Effect Of Sedation Depth On Postoperative Delirium In Elderly Patients Undergoing Hip Fracture Surgery With Nerve Block

BackgroundPostoperative Delirium(POD)is a kind of Perioperative Neurocognitive Disorders(PND)which occurs within 7 days after surgery or before discharge.It is an acute disorder of attention and cognition marked by sudden onset,fluctuating course,inattention,and an abnormal level of consciousness at times.POD tends to occur in elderly patients and is one of the major postoperative complications of surgical patients.The incidence varies with the type of surgery,and the prevalence of POD in hip fracture patients is as high as 50～62%.POD can lead to prolonged duration of hospital and increased hospital costs.Without diagnosis and treatment timely,it is associated with Neurocognitve Disorders(NCD),loss of self-care ability,increased incidence of postoperative complications and mortality,and heavy burden to patients’ families and society.There is still little effective measure for the treatment of POD,most clinical measures are controlling the symptom,so eliminating the delirium risk factors to prevent delirium is the most effective means.Surgery and anesthesia are the most interventional factors in perioperative period.People have kept exploring the effects of anesthesia on brain function of patients,especially elderly patients for long time.There are many studies in this area,but the conclusions are not consistent.Meta-analyses have found that general anesthesia and the general anesthetic drugs do not affect the occurrence of postoperative delirium,but many studies have suggested that excessive anesthesia(BIS<40)is a risk factor for POD.Therefore,it is necessary to design a clinical trial to determine the anesthesia depth as well as sedation depth in regional block on POD in elderly patients with high risk of POD,such as elderly patients with trauma,so as to provide evidence for the effective prevention of POD in perioperative period.Advanced age is known to be an independent risk factor for POD.Our country has already been in an aged society,Chinese elderly population aged over 65 is 158 million,accounting for 11.4%of the population according to the Development of Social Service Statistical Bulletin in 201 7.The decade incidence of hip fracture of 75-84 years old elderly people is 6.08%.Since the incidence of postoperative delirium in elderly patients with hip fracture surgery is as high as 62%,postoperative delirium affects the outcome of these patients seriously.Due to the decline of organ function,poor cardiopulmonary function reserve and more concurrent systemic diseases,there are high perioperative risk in elderly patients.Appropriate choice of anesthesia and reasonable application of anesthetic drugs are beneficial to perioperative safety and postoperative recovery.There is evidence that regional block anesthesia including intraspinal and plexus block anesthesia can improve patients’ outcomes and reduce postoperative complications.With the popularization of ultrasonic technology and the application of nerve stimulation localization technology,nerve block is more and more applied to elderly orthopedic surgery patients.Nerve block can provide perfect intraoperative analgesia and satisfactory postoperative analgesia for hip patients.In addition to the complete analgesia,sedation in regional block anesthesia for elderly patients is indispensable.Appropriate sedation level can reduce the body’s stress response and psychological trauma,and improve the comfort and satisfaction of patients during the perioperative period.However,deep sedation and excessive sedation drugs will affect the respiratory and hemodynamic stability of patients,and may cause damage to the fragile brain function of elderly patients.At present,the main methods for judging sedation depth include the Observer’s Assessment of Alertness/Sedation(OAA/s)and Bispectral Index(BIS).OAA/S can judge the sedation depth of patients by their response to commands and tactile sensations,without the need for special equipments and any consumables.In addition,OAA/S score is closely related to clinical manifestations,and varies with the concentration of sedative drugs,with high accuracy and good repeatability.However,OAA/S could not offer continuous score,and repeated assessment of OAA/S would affect the continuity of intraoperative sedation of patients,resulting in poor intraoperative experience.Several studies have confirmed that BIS has a good correlation with propofol anesthesia,which can accurately reflect the depth of propofol anesthesia and guide the use of propofol in general anesthesia and sedation.Studies have found that the BIS monitoring can reduce intraoperative awareness,reduce unnecessary general anesthetics exposed of elderly patients,and significantly reduce postoperative nausea and vomiting,PND and other complications.However,there are few studies on BIS monitoring for regional block sedation,and the optimal intraoperative BIS level for elderly patients undergoing non-general anesthesia surgery remains to be explored.Therefore,a rigorous randomized controlled trial should be designed to reflect the intraoperative sedation level of non-general anesthesia surgery by BIS monitoring and OAA/S score so as to explore the influence of different intraoperative sedation depth on POD in elderly patients.Delirium is the result of a combination of predisposing and precipitating factors.In addition to advanced age,other factors such as multiple diseases,perioperative hypoxemia,pain,opioid use,and infection are also considered as risk factors for POD.However,the POD risk factors obtained in previous studies were also different due to different selection groups,different types of surgery,different anesthesia schemes and anesthetic drugs,and different POD evaluation methods and different analysis methods.Therefore,it is still necessary to conduct multi-factor Logistc regression analysis for specific population,specific surgical methods and anesthesia methods to determine independent risk factors for POD in elderly patients,so as to help implement more targeted multi-component prevention strategies for POD in clinical practice.The pathophysiology of POD is still unclear,and due to the complexity of the etiology of senile delirium,it is difficult to explain the pathophysiological process of delirium with a single mechanism.At present,the hypothesis about the pathophysiological mechanism of delirium mainly includes neurotransmitter theory,stress mechanism,neuroinflammatory theory,brain blood supply/metabolism disorder,electrolyte disorder theory and gene theory.Biomarkers of delirium can help to reveal the pathophysiology of delirium in