Systematic Study Of Postoperative Delirium After Senile Non-cardiac Surgery With General Anesthesia

BackgroundPostoperative delirium(POD)is an acute confusional state,caused by neuronal activity regulation disorder secondary to systemic disorders.It is characterized by fluctuation of consciousness,inattention,confusion of thinking and change of consciousness level.As a subtype of delirium,it is a common complication of the central nervous system after surgery,which is more common in 1-3 days postoperatively.Delirium,whether in internal or surgica patients,can lead to longer hospital stays,higher case fatality,and higher hospital costs.It may even affect the long-term cognitive function and survival state,and bring serious influence and heavy economic burden to the patients and their families.Although POD is a very common problem,its pathogenesis is still not very clear.Inouye et al.pointed out that delirium is a syndrome,which is caused by the combination of multiple factors related to hospitalization and surgery on the basis of the patient’s susceptibility.These factors include:electrolyte metabolic disorders,history of psychotropic medication,physical activity limitations,malnutrition,dehydration,infection,indwelling catheters,and other iatrogenic factors.Preopera-tive risk factors for POD in elderly patients include age,comorbidities,impaired vision,impaired cognitive function,depressive symptoms,alcoholism,and low functional status.Many factors during and after surgery,such as anesthetic drugs,surgical trauma,postoperative pain and sleep disorders,can also be the cause of delirium.Early prevention for high-risk patients and correctable triggers can reduce the incidence and shorten the duration of POD.Therefore,early prevention is considered the most effective means to reduce the occurrence of delirium.In recent years,several different mechanisms have been proposed to explain the development of POD.It includes neuroinflammation,neurotransmitter disorders,decreased cerebral blood flow,blood-brain barrier destruction and oxidative stress.The cholinergic system is an important neural pathway in the human body.Cerejeira J et al.reported that the decreased activity of ChE can be used as a predictor of POD in the elderly.But a study in 2017 by John M et al.found no difference in postoperative ChE activity between delirium and non-delirium patients.There are few studies on the correlation between ChE activity and POD,and their is no research in China.There are few studies on genetic predisposition of POD at present.Only ApoE,5-HTR and NMDAR have been reported in the literature,and there are some conflicts between these studies.Genetic variations of AChE and BChE do exist in humans,but the absence of functional mutations is only found in the BChE gene.The most common BChE variant is Ala567Thr(A539T),or K variant,which is A single nucleotide polymorphism(rsl 803274)converted from G to A,resulting in the 539th amino acid changing from alanine to threonine,thus reducing enzyme activity by about 33%.Since POD is the result of the combined action of various susceptible and inducing factors,the intervention should be carried out for these risk factors first.According to the "Consensus of Chinese experts on POD prevention of elderly patients" by Chinese society of geriatric medicine in 2016,pain and sleep deprivation are the common causes of POD.It is required to control pain for any patients,and to avoid insufficient or excessive treatment.And try to make sure the patient have enough sleep at night and to avoid sleep deprivation.Section I The risk factors of POD after senile non-cardiac surgery with general anesthesiaObjective:To study the incidence of postoperative delirium in elderly patients with general anesthesia and non-cardiac surgery,and to analyze the risk factors of postoperative delirium in elderly patients.Methods:From January 2014 to January 2016,206 elderly patients transferred to the SICU after non-cardiac surgery under general anesthesia in Shandong Provincial Hospital were included.Preoperative information such as age,gender,alcohol consumption,general comorbidities(hypertension,diabetes,coronary heart disease),and intraoperative information such as surgical type,medication,operation time,blood loss were recorded.Postoperative information included blood pressure(BP),heart rate(HR),Acute Physiological and Chronic Health score(APACHE Ⅱ),postoperative analgesic mode and mechanical ventilation time.The state of mind was assessed three times a day using the RASS,and POD was assessed twice a day with the CAM-ICU.The risk factors of POD were analyzed by SPSS 22.0 software.Results:Among the 206 patients,46 developed delirium,and the incidence of POD was 22.3%.Univariate analysis showed that the occurrence of delirium was correlated with age,APACHE Ⅱ score,and had no significant correlation with gender,history of alcohol consumption,hypertension,diabetes,coronary heart disease,operative time and mechanical ventilation time.Logistic multivariate regression analysis showed that age and APACHE II score were high risk factor for POD after senile non-cardiac surgery.Conclusion:Age and APACHE Ⅱ scores are the risk factors for POD after senile general anesthesia non-cardiac surgery,gender has no significant correlation with POD,and the relationship between the history of basic diseases,alcohol consumption,anesthesia,operation time,mechanical ventilation time and delirium is uncertain,which needs further study to determine.Attention should be paid to these risk factors in order to predict the occurrence and early prevention and treatment of POD.Section II The correlation between ChE activity and delirium after senile non-cardiac surgery with general anesthesiaObjective:To investigate the correlation between serum ChE activity and POD after senile non-cardiac surgery in eldely patients.Methods:The activities of AChE and BChE were detected by using venous blood serum samples collected in section I.To quantify serum ChE concentration,a commercial enzyme immunoassay kit(Nanjing Jiancheng Bioengineering Institute)was used according to the manufacturer’s instructions.Statistical analysis was performed using SPSS 22.0 software package.Univariate analysis and multivariate Logistic regression analysis were used to investigate the relationship between POD and serum ChE activity.Results:Univariate analysis:the serum AChE and BChE activity of the delirium group were significantly lower than that of the non-delirium group(P<0.05).Multivariate Logistic regression