Clinical Study On Change Of Serum Cholinesterase And Its Significance In Multiple Trauma Patients

Background:Trauma has become a global health problem.It is the leading cause of death for people younger than 45 years.Acute-phase protein(APP) is a group of proteins synthesized by liver and defined as one whose plasma concentration increases or decreases by at least 25 percent during inflammatory disorders,including albumin (ALB),prealbumin(PAB),transferring(TRF) and C-reactive protein(CRP).They play important regulatory roles in the process of inflammatory response.Serum cholinesterase(ChE) is also synthesized by liver and mainly used for diagnosis of organophosphate poisoning and assessment of liver function in patients with chronic liver diseases.We found that serum ChE activity decreased in multiple trauma patients. However,there is no reported information about the change of serum ChE activity and its significance in multiple trauma patients in literature,and there is no study involved the relationship between serum ChE and inflammatory response.Objective:To study the regularity of dynamic change of serum cholinesterase activity in patients with multiple trauma and the factors which influence serum cholinesterase,then analyze the relationships between serum cholinesterase and severity,prognosis, acute-phase protein,and investigate the clinical significance and possible mechanism of the change of serum cholinesterase.Methods:This is a prospective observation study.81 Patients with multiple trauma admitted to emergency intensive care unit(EICU) from Oct.2005 to Oct.2007 were enrolled.76 healthy subjects were enrolled for control.Patients admitted to EICU within 24h after trauma,with an injury severity score(ISS) more than 16,and older than 18 years were included.And those with chronic liver diseases,exposure to orgnaophosphorus,active tuberculosis,tumor,infection of major organ before trauma or liver injury were excluded.ISS and Acute Physiology and Chronic Health EvaluationⅢ(APACHEⅢ) were assessed at admission,and APACHEⅢwas reassessed at day 3 and 7.Serum ChE,Alanine aminotransferase(ALT),Aspartate aminotransferase(AST),ALB,PAB, TRF,CRP and Hematocrit(HCT) in patients were detected at 1,3 and 7d after trauma. Serum ChE in the control was also detected.Statistics analysis was performed with SPSS 17.0 software for windows(SPSS Inc., Chicago,IL,USA).The change of serum ChE activity of patients was analyzed by one way repeated measures ANOVA,and compared with that of control by t test.We also compared the change of serum ChE between patients with different injury severity and prognosis by one way repeated measures ANOVA and t test or rank sum test.Then the relationships between serum ChE and ISS,APACHEⅢwere analyzed by Pearson correlation analysis.We drew the receiver operating characteristic(ROC) curves of serum ChE to judge prognosis,and determined the best critical points of serum ChE to judge prognosis at 1,3 and 7d after trauma,then compared their areas under the curves by z test.The relationships between serum ChE and AST/ALT,ALB,PAB,TRF,CRP, HCT were analyzed respectively by Pearson correlation analysis,and then the indices correlated significantly with serum ChE activity were filtrated by stepwise linear regression analysis.We then analyzed the change of common acute-phase proteins (ALB,PAB,TRF and CRP) after trauma by one way repeated measures ANOVA and the relationships between those acute-phase proteins and ISS,APACHEⅢrespectively by Pearson correlation analysis,and compared acute-phase proteins between patients with different outcome by t test or rank sum test.The independent risk factors for prognosis in serum ChE and those common acute-phase proteins were filtrated by binary logistic regression analysis.Finally,we drew the ROC curves of those common acute-phase proteins to judge prognosis at 1,3 and 7d after trauma,and compared areas under the curves separately and those of corresponding points of serum ChE by z test.Results:Among 81 patients,57 were male and 24 were female.The average age was 46±18 years,and the average ISS was 34.0±11.9.Serum ChE activities in patients were continuously decreased at day 1,3 and 7 after trauma[(181.8±65.7)U/L,(166.4±66.3 ) U/L,(156.9±63.9 ) U/L],and were significantly lower than those in healthy subjects(315.0±55.0 ) U/L.Serum ChE in patients with ISS≤25 decreased after trauma and resumed rapidly,and that with ISS＞25 decreased continuously.Patients with ISS＜25 had higher serum ChE activity than those with ISS＞25 at 1,3 and 7d after trauma[(206.8±70.0 ) U/L vs.