the elderly,and play a role in risk prediction,clinical diagnosis and judgment of severity.Low molecular calcium binding protein S100 beta is associated with trauma,shock,cardiopulmonary resuscitation(CPR),brain injury as a nonspecific biological marker.Astrocytes release S100 beta protein by inflammatory reaction,ischemia-reperfusion injury and apoptosis and oxidation reaction,then S100 beta protein can be released into the blood through the damaged blood brain barrier.Numbers of studies suggest S100 beta protein could be a biological marker of POD.The study of the correlation between serum concentration of S100 beta protein and POD risk factors is helpful to explore the possible pathological pathways of POD influenced by risk factors.Objectives1.To observe the effect of different intraoperative sedation depth of propofol measured by BIS on POD of elderly patients undergoing surgery for hip fracture under plexus block;2.To search the risk factors and independent risk factors of POD in elderly patients undergoing surgery for hip fracture,so as to provide the basis for the effective prediction and prevention of POD in clinic;3.To compare the changes of perioperative S100 beta serum concentration in POD patients and non-pod patients,explore the correlation between the serum concentration of S100 beta protein and BIS value of elderly patients during sedation period,so as to find the possible pathophysiology of intraoperative sedation depth affecting POD in elderly patients.MethodsThis study consists of two parts as follows.1.To explore the effects of sedation depth on POD during hip fracture surgery in elderly patients and analysis of POD risk factors,approved by the medical ethics committee of ZiBo central hospital,a total of 177 elderly patients aged more than 80 years old with hip fracture admitted to the department of orthopedics of ZiBo central hospital from January 2018 to June 2019 were selected and 53 cases were excluded according to the exclusion criteria.Then a total of 124 patients were included in the study.General information was recorded during preoperative visit and consent inform was signed.All patients received T12 paravertebral and lumbosacral plexus nerve block and intraoperative sedation conducted with propofol.The patients were randomly divided into two groups according to the sedation level.BIS value was maintained at 50-70 in the deep sedation group and 71-90 in the light sedation group.Patients were followed up 1 to 7 days after surgery,POD diagnosis was performed with CAM method,the incidence and duration of POD were recorded,postoperative analgesia and complications were recorded too.Divided the patients to two groups with or without POD,Chi square test or t test was performed as univariate analysis with preoperative factors,intraoperative factors and postoperative factors to explore risk factors for POD.Multivariate Logistic regression analysis was subsequently conducted to find independent risk factors for POD in elderly patients with all factors considered.2.To explore correlation of serum concentrations of brain injury markers S100 beta protein with POD in elderly patients,venous blood was collected respectively at arrival of operation room and erery day in 7 days postoperatively.Serum concentrations of S100 beta protein were measured by electrochemiluminescence immunoassay.The perioperative changes of S100 beta serum concentrations of POD patients and non-pod patients were observed and compared,and the S100 beta protein serum concentrations of POD patients at different periods were compared.Spearman correlation analysis was used to analyze the correlation between S100 beta serum concentration and BIS value during sedation or MAP during sedation in 7 days postoperatively,so as to explore the pathological pathway of intraoperative sedation depth affecting POD in elderly patients undergoing hip fracture surgery.Results1.124 elderly patients undergoing hip fracture surgery under plexus block were included in the study,including 34 males and 90 females,aged 80 to 94 years old.POD occurred in 44 patients during 7 days after surgery,with a total incidence of 35.5%,including 14 patients in the L group and 30 patients in the D group.POD incidence in the L group was lower than that in the D group(22.6%vs 48.4%,P=0.003<0.005),POD duration(days)in the L group was shorter than that in the D group(1.5±0.5 vs1.8±0.6,P=0.001<0.005).The effect compartment concentration of propofol in light sedation group was lower than that in deep sedation group,and the average BIS,OAA/S score,average MAP and HR during sedation and ADLs score on the 1st day after surgery were higher than that in deep sedation group,with statistically significant differences(P<0.01).2.Univariate analysis showed that age and VAS score on the 1st day after surgery were the POD risk factors for elderly hip surgery patients,and preoperative ADLs score,BIS during sedation,MAP during sedation,and ADLs score on the 1 st day after surgery were the protective factors for POD in elderly hip fracture surgery patients.Multivariate Logistic regression analysis showed that age and VAS score on the 1st day after surgery were independent risk factors for POD in elderly patients with hip fracture surgery(OR>1,P<0.05),while average BIS during sedation,average MAP during sedation,and ALDs score on the 1st day after surgery were protective factors for POD in elderly patients with hip fracture surgery(OR<1,P<0.05).3.The serum concentration of S100 beta protein in POD patients was higher than that in non-POD patients 1-7 days after the operation.Spearman correlation analysis showed that S100 beta serum concentration at 1-3 days after surgery had a low negative correlation with BIS during sedation,with rs of-0.380,-0.385 and-0.344,respectively,P=0.000.There was a low negative correlation between S100 beta serum concentration and MAP during sedation on the 1st to 2nd day after surgery,rs was-0.334,-0.400,P=0.000,respectively.Conclusions1.Compared with deep sedation,Incidence and duration of POD with light sedation in elderly patients undergoing hip fracture surgery under plexus block were lower,and the postoperative ADLs score was higher.2.Age,intraoperative deep sedation,intraoperative hypotension,postoperative pain,and postoperative low ADLs score were independent risk factors for POD in elderly patients undergoing hip fracture surgery.3.Serum S100 beta concentration increased in elderly patients with POD after hip fracture.Postoperative S100 beta serum concentration is correlated with intraoperative sedation depth and intraoperative blood pressure,and intraoperative deep sedation and hypotension may increase the incidence of POD by nerve cell damage.