Development Of Postoperative Delirium Research Articles

Feasibility and Acceptability of Using Wireless Limited Polysomnography to Capture Sleep Before, During, and After Hospitalization for Patients With Planned Cardiothoracic Surgery.

Sleep disruption, a common symptom among patients requiring cardiovascular surgery, is a potential risk factor for the development of postoperative delirium. Postoperative delirium is a disorder of acute disturbances in cognition associated with prolonged hospitalization, cognitive decline, and mortality. The aim of this study was to evaluate the feasibility and acceptability of using polysomnography (PSG) to capture sleep in patients with scheduled cardiothoracic surgery. Wireless limited PSG assessed sleep at baseline (presurgery at home), postoperatively in the intensive care unit, and at home post hospital discharge. Primary outcomes were quality and completeness of PSG signals, and acceptability by participants and nursing staff. Among 15 patients, PSG data were of high quality, and mean percentage of unscorable data was 5.5% ± 11.1%, 3.7% ± 5.4%, and 3.7% ± 8.4% for baseline, intensive care unit, and posthospitalization measurements, respectively. Nurses and patients found the PSG monitor acceptable. Wireless, limited PSG to capture sleep across the surgical continuum was feasible, and data were of high quality. Authors of future studies will evaluate associations of sleep indices and development of postoperative delirium in this high-risk population.

Preoperative Intrathecal Morphine is Associated With Reduced Postoperative Pain, Agitation, and Delirium In Living Donor Kidney Transplantation Recipients

BackgroundPostoperative delirium after organ transplantation can lead to increased length of hospital stay and mortality. Since pain is an important risk factor for delirium, perioperative analgesia with intrathecal morphine (ITM) may mitigate postoperative delirium development. We evaluated if ITM reduces postoperative delirium incidence in living donor kidney transplant (LDKT) recipients. Methods296 patients who received LDKT between 2014 and 2018 at our hospital were retrospectively analyzed. Recipients who received preoperative ITM (ITM group) were compared to those who did not (control group). Primary outcome was postoperative delirium based on Confusion Assessment Method for Intensive Care Unit results during the first four postoperative days. ResultsDelirium occurred in 2.6% (4/154) and 7.0% (10/142) of ITM and control groups, respectively. Multivariable analysis showed age (OR: 1.07, 95% CI: 1.01-1.14; P = 0.031), recent smoking (OR: 7.87, 95% CI: 1.43-43.31; P = 0.018), preoperative psychotropics (OR: 23.01, 95% CI: 3.22-164.66; P = 0.002) were risk factors while ITM was a protective factor (OR: 0.23, 95% CI: 0.06-0.89; P = 0.033). ConclusionPreoperative ITM showed an independent association with reduced post-LDKT delirium. Further studies and development of regional analgesia for delirium prevention may enhance postoperative recovery of transplant recipients.

Target flow deviations on the cardiopulmonary bypass cause postoperative delirium in cardiothoracic surgery-a retrospective study evaluating temporal fluctuations of perfusion data.

Postoperative delirium is common, costly, and associated with long-term morbidity and increased mortality. We conducted a cohort study to assess the contribution of cardiopulmonary bypass to the development of postoperative delirium by means of algorithm-based data processing. A database was compiled from three datasets of patients who underwent cardiac surgery between 2014 and 2019: Intensive care unit discharge files, cardiopulmonary bypass protocols, and medical quality management records. Following data extraction and structuring using novel algorithms, missing data was imputed. Ten independent imputations were analyzed by multiple logistic regression with stepwise deletion of factors to arrive at a minimal adequate model. Postoperative delirium was diagnosed in 456/3163 patients (14.4%). In addition to known demographic risk factors and comorbidities like male sex, age, carotid disease, acute kidney failure and diabetes mellitus, cardiopulmonary parameters like total blood volume at the cardiopulmonary bypass (AOR 1.001; CI 1.1001 to 1.002) were independent predictors of postoperative delirium. Higher values of the minimal blood flow were associated with a lower risk of postoperative delirium (AOR 0.993; CI 0.988 to 0.997). Flow rates at least 30% above target did emerge in the minimal adequate model as a potential risk factor, but the confidence interval suggested a lack of statistical significance (AOR 1.819; 95% CI: 0.955 to 3.463). Cardiopulmonary bypass data processing proved to be a useful tool for obtaining compact information to better identify the roles of individual operational states. Strict adherence to perfusion limits along with tighter control of blood flow and acid-base balance during cardiopulmonary bypass may help to further decrease the risk of postoperative delirium.

Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients.

Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fracture patients, exploring the possibility of integrating objective methods into future predictive models of delirium. Sixty hip fracture patients were recruited. Blood and CSF samples were collected at the time of spinal anesthesia when none of the subjects had delirium. Patients were assessed daily using the 4AT scale, and based on these results, they were divided into POD and non-POD groups. The Olink® platform was used to analyze 45 cytokines. Twenty-one patients (35%) developed POD. In the subsample of 30 patients on whom proteomic analyses were performed, a proteomic profile was associated with the incidence of POD. Chemokine (C-X-C motif) ligand 9 (CXCL9) had the strongest correlation between serum and CSF samples in patients with POD (rho = 0.663; p < 0.05). Although several cytokines in serum and CSF were associated with POD after hip fracture surgery in older adults, there was a significant association with lower preoperative levels of CXCL9 in CSF and serum. Despite the small sample size, this study provides preliminary evidence of the potential role of molecular biomarkers in POD, which may provide a basis for the development of new delirium predictive models.

Differential effects of sevoflurane and desflurane on frontal intraoperative electroencephalogram dynamics associated with postoperative delirium

Study objectiveIntraoperative electroencephalogram (EEG) patterns associated with postoperative delirium (POD) development have been studied, but the differences in EEG recordings between sevoflurane- and desflurane-induced anesthesia have not been clarified. We aimed to distinguish the EEG characteristics of sevoflurane and desflurane in relation to POD development. Design and patientsWe collected frontal four-channel EEG data during the maintenance of anesthesia from 148 elderly patients who received sevoflurane (n = 77) or desflurane (n = 71); 30 patients were diagnosed with delirium postoperatively. The patients were divided into four subgroups based on anesthetics and delirium status: sevoflurane delirium (n = 17), sevoflurane non-delirium (n = 60), desflurane delirium (n = 13), and desflurane non-delirium (n = 58). We compared spectral power, coherence, and pairwise phase consistency (PPC) between sevoflurane and desflurane, and between non-delirium and delirium groups for each anesthetic. Main resultsIn patients without POD, the sevoflurane non-delirium group exhibited higher EEG spectral power across 8.5–35 Hz (99.5% CI bootstrap analysis) and higher PPC from alpha to gamma bands (p < 0.005) compared to the desflurane non-delirium group. Conversely, in patients with POD, no significant EEG differences were observed between the sevoflurane and desflurane delirium groups. For the sevoflurane-induced patients, the sevoflurane delirium group had significantly lower power within 7.5–31.5 Hz (99.5% CI bootstrap analysis), reduced coherence over 8.9–23.8 Hz (99.5% CI bootstrap analysis), and lower PPC values in the alpha band (p < 0.005) compared with the sevoflurane non-delirium group. For the desflurane-induced patients, there were no significant differences in the EEG patterns between delirium and non-delirium groups. ConclusionsIn normal patients without POD, sevoflurane demonstrates a higher power spectrum and prefrontal connectivity than desflurane. Furthermore, reduced frontal alpha power, coherence, and connectivity of intraoperative EEG could be associated with an increased risk of POD. These intraoperative EEG characteristics associated with POD are more noticeable in sevoflurane-induced anesthesia than in desflurane-induced anesthesia.

Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium

Gene networks for use in metabolomic data analysis of blood plasma from patients with postoperative delirium

Comparison of the frailty index and frailty phenotype and their associations with postoperative delirium incidence and severity.

Recent studies have reported an association between presurgical frailty and postoperative delirium. However, it remains unclear whether the frailty-delirium relationship differs by measurement tool (e.g., frailty index vs. frailty phenotype) and whether frailty is associated with delirium, independent of preoperative cognition. We used the successful aging after elective surgery (SAGES) study, a prospective cohort of older adults age ≥70 undergoing major non-cardiac surgery (N = 505). Preoperative measurement of the modified mini-mental (3MS) test, frailty index and frailty phenotype were obtained. The confusion assessment method (CAM), supplemented by chart review, identified postoperative delirium. Delirium feature severity was measured by the sum of CAM-severity (CAM-S) scores. Generalized linear models were used to determine the relative risk of each frailty measure with delirium incidence and severity. Subsequent models adjusted for age, sex, surgery type, Charlson comorbidity index, and 3MS. On average, patients were 76.7 years old (standard deviation 5.22), 58.8% of women. For the frailty index, the incidence of delirium was 14% in robust, 17% in prefrail, and 31% in frail patients (p < 0.001). For the frailty phenotype, delirium incidence was 13% in robust, 21% in prefrail, and 27% in frail patients (p = 0.016). Frailty index, but not phenotype, was independently associated with delirium after adjustment for comorbidities (relative risk [RR] 2.13, 95% confidence interval [CI] 1.23-3.70; RR 1.61, 95% CI 0.77-3.37, respectively). Both frailty measures were associated with delirium feature severity. After adjustment for preoperative cognition, only the frailty index was associated with delirium incidence; neither index nor phenotype was associated with delirium feature severity. Both the frailty index and phenotype were associated with the development of postoperative delirium. The index showed stronger associations that remained significant after adjusting for baseline comorbidities and preoperative cognition. Measuring frailty prior to surgery can assist in identifying patients at risk for postoperative delirium.

