Potential risks of nonoperative management of appendicitis in high-risk patients.

INTRODUCTION: The popularity of nonoperative management for acute appendicitis is based on the untested assumption that it offers a lower risk alternative to surgery in patients who are at high risk for morbidity and mortality with appendectomy. We hypothesized that patients who were at a high risk with appendectomy would also be at a high risk for complications following nonoperative management. METHODS: This is a retrospective cohort study of patients with acute, uncomplicated appendicitis in the 2004-2017 National Inpatient Sample. We used a logistic regression model to predict the risk of morbidity or mortality following appendectomy and applied this model to predict the risk of patients managed nonoperatively. High risk was defined as ≥2 standard deviations above the mean predicted risk of morbidity or mortality. We used inverse probability weighting of the propensity score to compare outcomes of nonoperative versus operative management for high-risk patients. RESULTS: The sample included 21,242 high-risk patients with a median age of 68 years (interquartile range 57-78), and 31% were managed nonoperatively. Compared to surgery, nonoperative management was associated with a 9% decrease in complications (95% confidence interval [CI] 7%-10%), 2% increase in mortality (95% CI 2%-3%), $10,202 increase in hospital costs (95% CI $9,065-$11,339), 3-day increase in length of stay (95% CI 2-3), and 9% greater likelihood of discharge to skilled nursing facilities (95% CI 8%-10%). CONCLUSION: Nonoperative management of acute appendicitis in high-risk patients may reduce morbidity but increase mortality, duration of hospitalization, discharge to skilled facility, and costs. Surgeons should exercise caution when considering nonoperative management in these vulnerable patients.

Prediction of Post-Operative Delirium in Older Adults from Preoperative Cognition and Alpha Power from Resting-State EEG.

Postoperative Delirium (POD) is the most common complication following surgery among older adults, and has been consistently associated with increased mortality and morbidity, cognitive decline, and loss of independence, as well as markedly increased health-care costs. The development of new tools to identify individuals at high risk for POD could guide clinical decision-making and enable targeted interventions to potentially decrease delirium incidence and POD-related complications. In this study, we used machine learning techniques to evaluate whether baseline (pre-operative) cognitive function and resting-state electroencephalography could be used to identify patients at risk for POD. Pre-operative resting-state EEGs and the Montreal Cognitive Assessment (MoCA) were collected from 85 patients (age = 73 ± 6.4 years) undergoing elective surgery, 12 of whom subsequently developed POD. The model with the highest f1-score for predicting delirium, a linear-discriminant analysis (LDA) model incorporating MoCA scores and occipital alpha-band EEG features, was subsequently validated in an independent, prospective cohort of 51 older adults (age ≥ 60) undergoing elective surgery, 6 of whom developed POD. The LDA-based model, with a total of 7 features, was able to predict POD with area under the receiver operating characteristic curve, specificity and accuracy all >90%, and sensitivity > 80%, in the validation cohort. Notably, models incorporating both resting-state EEG and MoCA scores outperformed those including either EEG or MoCA alone. While requiring prospective validation in larger cohorts, these results suggest that prediction of POD with high accuracy may be feasible in clinical settings using simple and widely available clinical tools.

Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

Association between surgery and rate of incident dementia in older adults: A population-based retrospective cohort study.

