Evaluation On The Efficacy And Safety Of Ulinastain In Patients With Severe Burns

Objective:To observe and evaluate the efficacy and safety of ulinastatin(UTI)in patients with severe burns by using the real-world data derived from the Chinese Hospital Pharmacovigilance System(CHPS),and to provide the real-world evidence for clinical application value of ulinastatin in the field of severe burns.Methods:1.Literature research.Using"ulinastatin","severe burn","efficacy"and"safety"as the key words,the relevant Chinese documents were retrieved from the CNKI and Wanfang Database;and using"ulinastatin","burn","efficacy","safety"as the key words,the related English literatures were retrieved from Pubmed,Elsevier and other foreign databases,and the main application of ulinastatin in burn field was analyzed and summarized.2.Case-control analysis.Based on the CHPS platform,the patients with severe burns in G hospital from January 2015 to June 2018 were selected by single-center retrospective analysis.The patients were divided into the ulinastatin group(UTI group)and the routine treatment group(routine group).The routine emergency treatment was used in the routine group,while the UTI group was treated with ulinastatin(two hundred thousand U/time intravenous drip,3 times a day,for 7 days)on the basis of the routine group.The general conditions(total area of burn,admission time,age,sex,previous history,vital signs,etc.)were recorded in the two groups.The blood routine(WBC,PLT,NEUT%),LAC concentration,coagulation four items(APTT,PT,TT,FIB),related tissue and organ function index(CK-MB,SCr,BUN,TBIL)and clinical outcome were observed before and 3 days after treatment.The total length of hospital stay,the occurrence of complications and death during drug use was recorded.A week after the withdrawal of the drug,the abnormal conditions of the laboratory index values in the UTI group were compared with those in the routine group at the same time.The results were compared with those of the routine group by Chi-square test.The data were analyzed by statistical software SPSS 22.0.χ~2 test(expressed in%)was used to count data and t test(x±s)was used to measure data.P<0.05 was considered to be statistically significant.Efficacy evaluation:the changes in the blood biochemical indexes(platelet count,white blood cell count,neutrophil ratio,blood lactic acid),cardiac function index(creatine kinase isoenzyme),liver function index(total bilirubin),renal function indexes(serum creatinine,urea nitrogen),four indexes of coagulation(prothrombin time,activated partial thromboplastin time,thrombin time,fibrinogen),and the occurrence of complications and mortality were compared between the two groups on admission and at different time points after admission(3 days,7 days after admission),and on the basis of which the efficacy was evaluatd.Safety evaluation:(1)Clinical safety evaluation:the UTI safety was comprehensive monitored and evaluated through the combination of spontaneous report of patients and direct observation by the attending physician.(2)Safety evaluation of important indexes:the abnormal values of important laboratory indexes,including the blood routine test indexes(WBC,PLT,NEUT%),tissue perfusion indexes(LAC),liver function index(TBIL),cardiac function index(CK-MB),renal function index(SCr,BUN)and coagulation function biomarkers(APTT,PT,TT,FIB),were compared between the two groups one week after drug withdrawal to evaluate the safety of UTI.Results:Based on CHPS,98 cases with severe burns were included,including 43 cases in the UTI group and 55 cases in the routine group.(1)Baseline data:the basic data of severe burn cases in UTI group and routine group were sex,age,height,weight,previous history,complication,as well as the time of admission after injury,the total area of burn,vital signs,blood routine,major organ function test etc.There was no significant difference in baseline data(P>0.05).(2)Changes of general indexes:after 3 days of routine treatment,the levels of LAC,WBC,PLT,NEUT%in both groups decreased and the level of PLT in UTI group was higher than that in routine group at the same time(P<0.05).It was suggested that microcirculation and inflammation were improved(P<0.05).After 7 days of treatment,the levels of LAC,WBC,NEUT%in the UTI group were significantly lower than that in routine group at the same time(P<0.05).(3)Changes of coagulation indexes:FIB decreased after 7 days of treatment in the routine group(P<0.05),while FIB in the UTI group decreased at 3 days after treatment,and the effect is improved more obviously at 7 days.There was no significant difference in TT before and after treatment,but it remained within the normal range,and there were significant differences in the indexes of APTT,PT between the two groups at the same time after 7 days of treatment(P<0.05).(4)Changes of main organ function indexes:the indexes of heart,liver and kidney,such as BUN,SCr,TBIL and CK-MB,were higher than the normal values before treatment in the two groups after admission,and there was no statistical difference between the two groups(P>0.05).The levels of CK-MB,BUN,SCr in the two groups decreased after 3 days of treatment(P<0.05),but there was no significant difference between the two groups in the level of TBIL(P>0.05).After 7 days of treatment,the levels of SCr,BUN,TBIL,CK-MB in UTI group were lower than that in routine group(P<0.05),that is,the indexes of organ function in UTI group were better than that in routine group(P<0.05).Blood biochemical test(LAC,WBC,NEUT%,PLT),liver function(TBIL),renal function(BUN)were measured in UTI group and routine group at the same time after the withdrawal of UTI for one week.There were no significant differences between the abnormal values of SCr and cardiac function(CK-MB)by Chi-square test(P>0.05).(5)Incidence of complications:the incidences of sepsis and MODS in UTI group were significantly lower than that in routine group[(χ~2=5.153,P=0.020<0.05),(χ~2=5.385,P=0.018<0.05)].(6)Comparison of the total hospitalization time:the length of stay in UTI group was(37.23±13.09)days,which was significantly shorter than that in the routine group(48.89±24.06 days),and the difference was statistically significant(t=9.735,P<0.05).(7)Clinical outcome:there was no significant difference between UTI group and routine group(χ~2=1.292,P=0.439>0.05),(χ~2=1.952,P=0.190>0.05).The results showed that the mortality rate of UTI group was higher than that of routine group(χ~2=1.292,P=0.439>0.05),(χ~2=1.952,P=0.190>0.05),and there was no significant difference between the two groups(P<0.05).In addition,there was no significant difference in the prognosis between the UTI group and the routine group(P>0.05),but on the whole,the UTI group had a higher rate of good prognosis(74.42%vs63.64%).Conclusion:(1)Efficacy evaluation:On the basis of routine treatment,ulinastatin can improve the microcirculation,reduce the injury of main organs such as myocardium,liver and kidney,reduce the complications of ARDS,wound sepsis,MODS and so on,shorten the total hospitalization time and improve the prognosis in the patients with severe burns.(2)Safety evaluation:Compared with the routine group,there were no adverse reactions or adverse events during the treatment of patients with severe burns in UTI group,indicating that ulinastatin is safe and worthy of clinical application in the patients with severe burns.