Ulinastatin for Acute Pancreatitis: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

YANG Jinlin , GUO Zhen , WU Zongying , WANG Yiping , ZENG Chao

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Ulinastatin; Acute pancreatitis; Systematic review; Meta-analysis

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective 　To assess the effectiveness and safety of ulinastatin in the treatment of patients with acute pancreatitis.
Methods 　A systematic review of randomized controlled trials (RCT) of ulinastatin for acute pancreatitis was performed. Trials were identified by searching The Cochrane Library (issue 3, 2004), MEDLINE, EMBASE (1984-2004) and Chinese Biological Medicine Database (1978-2004), handsearching, and personal contact with pharmaceutical companies. All RCTs comparing ulinastatin with other interventions were included. Two reviewers assessed the quality of each studiy, and extracted data independently. Statisticsal analysis was performed by using RevMan 4.2.
Results 　Seventeen trials involving 1 199 patients were included. Most included trials were of poor quality. Only two trials reported death at the end of follow-up. Meta-analysis of 6 RCTs showed that the clinical effective rate of Ulinastatin plus basic treatment group was 93.12% (176/189), and was 73.33% in basic treatment group. A statistic significant difference was found between the two groups (Peto OR 4.29, 95%CI 2.49 to 7.37, P＜0.000 01). Compared with basic treatment group, Ulinastatin plus basic treatment group significantly reduced the mean hospitalization (WMD -4.93, 95%CI -7.76 to -2.09, P＜0.000 7). Meta-analysis of 2 RCTs showed that the clinical effective rate of Ulinastatin plus basic treatment group was 86.75% (131/151), and was 80.49% (99/123) in other drugs plus basic treatment group. No statistic significant difference was found between the two groups (Peto OR 1.46, 95%CI 1.76 to 2.80, P＜0.26). One trial found that comparing with control group (23.5±7.5 days), Ulinastatin group (34.0±6.4 days) significantly reduced the mean hospitalization (P＜0.05).The reported severe adverse events of ulinastatin appeared to be rare (7/488, 1.43%).
Conclusion 　Ulinastatin appears to be a modality of safe and effective treatment with a favorable trend, but there is no enough evidence to support this conclusion at present as the published trials with poor quality. More trials with enough sample size and scientifically sound methodology are required.

Citation： YANG Jinlin,GUO Zhen,WU Zongying,WANG Yiping,ZENG Chao. Ulinastatin for Acute Pancreatitis: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2005, 05(4): 323-330. doi: Copy

