The Effect of Ulinastatin on Postoperative Blood Loss in Patients Undergoing Open Heart Surgery with Cardiopulmonary Bypass

Abstract

This prospective, randomized, double-blind study evaluated the effect of ulinastatin on postoperative blood loss and transfusion requirements of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB) and aortic cross-clamping (ACC). CPB and ACC produce variable systemic inflammatory reactions that are associated with multiorgan dysfunction via leucocytes, especially polymorphonuclear neutrophils (PMNs). PMNs increase blood loss and transfusion requirements. Ulinastatin, a urinary trypsin inhibitor, inhibits PMN activity and reduces the systemic inflammatory response. Patients received either 5000 U/kg ulinastatin or the equivalent volume of normal saline (control group) before ACC. Postoperative blood loss and transfusion requirements were recorded. Duration of intubation and length of stay in the intensive care unit (ICU) were also noted. There were no statistically significant between-group differences in postoperative blood loss and transfusion requirements. Ulinastatin caused a non-significant decrease in duration of intubation. Patients who received ulinastatin had significantly shorter ICU stays than control patients.

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

“…The median sample size of the RCTs was 30 patients (range 15–60). With regard to the types of surgery, one trial assessed only aortic arch replacements [36], four trials only evaluated coronary artery bypass grafts (CABG) [23, 25, 29, 30], five trials reported only valve surgery [26, 28, 33–35], three trials evaluated only repairs of atrial or ventricular septal defects [22, 24, 32], and two trails were mixed in nature [27, 31]. All trials except one [25] were conducted with CPB.…”

“…Because all included studies were RCTs, the Jadad score for all studies was >2 with a mean overall Jadad score of 3.6 ± 1.1. Table 1 shows that twelve of the studies with a Jadad score > 3 were considered high-quality RCTs [20] and that four studies had a Jadad score = 5 [28, 29, 33, 35]. …”

“…Twelve RCTs reported data on early-postoperative complications [22, 24, 26, 27, 29–36] with 6 trials being zero-sum studies which reported that there were no patient suffering postoperative complications due to operation or CPB procedures [22, 26, 30, 31, 33, 34]. In the ulinastatin groups of the remaining 6 RCTs, postoperative complications included 6 cases of myocardial ischemia [27, 29, 35], 1 wound infection [36], 1 reoperation for bleeding [36], 7 respiratory failures [35], and 4 renal failures [35], whilst in the control groups, there were 13 cases of myocardial ischemia [27, 29, 36], 3 patients with excessive bleeding [24, 36], 4 respiratory failures [32, 35], 1 wound infection [36], and 5 renal failures [35, 36] (Table 3).…”

“…Eight RCTs (318 patients) evaluated the effect of ulinastatin on the length of stay in ICU [22, 27–30, 33, 34, 36]. Four of these trials reported a significantly shorter ICU length of stay in the ulinastatin treatment groups [27, 33, 34, 36]; however, meta-analysis using the random effects model showed that the ulinastatin treatment did not significantly decrease the length of stay in ICU (MD = −5.21 h; 95% CI, −11.64 h to 1.21 h; P = 0.11; Cochrane's χ 2 test, P < 0.00001) (Figure 5).…”

“…Eleven RCTs (385 patients) reported extubation time [22, 23, 25, 27–30, 33–36] with 5 of the trials recording a significantly reduced extubation time in the ulinastatin groups (27, 29, 30, 34, 36). Meta-analysis showed that ulinastatin treatment significantly reduced extubation time (MD = −4.18 h; 95% CI, −6.87 h to −1.49 h; P = 0.002; Cochrane's χ 2 test, P < 0.00001) (Figure 6).…”