvoort HC, et al. Current concepts in severe acute and necrotizing pancreatitis: an evidence-based approach. Gastroenterology, 2019, 156(7): 1994-2007.e3.
5.	Lewington AJ, Cerdá J, Mehta RL. Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int, 2013, 84(3): 457-467.
6.	Gao Y, Kang K, Liu H, et al. GTS-21 attenuates LPS-induced renal injury via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res, 2017, 9(10): 4673-4681.
7.	Matsuura R, Doi K, Hamasaki Y, et al. RRT selection for AKI patients with critical illness. Semin Nephrol, 2020, 40(5): 498-505.
8.	Abulimiti A, Husaiyin A, Sailai Y. Evaluation of HVHF for the treatment of severe acute pancreatitis accompanying MODS. Medicine (Baltimore), 2018, 97(1): e9417.
9.	Gao N, Yan C, Zhang G. Changes of serum procalcitonin (PCT), C-reactive protein (CRP), interleukin-17 (IL-17), interleukin-6 (IL-6), high mobility group protein-B1 (HMGB1) and D-dimer in patients with severe acute pancreatitis treated with continuous renal replacement therapy (CRRT) and its clinical significance. Med Sci Monit, 2018, 24: 5881-5886.
10.	Takada T, Isaji S, Mayumi T, et al. JPN clinical practice guidelines 2021 with easy-to-understand explanations for the management of acute pancreatitis. J Hepatobiliary Pancreat Sci, 2022: 7.
11.	高甘油三酯血症性急性胰腺炎诊治急诊共识专家组. 高甘油三酯血症性急性胰腺炎诊治急诊专家共识. 中华急诊医学杂志, 2021, 30(8): 937-947.
12.	Leppäniemi A, Tolonen M, Tarasconi A, et al. 2019 WSES guidelines for the management of severe acute pancreatitis. World J Emerg Surg, 2019, 14: 27.
13.	中华医学会消化病学分会胰腺疾病学组, 中华胰腺病杂志编辑委员会, 中华消化杂志编辑委员会. 中国急性胰腺炎诊治指南(2019 年, 沈阳). 中华消化杂志, 2019, 39(11): 721-730.
14.	中华医学会急诊分会, 京津冀急诊急救联盟, 北京医学会急诊分会, 等. 急性胰腺炎急诊诊断及治疗专家共识. 中华急诊医学杂志, 2021, 30(2): 161-172.
15.	STARRT-AKI Investigators, Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group, et al. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med, 2020, 383(3): 240-251.
16.	血液净化急诊临床应用专家共识组. 血液净化急诊临床应用专家共识. 中华急诊医学杂志, 2017, 26(1): 24-36.
17.	Garret C, Péron M, Reignier J, et al. Risk factors and outcomes of infected pancreatic necrosis: retrospective cohort of 148 patients admitted to the ICU for acute pancreatitis. United European Gastroenterol J, 2018, 6(6): 910-918.
18.	Bai Y, Liu Y, Jia L, et al. Severe acute pancreatitis in China: etiology and mortality in 1976 patients. Pancreas, 2007, 35(3): 232-237.
19.	NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128. 9 million children, adolescents, and adults. Lancet, 2017, 390(10113): 2627-2642.
20.	Zheng Y, Zhou Z, Li H, et al. A multicenter study on etiology of acute pancreatitis in Beijing during 5 years. Pancreas, 2015, 44(3): 409-414.
21.	Zhu Y, Pan X, Zeng H, et al. A study on the etiology, severity, and mortality of 3260 patients with acute pancreatitis according to the revised atlanta classification in Jiangxi, China over an 8-year period. Pancreas, 2017, 46(4): 504-509.
22.	Sha H, Ma Q, Jha RK. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis. Med Hypotheses, 2009, 72(2): 180-182.
23.	Opie EL. The etiology of acute hemorrhagic pancreatitis. Bull Johns Hopkins Hosp, 1901, 12: 182-185.
24.	Saharia P, Margolis S, Zuidema GD, et al. Acute pancreatitis with hyperlipemia: studies with an isolated perfused canine pancreas. Surgery, 1977, 82(1): 60-67.