1.	袁耀宗, 诸琦, 夏璐. 生长抑素及大黄素对犬急性坏死性胰腺炎Oddi括约肌的作用[J]. 中华消化杂志, 1999; 19(4): 252～255.
2.	关英, 米键, 许静. 抑肽酶药物不良反应与合理性用药的前瞻性观察[J]. 世界华人消化杂志, 2002; 10(6): 735.
3.	大西冶夫, 小雀浩司, 延原正弘. 蛋白酶抑制剂--乌司他丁的药理作用. 应用药理(日), 1986; 31(3): 663.
4.	中华医学会外科学会胰腺学组. 急性胰腺炎的临床诊断及分级标准[J]. 中华外科杂志, 1997; 35(12): 773.
5.	刘鸣, 张世洪. 临床试验中的意向处理分析[J]. 英国医学杂志中文版, 2001; 4(4): 223～224.
6.	刘全忠, 王永革, 胡琳琳. 乌司他丁治疗轻症急性胰腺炎21例临床观察[J]. 胃肠病学和肝病学杂志, 2002; 11(1): 28.
7.	李英, 陈血梅. 乌司他丁治疗急性胰腺炎30例[J]. 中国中西医结合消化杂志, 2002; 10(5): 311.
8.	李俊权. 乌司他丁治疗急性胰腺炎22例临床分析[J]. 中华医学写作杂志, 2002; 9(18): 1 412.
9.	王化虹, 胡伏莲, 林三仁. 国产乌司他丁治疗急性胰腺炎的疗效和安全性[J]. 中国新药杂志, 2001; 10(3): 204～206.
10.	陈血梅, 马加. 乌司他丁治疗急性胰腺炎的临床效果[J]. 中国误诊学杂志, 2001; 1(10): 1 486～1 487.
11.	王高彦, 赵广辉. 乌司他丁治疗急性胰腺炎20例疗效观察[J]. 华北煤炭医学院学报, 2001; 3(6): 754～755.
12.	侯旭东, 柴琛, 李玉民. 乌司他丁治疗急性胰腺炎的临床研究[J]. 临床外科杂志, 2001; 9(4): 222～223.
13.	黄宗文, 于迎春, 张颖. 乌司他丁治疗急性胰腺炎临床疗效观察[J]. 临床外科杂志, 2001; 9(1): 33～35.
14.	刘平, 张小勇, 赵志泉. 乌司他丁治疗急性胰腺炎疗效的初步观察[J]. 江苏医药杂志, 2001; 27(3): 214～215.
15.	上海乌司他丁临床试验协作组. 国产乌司他丁治疗急性胰腺炎的多中心临床研究[J]. 中华消化杂志, 2001; 21(5): 293～296.
16.	李海民, 冯全新, 窦科峰, 等. 乌司他丁治疗急性胰腺炎临床疗效观察[J]. 西北国防医学杂志, 2002; 23(3): 183～185.
17.	邓东, 顾明, 李凌云. 乌司他丁治疗急性重症胰腺炎的临床效果[A]. 注射用乌司他丁论文汇编[C], 2001: 17～18.
18.	张水军. 乌司他丁对急性重症胰腺炎病人的胰腺、肝脏及肾脏功能的作用[A]. 注射用乌司他丁论文汇编[C], 2001: 28～29.
19.	陈曼彤, 崔西玉, 邱小蕾. 乌司他丁治疗急性胰腺炎疗效观察[A]. 注射用乌司他丁论文汇编[C], 2001: 37～38.
20.	管强, 熊咏萍. 乌司他丁治疗急性胰腺炎临床小结[A]. 注射用乌司他丁论文汇编[C], 2001: 46～47.
21.	刘文斌, 张海蓉, 段丽平. 乌司他丁治疗急性胰腺炎临床观察[A]. 注射用乌司他丁论文汇编[C], 2001: 48～49.
22.	朱金照, 张捷, 许其增. 乌司他丁治疗胰腺炎的疗效分析[J]. 临床消化病杂志, 2002; 14(40): 153～155.
23.	Mckay CJ, Baxter JN, Imrie CW. A randomized, cotrolled trial of octreotide in moderate to severe acute pancreatitis[J]. Int J Pancreatol, 1997; 21(23): 13-21.
24.	Uhl W, Malfertheiner P, Adler G. The role of octreotide in human acute pancreatitis. A multicenter study[J]. Digestion, 1997; 58(320): 9(A32).
25.	Marton J, Szasz Z, Nagy Z, Jarmay K, Takacs T, Lonovics J, Balogh A, Farkas G Benefical effect of octreotide treatment in acute pancreatitis in rat[J]. Int J Pancreatol, 1998; 24(3): 203-210.
26.	Sanchez MJ, Landa GJ, Seco GJ. Octreotide: effects in experimental severe acute pancreatitis. Analysis of survival, biochemical findings and histomorphometry[J]. Rev Esp Enferm Dig, 1997; 89(63): 101-105.
27.	Plusczyk T, Rathgeb D, Westermann S, Feifel G. Somatostatin attenuates microcirculatory impairment in acute sodium taurocholate-induced pancreatitis[J]. Dig Dis Sci, 1998; 43(3): 575-585.
28.	Yuan YZ, Zhu Ji, Xia Lu. Effects of somatostatin and emodin on sphincter of oddi in acute necrotizing pancreatitis in dogs[J]. Chin J Dig, 1999; 19(4): 252-255.
29.	Buchler M, Malfertheiner P, Uhl W, Scholmerich J, Stockmann F, Adler G, Gaus W, Rolle K, Beger HG. Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group[J]. Gastroenterology, 1993; 104(4): 1 165-1 170.
30.	Pederzoli P, Cavallini G, Falconi M, Bassi C.Gabexate mesilate vs aprotinin in human acute pancreatitis (GA.ME.P.A.). A prospective, randomized, double-blind multicenter study[J]. Int J Pancreatol, 1993; 14(2): 117-124.
31.	Guan Y, Mi J, Xu J. The adverse effects of Aprotinin and prospective observation on rational medication[J]. World Chinese Journal of Digestology, 2002; 10(6): 735.