Anesthesia and surgery induce changes in endogenous brain protective protein (RNF146) and delirium-like behavior in aged rats.

Postoperative delirium (POD) is a common complication after anesthesia and surgery, especially in the elderly. RNF146 has neuroprotective effects in cerebral ischemia, hypoxia, and chronic neurological diseases. However, whether RNF146 expression is related to the occurrence and development of POD remains unclear. Therefore, in this study, we aimed to determine whether RNF146 is involved in the occurrence of POD. (Sprague-Dawley) male rats (18 months old) were splenectomized under sevoflurane anesthesia. The cognitive function of rats at 1, 3, and 7 d after anesthesia and surgery was evaluated. Changes in the expression of neuroinflammatory cytokines, IL-6 and IL-10, and RNF146 were measured in the hippocampus in both control group (con) and anesthesia (AS) group. We examined cognitive outcomes and expression of inflammatory factors and RNF146 in con and AS mice using cluster analysis. The cognitive ability and mobility of rats after anesthesia and surgery at day 1, 3, and 7 decreased, especially at day 3. Similarly, the expression of neuroinflammatory factors and RNF146 increased after anesthesia and surgery at day 1, 3, and 7, and the increase was highest at day 3. The clustering and correlation analysis of RNF146 expression in the hippocampi of elderly rats revealed a correlation between POD and neuroinflammation resulting from anesthesia and surgery. Anesthesia and surgery can lead to POD and neuroinflammation. The expression of RNF146 correlates with delirium and neuroinflammation caused by anesthesia and surgery.

Risk factors associated with postoperative delirium in elderly patients undergoing hip surgery.

We retrospectively analyzed the occurrence of postoperative delirium following hip surgery and the associated risk factors. The aim was to establish a clinical foundation for preventing postoperative delirium after hip surgery. We retrospectively selected elderly patients who had hip surgery at our hospital between January 2022 and August 2022. We included patients who experienced delirium in the observation group and those who did not encounter delirium in the control group. We then proceeded to compare various indicators among these two groups of patients. We analyzed a total of 97 cases of hip surgery, and among them, 32 cases experienced postoperative delirium, resulting in an incidence rate of 32.9%. Various factors were found to be linked to the development of postoperative delirium, including age, height, gender (male), preoperative erythrocyte sedimentation rate (ESR), postoperative ESR, preoperative lactate levels, pain scores on the first day after surgery, type of surgical procedure, and the occurrence of delirium in the post-anesthesia care unit (PACU delirium). Additionally, it was observed that 75% of patients who had PACU delirium also experienced postoperative delirium. Postoperative delirium in patients who have hip surgery had an incidence rate of 32.9%. This phenomenon is linked to various factors that pose a risk, such as the patient age, height, gender, preoperative ESR levels, postoperative ESR levels, preoperative lactate levels, pain scores on the day following surgery, and the specific surgical procedure performed. The likelihood of experiencing delirium increases by 12% for every additional 10 years in patient age. Additionally, the occurrence of delirium in the PACU is a strong indicator of the likelihood of experiencing postoperative delirium.

Relationship between preoperative neutrophil-to-lymphocyte ratio and postoperative delirium: The PNDABLE and the PNDRFAP cohort studies.

