A Prospective Clinical Randomized Controlled Trial About Application Of Continuous Blood Purification During The Early-Stage After Severe Burn Injury

Background: Although the survival rate of severe burn injury has significantly increased along with advances in clinical treatment strategies and measures,the mortality of severe burn injury remains high,which is an obstacle for further development of burn treatment.Effective treatments in the early stage play a crucial role in successful management of severe burn,deciding the mordilities of post-burn complications and the final outcomes.The intrinsic of burn injury is ischemia-hypoxia damage,mainly characterized by uncontrolled inflammation reaction due to excessive stress response.Hypoxia-ischemia,stress response and inflammatory reaction form a vicious circle which lays a pathophysiological basis for the development of complications post severe burn injury,but lacking of effective targeted therapy for it till now.Previous studies tried to mediate post-burn stress response by application of high dose of Glucocorticoid,protease inhibitors and proprietary Chinese medicine,while the efficacy was far from satisfactory.The inflammatory response has been confirmed to be the result of excessive secretion of various inflammatory factors such as TNF-?,IL-1,IL-6,endotoxin,etc.Aiming at the nature of Systemic Inflammatory Response Syndrome(SIRS),many clinical researchers attempted to attenuate post-burn stress response by deactivating and antagonizing the inflammatory mediators,but no satisfying results were achieved either.In recent years,more and more studies have demonstrated that extracorporal blood purification can effectively mediate the stress response and inflammatory reaction by eliminating inflammatory mediators.Besides it can maintain a stable internal environment by adjusting the balance of acid-base,water and electrolyte.What's more,it help regulate immune function.Therefore,we postulated that blood purification was hopeful to be an effective measurement in early treatments for severe burn injury,so the efficacy of continuous blood purification(CBP)in the early stage after severe burn injury was investigated in this studyObjective: To provide clinical evidences for the application of CBP by preliminary observation and assessment of the feasibility and therapeutic efficacy of CBP as an early treatment for severe burn injury.Method: Forty-one patients suffered more than 50%TBSA burn admitted to our department from January 2013 to July 2015,conforming to the study criteria,were divided into conventional treatment group(CT,n=21)and blood purification group(BP,n=20)according to the random number table.Patients in group CT received conventional treatments,while patients in group BP were given additional continuous blood purification in the mode of venous-venous hemodiafiltration up to 72 hour post burn injury(PBH).During the 1st,2nd,3rd day post burn injury(PBD),the vital signs,volume of fluid input and urine output of patients were observed and recorded;femoral artery blood was drawn to determine lactate,bicarbonate and base excess,and the oxygen index was calculated.At PBH 12,24,48 and 72,femoral blood was drawn to determine white blood cell count(WBC),platelet count(PLT),the ratio of neutrophils(Neu%),creatine kinase-MB(CK-MB),creatine kinase(CK),lactic dehydrogenase(LDH),glutamic-oxaloacetic transaminase(AST),alanine aminatransfrase(ALT),creatinine(Scr),urea nitrogen(BUN)and blood Glucose(Glu)(the ratio of AST to ALT was calculated);five milliliters of femoral venous blood were collected before and after treatment,centrifuged after quiescence,took the upper serum,saved it at low temperature(-80?)for late detection of TNF-?(tumor necrosis factor-?),IL-1?