32.	Umknawn Authors. A Protease inhibitor: pharmacology of Ulinastatin (Miraclid) [J]. Application of pharmacology, 1986; 31(3): 663.
33.	Edward L. A clinically based classification system for acute pancreatitis[J]. Arch Surg, 1993; 128(5): 586-590.
34.	The pancreas group of surgery institute in Chinese Medical Association.The clinical diagnosis and the standard of grading[J]. Chinese Journal of Surgery, 1997; 35(12): 773.
35.	Clarke M, Oxman AD, editors. Cochrane Reviewers Handbook 4.1 [updated June 2000]. In: Review Manager (RevMan) [Computer program]. Version 4.1. Oxford, England: The Cochrane Collaboration, 2000.
36.	Liu M, Zhang SH. Intention to treat analysis in clinical trials[J]. BMJ (Chinese edition), 2001; 4(4): 223-224.
37.	Liu QZ, Wang YG, Hu LL. Clinical observation of Ulinastatin for mild acute pancreatitis in twenty one patients[J]. Chin J Gastro Hepa, 2002; 11(1): 28.
38.	Li Y, Chen XM. Observation of Ulinastatin for acute pancreatitis in thirty patients[J]. Chin J Integr Trad West Med Dig, 2002; 10(5): 311.
39.	Li JQ. Clinical analysis of Ulinstatin for acute pancreatitis in twenty two patients[J]. Chinese Journal of Medical Writing, 2002; 9(18): 1 412.
40.	Wang HH, Hu FL, Lin SR. Effects and safety of Ulinastatin for acute pancreatitis[J]. Chinese Journal of New Medicine, 2001; 10(3): 204-206.
41.	Chen XM, Ma J. Clinical effects of Ulinastatin for acute pancreatitis[J]. Chinese Journal of Misdiagnostics, 2001; 1(10): 1 486-1 487.
42.	Wang GY, Zhao GH. Observation of effects of Ulinastatin for acute pancreatitis in twenty cases[J]. J North China Coal Medical College, 2001; 3(6): 754-755.
43.	Hou XD, Chai C, Li YM. Clinical studies of Ulinastatin for acute pancreatitis[J]. J Clin Surg, 2001; 9(4): 222-223.
44.	Huang ZW, Yu YC, Zhang Y. Observation of clinical effects of Ulinastatin for acute pancreatitis[J]. J Clin Surg, 2001; 9(1): 33-35.
45.	Liu P, Zhang XY, Zhao ZQ. Primary observation of Ulinastatin for acute pancreatitis[J]. Journal of Jiangsu Medicine, 2001; 27(3): 214-215.
46.	Shanghai collbaration group on ulinastatin clinical trial. Multi-center clinical trial on the treatment of acute pancreatitis by Ulinastatin[J]. Chinese Journal of Digestion, 2001; 21(5): 293-296.
47.	Li HM, Feng QX, Dou KF, et al. Clinical observation of Ulinastatin for acute pancreatitis[J]. Medical Journal of National Defending Forces In North West China, 2002; 23(3): 183-185.
48.	Deng D, Gu M, Li LY. Clinical effects on the treatment of severe acute pancreatitis by Ulinastatin[A]. Article Collection of Ulinastatin Injection[C], 2001: 17-18.
49.	Zhang SJ. The effects of Ulinastatin on the pancreatic, liver, kidney in the patients of severe acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001. 28-29.
50.	Chen MT, Cui XY, Qiu XL. Clincal observation of Ulinatatin for acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001: 37-38.
51.	Guan Q, Xiong YP. Clinical summary of Ulinastatin for acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001: 46-47.
52.	Liu WB, Zhang HR, Duan LP. Clincal observation of Ulinatatin for acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001. 48-49.
53.	Zhu JZ, Zhang J, Xu QZ. clinical effect of Ulinastatin in treatment of pancreatitis[J]. Journal of Cinical Digestion, 2002; 14(40): 153-155.

