Changes Of 12(S)-HETE Levels In Plasma Of Patients With Severe Trauma And Its Clinical Significance

Background:12(S)-Hydroxyeicosatetraenoic acid(12(S)-HETE),as a classic metabolite of arachidonic acid,was shown to play an important role in many diseases including oxidative stress,inflammatory processes,cancer,atherosclerosis,cardiovascular diseases,and so forth.However,the relationship between 12(S)-HETE and severe trauma is unclear.The aim of this study was to determine the utility of plasma 12(S)-HETE as a potentially novel biomarker of mortality and unfavorable outcomes in patients with severe trauma.Methods: This is a prospective observational study of 76 trauma patients recruited from emergency department of two tertiary teaching hospitals in Chongqing.Based on the injury severity score(ISS),traumatic patients were classified into two subgroups: mild trauma patients(ISS<16)and severe trauma patients(ISS?16).Blood samples from trauma patients were taken prospectively in three consecutive time phases from the site of the accident: at hospital admission(the first 48 hours),3-5days and 6-9days,respectively.Basic demographics and clinical characteristics and laboratorydata were recorded at the same time.Admission GCS,ISS,RTS and APACHE ? scores were calculated and the prognosis of trauma patients were recorded.In addition,25 healthy subjects who underwent physical examination at the same time in our hospital were randomly included as the control group.Gender and age were matched with the trauma group.Baseline data and plasma samples of the control group were collected for detection of 12(S)-HETE concentration.Results: In this study,patients with severe trauma had markedly increased admission levels of plasma 12(S)-HETE compared with patients with mild trauma or healthy control subjects(Severe VS.Mild:4.26[1.270-7.400] VS.1.54[0.240-2.713] ng/ml,P =0.005,Severe VS.Control: 4.26[1.270-7.400] VS.0.547[0.125-1.125] ng/ml,P<0.001).The Spearman's correlation analysis showed admission 12(S)-HETE levels were positively correlated with admission ISS(r=0.419,P < 0.001),admission APACHE ?(r=0.499,P < 0.001)and admission hypoxemia(r=0.444,P<0.001)and negatively correlated to admission RTS(r=-0.477,P<0.001),admission TRISS(r=-0.508,P<0.001)and admission GCS(r =-0.366,P = 0.001).Lesion type was divided into three parts(isolated intra-[IL] or extracranial lesions[EL] and combination of both lesion types[IL+EL]).No significant difference of admission 12(S)-HETE concentrations could be observed among these three subgroups(P=0.120).APACHE ? scores at admission,hypoxia at admission,external AIS,headand neck AIS and time from injury to first blood extraction are the factors independently related to admission 12(S)-HETE levels.Binary logistic regression analysis showed that admission 12(S)-HETE concentrations remained independently related to mortality at hospital discharge(HD),which was adjusted with gender,age,severity of trauma,cause of injury and lesion type(P=0.016,Exp(B)=1.499).The area under the receiver operating characteristic(ROC)for admission levels of 12(S)-HETE with mortality at HD was 0.936(95%CI: 0.878-0.993),which has no significant difference compared with the area under the curve(AUC)for APACHE II(AUC=0.923;95%CI:0.842-1.000)or RTS(AUC=0.874;95%CI:0.780-0.968)or TRISS(AUC=0.922;95%CI:0.837-0.971).For12(S)-HETE concentrations,a cut-off value of 6.415ng/ml showed 100%sensitivity and 83.8% specificity for mortality prediction.What's more,it is also kept independently related to dichotomized outcome at HD(assessed by GOS,P=0.001,Exp(B)=1.370)or 6 months after discharge(assessed by GOSE,P=0.015,Exp(B)=1.237),adjusting by means of logistic regression analysis with gender,age,severity of trauma,cause of injury and lesion type,with an AUC of 0.765 or 0.706.Conclusions : We can conclude that admission 12(S)-HETE was elevated in patients with severe trauma and correlated with the severity of systemic injury.Determining plasma 12(S)-HETE concentrations at hospital admission was of great value in identifying severe trauma frommild trauma and predicting in-hospital mortality and short-and long-term outcomes in adult patients with severe trauma.