(Interleukin-1?),IL-6(Interleukin-6),IL-10(Interleukin-10),cortisol,procalcitonin(PCT),cardiac troponin T(c TnT)and diamine oxidase(DAO).The morbidity of infection,sepsis and multiple organ dysfunction syndrome(MODS),twenty-eight-day mortality,final mortality of patients were recorded during 2 months post burn.Data were analyzed by SPSS version 16.Chi-square test,analysis of variance for repeated measurement,t test and Wilcoxon test were conducted accordingly,and the P values were adjusted with Bonferroni correction.Results:1.Forty-one patients completed the study without exclusion.2.Vital signs,the volume fluid input and urine output: There were no statistical differences about vital signs,volume of fluid input and urine output of patients between the two groups on PBD 1,2,3(P> 0.05).3.Blood routine indexes: The three indexes of WBC?PLT and Neu% at PBH 12,24,48 and 72 showed no significant differences between group CT and BP,especially PLT(P> 0.05).4.Scr and BUN: Compared with group CT,the levels of Scr at PBH 48 and BUN at PBH 24,48,72 in group BP were significantly lower(P<0.05 or 0.01),while at other time points the two indexes between the two groups had no statistical differences(P> 0.05).5.Blood Glucose(Glu):The levels of Glu in group BP were(7.9±2.0),(6.7±0.9)and(6.9±1.8)mmol/L,respectively,which were much lower than(10.1±3.8),(9.1±2.4)and(8.8±4.1)in group CT at PBH 24,48 and 72(P<0.05 or 0.01),while the levels of GLU in the two groups at PBH 12 were close.6.Oxygenation Index(OI): On BPD 3,the mean value of OI in group BP was 370±98,which is obviously higher than 305±81 in group CT(P<0.05),while on BPD 1 and 2,the value of OI between the two groups had no statistical differences(P> 0.05).7.Lac: Compared with those in group CT,the levels of Lac in group BP declined significantly on PBD 2 and 3(P<0.05),while no difference was shown on BPD 1 between the two groups(P> 0.05).8.Myocardial zymogram: Except for that CK-MB in group BP at PBH 24,48 and 72 with mean values(81±43),(55±34),(58±40)U/L were significantly lower than(179±184),(124±71),(103±57)U/L in group CT(P<0.05 or 0.01)and the mean value of CK-MB in group BP at PBH 12 was close to that in group CT(P> 0.05),the other two myocardial enzymes CK and LDH had no statistical differences between two groups at all time points(P> 0.05).9.Inflammatory cytokines TNF-a,IL-1?,IL-6,IL-10: Before treatment,the levels of all the four cytokines were close in group CT and BP(P> 0.05),while they all sharply declined after treatment(PBH 72)in group BP compared with those in group CT(P<0.05 or 0.01)except for TNF-a which still showed no obvious difference between the two groups(P> 0.05).10.PCT and cortisol: Neither of PCT and cortisol showed statistical differences between the two groups before treatment(P> 0.05),while after treatment both of them significantly declined in group BP compared with those in group CT(P<0.05).11.c TnT and DAO: The levels of cTn T and DAO in group CT and BP were close before treatment(P> 0.05),while after treatment they both significantly declined in group BP compared with those in group CT(P<0.05 or 0.01).12.Bicarbonnate and base excess: Compared with those in group CT,levels of Bicarbonnate and base excess in group BP declined significantly on PBD 3(P<0.05),while no differences were shown on BPD 1 and 2 between the two groups(P> 0.05).13.Hepatic function indexes: AST,ALT and the ratio AST/ALT showed no obvious differences between the two groups at PBH 12,24,48 and 72.14.Post-burn complications and mortality: During two months post burn injury,the mordilities of sepsis and MODS,twenty-eight-day mortality,final mortality in group BP were lower than those in group CT but without significance,however,the rate of infection was significantly lower in group BP than that in group CT.(P<0.05).Conclusion:In addition to conventional treatments,treating patients with continuous blood purification(CBP)in the early stage(within 24 h post burn)post severe burn injury was observed to be safe and feasible,based on the fact that patients' vital signs were stable,volume of fluid input and urine output and PLT were not affected.Besides,CBP showed therapeutic value for severe burn injury in the study as following: CBP kept internal environment stable and relieved systemic edema especially pneumonedema,which help improve respiratory function;CBP improved many biochemical indicators by protecting vital viscera;CBP could treat stress hyperglycemia,which is good for burn wound healing and energy metabolism;CBP could lower the morbidity of post-burn complications and mortality especially infection rate.In our study we found that treating with continous blood purification in the early stage after severe burn injury was safe and feasible and had therapeutucal value.