About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2014 (2014), Article ID 630835, 15 pages
http://dx.doi.org/10.1155/2014/630835
Review Article

Does Intraoperative Ulinastatin Improve Postoperative Clinical Outcomes in Patients Undergoing Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

1Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China
2School of Public Health, Sun Yat-sen University, No. 74 Zhongshan 2nd Road, Guangzhou, Guangdong 510080, China
3Guangzhou Municipal Center for Disease Control and Prevention, Guangzhou 0086-510080, China

Received 1 July 2013; Revised 4 November 2013; Accepted 2 December 2013; Published 9 March 2014

Academic Editor: Sebastian Straube

Copyright © 2014 Qiu-Lan He et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Rossaint, C. Berger, H. van Aken et al., “Cardiopulmonary bypass during cardiac surgery modulates systemic inflammation by affecting different steps of the leukocyte recruitment cascade,” PLoS ONE, vol. 7, no. 9, Article ID e45738, 2012. View at Publisher · View at Google Scholar
  2. M. A. Munger, B. Johnson, I. J. Amber, K. S. Callahan, and E. M. Gilbert, “Circulating concentrations of proinflammatory cytokines in mild or moderate heart failure secondary to ischemic or idiopathic dilated cardiomyopathy,” The American Journal of Cardiology, vol. 77, no. 9, pp. 723–727, 1996. View at Publisher · View at Google Scholar · View at Scopus
  3. C. Tentolouris, D. Tousoulis, C. Antoniades et al., “Endothelial function and proinflammatory cytokines in patients with ischemic heart disease and dilated cardiomyopathy,” International Journal of Cardiology, vol. 94, no. 2-3, pp. 301–305, 2004. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. L. Yang, K. L. Huang, H. L. Liou, and H. I. Chen, “The involvement of nitric oxide, nitric oxide synthase, neutrophil elastase, myeloperoxidase and proinflammatory cytokines in the acute lung injury caused by phorbol myristate acetate,” Journal of Biomedical Science, vol. 15, no. 4, pp. 499–507, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. J. H. Holmes, N. C. Connolly, D. L. Paull et al., “Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes,” Inflammation Research, vol. 51, no. 12, pp. 579–586, 2002. View at Publisher · View at Google Scholar · View at Scopus
  6. T. S. Sun, X. B. Chen, Z. Liu, Z. Y. Ma, and J. Z. Zhang, “Relationship between the operation time of multiple fractures with system inflammation changes and clinical outcomes,” Zhonghua Wai Ke Za Zhi, vol. 46, no. 13, pp. 961–965, 2008. View at Scopus
  7. L. F. Gentile, A. G. Cuenca, P. A. Efron et al., “Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care,” Journal of Trauma and Acute Care Surgery, vol. 72, no. 6, pp. 1491–1501, 2012. View at Publisher · View at Google Scholar
  8. J. Hirose, T. Ozawa, T. Miura et al., “Human neutrophil elastase degrades inter-α-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins,” Biological and Pharmaceutical Bulletin, vol. 21, no. 7, pp. 651–656, 1998. View at Scopus
  9. Q. Zhou, G. Wang, C. Gao, and T. Chen, “Effect of ulinastatin on perioperative inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass,” Zhong Nan Da Xue Xue Bao Yi Xue Ban, vol. 35, no. 2, pp. 107–110, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. X. Y. Yu and L. L. Fan, “Effects of different doses of ulinastatin on inflammatory response and pulmonary function after cardiopulmonary bypass,” Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, vol. 21, no. 11, pp. 664–667, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. J. M. Shen, L. Li, and X. J. He, “Effects of ulinastatin on erythrocyte lipid peroxidation in patients undergoing open heart surgery,” Zhong Nan Da Xue Xue Bao Yi Xue Ban, vol. 29, no. 2, pp. 187–189, 2004. View at Scopus
  12. T. Kawamura, K. Inada, O. Kimura, N. Akasaka, and R. Wakusawa, “The inhibitory effects of ulinastatin on the increase of interleukin 8 and 6 during open heart surgery,” Masui, vol. 43, no. 12, pp. 1818–1823, 1994. View at Scopus
  13. T. Kawai, Y. Wada, K. Nishiyama et al., “Usefulness of ulinastatin as a radical scavenger for protection of reperfusion injury after myocardial ischemia in open heart surgery,” Journal of the Japanese Association for Thoracic Surgery, vol. 39, no. 12, pp. 2157–2162, 1991. View at Scopus
  14. T. Kawamura, K. Inada, N. Akasaka, and R. Wakusawa, “Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery,” Canadian Journal of Anaesthesia, vol. 43, no. 5 I, pp. 456–460, 1996. View at Scopus
  15. K. Inoue and H. Takano, “Urinary trypsin inhibitor as a therapeutic option for endotoxin-related inflammatory disorders,” Expert Opinion on Investigational Drugs, vol. 19, no. 4, pp. 513–520, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. J. I. Han, “Urinary trypsin inhibitor: miraculous medicine in many surgical situations?” Korean Journal of Anesthesiology, vol. 58, no. 4, pp. 325–327, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. J. P. T. Higgins and S. Green, Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0, The Cochrane Collaboration, 2011.
