Objective To study the protective effects of ulinastatin( UTI) on lung function after cardiopulmonary bypass( CPB) . Methods 42 Patients, ASA score Ⅱ ～Ⅲ, scheduled for elective cardiac valve replacement, were randomly allocated into three groups, ie. a control group, a low dose UTI group( UTI 8000U/kg) , and a high dose UTI group( UTI 12 000 U/kg) . Inspiratory pressure( PIP) , Plateau pressure ( Pplat) , alveolar-arterial oxygen pressure difference ( AaDO2 ) , static lung compliance ( Cs) and dynamic lung compliance ( Cd) were recorded before operation ( T1 ) and at 1 hour ( T2 ) , 4 hours ( T3 ) , 24 hours ( T4 ) after CPB termination. Results Compared with pre-CPB, postoperative PIP, Pplat and AaDO2 increased, and Cs and Cd decreased significantly in the control group( all P lt; 0. 05) . Compared with the control group at T2 ～T3 , postoperative PIP, Pplat, AaDO2 were significantly lower( P lt;0. 05) , and Cs and Cd were significantly higher in the two UTI groups( P lt;0. 05) . Compared with the low dose UTI group at T2 ～T3 , the PIP, Pplat and AaDO2 were significantly reduced( P lt;0. 05) , and the Cs and Cd were significantly increased in the high dose UTI group( P lt; 0. 05) . Conclusion UTI can alleviate lung injury and improve lung function during valve replacement surgery with CPB in a dose dependent manner.
Abstract: Objective To evaluate the protective effects of Ulinastatin on the peri-operative liver and renal function in patients undergoing cardiac surgery for tetralogy of Fallot (TO F). Methods Thirty-eight patients with TOF were divided into Ulinastatin group and control group according to admission sequence, 19 cases in each group.For Ulinastatin group, intravenous Ulinastatin was given with a dosage of 10 000U /kg at 1h before operation, 1h and 24 h after operation. For control group, no Ulinastatin was given. 10 ml fresh urine and 2 ml blood samples were collected before operation, and postoperative 1h, 10h, 24h, 48h and 72h, respect ively. The liver and renal functions were measured. Fluid intake, urine output, chest drainage, dosage of furosemide, durations of mechanical ventilation and intensive care unit ( ICU ) stay were recorded. Results Neither arrhythmia nor low cardiac output syndrome occurred for both groups. No peri-operative death. Compared with control group, dose of furosemide, period of mechanical ventilation were lower, while urine output was higher in Ulinastat in group; the aberrant climax value of urine pro tein and N-acetylglucosam inidase (NAG) were lower in Ulinastatin group (10h post-operat ively, urinem icroalbum in: 65. 2 ± 58. 3mg/L vs. 71. 8 ±58. 9mg/L ; urine transferrin: 5. 8 ± 3. 6mg/L vs. 7. 4 ± 5. 4mg/L ; urine immunoglobulin G: 26. 9±20. 3mg/L vs. 31. 3±23. 3mg/L ; 1h post-operat ively; urine NAG: 61. 4±81. 6U /L vs. 76.1±48. 5 U /L ; P lt; 0. 05) and maintained in shorter period (P lt; 0. 05) , it returned to baseline value at 48h and 72 h post-operatively. The value of alanine aminotransferase (ALT) significantly increased post-operatively at every time points in control group (P lt; 0. 01) , w hile no obvious change in Ulinastat in group (P gt; 0. 05). The increased value of aspartate aminotransferase (AST ) in Ulinastatin group was significantly lower than that in control group (10h post-operat ively: 144. 4±20. 8U /L vs. 202. 7±74. 1U /L ; P lt; 0. 01). The value of AST returned to baseline value at 48h and 72h post-operat ively. Conclusion U linastatin is an effect ive strategy for protecting peri-operat ive liver and renal function of the patients with tetralogy of Fallot and the clinical application of Ulinastatin is safe and effective.
Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemiareperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirtyone HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16)， 1×105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P＜0.05). On the first postoperative day, the plasma CRP concentration in the UTI group was significantly lower than that in the control group(P＜0.01). The plasma cortisol level in the control group markedly increased compared with the level before operation(P=0.046). However, there was no significant difference in the UTI group between before and after operation. Conclusion Ulinastatin can effectively protect liver from ischemia/reperfusion injury in HCC patients undergoing hepatectomy performed after hepatic inflow occlusion. Also, it can relieve the surgical stress for patients.