25.	Johnstone C. Pathophysiology and nursing management of acute pancreatitis. Nurs Stand, 2018: 28.
26.	Yang ZW, Meng XX, Xu P. Central role of neutrophil in the pathogenesis of severe acute pancreatitis. J Cell Mol Med, 2015, 19(11): 2513-2520.
27.	Bhatia M, Neoptolemos JP, Slavin J. Inflammatory mediators as therapeutic targets in acute pancreatitis. Curr Opin Investig Drugs, 2001, 2(4): 496-501.
28.	Zhang XP, Li ZJ, Zhang J. Inflammatory mediators and microcirculatory disturbance in acute pancreatitis. Hepatobiliary Pancreat Dis Int, 2009, 8(4): 351-357.
29.	Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol, 2019, 16(8): 479-496.
30.	Lugea A, Waldron RT, Mareninova OA, et al. Human pancreatic acinar cells: proteomic characterization, physiologic responses, and organellar disorders in ex vivo pancreatitis. Am J Pathol, 2017, 187(12): 2726-2743.
31.	Lee B, Zhao Q, Habtezion A. Immunology of pancreatitis and environmental factors. Curr Opin Gastroenterol, 2017, 33(5): 383-389.
32.	Watanabe T, Kudo M, Strober W. Immunopathogenesis of pancreatitis. Mucosal Immunol, 2017, 10(2): 283-298.
33.	Mehta RL. The 9th international conference on continuous renal replacement therapies (CRRT). Blood Purif, 2004, 22(2): 229-247.
34.	Zhou J, Li Y, Tang Y, et al. Effect of acute kidney injury on mortality and hospital stay in patient with severe acute pancreatitis. Nephrology (Carlton), 2015, 20(7): 485-491.
35.	Shi N, Sun GD, Ji YY, et al. Effects of acute kidney injury on acute pancreatitis patients’ survival rate in intensive care unit: a retrospective study. World J Gastroenterol, 2021, 27(38): 6453-6464.
36.	Tomescu D, Popescu M, David C, et al. Clinical effects of hemoadsorption with CytoSorb^® in patients with severe acute pancreatitis: a case series. Int J Artif Organs, 2019, 42(4): 190-193.
37.	Guo H, Suo DW, Zhu HP, et al. Early blood purification therapy of severe acute pancreatitis complicated by acute lung injury. Eur Rev Med Pharmacol Sci, 2016, 20(5): 873-878.
38.	Wu C, Wang X, Jiang T, et al. Improved effect of continuous renal replacement therapy in metabolic status and body composition of early phase of acute pancreatitis. Int J Artif Organs, 2015, 38(10): 523-529.
39.	Lu Z, Li M, Guo F, et al. Timely reduction of triglyceride levels is associated with decreased persistent organ failure in hypertriglyceridemic pancreatitis. Pancreas, 2020, 49(1): 105-110.
40.	Luckianow GM, Ellis M, Governale D, et al. Abdominal compartment syndrome: risk factors, diagnosis, and current therapy. Crit Care Res Pract, 2012, 2012: 908169.
41.	Karvellas CJ, Farhat MR, Sajjad I, et al. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care, 2011, 15(1): R72.
42.	Christiansen S, Christensen S, Pedersen L, et al. Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury. Crit Care, 2017, 21(1): 326.
43.	Moreira FT, Palomba H, Chaves RCF, et al. Early versus delayed initiation of renal replacement therapy for acute kidney injury: an updated systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials. Rev Bras Ter Intensiva, 2018, 30(3): 376-384.
44.	Gaudry S, Hajage D, Martin-Lefevre L, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet, 2021, 397(10281): 1293-1300.
45.	Nassar TI, Qunibi WY. AKI associated with acute pancreatitis. Clin J Am Soc Nephrol, 2019, 14(7): 1106-1115.
46.	Click B, Ketchum AM, Turner R, et al. The role of apheresis in hypertriglyceridemia-induced acute pancreatitis: a systematic review. Pancreatology, 2015, 15(4): 313-320.
47.	Scherer J, Singh VP, Pitchumoni CS, et al. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol, 2014, 48(3): 195-203.
48.	文明波, 吴定国. 不同治疗时机的连续性肾脏替代治疗对重症急性胰腺炎疗效的影响. 中华消化外科杂志, 2011, 10(2): 137-138.
