The Study Of The Risk Factors And The Serum Predictors Of Postoperative Cognitive Dysfunction After Coronary Artery Bypass Grafting

BackgroudPostoperative cognitive dysfunction(POCD)is one of the most common complications after coronary artery bypass grafting(CABG).POCD comprises a wide range of cognitive functions,including longterm memory,abstract generalization ability,mental concentration,and analysis of the ability to apply knowledge,thus affecting quality of life and increasing mortality.The clinical diagnosis of POCD is involving a series of neuropsychological tests.However,there is no unified standard of the choices of tests,main reference points and the duration of follow-up,leading to the different prevalences of POCD in different institutions.Therefore,systemic,effective and simpler diagnostic criteria should be developed for POCD.POCD pathogenesis has not been properly clarified,but it is affirmatory that POCD is a complication of cardial surgery which induced by multiple factor.The advanced age,combined metabolic diseases,operative procedure,anesthesia induction,pre-existing cerebrovascular and systemic vascular disease and systemic inflammation have been considered important risk factors of POCD.However,the risk factors exhibit variability in different studies because of the variant diagnosis of POCD,the diverse analytic procedure and the subjective effect.Therefore,systemic and indepth research should be performed to quest the high correlation with POCD risk factors and provide the basis for the clinical prevention of POCD,and establish an effective behavior evaluation method.Previous data has indicated that cardiac surgery can induce the increase of serum levels of S100B protein,neuron-specific enolase(NSE),glial fibrillary acidic protein(GFAP)and ?-amyloid 42(A?42),which are well known as potential markers of brain injury.Previous reports indicated that the elevation of these serum biochemical markers may be related to the occurrence of POCD,and can act as early diagnosis indexs of POCD.Present studies of the relationship of the level of serum markers and brain injury and prognosis were prevalently,but most of these studies paid much attention to the peak levels of the markers in serum.Moreover,most studies of the relationship between the biomarkers of brain injury and POCD were limited to detect the change of the levels of serum marker in perioperative,the longitudinal and advanced statistical analysis were not used for the research of the relationships and its efficiency of diagnosis.Futhermore,the cross-sectional study about the relationship between biomarkers of brain injury and POCD in different periods after surgery were not performed.Therefore,a systematic study of the relationship between the above-mentioned protein with POCD,and the accuracy and specificity of these markers for prediction of POCD should be expored to guide the clinical early diagnosis and targeted treatment of POCD.ObjectivesTo discuss a systematic,effective and convenient standard for the diagnosis of POCD.To research the risk factors of POCD systematicly and indepth for prevention of the occurrence of POCD in early stage.To study of the proteins of brain damage and POCD,as well as embedded reaserch of the accuracy and specificity of these serum biochemical markers in the prediction of POCD,which are important to the early diagnosis and definitive therapy of POCD in clinical.MethodsThe research included two parts,the study of risk factors of POCD after CABG and the relationship bewteen serum biochemical markers of brain injury and POCD after CABG.To study the risk factors of POCD after CABG.The adults between 40 and 80 years of age and scheduled for CABG in June 2015 to May 2017 in Qianfoshan hospital affiliated Shan Dong,China,were considered to be eligible for this prospective observational study(n=129).All the patients were approved by the Ethics Committee of Qian Fo Shan hospital and signed a consent form.After screening,88 patients were included as the research objects,and the general information were collected.After anaesthesia induction,patients were received On-pump(n=52)or Off-pump(n=36)CABG surgery.The diagnosis of postoperative delirium employed the Confusion Assessment Method for the ICU(CAM-ICU)on the third and seventh postoperative days.The overall assessment of cognition was carried out using the Telephone Interview Cognitive Status(TICS)at 3,7,21st,90th and 180th postoperative days.Patients suffered POCD were definitized before surgery,21 and 180 days after surgery by applying a validated cognitive test battery:Verbal Learning Test(VLT),Stroop Colour Word Test(SCWT),Trail Making Test(TMT)and Symbol Digit Modalities Test(SDMT).The single factor analyses(Chi square tests or t tests)were applied for the evaluation of the risk factors in pre-surgery(age,sex,smoking and drinking,history of myocardial infarction,combined metabolic diseases and pre-existing cerebrovascular and systemic vascular disease,etc.),intra-surgery(time of anesthesia and