In this study, the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and Alzheimer-related biomarkers in cerebrospinal fluid (CSF) was investigated to determine whether high NLR is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy. We selected 1000 patients from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) database and 999 patients from the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) database. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ40 , Aβ42 , P-tau, and tau protein). Mini-mental state examination was used to assess the preoperative mental status of patients. POD was diagnosed using the confusion assessment method and assessed for severity using the memorial delirium assessment scale. Logistic regression analysis was utilized to explore the association of preoperative NLR with POD. What's more, we also performed sensitivity analysis by adding corrected confounders, and the results were almost unchanged. Spearman's rank correlation was used to determine the associations between NLR and Alzheimer-related biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we use decision curves and the nomogram model to evaluate the efficacy of preoperative NLR in predicting POD; we also performed external validation using data from Qilu Hospital. Logistic regression results showed that an elevated preoperative NLR was a risk factor for the development of POD in patients (PNDRFAP: OR=1.067, 95% CI 1.020-1.116; PNDABLE: OR=1.182, 95% CI 1.048-1.335, p<.05). Spearman's rank correlation analysis showed a positive but weak correlation between NLR and P-tau/T-tau (R=.065). The mediating effect results indicate that NLR likely mediates the occurrence of POD through elevated tau protein levels (proportion: 47.47%). The results of the box plots showed statistically significant NLR and CSF biomarkers between the POD and non-POD (NPOD) groups (p<.05), with higher NLR, P-tau, and T-tau in the POD group than in the NPOD group. In contrast, the NPOD group had higher Aβ42 levels compared to the POD group. In addition, we used R package to plot the decision curve and nomogram both suggesting a good predictive effect of preoperative NLR on the occurrence of POD. Elevated preoperative NLR levels may be a risk factor for POD and likely mediate the development of POD through elevated P-tau/T-tau levels.

The Effect of ACE Inhibitors/ARBs Withdrawal on the Risk of Postoperative Complications in Abdominal Surgery

A significant proportion of patients undergoing non-cardiac surgery receive therapy with angiotensin converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), which are usually prescribed for treatment of arterial hypertension and CHF. Current guidelines fail to provide clear consensus on whether it is worth discontinuing ACEi/ARBs before non-cardiac surgery. The aim of this research was to assess the contribution of pre-op ACEi/ARBs withdrawal to the development of postoperative complications in patients after abdominal surgery using data from STOPRISK database.Materials and methods. Data of 1945 patients from of the STOPRISK database was used for the analysis. Patients were retrospectively divided into two groups: first group (N=471, 24.2%) included patients subjected to ACEi/ARBs withdrawal 24 hours before surgery, second group (N=1474, 75.8%) included patients continuing on ACEi/ARBs therapy. The 30-day outcomes were analyzed — postoperative complications (acute kidney injury, acute respiratory distress syndrome, anastomosis failure, arrhythmias, circulatory arrest, cardiogenic pulmonary edema, postoperative delirium, myocardial infarction, pneumonia, ileus, postoperative bleeding, pulmonary embolism, acute cerebrovascular accident, wound infection) and mortality. We were not evaluating intraoperative and postoperative arterial hypotension and hypertension, we analyzed the use of vasopressors as a surrogate marker. ACEi/ARBs re-initiation after surgery was not evaluated.Results. One or more post-operative complications were documented in 113 patients (5.8%). Only postoperative delirium was more common in patients (1.06% vs. 0.27%, P=0.027) after ACEi/ARBs withdrawal 24 hours before surgery, the difference reached statistical significance. Sub-analysis in the group of patients with arterial hypertension as the only comorbidity showed no statistically significant differences in the outcomes. Sub-analysis in the group of patients with CFH showed higher incidence of postoperative delirium after ACEi/ARBs withdrawal (2.68% vs. 0.6%, P=0.023). The logistic regression analysis showed that the risk of developing postoperative delirium is influenced by age, vasopressor support, and ACEi/ARBs withdrawal (the area under the curve for the model was 0.92 (0.90–0.93).Conclusion. Rates of pre-op ACEi/ARBs withdrawal (24.2%) are consistent with published data. In the entire cohort, ACEi/ARBs withdrawal resulted in higher incidence of postoperative delirium, as well as in the subgroup of patients with CHF, while ACEi/ARBs withdrawal in the subgroup of patients with arterial hypertension had no influence on postop complications.ACEi/ARBs withdrawal, along with hemodynamic instability and older age, contributes to the development of postoperative delirium, which is the subject of future research. 

Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium.

Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to a lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with the development of postoperative delirium in older surgical patients. We employed a nested case-control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort, and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p < 0.05). Due to the limited sample size, these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, and principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identified 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Intraoperative neurological pupil index and postoperative delirium and neurologic adverse events after cardiac surgery: an observational study

Neurological pupil index (NPi) calculated by automated pupillometry predicts clinical outcomes in critically ill patients. However, there are few data on intraoperative NPi and postoperative outcome after cardiac surgery. We evaluated the relationships between intraoperative NPi and clinical outcomes, such as delirium, in cardiac surgery patients. NPi was measured at baseline, after anesthesia induction, at 30 min intervals after initiation of cardiopulmonary bypass or anastomosis of coronary artery bypass graft, and at skin closure. Abnormal NPi was defined as one or more measurements of NPi < 3.0 during surgery. The worst intraoperative NPi was recorded, then multivariate logistic regression analysis was performed to evaluate the relationship between abnormal NPi and postoperative delirium following cardiac surgery. Among 123 included patients, postoperative delirium developed in 19.5% (24/123) of patients. Intraoperative abnormal NPi was significantly associated with postoperative delirium (odds ratio 6.078; 95% confidence interval 1.845–20.025; P = 0.003) after adjustment for Society of Thoracic Surgeons Predicted Risk of Mortality score, coronary artery disease, and use of calcium channel blockers. In conclusion, abnormal intraoperative NPi independently predicted postoperative delirium following cardiac surgery. Intraoperative application of pupillometry may have prognostic value for development of postoperative delirium, thereby enabling close surveillance and early intervention in high-risk patients.Registry number: ClinicalTrials.gov (NCT04136210).

A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months. Patients were randomized to receive either inhalation anesthesia (ISO) with isoflurane or total intravenous anesthesia (TIVA) with propofol for maintenance anesthesia. ISO (n = 99) and TIVA (n = 100) groups were similar in demographics, preoperative cognition, and incidence of post-operative delirium. Groups did not differ in terms of mean change in memory or executive function from baseline to follow-up. Pre-surgical cognitive function is the only variable predictive of the development of POCD. Anesthetic type was not predictive of POCD. However, ADLs were predictive of post-operative delirium development. Overall, this pilot study represents a prospective, randomized study demonstrating that when examining ISO versus TIVA for maintenance of general anesthesia, there is no significant difference in cognition between anesthetic types. There is also no difference in the occurrence of postoperative delirium. Postoperative cognitive decline was best predicted by lower baseline cognition and functional status.

Potentials of Acetylcholinesterase and Butyrylcholinesterase Alterations in On-Pump Coronary Artery Bypass Surgery in Postoperative Delirium: An Observational Trial.

Cardiac surgery is regularly associated with postoperative delirium (POD), affected by neuro-inflammation and changes in cholinergic activity. Therefore, this prospective observational study aimed to evaluate whether pre- and perioperative changes in blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity were associated with POD development in patients undergoing isolated elective coronary artery bypass graft (CABG) surgery. It included 93 patients. Pre- and postoperative blood AChE and BChE activities were measured with photometric rapid-point-of-care-testing. The Intensive Care Delirium Screening Checklist and the Confusion Assessment Method for the Intensive Care Unit were used to screen patients for POD. POD developed in 20 patients (21.5%), who were older (p = 0.003), had higher EuroSCOREs (p ≤ 0.001), and had longer intensive care unit stays (p < 0.001). On postoperative day one, BChE activity decreased from preoperative values more in patients with (31.9%) than without (23.7%) POD (group difference p = 0.002). Applying a cutoff of ≥32.0% for BChE activity changes, receiver operating characteristic analysis demonstrated a moderate prediction capability for POD (area under the curve = 0.72, p = 0.002). The risk of developing POD was 4.31 times higher with a BChE activity change of ≥32.0% (p = 0.010). Monitoring the pre- to postoperative reduction in BChE activity might be a clinically practicable biomarker for detecting patients at risk of developing POD after CABG surgery.

Emergence delirium and postoperative delirium associated with high plasma NfL and GFAP: an observational study.

Neuroinflammation and neuronal injury have been reported to be associated with the development of postoperative delirium in both preclinical and clinical settings. This study aimed to investigate the potential correlation between biomarkers of neurofilament light chain and glial fibrillary acidic protein and emergence and postoperative delirium in elderly patients undergoing surgery. Patients who developed emergence delirium (n = 30) and postoperative delirium (n = 32), along with their matched controls, were enrolled after obtaining ethics approval and written informed consent. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit or Confusion Assessment Method scale, and blood samples were collected before and after surgery for plasma neurofilament light chain and glial fibrillary acidic protein measurements using a single-molecule array. The study found that in patients with emergence delirium, the increase in plasma neurofilament light chain protein levels during surgery was significantly higher than in non-delirium patients (P = 0.002). Additionally, in patients with postoperative delirium, both the increase in plasma neurofilament light chain protein levels (P < 0.001) and the increase in plasma glial fibrillary acidic protein levels during surgery (P = 0.008) were significantly higher than in non-delirium patients. Multivariate logistic regression analysis showed that the increase in plasma neurofilament light chain protein was associated with emergence delirium (adjusted OR = 1.872, P = 0.005), and the increase in plasma glial fibrillary acidic protein was associated with postoperative delirium (adjusted OR = 1.419, P = 0.016). Moreover, the American Society of Anesthesiologists Physical Status Classification and surgical duration were also found to be associated with delirium in elderly patients. Our findings suggest that emergence delirium is linked to elevated levels of neurofilament light chain, a biomarker of axonal injury, during surgery. Furthermore, in addition to axonal injury, postoperative delirium was also associated with an increase in glial fibrillary acidic protein, a marker of astrocyte activation.

Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00-1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

Routine Perioperative Assessment of Risk Factors Regarding Development of Postoperative Delirium During Elective Bariatric Surgery

Routine Perioperative Assessment of Risk Factors Regarding Development of Postoperative Delirium During Elective Bariatric Surgery

A retrospective study of the effects of anesthesia methods on post-operative delirium in geriatric patients having orthopedic surgery: Anesthesia methods on post-operative delirium

Background/Aim: Post-operative delirium, which usually develops in geriatric patients, also causes an increase in mortality and morbidity for various reasons, such as difficulty in compliance with treatment. Estimating the effects of the anesthesia method on delirium contributes to the prevention of possible complications. In this study, effects due to use of different anesthesia methods on the post-operative delirium development in geriatric patients who underwent orthopedic surgery were investigated. Methods: In our retrospective cohort study, scanning of the patient files was performed for 276 patients who were older than 65 years and who had undergone surgery for lower extremity fractures in Malatya education and research hospital, orthopedics department between May 1, 2022 and October 15, 2022. Demographic data, comorbid conditions, anesthesia type, lengths of surgery, and level of delirium development were recorded for each scanned patient. Results: In our study, 201 patients were included. The mean age of the patients was 74.1 (7.3) (min–max: 65–98); 133 (66.2%) were female, and 68 (33.8%) were male. It was noticed that patients who had undergone regional anesthesia developed a significantly smaller rate of delirium development (8.1%) compared to those who had received general anesthesia (20.6%; P=0.012). Ages (P&lt;0.001), lengths of surgery (P&lt;0.001), and lengths of hospitalization stays (P&lt;0.001) were significantly higher in patients with delirium compared to those without. Conclusion: Based on the data obtained in this study, it was concluded that to reduce the risk of delirium development after orthopedic surgery, regional rather than general anesthesia should be selected, and the time of hospitalization stay should be minimized.

β-arrestin1 regulates astrocytic reactivity via Drp1-dependent mitochondrial fission: implications in postoperative delirium

Postoperative delirium (POD) is a frequent and debilitating complication, especially amongst high risk procedures, such as orthopedic surgery. This kind of neurocognitive disorder negatively affects cognitive domains, such as memory, awareness, attention, and concentration after surgery; however, its pathophysiology remains unknown. Multiple lines of evidence supporting the occurrence of inflammatory events have come forward from studies in human patients’ brain and bio-fluids (CSF and serum), as well as in animal models for POD. β-arrestins are downstream molecules of guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). As versatile proteins, they regulate numerous pathophysiological processes of inflammatory diseases by scaffolding with inflammation-linked partners. Here we report that β-arrestin1, one type of β-arrestins, decreases significantly in the reactive astrocytes of a mouse model for POD. Using β-arrestin1 knockout (KO) mice, we find aggravating effect of β-arrestin1 deficiency on the cognitive dysfunctions and inflammatory phenotype of astrocytes in POD model mice. We conduct the in vitro experiments to investigate the regulatory roles of β-arrestin1 and demonstrate that β-arrestin1 in astrocytes interacts with the dynamin-related protein 1 (Drp1) to regulate mitochondrial fusion/fission process. β-arrestin1 deletion cancels the combination of β-arrestin1 and cellular Drp1, thus promoting the translocation of Drp1 to mitochondrial membrane to provoke the mitochondrial fragments and the subsequent mitochondrial malfunctions. Using β-arrestin1-biased agonist, cognitive dysfunctions of POD mice and pathogenic activation of astrocytes in the POD-linked brain region are reduced. We, therefore, conclude that β-arrestin1 is a promising target for the understanding of POD pathology and development of POD therapeutics.