  18. D. Moher, A. Liberati, J. Tetzlaff, et al., “Preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement,” PLoS Medicine, vol. 6, no. 7, Article ID e1000097, 2009. View at Publisher · View at Google Scholar
  19. L. Zhang, I. Ajiferuke, and M. Sampson, “Optimizing search strategies to identify randomized controlled trials in MEDLINE,” BMC Medical Research Methodology, vol. 6, article 23, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. A. R. Jadad, R. A. Moore, D. Carroll et al., “Assessing the quality of reports of randomized clinical trials: is blinding necessary?” Controlled Clinical Trials, vol. 17, no. 1, pp. 1–12, 1996. View at Publisher · View at Google Scholar · View at Scopus
  21. M. Egger, G. D. Smith, M. Schneider, and C. Minder, “Bias in meta-analysis detected by a simple, graphical test,” The British Medical Journal, vol. 315, no. 7109, pp. 629–634, 1997. View at Scopus
  22. Y. F. Jiang, W. W. Wang, W. L. Ye et al., “Effects of alprostadil and ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass in pediatric patients with congenital heart diseases,” Zhonghua Yi Xue Za Zhi, vol. 88, no. 41, pp. 2893–2897, 2008. View at Scopus
  23. A. Mishima, Y. Takeuti, S. Usami, H. Kotani, Y. Suzuki, and J. Yura, “Effects of ulinastatin on plasma polymorphonuclear leukocyte elastase activity and respiratory function in patients undergoing cardiopulmonary bypass,” Nihon Kyobu Geka Gakkai Zasshi, vol. 38, no. 4, pp. 607–612, 1990. View at Scopus
  24. T. Y. Ren, X. W. Yang, Y. Ma, F. Wang, and W. D. Qiang, “Myocardial protective effect of ulinastatin against ischemia/reperfusion injury during open heart surgery with cardiopulmonary bypass,” Zhonghua Yi Xue Za Zhi, vol. 83, no. 16, pp. 1391–1393, 2003. View at Scopus
  25. G. Y. Wang, H. B. Qiu, S. G. Zhan, and L. H. Li, “Protection of ulinastatin against myocardial injury induced by off-pump coronary artery bypass graft surgery: report of 24 cases,” Zhonghua Yi Xue Za Zhi, vol. 87, no. 35, pp. 2502–2504, 2007. View at Scopus
  26. D. J. Wang, J. X. Liu, and B. L. Yin, “Protective effects of ulinastatin on the lung injury during cardiopulmonary bypass,” Zhong Nan Da Xue Xue Bao Yi Xue Ban, vol. 30, no. 6, pp. 670–672, 2005. View at Scopus
  27. X. Zhang and X. G. Qin, “Effect of ulinastatin on cardiac and lung function of patients with moderate and high risk in cardiac surgery under cardiopulmonary bypass,” Modern Preventive Medicine, vol. 7, pp. 1822–1824, 2012.