ObjectiveTo observe the clinical efficacy of ulinastatin combined with low-dose arginine vasopressin in treating severe pulmonary contusion. MethodSixty patients with severe pulmonary contusion were enrolled in our hospital between April 2012 to June 2014 year. All the patients were randomly divided into three groups. They were respectively defined as a routine treatment group (group A, n=20), an ulinastatin treatment group (group B, n=20), and a combined treatment group (group C, n=20). The respiratory frequency (RR), oxygenation index, partial pressure of carbon dioxide (PaCO2), the change of chest X-ray and the change of serum interleukin-6 (IL-6), IL-8 levels were compared among three groups before and after therapy. ResultThe respiration frequency(RR) and the concentration of serum IL-6, IL-8 levels were decreased in the group C before and after treatment with statistical differences (P=0.000, 0.000, 0.000). PaO2/FiO2 and PaCO2 were significantly increased in the group C before and after treatment (P=0.000, 0.000). After treatment for 7 d, the respiration frequency (RR) and the concentration of serum IL-6, IL-8 of patients in the group B decreased significantly compared with those in the group A (P=0.000, 0.043, 0.000). While PaO2/FiO2, PaCO 2 and the score of chest X-ray increased significantly in the group B (P=0.010, 0.000, 0.000). Compared with those in the group B, RR and the concentration of serum IL-6, IL-8 of patients in the group C decreased significantly (P=0.000, 0.045, 0.000), while PaO2/FiO2, PaCO2 and the score of chest X-ray increased significantly (P=0.043, 0.010, 0.001). ConclusionUlinastatin combined with low-dose arginine vasopressin shows obvious effects in the patients with severe pulmonary contusion. And its therapeutical effects are better than that of the other two treatment options.
Objective To investigate the protective mechanism of ulinastatin（UTI） in pulmonary microvascular endothelial cells （PMVECs） attacked by serum from the patients with severe sepsis. Methods PMVECs were cultured in vitro and randomly divided into 4 groups，ie. a normal group （culture medium with 10% fetal bovine serum，group N），a health group （culture medium with 10% healthy human serum，group H），a patient group （culture medium with 10% human septic shock serum，group S），and a ulinastatin group （culture medium with 1000 U/mL UTI and 10% human septic shock serum，group U）. The proliferation activity of PMVECs was measured by MTT expressed by optical density （OD）. The concentration of TNF-α in supernatant of culture medium was examined by ELISA at 0，1，2，4，6 hours. The expression of NF-κB was examined by immunohistochemistry at 1 hour. Results Compared with group N，the cell proliferation activity of group S decreased significantly，and the cell proliferation activity of group U decreased slightly at each time poi nt. Compared with group N，the cell proliferation activity of group S and group U at 1，4，6 hours were significant different （Plt;0.05 ）. Compared with group S，the cell proliferation activity of group U at 1，2，6 hours increased significantly （Plt;0.05）. Obviously positive expression of NF-κB in PMVECs could be seen in group S，a little positive expression in group S，and no expression in group N and group H. Compared with group N，the TNF-α levels of group S and group U increased significantly at each time point with significant differences （Plt;0.01）. Compared with group S，the TNF-α levels were significantly reduced at each time point in group U （Plt;0.01）. Conclusions UTI can reduce the release of TNF-α by inhibiting NF-κB activation，thus reduce PMVECs injury attacked by serum from severe sepsis patients.
ObjectiveTo systematically review the effects of ulinastatin on postoperative intensive care unit (ICU) stay time and mechanical ventilation time in patients with cardiopulmonary bypass (CPB). MethodsWe 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. ResultsA 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). ConclusionCurrent 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.
Objective To assess the effectiveness and safety of ulinastatin in the treatment of patients with acute pancreatitis. Methods A systematic review of randomized controlled trials (RCT) of ulinastatin for acute pancreatitis was performed. Trials were identified by searching The Cochrane Library (issue 3, 2004), MEDLINE, EMBASE (1984-2004) and Chinese Biological Medicine Database (1978-2004), handsearching, and personal contact with pharmaceutical companies. All RCTs comparing ulinastatin with other interventions were included. Two reviewers assessed the quality of each studiy, and extracted data independently. Statisticsal analysis was performed by using RevMan 4.2. Results Seventeen trials involving 1 199 patients were included. Most included trials were of poor quality. Only two trials reported death at the end of follow-up. Meta-analysis of 6 RCTs showed that the clinical effective rate of Ulinastatin plus basic treatment group was 93.12% (176/189), and was 73.33% in basic treatment group. A statistic significant difference was found between the two groups (Peto OR 4.29, 95%CI 2.49 to 7.37, P＜0.000 01). Compared with basic treatment group, Ulinastatin plus basic treatment group significantly reduced the mean hospitalization (WMD -4.93, 95%CI -7.76 to -2.09, P＜0.000 7). Meta-analysis of 2 RCTs showed that the clinical effective rate of Ulinastatin plus basic treatment group was 86.75% (131/151), and was 80.49% (99/123) in other drugs plus basic treatment group. No statistic significant difference was found between the two groups (Peto OR 1.46, 95%CI 1.76 to 2.80, P＜0.26). One trial found that comparing with control group (23.5±7.5 days), Ulinastatin group (34.0±6.4 days) significantly reduced the mean hospitalization (P＜0.05).The reported severe adverse events of ulinastatin appeared to be rare (7/488, 1.43%). Conclusion Ulinastatin appears to be a modality of safe and effective treatment with a favorable trend, but there is no enough evidence to support this conclusion at present as the published trials with poor quality. More trials with enough sample size and scientifically sound methodology are required.