1. 袁耀宗, 诸琦, 夏璐. 生长抑素及大黄素对犬急性坏死性胰腺炎Oddi括约肌的作用[J]. 中华消化杂志, 1999; 19(4): 252～255.
2. 关英, 米键, 许静. 抑肽酶药物不良反应与合理性用药的前瞻性观察[J]. 世界华人消化杂志, 2002; 10(6): 735.
3. 大西冶夫, 小雀浩司, 延原正弘. 蛋白酶抑制剂--乌司他丁的药理作用. 应用药理(日), 1986; 31(3): 663.
4. 中华医学会外科学会胰腺学组. 急性胰腺炎的临床诊断及分级标准[J]. 中华外科杂志, 1997; 35(12): 773.
5. 刘鸣, 张世洪. 临床试验中的意向处理分析[J]. 英国医学杂志中文版, 2001; 4(4): 223～224.
6. 刘全忠, 王永革, 胡琳琳. 乌司他丁治疗轻症急性胰腺炎21例临床观察[J]. 胃肠病学和肝病学杂志, 2002; 11(1): 28.
7. 李英, 陈血梅. 乌司他丁治疗急性胰腺炎30例[J]. 中国中西医结合消化杂志, 2002; 10(5): 311.
8. 李俊权. 乌司他丁治疗急性胰腺炎22例临床分析[J]. 中华医学写作杂志, 2002; 9(18): 1 412.
9. 王化虹, 胡伏莲, 林三仁. 国产乌司他丁治疗急性胰腺炎的疗效和安全性[J]. 中国新药杂志, 2001; 10(3): 204～206.
10. 陈血梅, 马加. 乌司他丁治疗急性胰腺炎的临床效果[J]. 中国误诊学杂志, 2001; 1(10): 1 486～1 487.
11. 王高彦, 赵广辉. 乌司他丁治疗急性胰腺炎20例疗效观察[J]. 华北煤炭医学院学报, 2001; 3(6): 754～755.
12. 侯旭东, 柴琛, 李玉民. 乌司他丁治疗急性胰腺炎的临床研究[J]. 临床外科杂志, 2001; 9(4): 222～223.
13. 黄宗文, 于迎春, 张颖. 乌司他丁治疗急性胰腺炎临床疗效观察[J]. 临床外科杂志, 2001; 9(1): 33～35.
14. 刘平, 张小勇, 赵志泉. 乌司他丁治疗急性胰腺炎疗效的初步观察[J]. 江苏医药杂志, 2001; 27(3): 214～215.
15. 上海乌司他丁临床试验协作组. 国产乌司他丁治疗急性胰腺炎的多中心临床研究[J]. 中华消化杂志, 2001; 21(5): 293～296.
16. 李海民, 冯全新, 窦科峰, 等. 乌司他丁治疗急性胰腺炎临床疗效观察[J]. 西北国防医学杂志, 2002; 23(3): 183～185.
17. 邓东, 顾明, 李凌云. 乌司他丁治疗急性重症胰腺炎的临床效果[A]. 注射用乌司他丁论文汇编[C], 2001: 17～18.
18. 张水军. 乌司他丁对急性重症胰腺炎病人的胰腺、肝脏及肾脏功能的作用[A]. 注射用乌司他丁论文汇编[C], 2001: 28～29.
19. 陈曼彤, 崔西玉, 邱小蕾. 乌司他丁治疗急性胰腺炎疗效观察[A]. 注射用乌司他丁论文汇编[C], 2001: 37～38.
20. 管强, 熊咏萍. 乌司他丁治疗急性胰腺炎临床小结[A]. 注射用乌司他丁论文汇编[C], 2001: 46～47.
21. 刘文斌, 张海蓉, 段丽平. 乌司他丁治疗急性胰腺炎临床观察[A]. 注射用乌司他丁论文汇编[C], 2001: 48～49.
22. 朱金照, 张捷, 许其增. 乌司他丁治疗胰腺炎的疗效分析[J]. 临床消化病杂志, 2002; 14(40): 153～155.
23. Mckay CJ, Baxter JN, Imrie CW. A randomized, cotrolled trial of octreotide in moderate to severe acute pancreatitis[J]. Int J Pancreatol, 1997; 21(23): 13-21.
24. Uhl W, Malfertheiner P, Adler G. The role of octreotide in human acute pancreatitis. A multicenter study[J]. Digestion, 1997; 58(320): 9(A32).
25. Marton J, Szasz Z, Nagy Z, Jarmay K, Takacs T, Lonovics J, Balogh A, Farkas G Benefical effect of octreotide treatment in acute pancreatitis in rat[J]. Int J Pancreatol, 1998; 24(3): 203-210.
26. Sanchez MJ, Landa GJ, Seco GJ. Octreotide: effects in experimental severe acute pancreatitis. Analysis of survival, biochemical findings and histomorphometry[J]. Rev Esp Enferm Dig, 1997; 89(63): 101-105.
27. Plusczyk T, Rathgeb D, Westermann S, Feifel G. Somatostatin attenuates microcirculatory impairment in acute sodium taurocholate-induced pancreatitis[J]. Dig Dis Sci, 1998; 43(3): 575-585.
28. Yuan YZ, Zhu Ji, Xia Lu. Effects of somatostatin and emodin on sphincter of oddi in acute necrotizing pancreatitis in dogs[J]. Chin J Dig, 1999; 19(4): 252-255.
29. Buchler M, Malfertheiner P, Uhl W, Scholmerich J, Stockmann F, Adler G, Gaus W, Rolle K, Beger HG. Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group[J]. Gastroenterology, 1993; 104(4): 1 165-1 170.
30. Pederzoli P, Cavallini G, Falconi M, Bassi C.Gabexate mesilate vs aprotinin in human acute pancreatitis (GA.ME.P.A.). A prospective, randomized, double-blind multicenter study[J]. Int J Pancreatol, 1993; 14(2): 117-124.
31. Guan Y, Mi J, Xu J. The adverse effects of Aprotinin and prospective observation on rational medication[J]. World Chinese Journal of Digestology, 2002; 10(6): 735.
32. Umknawn Authors. A Protease inhibitor: pharmacology of Ulinastatin (Miraclid) [J]. Application of pharmacology, 1986; 31(3): 663.
