Effects of Ulinastatin on Postoperative ICU Stay Time and Mechanical Ventilation Time in Patients with Cardiopulmonary Bypass: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 HUAn-min , YUJie , LIUJin ,  DUGui-zhi

Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

DUGui-zhi, Email: du_guizhi@yahoo.com

Keywords：

Urinastatin; Caridiopulmonary bypass; ICU stay time; Mechanical ventilation time; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20150162

Video：

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Objective To systematically review the effects of ulinastatin on postoperative intensive care unit (ICU) stay time and mechanical ventilation time in patients with cardiopulmonary bypass (CPB). Methods We searched databases including MEDLINE, EMbase, Web of Science, The Cochrane Library (Issue 5, 2014), CBM, CNKI, WanFang Data and VIP from inception to May, 2014, to collect randomized controlled trials (RCTs) of ulinastatin for patients with CPB. Meanwhile, conference papers, dissertation and references of included studies were also retrieved manually to collect additional studies. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2.0 software. Results A total of 7 RCTs involving 299 patients were included. The results of meta-analysis showed that:(1) There was no difference between two groups in ICU stay time (MD=-5.40, 95%CI -17.75 to 6.94, P=0.39); (2) The time of mechanical ventilation of the urinastatin group was significantly shorter than that of the saline group (MD=-6.58, 95%CI -10.61 to -2.56, P=0.000 1). The results of subgroup analysis showed that:in the CPB time >100 min subgroup, the time of mechanical ventilation of the urinastatin group was significantly shorter than that of the saline group (MD=-13.85, 95%CI -21.28 to -6.42, P=0.000 3); however, in the CPB time <100 min subgroup, there was no significant difference between two groups in the time of mechanical ventilation (MD=-1.39, 95%CI -3.22 to 0.45, P=0.14). Conclusion Current evidence shows, compared with saline, the administration of urinastatin during CPB can reduce postoperative mechanical ventilation time, but cannot reduce ICU stay time. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.

Citation： HUAn-min, YUJie, LIUJin, DUGui-zhi. Effects of Ulinastatin on Postoperative ICU Stay Time and Mechanical Ventilation Time in Patients with Cardiopulmonary Bypass: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2015, 15(8): 974-979. doi: 10.7507/1672-2531.20150162 Copy

1.	Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery:implications for the anesthesiologist. Anesthesiology, 2002, 97(1):215-252.
2.	Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood, 2005, 105(6):2266-2273.
3.	Massoudy P, Zahler S, Becker BF, et al. Evidence for inflammatory responses of the lungs during coronary artery bypass grafting with cardiopulmonary bypass. Chest, 2001, 119(1):31-36.
4.	Rajakaruna C, Rogers CA, Angelini GD, et al. Risk factors for and economic implications of prolonged ventilation after cardiac surgery. J Thorac Cardiovasc Surg, 2005, 130(5):1270-1277.
5.	De Jonghe B, Bastuji-Garin S, Durand MC, et al. Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit Care Med, 2007, 35(9):2007-2015.
6.	Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest, 2002, 122(6):2115-2121.
7.	Xu L, Ren B, Li M, et al. Ulinastatin suppresses systemic inflammatory response following lung ischemia-reperfusion injury in rats. Transplant Proc, 2008, 40(5):1301-1310.
8.	Cao ZL, Okazaki Y, Naito K, et al. Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart. Ann Thorac Surg, 2000, 69(4):1121-1126.
9.	Nakahama H, Obata K, Sugita M. Ulinastatin ameliorates acute ischemic renal injury in rats. Ren Fail, 1996, 18(6):893-898.
10.	Aihara T, Shiraishi M, Hiroyasu S, et al. Ulinastatin, a protease inhibitor, attenuates hepatic ischemia/reperfusion injury by downregulating TNF-α in the liver. Transplant Proc, 1998, 30(7):3732-3734.
11.	Sugita T, Watarida S, Katsuyama K, et al. Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. J Cardiovasc Surg (Torino), 2002, 43(4):437-440.
12.	Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011. Availabe at:www.Cochrane-hand-book.org.
13.	Xu CE, Zou CW, Zhang MY, et al. 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. J Cardiothorac Vasc Anesth, 2013, 27(3):479-484.
14.	Chen TT, Liu J, Wang G, et al. Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery. Heart Surg Forum, 2013, 16(1):E38-E47.
15.	Oh SY, Kim JC, Choi YS, et al. Effects of ulinastatin treatment on myocardial and renal injury in patients undergoing aortic valve replacement with cardiopulmonary bypass. Korean J Anesthesiol, 2012, 62(2):148-153.
16.	Zhou Q, Wang G, Gao C, et al. Effect of ulinastatin on perioperative inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2010, 35(2):107-110.
17.	赵琦峰, 胡型锑, 杜杰, 等. 乌司他丁和抑肽酶对小儿体外循环炎性反应的保护作用. 温州医学院学报. 2007, 37(5):465-469.
18.	Bingyang J, Jinping L, Mingzheng L, et al. Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response. J Cardiovasc Surg (Torino), 2007, 48(4):497-503.
19.	Nakanishi K, Takeda S, Sakamoto A, et al. Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction. Crit Care Med, 2006, 34(5):1351-1357.
20.	Cao ZL, Okazaki Y, Naito K, et al. Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart. Ann Thorac Surg, 2000, 69(4):1121-1126.
21.	Ito H, Hamano K, Gohra H, et al. Relationship between respiratory distress and cytokine response after cardiopulmonary bypass. Surg Today, 1997, 27(3):220-225.

1. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery:implications for the anesthesiologist. Anesthesiology, 2002, 97(1):215-252.
2. Silliman CC, Ambruso DR, Boshkov LK. Transfusion-related acute lung injury. Blood, 2005, 105(6):2266-2273.
3. Massoudy P, Zahler S, Becker BF, et al. Evidence for inflammatory responses of the lungs during coronary artery bypass grafting with cardiopulmonary bypass. Chest, 2001, 119(1):31-36.
4. Rajakaruna C, Rogers CA, Angelini GD, et al. Risk factors for and economic implications of prolonged ventilation after cardiac surgery. J Thorac Cardiovasc Surg, 2005, 130(5):1270-1277.
5. De Jonghe B, Bastuji-Garin S, Durand MC, et al. Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit Care Med, 2007, 35(9):2007-2015.
6. Rello J, Ollendorf DA, Oster G, et al. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest, 2002, 122(6):2115-2121.
7. Xu L, Ren B, Li M, et al. Ulinastatin suppresses systemic inflammatory response following lung ischemia-reperfusion injury in rats. Transplant Proc, 2008, 40(5):1301-1310.
8. Cao ZL, Okazaki Y, Naito K, et al. Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart. Ann Thorac Surg, 2000, 69(4):1121-1126.
9. Nakahama H, Obata K, Sugita M. Ulinastatin ameliorates acute ischemic renal injury in rats. Ren Fail, 1996, 18(6):893-898.
10. Aihara T, Shiraishi M, Hiroyasu S, et al. Ulinastatin, a protease inhibitor, attenuates hepatic ischemia/reperfusion injury by downregulating TNF-α in the liver. Transplant Proc, 1998, 30(7):3732-3734.
11. Sugita T, Watarida S, Katsuyama K, et al. Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. J Cardiovasc Surg (Torino), 2002, 43(4):437-440.
12. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions Version 5.1.0[updated March 2011]. The Cochrane Collaboration, 2011. Availabe at:www.Cochrane-hand-book.org.
13. Xu CE, Zou CW, Zhang MY, et al. 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. J Cardiothorac Vasc Anesth, 2013, 27(3):479-484.
14. Chen TT, Liu J, Wang G, et al. Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery. Heart Surg Forum, 2013, 16(1):E38-E47.
15. Oh SY, Kim JC, Choi YS, et al. Effects of ulinastatin treatment on myocardial and renal injury in patients undergoing aortic valve replacement with cardiopulmonary bypass. Korean J Anesthesiol, 2012, 62(2):148-153.
16. Zhou Q, Wang G, Gao C, et al. Effect of ulinastatin on perioperative inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2010, 35(2):107-110.
17. 赵琦峰, 胡型锑, 杜杰, 等. 乌司他丁和抑肽酶对小儿体外循环炎性反应的保护作用. 温州医学院学报. 2007, 37(5):465-469.
18. Bingyang J, Jinping L, Mingzheng L, et al. Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response. J Cardiovasc Surg (Torino), 2007, 48(4):497-503.
19. Nakanishi K, Takeda S, Sakamoto A, et al. Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction. Crit Care Med, 2006, 34(5):1351-1357.
20. Cao ZL, Okazaki Y, Naito K, et al. Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart. Ann Thorac Surg, 2000, 69(4):1121-1126.
21. Ito H, Hamano K, Gohra H, et al. Relationship between respiratory distress and cytokine response after cardiopulmonary bypass. Surg Today, 1997, 27(3):220-225.

Chinese Journal of Evidence-Based Medicine

Effects of Ulinastatin on Postoperative ICU Stay Time and Mechanical Ventilation Time in Patients with Cardiopulmonary Bypass: A Systematic Review

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