| BackgroundSepsis is a complex syndrome caused by an uncontrolled systemic inflammatory response of infectious origin , characterized by multiple manifestations and which can result in dysfunction or failure of one or more organ and even death. Severe sepsis refers to sepsis is complicated by organ dysfunction. Severe sepsis is now considered to be the most common cause of death in non-coronary critical care units. Approximately 500, 000 persons suffered with sepsis and more than 200,000 die annually in the United States. Surviving Sepsis Campaign, an international effort to increase awareness and improve survival in severe sepsis, was initiated by ESICM, ISF, SCCM in October 2002 with the Barcelona Declaration.Although a large variety of mediators have been implicated in the development of sepsis syndrome, a rapidly growing body of experimental evidence suggest that cytokines family are decisive factors in determining the pathophysiology of sepsis syndrome. When stimulated by inflammatory material, cytokines such as tumor necrosis factor alpha (TNF-a), interleukin-l(IL-l), interleukin-4(IL-4), interleukin-6(IL-6) and interleukin-10(IL-lO) released by monocytes and macrophages and playcritical roles in the initiation and perpetuation of sepsis syndrome. If the balance between pro-inflammatory and anti- inflammatory immune mechanism is broken by severe infections , traumas or operations, severe sepsis would take place. And at the same time, polymorphonuclear leukocyte elastase (PMNE), protease, oxygen free radical released by actived neutrophils and macrophages also leads to tissue damage and organ dysfunction .Ulinastatin, a urinal typsin protease inhibitor, can inhibit macrophage and neutrophils releasing pro-inflammatory cytokines, but promote to release anti-inflammatory cytokines. So the balance between pro-inflammatory and anti- inflammatory may restore again. It can also inhibit polymorphonuclear leukocyte elastase and many other kinds of protease, and clear oxygen free radical. So it can protect organs and reduce the mortality of severe sepsis patients.ObjectiveTo evaluate the efficacy and safety of ulinastatin in treating patients with severe sepsis and investigate some cytokines in those patients to explore the mechanisms of the drug.MethodsFrom September 2003 to February 2004, we conducted a randomized, placebo-controlled trail of intravenous ulinastatin in patients with severe sepsis. 56 patients who had severe sepsis were randomly divided into ulinastatin treatment group (group U) and control group (group C). Patients in the group U received ulinastatin 200,000 units intravenous twice a day for 5 days , while those who in the group C received equal quantity of normal saline as placebo. At the time of admission and 24 ,48 ,120 hours after initiation of treatment,serum levels of procalcitonin were recorded and APACHEII scores were made. At the same time, 5mL arterial blood was drawn from right radial artery of each patient.The levels of serum tumor necrosis factor-a (TNF-a), interleukin-1 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), interleukin-10 (IL-10) were determined by using enzyme-linked immunosorbent assay technique (ELISA). The 28-day all-caused mortality was contrasted between the two groups.ResultsThe patients ' serum levels of procalcitonin and APACHEII scores in both groups had no difference significantly before treatment. They were all decreased during the treatment . Those indexes of group U was lower than that of group C significantly (P<0. 05) on the 5th day after treatment . The 28-day all-cause mortality rate was 28. 57%(8/28) in group U, while the mortality rate in group C was 57. 14%(16/28), and there was a significant difference between the two groups (P<0. 05). No severe adverse effect of ulinastatin was observed during treatment. The concentration of TNF-a in patients of group U.decreased more obviously than that in group C 48 hours after treatment. So did the IL-6. However, the blood concentration of IL-10 increased more obviously in...
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