analysis was performed with POD in senile general anesthesia as the dependent variable and with the univariate analysis results(age,APACHE Ⅱ score,ChE activity)as the independent variable.The results showed that serum AChE and BChE activity were independent risk factors for POD(P<0.05).Conclusion:The determination of serum AChE and BChE activity is very important for senile non-cardiac surgery in eldely patients.ChE can be used as a predictor of POD.Section III The correlation between the variation of BCHE gene K and delirium after senile non-cardiac surgery with general anesthesiaObjective:To explore the relationship between the variation of BChE gene K and POD after non-cardiac surgery in elderly patients with general anesthesia.Methods:A total of 100 elderly patients with POD after general anesthesia and non-cardiac surgery in Shandong Provincial Hospital from January 2014 to December 2016 were enrolled into the delirium group by the method of continuous enrollment(including the 46 casest from section I and section Ⅱ).Another 108 patients without delirium were enrolled into the non-delirium group.Polymerase chain reaction(PCR)and direct sequencing were used to determine the K variant of BCHE gene,and the correlation between different BCHE genotypes and BChE activity was analyzed.Results:There was no significant difference in BCHE genotype and allele distribution between the delirium group and e non-delirium group(P>0.05).There was no significant difference in the activity group of different genotypes of BChE(P>0.05).Conclusion:Although the activity of BChE in the delirium group was significantly lower than that in the non-delirium group,the decrease in enzyme activity was not due to the variation of BChE gene K.There was no significant correlation between the variation of BCHE gene K and POD after senile non-cardiac surgery.Section IV Effect of dexmedetomidine combined with oxycodone on POD after senile non-cardiac surgery with general anesthesiaObjective:To explore the effects of dexmedetomidine and dexmedetomidine combined with oxycodone hydrochloride on POD after senile non-cardiac surgery.Methods:A total of 212 elderly patients were selected from March 2017 to August 2017 who were transferred to SICU after general anesthesia in Shandong Provincial Hospital.Forty patients were excluded or withdrawn from the trial,and 172 patients were finally included in the statistical analysis,including 58 patients in the dexmedetomidine group(group A),59 patients in the dexmedetomidine combined with oxycodone hydrochloride group(group B),and 55 patients in the traditional treatment group(group C).In group A,dexmedetomidine was given for night-time assisted sleep.The application plan was as follows:one hour of initial load dosage:1.0 g/kg·h-1,and adjust the maintenance dosage to maintain the sedation depth at RASS score of-2-+1.Group B was given dexmedetomidine 0.5g/kg·h-1 for one hour,and then the dosage was adjusted according to the sedative effect.Meanwhile,analgesia management was strengthened,and its resting and sports digital pain score(NRS)were strictly controlled for<4.The analgesic drug was oxycodone hydrochloride injection,and the application method was as follows:the loading dosage was 2-3mg and the maintenance dosage 1-2mg/h according to the NRS score.In group C,no other treatment was given except the self-controlled analgesia pump.Main observa-tion indexes:the incidence and duration of delirium in patients were assessed twice a day using CAM-ICU method until 72 hours after surgery.Secondary observation indexes:postoperative pain,NRS score,sedation score(RASS),blood pressure,heart rate,SpO2 from the first to the third day after surgery.Patients’ overall satisfaction with postoperative analgesia effect was recorded,which was divided into four grades:very satisfied,satisfied,dissatisfied and very dissatisfied,among which,very satisfied and satisfied were generally defined as satisfied,dissatisfied and very dissatisfied were generally defined as dissatisfied.Meanwhile,the incidence of adverse reactions such as nausea,vomiting,chills,bradycardia,hypotension and respiratory depression were recorded.Results:There was no significant differences in gender,age,height,weight,operation time and blood loss among the three groups(P>0.05).In group A,eight patients developed delirium(13.8%)with an average duration of 0.8±0.3 d.In group B,six patients developed delirium(10.2%)with an average duration of 0.77±0.4 d.In group C,thirteen patients developed delirium(23.6%)with an average duration of 2.0±0.9 d.Compared with group C,the incidence and duration of delirium in group A and group B were significantly reduced(P<0.05),while the difference between group A and group B was not statistically significant(P>0.05).Six patients in groupC withdrew from the observation because of moderate to severe pain required the use of analgesic drugs.The NRS scores of the patients in group A and group B were significantly lower than that of group C,and the differences were statistically significant(P<0.05),indicating that the pain control effect was significantly better than that of the traditional group.There was no significant difference in NRS scores between group A and group B(P>0.05).Overall satisfaction with postoperative analgesia was significantly better in group A and group B than in group C(P<0.05).No significant difference was found between group A and group B(P>0.05),but the number of very satisfaction in group B was higher than that in group A(34 VS 48,P<0.05).Two patients in group A withdrew from observation due to the withdrawal of dexmedetomidine because of hypotension.Four patients in group A had decreased BP,three had bradycardia,and one in group B and one in group C had bradycardia,but all the patients were relieved by drug dosage reduction or fluid supplementation.There was no statistically significant difference between the three groups in adverse reactions such as nausea,vomiting,shiver and respiratory depression(P>0.05).Conclusion:Using dexmedetomidine combined with oxycodone hydrochloride,the incidence and duration of delirium after non-cardiac surgery under general anesthesia can be reduced.Short-term and low-dose oxycodone hydrochloride won’t increase the incidence of POD.Compared with the application of dexmedetomidine alone,the combination of low-dose dexmedetomidine with oxycodone hydrochloride resulted in fewer adverse reactions and complications,which is worthy to be popularized in the clinical application of postoperative analgesic sedation.