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 change of the platelet parameter and to study the therapeutic effects of ulinastatin (UTI) on platelet parameter in patients with acute pancreatitis (AP). Methods The data of 80 patients with AP were analyzed retrospectively. All patients were divided into two groups: mild acute pancreatitis (MAP, n=43) and severe acute pancreatitis (SAP, n=37). Thirty people who took the medical examination and whose results were normal were included as control group. The autocytometer was used to test PLT, PCT, MPV and PDW in different periods of SAP. Results On admission, there were no significant differences of PLT, PCT between MAP group and control group (Pgt;0.05), but MPV and PDW in MAP group were higher than those of control group (plt;0.05). Compared with MAP group, PLT and PCT decreased markedly in SAP group (plt;0.01), while MPV and PDW significantly increased (plt;0.05). After 1-week treatment of UTI, PLT and PCT in MAP group didn’t change dramatically, while MPV and PDW decreased significantly (plt;0.05). While in SAP group, PLT and PCT increased significantly (plt;0.05, plt;0.01), and MPV and PDW decreased significantly (plt;0.01, plt;0.05). Compared with conventional treatment， PLT and PCT in MAP group increased significantly in UTI treatment group （plt;0.05）, but there was no statistical difference in terms of MPV and PDW （Pgt;0.05）. However, SAP group showed significant increase of PLT and PCT （plt;0.01， plt;0.05） and decrease of MPV and PDW in UTI treatment group compared with patients treated by conventional methods （plt;0.01）. Conclusion The platelet parameter changes in patients with acute pancreatitis, and the changes of SAP patients are more mark than those of MAP patients. UTI can significantly increase PLT and PCT, and significantly decrease the activity of the platelet. Therefore, UTI may take a role in the treatment and prevention for SAP.
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.
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.
Objective To evaluate the effectiveness and safety of Octreotide combined with Ulinastatin for treating acute pancreatitis in China. Methods The databases such as CBM, VIP, CNKI and WanFang Data were searched to collect randomized controlled trials (RCTs) from the date of their establishment to February 2011, and the relevant references of the included studies were also retrieved. Studie were screened, data were extracted, and the methodological quality was assessed by two reviewers independently. Meta-analyses were conducted by using RevMan 5.1 software. Results A total of 12 studies involving 1 023 participants were included. The results showed that compared with the group of routine therapies and the group of single administration of either Octreotide or Ulinastatin, the experimental group of Octreotide combined with Ulinastatin was superior in the following aspects with singnificant differences: the total effective rate (RR= 0.34, 95%CI 0.23 to 0.52), the remission time of abdominal pain and distention (SMD= –0.89, 95%CI –1.09 to –0.70), the remission time of signs of abdominal tenderness (SMD= –0.95, 95%CI –1.48 to –0.42), the average length of hospital stay (SMD= –1.10, 95%CI –1.58 to –0.63), the time for blood amylase returning to normal (SMD= –1.14, 95%CI –2.10 to –0.17) and the positive cases at the end of treatment (RR= 0.20, 95%CI 0.08 to 0.51), the time for urine amylase returning to normal (SMD= –0.86, 95%CI –1.04 to –0.68) and the positive cases at the end of treatment (RR= 0.27, 95%CI 0.12 to 0.63), the IL-6 level at the end of treatment (SMD= –2.25, 95%CI –4.39 to –0.11), the incidence rate of complications (RR= 0.39, 95%CI 0.28 to 0.55), the required rate of operation (RR= 0.41, 95%CI 0.24 to 0.69), and the mortality (RR= 0.43, 95%CI 0.29 to 0.64). But the experimental group showed a little longer time for blood calcium returning to normal without statistic difference (MD =0.15, 95%CI 0.05 to 0.26).Conclusion According to the domestic evidence, Octreotide combined with Ulinastatin for treating acute pancreatitis is superior to both the routine therapies and the singe administration of either Octreotide or Ulinastatin. It provides a new and prospective therapeutic method for AP. However, this conclusion has to be further verified by high quality, large scale and double blinded RCTs.
