Effect of Urinary Protease Inhibitor (Ulinastatin) on Cardiopulmonary Bypass: A Meta-Analysis for China and Japan

OBJECTIVES: A meta-analysis was conducted to investigate the effects of ulinastatin treatment on adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB). METHODS: Seven electronic databases were searched for reports of randomized, controlled trials conducted up to February 2014 in which patients undergoing cardiac surgery with CPB were administered ulinastatin in the perioperative period. RESULTS: Fifty-two studies with 2025 patients were retained for analysis. The results showed that the ulinastatin can attenuate the plasma levels of pro-inflammatory cytokines and enhance the anti-inflammatory cytokine levels in patients undergoing cardiac surgery with CPB. Meanwhile, the ulinastatin had a significant beneficial effect on myocardial injury. The mean differences (MD) and 95% confidence intervals (95% CI) of biochemical markers were −63.54 (−79.36, −47.72) for lactate dehydrogenase, −224.99 (−304.83, −145.14) for creatine kinase, −8.75 (−14.23, −3.28) for creatine kinase-MB, and −0.14 (−0.20, −0.09] for troponin I (all P<0.01). However, neither hemodynamics nor cardiac function improved significantly, except that the MD and 95% CI of mean arterial pressure were 2.50 (0.19, 4.80) (P = 0.03). There were no statistically significant differences in the use of inotropes, postoperative bleeding, postoperative complications, the intensive care unit (ICU) stay, and the hospital stay; however, the frequency of auto resuscitation increased significantly (OR 1.98, 95%CI 1.19 to 3.30, P<0.01), the duration of intubation (MD −1.58, 95%CI −2.84 to −0.32, P<0.01) and the duration of mechanical ventilation (MD −3.29, 95%CI −4.41 to −2.17, P<0.01) shortened significantly in patients who were treated with ulinastatin. CONCLUSIONS: Ulinastatin can reduce the plasma levels of pro-inflammatory cytokines and elevate anti-inflammatory cytokine in patients from China and Japan undergoing cardiac surgery with CPB. Ulinastatin treatment may have protective effects on myocardial injury, and can increase the frequency of auto resuscitation, shorten the duration of intubation and mechanical ventilation.