  28. S. Y. Oh, J. C. Kim, Y. S. Choi, W. K. Lee, Y. K. Lee, and Y. L. Kwak, “Effects of ulinastatin treatment on myocardial and renal injury in patients undergoing aortic valve replacement with cardiopulmonary bypass,” Korean Journal of Anesthesiology, vol. 62, no. 2, pp. 148–153, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Nakanishi, S. Takeda, A. Sakamoto, and A. Kitamura, “Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction,” Critical Care Medicine, vol. 34, no. 5, pp. 1351–1357, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Bingyang, L. Jinping, L. Mingzheng, W. Guyan, and F. Zhengyi, “Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response,” Journal of Cardiovascular Surgery, vol. 48, no. 4, pp. 497–503, 2007. View at Scopus
  31. Y. Sato, S. Ishikawa, A. Otaki et al., “Induction of acute-phase reactive substances during open-heart surgery and efficacy of ulinastatin. Inhibiting cytokines and postoperative organ injury,” The Japanese Journal of Thoracic and Cardiovascular Surgery, vol. 48, no. 7, pp. 428–434, 2000. View at Scopus
  32. H. Q. Tu and T. Ming, “Postoperative application of ulinastatin in infants with critical congenital heart disease,” Journal of Nanchang University (Medical Science), vol. 51, no. 2, pp. 37–40, 2011.
  33. J. E. Song, W. S. Kang, D. K. Kim et al., “The effect of ulinastatin on postoperative blood loss in patients undergoing open heart surgery with cardiopulmonary bypass,” Journal of International Medical Research, vol. 39, no. 4, pp. 1201–1210, 2011. View at Scopus
  34. J. Li, Z. Wang, Z. Xu, S. Huang, and F. Qiao, “The role of ulinastatin in management of systemic inflammatory response syndrome post—CPB,” Internationl Journal of Emergency and Critical Car, vol. 4, no. 4, pp. 1929–1933, 2007.
  35. J. Song, J. Park, J. Y. Kim et al., “Effect of ulinastatin on perioperative organ function and systemic inflammatory reaction during cardiac surgery: a randomized double-blinded study,” Korean Journal of Anesthesiology, vol. 64, no. 4, pp. 334–340, 2013. View at Publisher · View at Google Scholar
  36. E. X. Chong, C. W. Zou, M. Y. Zhang, and L. Guo, “Effects of high-dose ulinastatin on inflammatory response and pulmonary function in patients with type-A aortic dissection after cardiopulmonary bypass under deep hypothermic circulatory arrest,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 27, no. 3, pp. 479–484, 2013. View at Publisher · View at Google Scholar
  37. A. Hiyama, J. Takeda, Y. Kotake, H. Morisaki, and K. Fukushima, “A human urinary protease inhibitor (ulinastatin) inhibits neutrophil extracellular release of elastase during cardiopulmonary bypass,” Journal of Cardiothoracic and Vascular Anesthesia, vol. 11, no. 5, pp. 580–584, 1997. View at Publisher · View at Google Scholar · View at Scopus
  38. N. Sato, K. Murakami, K. Ishida, K. Ikeda, and K. Saito, “Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations,” Annals of Thoracic Surgery, vol. 51, no. 5, pp. 754–758, 1991. View at Scopus
  39. A. Sato, Y. Kuwabara, N. Shinoda, M. Kimura, H. Ishiguro, and Y. Fujii, “Use of low dose dopamine, gabexate mesilate and ulinastatin reduces the water balance and pulmonary complication in thoracic esophagectomy patients,” Diseases of the Esophagus, vol. 18, no. 3, pp. 151–154, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. D. Paparella, T. M. Yau, and E. Young, “Cardiopulmonary bypass induced inflammation: pathophysiology and treatment,” European Journal of Cardio-Thoracic Surgery, vol. 21, no. 2, pp. 232–244, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. A. Sablotzki, M. G. Dehne, I. Friedrich et al., “Different expression of cytokines in survivors and non-survivors from MODS following cardiovascular surgery,” European Journal of Medical Research, vol. 8, no. 2, pp. 71–76, 2003. View at Scopus
  42. E. E. Apostolakis, E. N. Koletsis, N. G. Baikoussis, S. N. Siminelakis, and G. S. Papadopoulos, “Strategies to prevent intraoperative lung injury during cardiopulmonary bypass,” Journal of Cardiothoracic Surgery, vol. 5, no. 1, article 1, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. C. A. Dinarello, “Biologic basis for interleukin-1 in disease,” Blood, vol. 87, no. 6, pp. 2095–2147, 1996. View at Scopus
