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.
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.
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 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.
【Abstract】Objective To investigate therapeutic effect and mechanism of hyperbaric oxygen and ulinastatin respectively or combinatively used to treat acute necrotizing pancreatitis (ANP). Methods One hundred and twenty SD rats were divided into 6 groups randomly: group of normal control, group receiving sham operation, group of untreated acute necrotizing pancreatitis (ANP group), group of acute necrotizing pancreatitis treated with hyperbaric oxygen (HBO group), group of acute necrotizing pancreatitis treated with ulinastatin (ULT group), and group of acute necrotizing pancreatitis treated with combined hyperbaric oxygen and ulinastatin (HBO+ULT group). The rat model of acute necrotizing pancreatitis was established according to Aho HJ et al. Concentrations of amylase, TNFα, TXB2 and 6ketoPGF1α in blood were measured through ELISA or radioimmunoassay. Changes of pancreatic histopathology were investigated. SPSS 10.0 was used in statistical analysis. Results The concentrations of amylase, TNFα, TXB2 in the ANPtreated groups were significantly lower than those of ANP group (P＜0.01) except for 6ketoPGF1α and the levels of amylase and TNFα of HBO group were strikingly higher than those in HBO+ULT group. Only the level of AMS was significantly different between ULT group and HBO+ULT group (P＜0.01). Pancreas histopathological scores(HS) and CD8 counts of ANP group were significantly higher than those the other three group, but CD4 counts and CD4/CD8 ratio were on the contrary (P＜0.05). HS of HBO and ULT were strikingly higher than those of HBO+ULT (P＜0.05).Conclusion ①Hyperbaric oxygen or ulinastatin can effectively decrease the blood levels of enzymes and cytokines and improve the pancreatic immunity. ②Hyperbaric oxygen in combination with ulinastatin are more effective than either of them in the treatment of ANP.
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.
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.
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.