BACKGROUND: The risk of incident dementia after surgery in older adults is unclear. The study objective was to examine the rate of incident dementia among older adults after elective surgery compared with a matched nonsurgical control group. METHODS: We conducted a population-based, propensity-matched retrospective cohort study using data from linked administrative databases in Ontario, Canada. All community-dwelling individuals aged 66 years and older who underwent one of five major elective surgeries between April 1, 2007 and March 31, 2011 were included. Each surgical patient was matched 1:1 on surgical specialty of the surgeon at consultation, age, sex, fiscal year of entry, and propensity score with a patient who attended an outpatient visit with a surgeon of the same surgical specialty but did not undergo surgery. Patients were followed for up to 5 years after cohort entry for the occurrence of a new dementia diagnosis, defined from administrative data. Cause-specific hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between surgery and the hazard of incident dementia. Subgroup and sensitivity analyses were performed. RESULTS: A total of 27,878 individuals (13,939 matched pairs) were included in the analysis. A total of 640 (4.6%) individuals in the surgical group and 965 (6.9%) individuals in the control group developed dementia over the 5-year follow-up period. Individuals who underwent surgery had a reduced rate of incident dementia compared with their matched nonsurgical controls (HR 0.88; 95% CI 0.80-0.97; p = 0.01). This association was persistent in most subgroups and after sensitivity analyses. CONCLUSIONS: Elective surgery did not increase the rate of incident dementia when compared with matched nonsurgical controls. This could be an important consideration for patients and surgeons when elective surgery is considered.

Preoperative electroencephalographic alpha-power changes with eyes opening are associated with postoperative attention impairment and inattention-related delirium severity.

BACKGROUND: In the eyes-closed, awake condition, EEG oscillatory power in the alpha band (7-13 Hz) dominates human spectral activity. With eyes open, however, EEG alpha power substantially decreases. Less alpha attenuation with eyes opening has been associated with inattention; thus, we analysed whether reduced preoperative alpha attenuation with eyes opening is associated with postoperative inattention, a delirium-defining feature. METHODS: Preoperative awake 32-channel EEG was recorded with eyes open and eyes closed in 71 non-neurological, noncardiac surgery patients aged ≥ 60 years. Inattention and other delirium features were assessed before surgery and twice daily after surgery until discharge. Eyes-opening EEG alpha-attenuation magnitude was analysed for associations with postoperative inattention, primarily, and with delirium severity, secondarily, using multivariate age- and Mini-Mental Status Examination (MMSE)-adjusted logistic and proportional-odds regression analyses. RESULTS: Preoperative alpha attenuation with eyes opening was inversely associated with postoperative inattention (odds ratio [OR] 0.73, 95% confidence interval [CI]: 0.57, 0.94; P=0.038). Sensitivity analyses showed an inverse relationship between alpha-attenuation magnitude and inattention chronicity, defined as 'never', 'newly', or 'chronically' inattentive (OR 0.76, 95% CI: 0.62, 0.93; P=0.019). In addition, preoperative alpha-attenuation magnitude was inversely associated with postoperative delirium severity (OR 0.79, 95% CI: 0.65, 0.95; P=0.040), predominantly as a result of the inattention feature. CONCLUSIONS: Preoperative awake, resting, EEG alpha attenuation with eyes opening might represent a neural biomarker for risk of postoperative attentional impairment. Further, eyes-opening alpha attenuation could provide insight into the neural mechanisms underlying postoperative inattention risk.

Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study.

PURPOSE: Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratification remains challenging. Neuroinflammation has emerged as a key mechanism of persistent pain and depression in nonobstetric populations. Nevertheless, most studies focus on plasma cytokines, and the relationship between plasma and cerebrospinal fluid (CSF) cytokine levels is unclear. Our primary aim was to compare inflammatory marker levels between patients who developed the composite outcome of persistent pain and/or PPD vs those who did not. METHODS: We recruited term patients with singleton pregnancies undergoing elective Cesarean delivery under neuraxial anesthesia into an exploratory prospective cohort study. We collected baseline demographic, obstetric, and Edinburgh Postnatal Depression Scale information, and performed quantitative sensory tests. Plasma was collected preoperatively and 48 hr postoperatively. In the operating room, 10 mL of CSF was collected, followed by a standardized anesthetic. Intra- and postoperative management were according to standard practice. We obtained Edinburgh Postnatal Depression Scale and pain scores at six weeks and three months after delivery. The primary outcome was persistent pain and/or PPD at three months. We analyzed the difference in inflammatory marker levels between the groups (primary aim) using two-sided Mann-Whitney tests. RESULTS: Eighty participants were enrolled, and 63 patients completed the study; 23 (37%) experienced the primary outcome at three months. Preoperative plasma transforming growth factor beta 1 (TGF-ß1) concentration was higher in patients who developed the primary outcome compared with those who did not (median [interquartile range (IQR)], 2,879 [2,241-5,494] vs 2,292 [1,676-2,960] pg·mL-1; P = 0.04), while CSF IL-1ß concentration was higher in patients who developed the primary outcome than in those who did not (median [IQR], 0.36 [0.29-0.39] vs 0.30 [0.25-0.35] pg·mL-1; P = 0.03). CONCLUSIONS: We observed differential levels of plasma and CSF inflammatory biomarkers in patients who developed persistent pain and PPD compared with those who did not. We showed the feasibility of collecting plasma and CSF samples at Cesarean delivery, which may prove useful for future risk-stratification. STUDY REGISTRATION: ClinicalTrials.gov (NCT04271072); registered 17 February 2020.