49.	Mao E. Intensive management of severe acute pancreatitis. Ann Transl Med, 2019, 7(22): 687.
50.	Zhang X, Cao Y, Pan CK, et al. Effect of initiation of renal replacement therapy on mortality in acute pancreatitis patients. Medicine (Baltimore), 2020, 99(47): e23413.
51.	韩莉, 张凌, 康焰. 重症急性胰腺炎合并急性肾损伤的连续性肾替代治疗开始时机. 中国血液净化, 2015(8): 486-489.
52.	Jiang HL, Xue WJ, Li DQ, et al. Influence of continuous veno-venous hemofiltration on the course of acute pancreatitis. World J Gastroenterol, 2005, 11(31): 4815-4821.
53.	Yadav SC, Zhang B. Effect of early continuous veno-venous haemofiltration in severe acute pancreatitis for the prevention of local pancreatic complications. Gastroenterol Res Pract, 2022, 2022: 7575231.
54.	Guo J, Huang W, Yang XN, et al. Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis. Pancreas, 2014, 43(2): 250-254.
55.	Jiang K, Chen XZ, Xia Q, et al. Cost-effectiveness analysis of early veno-venous hemofiltration for severe acute pancreatitis in China. World J Gastroenterol, 2008, 14(12): 1872-1877.
56.	Zhang X, Sun S, Li S, et al. Early classic hemofiltration exhibits no benefits in severe acute pancreatitis with early organ failure: a retrospective case-matched study. Artif Organs, 2014, 38(4): 335-341.
57.	Lin Y, He S, Gong J, et al. Continuous veno-venous hemofiltration for severe acute pancreatitis. Cochrane Database Syst Rev, 2019, 10(10): CD012959.

1. Mederos MA, Reber HA, Girgis MD. Acute pancreatitis: a review. JAMA, 2021, 325(4): 382-390.
2. Forsmark ChE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med, 2017, 376(6): 598-599.
3. Gapp J, Hall AG, Walters RW, et al. Trends and outcomes of hospitalizations related to acute pancreatitis: epidemiology from 2001 to 2014 in the United States. Pancreas, 2019, 48(4): 548-554.
4. Trikudanathan G, Wolbrink DRJ, van Santvoort HC, et al. Current concepts in severe acute and necrotizing pancreatitis: an evidence-based approach. Gastroenterology, 2019, 156(7): 1994-2007.e3.
5. Lewington AJ, Cerdá J, Mehta RL. Raising awareness of acute kidney injury: a global perspective of a silent killer. Kidney Int, 2013, 84(3): 457-467.
6. Gao Y, Kang K, Liu H, et al. GTS-21 attenuates LPS-induced renal injury via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res, 2017, 9(10): 4673-4681.
7. Matsuura R, Doi K, Hamasaki Y, et al. RRT selection for AKI patients with critical illness. Semin Nephrol, 2020, 40(5): 498-505.
8. Abulimiti A, Husaiyin A, Sailai Y. Evaluation of HVHF for the treatment of severe acute pancreatitis accompanying MODS. Medicine (Baltimore), 2018, 97(1): e9417.
9. Gao N, Yan C, Zhang G. Changes of serum procalcitonin (PCT), C-reactive protein (CRP), interleukin-17 (IL-17), interleukin-6 (IL-6), high mobility group protein-B1 (HMGB1) and D-dimer in patients with severe acute pancreatitis treated with continuous renal replacement therapy (CRRT) and its clinical significance. Med Sci Monit, 2018, 24: 5881-5886.
10. Takada T, Isaji S, Mayumi T, et al. JPN clinical practice guidelines 2021 with easy-to-understand explanations for the management of acute pancreatitis. J Hepatobiliary Pancreat Sci, 2022: 7.
11. 高甘油三酯血症性急性胰腺炎诊治急诊共识专家组. 高甘油三酯血症性急性胰腺炎诊治急诊专家共识. 中华急诊医学杂志, 2021, 30(8): 937-947.
12. Leppäniemi A, Tolonen M, Tarasconi A, et al. 2019 WSES guidelines for the management of severe acute pancreatitis. World J Emerg Surg, 2019, 14: 27.