(168.5±59.9 ) U/L,(194.7±64.2 ) U/L vs.(153.2±63.6 ) U/L,(207.7±59.0 ) U/L vs.(128.0±46.4 ) U/L].Serum ChE activities in both non-survivors and survivors decreased significantly at day 1,3 and 7 after trauma, and they were significantly lower in non-survivors than survivors[(141.6±32.2 ) U/L vs.(199.7±69.9 ) U/L,(133.0±36.6 ) U/L vs.(179.6±70.9 ) U/L,(105.1± 9.28 ) U/L vs.(171.3±65.1 ) U/L].Serum ChE was negatively correlated with APACHEⅢand ISS at 1,3 and 7d after trauma.The areas under the ROC curves of serum ChE to judge prognosis were 0.796±0.049,0.761±0.056,0.869±0.044 separately at 1,3 and 7d post trauma,and they were all more than 0.5 significantly. There were no significant differences among them.The best critical points of serum ChE to judge prognosis were 197.0 U/L,152.5U/L,120.0U/L separately at 1,3 and 7d after trauma.Serum ChE was negatively correlated with AST/ALT,and positively correlated with ALB,PAB,TRF and HCT at 1,3 and 7d after trauma,and negatively correlated with CRP at 3 and 7d after trauma.The indices correlated significantly with serum ChE were PAB,TRF and HCT at 1d,and were TRF,ALB,CRP and HCT at 3d,and were PAB,HCT,CRP,TRF and ISS at 7d after trauma.PAB and TRF showed tendency to decrease after trauma,and ALB and CRP showed tendency to increase after trauma.At 1,3 and 7d after trauma,APACHEⅢin patients was negatively correlated with TRF,but negatively correlated with PAB only at 1 and 7d,and negatively correlated with ALB only at 1d,and positively correlated with CRP only at 7d.ISS in patients was negatively correlated with TRF at 1,3 and 7d,but negatively correlated with PAB only at 1 and 7d,and negatively correlated with ALB only at 1 and 7d,and positively correlated with CRP only at 3 and 7d after trauma. Non-survivors had lower TRF than survivors at 1,3 and 7d after trauma[(1.3±0.4)g/L vs.(1.6±0.4)g/L,(1.2±0.3)g/L vs.(1.6±0.6)g/L,(1.1±0.3)g/L vs.(1.5±0.5)g/L], but had lower PAB only at 1 and 7d[(129.0±28.8) mg/L vs.(155.3±39.8) mg/L,(99.6±38.3) mg/L vs.(126.6±45.5) mg/L]and had lower ALB only at 7d[(3.3±0.2) g/dL vs.(3.7±0.6 ) g/dL]after trauma than survivors,and had higher CRP than survivors only at 7d after trauma[(160.2±96.6) mg/L vs.(92.0±78.5)mg/L].Logistic regression analysis showed serum ChE and PAB were independent risk factors to judge prognosis. The ROC curves analysis showed that the areas under curves of ALB at 7d after trauma, PAB at 1 and 7d after trauma,TRF at 1,3 and 7d after trauma and CRP at 7d after trauma were more significantly than 0.5.The areas under curves of ALB at 1,3 and 7d after trauma,PAB at 3 and 7d after trauma,TRF at ld after trauma and CRP at 1 and 7d after trauma were smaller significantly than those of serum ChE at the corresponding points,and there was no significant difference between the areas under curves of those acute-phase proteins and those of serum ChE at the other points.Conclusion:The decrease of serum ChE in patients with multiple trauma is related to the severity of injury and is a good predictor of unfavorable prognosis.Severity of primary injury,decrease of liver synthesis,blood dilution,and inflammatory response are maybe the factors which can influence serum ChE activity to change.Serum ChE may be included as negative APP,and is better than other traditional acute-phase proteins in reflecting injury severity and prognosis in patients with multiple trauma.Therefore serum ChE may be used as a simple and useful index in the treatment with multiple trauma patients.