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 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 investigate the possible role of ulinastatin(UTI) in f lipopolysacccharide (LPS)-induced acute lung injury(ALI).Methods Thirty male SD rats were randomly divided into three groups，ie.a normal control group，a LPS group and a LPS plus UTI group.The rats were injected with 1 mL of normal saline via caudal vein in the control group，with LPS 5 mg/kg via caudal vein in the LPS group，and with UTI 100000 U/kg shortly after injection with LPS in the LPS plus UTI group.The rats were sacrificed 4 h after the injection.Lung wet/dry weight ratio was measured.IL-18 level in serum and lung tissue was determined by ELISA and the expression of NF-κB in lung tissue was determined by immunohistochemistry.Pathological changes of rats’ lung were observed by optical and electron microscope.Results Compared with the control group，IL-18 level in serum and NF-κB expression in lung tissue were significantly higher in the LPS group(Plt;0.01).The IL-8 level was somewhat elevated in the LPS+UTI group but with no significant difference from that in control group was found (Pgt;0.05).The lung inflammation in the LPS+UTI group was milder than that in the LPS rats.Conclusion UTI can alleviate LPS-induced inflammatory reaction and lung injury in rat model.
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.
ObjectiveTo explore the effects of urinastatin(UTI) on microcirculation of extrapancreatic organs in rats with acute necrotizing pancreatitis(ANP). Methods A total of 48 rats were randomized into control group, ANP group and UTI group. The model of ANP was established by uniform injection of 5% sodium taurocholate solution under pancreatic capsule, only injection of normal saline in control group. Then the rats of UTI group were injected with UTI through the femoral vein, the rats of ANP group and control group were injected with normal saline. The blood flow of lung, kidney and distal small intestine was measured by radioactive biomicrosphere technique at 2 h and 6 h after ANP.ResultsCompared with the control group, the blood flow of lung, kidney and intestine was decreased significantly in the ANP group at the 2 h and 6 h after ANP （P＜0.05）, compared with the ANP group, the blood flow was increased significantly in UTI group （P＜0.05）. ConclusionMicrocirculation disorder is an important factor of the extrapancreatic organ damage in ANP, and UTI plays a protective role against microcirculation disorder of the extrapancreatic organ in ANP.
目的 观察乌司他丁对多发伤患者的治疗作用和对肝、肾功能的保护作用。方法 46例多发伤患者随机分为治疗组（23例）和对照组（23例）。治疗组从入院第1天开始，每天静脉点滴乌司他丁10万单位+生理盐水100 ml，每8 h 1次，连续用药6 d，观察患者的临床指标判断疗效，并在入院时以及术后第1、3、5、7天检测谷丙转氨酶（ALT）、谷草转氨酶（AST）、血尿素氮（BUN）、血肌酐（Scr）、血浆肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）以及白细胞介素-8（IL-8）含量的变化。结果 多发伤患者治疗组平均住院时间及平均住ICU时间均低于对照组，差异有显著性意义（P＜0.05）； 治疗组术后血浆ALT、AST、BUN及Scr浓度均明显低于对照组（P＜0.05）； 治疗组术后血浆TNF-α水平逐渐降低，对照组维持在较高水平； IL-2、IL-6及IL-8水平低于对照组（P＜0.05）。结论 乌司他丁对多发伤有治疗作用，并能减轻机体的全身炎症反应程度，有保护和改善肝、肾功能的作用。
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 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.