13. 中华医学会消化病学分会胰腺疾病学组, 中华胰腺病杂志编辑委员会, 中华消化杂志编辑委员会. 中国急性胰腺炎诊治指南(2019 年, 沈阳). 中华消化杂志, 2019, 39(11): 721-730.
14. 中华医学会急诊分会, 京津冀急诊急救联盟, 北京医学会急诊分会, 等. 急性胰腺炎急诊诊断及治疗专家共识. 中华急诊医学杂志, 2021, 30(2): 161-172.
15. STARRT-AKI Investigators, Canadian Critical Care Trials Group, Australian and New Zealand Intensive Care Society Clinical Trials Group, et al. Timing of initiation of renal-replacement therapy in acute kidney injury. N Engl J Med, 2020, 383(3): 240-251.
16. 血液净化急诊临床应用专家共识组. 血液净化急诊临床应用专家共识. 中华急诊医学杂志, 2017, 26(1): 24-36.
17. Garret C, Péron M, Reignier J, et al. Risk factors and outcomes of infected pancreatic necrosis: retrospective cohort of 148 patients admitted to the ICU for acute pancreatitis. United European Gastroenterol J, 2018, 6(6): 910-918.
18. Bai Y, Liu Y, Jia L, et al. Severe acute pancreatitis in China: etiology and mortality in 1976 patients. Pancreas, 2007, 35(3): 232-237.
19. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128. 9 million children, adolescents, and adults. Lancet, 2017, 390(10113): 2627-2642.
20. Zheng Y, Zhou Z, Li H, et al. A multicenter study on etiology of acute pancreatitis in Beijing during 5 years. Pancreas, 2015, 44(3): 409-414.
21. Zhu Y, Pan X, Zeng H, et al. A study on the etiology, severity, and mortality of 3260 patients with acute pancreatitis according to the revised atlanta classification in Jiangxi, China over an 8-year period. Pancreas, 2017, 46(4): 504-509.
22. Sha H, Ma Q, Jha RK. Trypsin is the culprit of multiple organ injury with severe acute pancreatitis. Med Hypotheses, 2009, 72(2): 180-182.
23. Opie EL. The etiology of acute hemorrhagic pancreatitis. Bull Johns Hopkins Hosp, 1901, 12: 182-185.
24. Saharia P, Margolis S, Zuidema GD, et al. Acute pancreatitis with hyperlipemia: studies with an isolated perfused canine pancreas. Surgery, 1977, 82(1): 60-67.
25. Johnstone C. Pathophysiology and nursing management of acute pancreatitis. Nurs Stand, 2018: 28.
26. Yang ZW, Meng XX, Xu P. Central role of neutrophil in the pathogenesis of severe acute pancreatitis. J Cell Mol Med, 2015, 19(11): 2513-2520.
27. Bhatia M, Neoptolemos JP, Slavin J. Inflammatory mediators as therapeutic targets in acute pancreatitis. Curr Opin Investig Drugs, 2001, 2(4): 496-501.
28. Zhang XP, Li ZJ, Zhang J. Inflammatory mediators and microcirculatory disturbance in acute pancreatitis. Hepatobiliary Pancreat Dis Int, 2009, 8(4): 351-357.
29. Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol, 2019, 16(8): 479-496.
30. Lugea A, Waldron RT, Mareninova OA, et al. Human pancreatic acinar cells: proteomic characterization, physiologic responses, and organellar disorders in ex vivo pancreatitis. Am J Pathol, 2017, 187(12): 2726-2743.
31. Lee B, Zhao Q, Habtezion A. Immunology of pancreatitis and environmental factors. Curr Opin Gastroenterol, 2017, 33(5): 383-389.
32. Watanabe T, Kudo M, Strober W. Immunopathogenesis of pancreatitis. Mucosal Immunol, 2017, 10(2): 283-298.
33. Mehta RL. The 9th international conference on continuous renal replacement therapies (CRRT). Blood Purif, 2004, 22(2): 229-247.
34. Zhou J, Li Y, Tang Y, et al. Effect of acute kidney injury on mortality and hospital stay in patient with severe acute pancreatitis. Nephrology (Carlton), 2015, 20(7): 485-491.