Objective To investigate the effects of ulinastatin on Treg/Th17 and immune status in patients with severe sepsis.Methods A total of 80 patients with severe sepsis, who were hospitalized in ICU during October 2011 to July 2012, were randomly divided into a routine group and a ulinastatin group. The patients in the ulinastatin group were intravenously administered 30mg ulinastatin three times per day for 5 days in addition to routine bundle treatment. The expression of Treg, Th17 and HLA-DR were detected on the first day in ICU and 5 days after treatment. 20 healthy individuals served as controls. Results Compared with the control group, the severe sepsis group had overexpression of Treg and Th17 ( P lt;0. 01) , higher ratio of Treg/Th17( P lt;0. 01) , and decreased HLA-DR expression of CD14 monocyte ( P lt; 0. 01) . In the severe sepsis patients, ulinastatin injection reduced the abnormal expression of Treg and Th17 ( P lt; 0. 01) , decreased the ratio of Treg/Th17( P lt; 0. 01) , and improved the expression of HLA-DR ( P lt; 0. 01) more effectively compared with the routine treatment. Ulinastatin also lowered 28-day mortality of the patients with sepsis, but the difference between the ulinastatin group and the routine group was not significant. Conclusions In severe sepsis patients, there were abnormal overexpression of Treg and Th17, imbalance of Treg/Th17, and underexpression of HLA-DR which imply an immune suppression. Ulinastatin can decrease the expression of Treg and Th17, inverses the ratio of Treg/Th17, and improve the expression of HLA-DR, so as to improve the prognosis of severe sepsis patients.
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.
Objective To investigate the effects of high dose ulinastatin with lung protective ventilatory strategies on respiratory function and prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome. Methods Using retrospective analysis, we involved the critical disease patients combined with ALI/ARDS in ICU of The Second Affiliated Hospital of Anhui Medical University. According to whether they were treated with high dose ulinastatin with lung protective ventilatory strategies or not, the patients were divided into the treatment group and the control group. Then pulmonary vascular permeability index (PVPI), extravascular lung water index (EVLWI), oxygenation index, length of SIRS, length of stay in ICU and APACHE Ⅱ score were observed. Statistic analysis was conducted using SPSS 19.0 software. Results A total of 24 patients were included, 13 cases in the treatment group and 11 cases in the control group. After 72 h, PVPI (P=0.016), EVLWI (P=0.045), length of SIRS (P=0.002), length of stay in ICU (P=0.024) and APACHE Ⅱ score (P=0.002) decreased significantly, while oxygenation index (P=0.004) increased significantly in the treatment group compared with the control group. Conclusion High dose ulinastatin with lung protective ventilatory strategies decreased lung capillary permeability, reduced lung blood capillary leakage and extravascular lung water, resulted in the improvement of lung oxygenation function, decreased of length of stay in ICU and the improvement of prognosis in critical disease patients combined with acute lung injury/acute respiratory distress syndrome.
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 observe the level of extravascular lung water index (ELWI) in serious septic patients with ARDS,and the effects of ulinastatin (UTI) on ELWI. MethodsA perspective control study was performed on 48 severe septic patients with ARDS from the emergency department and ICU in Shanghai Changzhen Hospital from January 2010 to December 2012. Pulse indicator continuous cardiac output (PICCO) technique was utilized for measuring ELWI. Meanwhile the oxygenation index (PaO2/FiO2) was detected. The patients were randomized as an UTI group (n=30) and a control group (n=18). Both groups received routine comprehensive treatments,and the UTI group additionally received 30 000 units/kg UTI intravenous drip 4 times a day for continuous 3 days. The PaO2/FiO2,ELWI,Murray lung injury score,APACHEⅡ score,SOFA score and 28-day mortality were determined. ResultsThe APACHE Ⅱ score,Murray and SOFA score had no statistical difference between the UTI group and the control group before treatment (P>0.05),and decreased significantly after 4 and 7 days of treatment in both groups compared with those before treatment (P<0.05). There were varying degrees of PaO2/FiO2 decrease and ELWI increase before treatment in both groups with no significant difference between two groups (P>0.05). After treatment,the PaO2/FiO2 increased and ELWI decreased in both groups,and the UTI group had better PaO2/FiO2 and ELWI than the control group (P<0.05). The difference in 28-day mortality between the UTI group and the control group was statistically significant (10.0% vs. 33.3%,P<0.05). ConclusionsSevere septic patients with ARDS are all complicated with ELWI increase. Routine therapy combined with UTI can decrease ELWI,improve clinical symptoms,and decrease 28-day mortality.