RéSUMé: OBJECTIF: La douleur aiguë sévère après un accouchement par césarienne augmente le risque de douleur persistante (~20 % d'incidence) et de dépression post-partum (DPP) (~15 % d'incidence). Ces deux conditions contribuent à la morbidité et à la mortalité maternelles, mais la stratification précoce des risques demeure difficile. La neuroinflammation est apparue comme un mécanisme clé de la douleur persistante et de la dépression dans les populations non obstétricales. Néanmoins, la plupart des études se concentrent sur les cytokines plasmatiques, et la relation entre les taux de cytokines plasmatiques et de liquide céphalorachidien (LCR) n'est pas claire. Notre objectif principal était de comparer les taux de marqueurs inflammatoires entre les patient·es qui ont eu un résultat composite de douleur persistante et/ou de DPP vs les personnes qui n'en ont pas eu. MéTHODE: Nous avons recruté des patient·es à terme avec des grossesses uniques bénéficiant d'une césarienne programmée sous anesthésie neuraxiale dans une étude de cohorte prospective exploratoire. Nous avons recueilli des informations démographiques de base, obstétricales et tirées de l'Échelle de dépression postnatale d'Édimbourg, et effectué des tests sensoriels quantitatifs. Le plasma a été prélevé avant l'opération et 48 heures après l'opération. En salle d'opération, 10 mL de LCR ont été recueillis, suivis d'un anesthésie standardisée. La prise en charge per- et postopératoire était conforme à la pratique courante. Nous avons obtenu les scores sur l'Échelle de dépression postnatale d'Édimbourg et les scores de douleur six semaines et trois mois après l'accouchement. Le critère d'évaluation principal était la douleur persistante et/ou la DPP à trois mois. Nous avons analysé la différence dans les niveaux de marqueurs inflammatoires entre les groupes (objectif principal) en utilisant des tests bilatéraux de Mann-Whitney. RéSULTATS: Quatre-vingts personnes ont été recrutées et 63 patient·es ont terminé l'étude; 23 (37 %) ont rapporté le critère d'évaluation principal à trois mois. Le facteur TGF-ß1 (transforming growth factor beta 1) plasmatique préopératoire était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal par rapport aux personnes qui ne l'ont pas manifesté (médiane [écart interquartile (ÉIQ)], 2879 [2241-5494] vs 2292 [1676­2960] pg·mL−1; P = 0,04), tandis que le IL-1ß dans le LCR était plus élevé chez les patient·es qui ont manifesté le critère d'évaluation principal que chez les personnes qui ne l'ont pas manifesté (médiane [ÉIQ], 0,36 [0,29-0,39] vs 0,30 [0,25­0,35] pg·mL−1; P = 0,03). CONCLUSION: Nous avons observé des taux différentiels de biomarqueurs inflammatoires plasmatiques et de LCR chez les patient·es qui ont manifesté une douleur persistante et une DPP par rapport aux personnes qui n'en ont pas manifesté. Nous avons montré la faisabilité de la collecte d'échantillons de plasma et de LCR lors de l'accouchement par césarienne, ce qui pourrait s'avérer utile pour la stratification future des risques. ENREGISTREMENT DE L'éTUDE: clinicaltrials.gov (NCT04271072); enregistrée le 17 février 2020.