35. Shi N, Sun GD, Ji YY, et al. Effects of acute kidney injury on acute pancreatitis patients’ survival rate in intensive care unit: a retrospective study. World J Gastroenterol, 2021, 27(38): 6453-6464.
36. Tomescu D, Popescu M, David C, et al. Clinical effects of hemoadsorption with CytoSorb^® in patients with severe acute pancreatitis: a case series. Int J Artif Organs, 2019, 42(4): 190-193.
37. Guo H, Suo DW, Zhu HP, et al. Early blood purification therapy of severe acute pancreatitis complicated by acute lung injury. Eur Rev Med Pharmacol Sci, 2016, 20(5): 873-878.
38. Wu C, Wang X, Jiang T, et al. Improved effect of continuous renal replacement therapy in metabolic status and body composition of early phase of acute pancreatitis. Int J Artif Organs, 2015, 38(10): 523-529.
39. Lu Z, Li M, Guo F, et al. Timely reduction of triglyceride levels is associated with decreased persistent organ failure in hypertriglyceridemic pancreatitis. Pancreas, 2020, 49(1): 105-110.
40. Luckianow GM, Ellis M, Governale D, et al. Abdominal compartment syndrome: risk factors, diagnosis, and current therapy. Crit Care Res Pract, 2012, 2012: 908169.
41. Karvellas CJ, Farhat MR, Sajjad I, et al. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care, 2011, 15(1): R72.
42. Christiansen S, Christensen S, Pedersen L, et al. Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury. Crit Care, 2017, 21(1): 326.
43. Moreira FT, Palomba H, Chaves RCF, et al. Early versus delayed initiation of renal replacement therapy for acute kidney injury: an updated systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials. Rev Bras Ter Intensiva, 2018, 30(3): 376-384.
44. Gaudry S, Hajage D, Martin-Lefevre L, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet, 2021, 397(10281): 1293-1300.
45. Nassar TI, Qunibi WY. AKI associated with acute pancreatitis. Clin J Am Soc Nephrol, 2019, 14(7): 1106-1115.
46. Click B, Ketchum AM, Turner R, et al. The role of apheresis in hypertriglyceridemia-induced acute pancreatitis: a systematic review. Pancreatology, 2015, 15(4): 313-320.
47. Scherer J, Singh VP, Pitchumoni CS, et al. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol, 2014, 48(3): 195-203.
48. 文明波, 吴定国. 不同治疗时机的连续性肾脏替代治疗对重症急性胰腺炎疗效的影响. 中华消化外科杂志, 2011, 10(2): 137-138.
49. Mao E. Intensive management of severe acute pancreatitis. Ann Transl Med, 2019, 7(22): 687.
50. Zhang X, Cao Y, Pan CK, et al. Effect of initiation of renal replacement therapy on mortality in acute pancreatitis patients. Medicine (Baltimore), 2020, 99(47): e23413.
51. 韩莉, 张凌, 康焰. 重症急性胰腺炎合并急性肾损伤的连续性肾替代治疗开始时机. 中国血液净化, 2015(8): 486-489.
52. Jiang HL, Xue WJ, Li DQ, et al. Influence of continuous veno-venous hemofiltration on the course of acute pancreatitis. World J Gastroenterol, 2005, 11(31): 4815-4821.
53. Yadav SC, Zhang B. Effect of early continuous veno-venous haemofiltration in severe acute pancreatitis for the prevention of local pancreatic complications. Gastroenterol Res Pract, 2022, 2022: 7575231.
54. Guo J, Huang W, Yang XN, et al. Short-term continuous high-volume hemofiltration on clinical outcomes of severe acute pancreatitis. Pancreas, 2014, 43(2): 250-254.
55. Jiang K, Chen XZ, Xia Q, et al. Cost-effectiveness analysis of early veno-venous hemofiltration for severe acute pancreatitis in China. World J Gastroenterol, 2008, 14(12): 1872-1877.
56. Zhang X, Sun S, Li S, et al. Early classic hemofiltration exhibits no benefits in severe acute pancreatitis with early organ failure: a retrospective case-matched study. Artif Organs, 2014, 38(4): 335-341.
57. Lin Y, He S, Gong J, et al. Continuous veno-venous hemofiltration for severe acute pancreatitis. Cochrane Database Syst Rev, 2019, 10(10): CD012959.

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