Does intraoperative ulinastatin improve postoperative clinical outcomes in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials

Abstract

Introduction: The systematic meta-analysis of randomized controlled trials (RCTs) evaluated the effects of intraoperative ulinastatin on early-postoperative recovery in patients undergoing cardiac surgery.

Methods: RCTs comparing intraoperative ulinastatin with placebo in cardiac surgery were searched through PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital mortality, postoperative complication rate, length of stay in intensive care unit, and extubation time. The physiological and biochemical parameters illustrating postoperative cardiac and pulmonary function as well as inflammation response were considered as secondary endpoints.

Results: Fifteen RCTs (509 patients) met the inclusion criteria. Ulinastatin did not affect hospital mortality, postoperative complication rate, or ICU length of stay but reduced extubation time. Ulinastatin also increased the oxygenation index on postoperative day 1 and reduced the plasma level of cardiac troponin-I. Additionally, ulinastatin inhibited the increased level of tumor necrosis factor-alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8 associated with cardiac surgery.

Conclusion: Ulinastatin may be of value for the inhibition of postoperative increased inflammatory agents and most likely provided pulmonary protective effects in cardiac surgery. However, larger adequately powered RCTs are required to define the clinical effect of ulinastatin on postoperative outcomes in cardiac surgery.

Figure 1

Process of trial selection.

Figure 2

Risk of bias summary.

Figure 3

Impact of ulinastatin on hospital mortality. M-H = Mantel-Haenszel, 95% CI = 95% confidence intervals, Chi²= Chi-square test, df = degrees of freedom, I ² = I ² index (quantify the degree of heterogeneity), and Z = Z test.

Figure 4

Impact of ulinastatin on early-complication rate. M-H = Mantel-Haenszel, 95% CI = 95% confidence intervals, Chi²= Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 5

Impact of ulinastatin on length of stay in ICU (hours). ICU = intensive care unit, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 6

Impact of ulinastatin on extubation time (hours). IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 7

Impact of ulinastatin on postoperative oxygenation index (OI); IV = inverse variance, 95% CI = 95% confidence intervals, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 8

Impact of ulinastatin on postoperative cardiac index (CI). IV = inverse variance, 95% CI = 95% confidence intervals, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 9

Impact of ulinastatin on the level of cTnI on postoperative first day (POD1). cTnI = cardiac troponin-I, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 10

Impact of ulinastatin on the level of CKMB on postoperative first day (POD1). CKMB = creatine kinase MB isoenzyme, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 11

Impact of ulinastatin on the level of TNF-α on postoperative first day (POD1). TNF-α = tumor necrosis factor-alpha, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 12

Impact of ulinastatin on the level of PMNE on postoperative first day (POD1). PMNE = polymorphonuclear neutrophil elastase, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 13

Impact of ulinastatin on the level of IL-6 on postoperative first day (POD1). IL-6 = interleukin-6, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² = Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.

Figure 14

Impact of ulinastatin on the level of IL-8 on postoperative first day (POD1). IL-8 = interleukin-8, IV = inverse variance, 95% CI = 95% confidence intervals, Tau² =Tau-squared test, Chi² = Chi-square test, df = degrees of freedom, I ² = I ² index, and Z = Z test.