operation,operative procedure,regional cerebral oxygen saturation and the decrease of hemoglobin),and post-surgery(time of tracheal tube,visual analogue scale/score and systemic inflammatory response syndrome)of POCD.The relationship of the risk factors and POCD was analyzed by multiplicity using logistic regression.To study the relationship bewteen serum biochemical markers of brain injury and POCD after CABG.Serum levels of S100B protein,NSE,GFAP and A?42 were obtained from venous blood samples collected before surgery,after the anaesthetic induction,immediately after surgery and 6 and 24 h postoperatively.S100B protein,NSE and GFAP were measured by ELISA,and NSE was measured using chemiluminescent assay(CLIA).The levels of serum biochemical markers of brain injury in perioperative period were measured,and the difference of serum levels in On-pump and Off-pump patients was studied.The relationship of serum biochemical markers and postoperative delirium and general cognition using TICS was analyzed.The comparison of S100B protein,NSE,GFAP and A?42 serum levels in patients displaying POCD and patients without POCD 21 and 180 days after surgery were performed.The two-way ANOVA was used for analysis of the interaction between time and POCD regarding serum biochemical markers.Receiver operating characteristic(ROC)curve analysis was performed for the prediction of outcome related to biochemical markers and calculation of area under the curve(AUC).ResultsFrom a total of 129 patients,88 were ultimately included in the study analysis.About 46.6%and 31.8%of patients were displayed postoperative delirium at 3 days and 7 days after surgery respectively,as evidenced by the CAM-ICU.Analysis of general cognition using TICS-M showed some cognitive impairment in 69.8,50.7,47.9,36.8 and 41.0%of patients in the third,seventh,21st,90th and 180th postoperative days,respectively.Through the applying cognitive test battery,a composite cognitive index was arbitrarily established by the authors and defined by the occurrence of cognitive impairment in at least two of eight possible cognitive deficits and the "Z-score" comprehensive score was used for the determine of POCD.There were 26.1%of patients had pre-established criteria for POCD diagnosis,and POCD was observed in 22.7%of patients at the 180th postoperative day.There was no statistically significant difference of incidence of POCD after surgery between off-pump and On-pump CABG.The single factor analyses indicated that the age,combined hypertension,pre-existing aortic plaque,carotid artery stenosis,cerebrovascular disease,time of anesthesia and operation,decrease of hemoglobin,and SIRS scores were significantly influence the occurrence of POCD(P<0.05).However,multiplicity analysis demonstrated only pre-existing aortic plaque,carotid artery stenosis,time of anesthesia and SIRS scores had the significant relationship with POCD,and could be the important risk factors of POCD(OR>1,P<0.05).A significant increase in serum levels of S100B protein,NSE,GFAP and A?42 in 24 h after surgery were observsed,which were indicated the injury of brain.The serum levels of S100B protein,NSE and GFAP in patients who received On-pump surgery were significant higher than that received Off-pump surgery,indicated the using of cardiopulmonary bypass(CPB)may increase the brain damage.Analyses of the correlation of postoperative delirium and levels of serum markers were not statistically significant(P>0.05)in all time points.The study failed to demonstrate a solid association between serum NSE and A?42 and POCD(P>0.05),since only a weak association between NSE levels immediately after surgery and TICS-M scores in the seventh and 180th postoperative day(P<0.05)and a small interaction between time and POCD regarding NSE serum levels were found(P=0.033).Nevertheless,S100B protein and GFAP serum levels were significantly increased postoperatively in patients displaying POCD as compared with patients without cognitive dysfunction 21 and 180 days after surgery.Additionally,ROC curve analysis demonstrated that S100B serum levels could significantly predict POCD 21 and 180 days after surgery(AUC>0.5,P<0.05),and GFAP serum levels only could predict POCD 21 days after surgery(AUC>0.5,P<0.05).Of note,although not statistically significant,levels of S100B protein and NSE after anaesthesia induction displayed some negative predictive value for POCD 21 days after surgery.ConclusionThe incidence of POCD 21 days after CABG surgery was 26.1%and the incidence of POCD remained high about 22.7 percent after 6 months.The preexisting aortic plaque,carotid artery stenosis,time of anesthesia and SIRS scores had the significant relationship with POCD,and could be the important risk factors of POCD.CABG can induce the increase in serum levels of S100B protein,NSE,GFAP and A?42 in 24 h after surgery.The using of CPB may increase the brain damage.S100B protein seems to be more useful as a biochemical marker of POCD than GFAP,the efficiency of prediction of POCD using NSE and A?42 was low.