33. Edward L. A clinically based classification system for acute pancreatitis[J]. Arch Surg, 1993; 128(5): 586-590.
34. The pancreas group of surgery institute in Chinese Medical Association.The clinical diagnosis and the standard of grading[J]. Chinese Journal of Surgery, 1997; 35(12): 773.
35. Clarke M, Oxman AD, editors. Cochrane Reviewers Handbook 4.1 [updated June 2000]. In: Review Manager (RevMan) [Computer program]. Version 4.1. Oxford, England: The Cochrane Collaboration, 2000.
36. Liu M, Zhang SH. Intention to treat analysis in clinical trials[J]. BMJ (Chinese edition), 2001; 4(4): 223-224.
37. Liu QZ, Wang YG, Hu LL. Clinical observation of Ulinastatin for mild acute pancreatitis in twenty one patients[J]. Chin J Gastro Hepa, 2002; 11(1): 28.
38. Li Y, Chen XM. Observation of Ulinastatin for acute pancreatitis in thirty patients[J]. Chin J Integr Trad West Med Dig, 2002; 10(5): 311.
39. Li JQ. Clinical analysis of Ulinstatin for acute pancreatitis in twenty two patients[J]. Chinese Journal of Medical Writing, 2002; 9(18): 1 412.
40. Wang HH, Hu FL, Lin SR. Effects and safety of Ulinastatin for acute pancreatitis[J]. Chinese Journal of New Medicine, 2001; 10(3): 204-206.
41. Chen XM, Ma J. Clinical effects of Ulinastatin for acute pancreatitis[J]. Chinese Journal of Misdiagnostics, 2001; 1(10): 1 486-1 487.
42. Wang GY, Zhao GH. Observation of effects of Ulinastatin for acute pancreatitis in twenty cases[J]. J North China Coal Medical College, 2001; 3(6): 754-755.
43. Hou XD, Chai C, Li YM. Clinical studies of Ulinastatin for acute pancreatitis[J]. J Clin Surg, 2001; 9(4): 222-223.
44. Huang ZW, Yu YC, Zhang Y. Observation of clinical effects of Ulinastatin for acute pancreatitis[J]. J Clin Surg, 2001; 9(1): 33-35.
45. Liu P, Zhang XY, Zhao ZQ. Primary observation of Ulinastatin for acute pancreatitis[J]. Journal of Jiangsu Medicine, 2001; 27(3): 214-215.
46. Shanghai collbaration group on ulinastatin clinical trial. Multi-center clinical trial on the treatment of acute pancreatitis by Ulinastatin[J]. Chinese Journal of Digestion, 2001; 21(5): 293-296.
47. Li HM, Feng QX, Dou KF, et al. Clinical observation of Ulinastatin for acute pancreatitis[J]. Medical Journal of National Defending Forces In North West China, 2002; 23(3): 183-185.
48. Deng D, Gu M, Li LY. Clinical effects on the treatment of severe acute pancreatitis by Ulinastatin[A]. Article Collection of Ulinastatin Injection[C], 2001: 17-18.
49. Zhang SJ. The effects of Ulinastatin on the pancreatic, liver, kidney in the patients of severe acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001. 28-29.
50. Chen MT, Cui XY, Qiu XL. Clincal observation of Ulinatatin for acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001: 37-38.
51. Guan Q, Xiong YP. Clinical summary of Ulinastatin for acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001: 46-47.
52. Liu WB, Zhang HR, Duan LP. Clincal observation of Ulinatatin for acute pancreatitis[A]. Article Collection of Ulinastatin Injection[C], 2001. 48-49.
53. Zhu JZ, Zhang J, Xu QZ. clinical effect of Ulinastatin in treatment of pancreatitis[J]. Journal of Cinical Digestion, 2002; 14(40): 153-155.

Chinese Journal of Evidence-Based Medicine

Ulinastatin for Acute Pancreatitis: A Systematic Review

Abstract Full text Figures/Tables Video References Cited by

Format

Content