  44. P. Kelk, R. Claesson, L. Hänström, U. H. Lerner, S. Kalfas, and A. Johansson, “Abundant secretion of bioactive interleukin-1β by human macrophages induced by Actinobacillus actinomycetemcomitans leukotoxin,” Infection and Immunity, vol. 73, no. 1, pp. 453–458, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Inoue, H. Takano, A. Shimada et al., “Urinary trypsin inhibitor protects against systemic inflammation induced by lipopolysaccharide,” Molecular Pharmacology, vol. 67, no. 3, pp. 673–680, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. M. Shao, L. Q. Zhang, L. H. Deng, and H. G. Yao, “Clinical study on effects of ulinastatin on patients with systemic inflammatory response syndrome,” Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, vol. 17, no. 4, pp. 228–230, 2005. View at Scopus
  47. X. Y. Lu, W. A. Zeng, W. Q. Lin, B. X. Chen, and W. X. He, “Effect of ulinastatin on inflammatory responses induced by oesophagectomy,” Nan Fang Yi Ke Da Xue Xue Bao, vol. 27, no. 1, pp. 81–83, 2007. View at Scopus
  48. T. Nishiyama and K. Hanaoka, “Do the effects of a protease inhibitor, ulinastatin, on elastase release by blood transfusion depend on interleukin 6?” Critical Care Medicine, vol. 29, no. 11, pp. 2106–2110, 2001. View at Scopus
  49. J. H. Park, S. H. Kwak, C. W. Jeong, H. B. Bae, and S. J. Kim, “Effect of ulinastatin on cytokine reaction during gastrectomy,” Korean Journal of Anesthesiology, vol. 58, no. 4, pp. 334–337, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Tani, H. Abe, Y. Endo, K. Hanasawa, and M. Kodama, “Effects of a urinary trypsin inhibitor on acute circulatory insufficiency after surgical operation,” The American Journal of Surgery, vol. 175, no. 2, pp. 142–145, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. K. Hamazaki, N. Matsubara, Y. Yunoki, M. Mori, H. Mimura, and K. Orita, “Effects of ulinastatin on polymorphonuclear leukocyte elastase and interleukin 6 levels after hepatectomy,” Clinical Therapeutics, vol. 16, no. 4, pp. 680–685, 1994. View at Scopus
  52. N. Sato, S. Endo, Y. Kimura et al., “Influence of a human protease inhibitor on surgical stress induced immunosuppression,” Digestive Surgery, vol. 19, no. 4, pp. 300–305, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. Y. Huang, K. Xie, J. Zhang, Y. Dang, and Z. Qiong, “Prospective clinical and experimental studies on the cardioprotective effect of ulinastatin following severe burns,” Burns, vol. 34, no. 5, pp. 674–680, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. K. H. Park, K. H. Lee, H. Kim, and S. O. Hwang, “The anti-inflammatory effects of ulinastatin in trauma patients with hemorrhagic shock,” Journal of Korean Medical Science, vol. 25, no. 1, pp. 128–134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. H. Chen, M. Y. He, and Y. M. Li, “Treatment of patients with severe sepsis using Ulinastatin and Thymosin α1: a prospective, randomized, controlled pilot study,” Chinese Medical Journal, vol. 122, no. 8, pp. 883–888, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. K. Inoue, H. Takano, R. Yanagisawa, and T. Yoshikawa, “Protective effects of urinary trypsin inhibitor on systemic inflammatory response induced by lipopolysaccharide,” Journal of Clinical Biochemistry and Nutrition, vol. 43, no. 3, pp. 139–142, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. Fang, P. Xu, C. Gu et al., “Ulinastatin improves pulmonary function in severe burn-induced acute lung injury by attenuating inflammatory response,” Journal of Trauma—Injury, Infection and Critical Care, vol. 71, no. 5, pp. 1297–1304, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. B. Blackwood, M. Murray, A. Chisakuta, C. R. Cardwell, and P. O'Halloran, “Protocolized versus non-protocolized weaning for reducing the duration of invasive mechanical ventilation in critically ill paediatric patients,” Cochrane Database of Systematic Reviews, no. 7, Article ID CD009082, 2013.
  59. C. W. Tang, P. Y. Liu, Y. F. Huang et al., “Ventilator-associated pneumonia after pediatric cardiac surgery in southern Taiwan,” Journal of Microbiology, Immunology and Infection, vol. 42, no. 5, pp. 413–419, 2009. View at Scopus
  60. Y. Lin, X. Zhu, F. Liu et al., “Analysis of risk factors of prolonged intensive care unit stay of critically ill obstetric patients: a 5-year retrospective review in 3 hospitals in Beijing,” Chinese Critical Care Medicine, vol. 23, no. 8, pp. 449–453, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Silberman, D. Bitran, D. Fink, R. Tauber, and O. Merin, “Very prolonged stay in the intensive care unit after cardiac operations: early results and late survival,” Annals of Thoracic Surgery, vol. 96, no. 1, pp. 15–21, 2013. View at Publisher · View at Google Scholar
  62. D. Joskowiak, U. Kappert, K. Matschke, and S. Tugtekin, “Prolonged intensive care unit stay of patients after cardiac surgery: initial clinical results and follow-up,” Thoracic and Cardiovascular Surgeon, vol. 61, no. 8, pp. 701–707, 2013. View at Publisher · View at Google Scholar
  63. R. P. Whitlock, S. Chan, P. J. Devereaux et al., “Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: a meta-analysis of randomized trials,” European Heart Journal, vol. 29, no. 21, pp. 2592–2600, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Y. Jia, L. Wang, Z. G. Mao, J. L. Zhang, and L. Zhang, “Combined myocardial injury markers for diagnosis of acute myocardial infarction,” Sichuan Da Xue Xue Bao Yi Xue Ban, vol. 40, no. 6, pp. 1082–1085, 2009. View at Scopus
  65. J. Dawie, R. Chawla, Y. Worku, and A. Azazh, “Diagnosis of ischemic heart disease using CK-MB, troponin-i and ischemia modified albumin,” Ethiopian Medical Journal, vol. 49, no. 1, pp. 25–33, 2011. View at Scopus
  66. P. Collinson, S. Goodacre, D. Gaze, and A. Gray, “Very early diagnosis of chest pain by point-of-care testing: comparison of the diagnostic efficiency of a panel of cardiac biomarkers compared with troponin measurement alone in the RATPAC trial,” Heart, vol. 98, no. 4, pp. 312–318, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. J. W. Yoo, J. K. Ryu, S. H. Lee et al., “Preventive effects of ulinastatin on post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a prospective, randomized, placebo-controlled trial,” Pancreas, vol. 37, no. 4, pp. 366–370, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. K. Uemura, Y. Murakami, Y. Hayashidani et al., “Randomized clinical trial to assess the efficacy of ulinastatin for postoperative pancreatitis following pancreaticoduodenectomy,” Journal of Surgical Oncology, vol. 98, no. 5, pp. 309–313, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Fujishiro, K. Adachi, T. Imaoka et al., “Ulinastatin shows preventive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study,” Journal of Gastroenterology and Hepatology, vol. 21, no. 6, pp. 1065–1069, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. R. Levin, M. Degrange, C. Del Mazo, E. Tanus, and R. Porcile, “Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass,” Experimental and Clinical Cardiology, vol. 17, no. 3, pp. 125–130, 2012.