EEG pre-burst suppression: characterization and inverse association with preoperative cognitive function in older adults.

The most common complication in older surgical patients is postoperative delirium (POD). POD is associated with preoperative cognitive impairment and longer durations of intraoperative burst suppression (BSup) - electroencephalography (EEG) with repeated periods of suppression (very low-voltage brain activity). However, BSup has modest sensitivity for predicting POD. We hypothesized that a brain state of lowered EEG power immediately precedes BSup, which we have termed "pre-burst suppression" (preBSup). Further, we hypothesized that even patients without BSup experience these preBSup transient reductions in EEG power, and that preBSup (like BSup) would be associated with preoperative cognitive function and delirium risk. Data included 83 32-channel intraoperative EEG recordings of the first hour of surgery from 2 prospective cohort studies of patients ≥age 60 scheduled for ≥2-h non-cardiac, non-neurologic surgery under general anesthesia (maintained with a potent inhaled anesthetic or a propofol infusion). Among patients with BSup, we defined preBSup as the difference in 3-35 Hz power (dB) during the 1-s preceding BSup relative to the average 3-35 Hz power of their intraoperative EEG recording. We then recorded the percentage of time that each patient spent in preBSup, including those without BSup. Next, we characterized the association between percentage of time in preBSup and (1) percentage of time in BSup, (2) preoperative cognitive function, and (3) POD incidence. The percentage of time in preBSup and BSup were correlated (Spearman's ρ [95% CI]: 0.52 [0.34, 0.66], p < 0.001). The percentage of time in BSup, preBSup, or their combination were each inversely associated with preoperative cognitive function (ß [95% CI]: -0.10 [-0.19, -0.01], p = 0.024; -0.04 [-0.06, -0.01], p = 0.009; -0.04 [-0.06, -0.01], p = 0.003, respectively). Consistent with prior literature, BSup was significantly associated with POD (odds ratio [95% CI]: 1.34 [1.01, 1.78], p = 0.043), though this association did not hold for preBSup (odds ratio [95% CI]: 1.04 [0.95, 1.14], p = 0.421). While all patients had ≥1 preBSup instance, only 20.5% of patients had ≥1 BSup instance. These exploratory findings suggest that future studies are warranted to further study the extent to which preBSup, even in the absence of BSup, can identify patients with impaired preoperative cognition and/or POD risk.

Role of Blood-Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults.

OBJECTIVE: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients. METHODS: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR). RESULTS: Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = -0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [-0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03-1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09-1.22, p < 0.001). INTERPRETATION: Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024-1035.

A Real-Time Neurophysiologic Stress Test for the Aging Brain: Novel Perioperative and ICU Applications of EEG in Older Surgical Patients.

As of 2022, individuals age 65 and older represent approximately 10% of the global population [1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [2, 3]. With approximately > 234 million major surgical procedures performed annually worldwide [4], this suggests that > 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [5], greater economic burden [6, 7], and greater risk for developing long-term cognitive decline [8] such as Alzheimer's disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological "stress test" for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline (see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient "passed" or "failed" this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a "predictor" of delirium and perioperative cognitive decline in older surgical patients.

PD-L1/PD-1 checkpoint pathway regulates hippocampal neuronal excitability and learning and memory behavior.

Programmed death protein 1 (PD-1) and its ligand PD-L1 constitute an immune checkpoint pathway. We report that neuronal PD-1 signaling regulates learning/memory in health and disease. Mice lacking PD-1 (encoded by Pdcd1) exhibit enhanced long-term potentiation (LTP) and memory. Intraventricular administration of anti-mouse PD-1 monoclonal antibody (RMP1-14) potentiated learning and memory. Selective deletion of PD-1 in excitatory neurons (but not microglia) also enhances LTP and memory. Traumatic brain injury (TBI) impairs learning and memory, which is rescued by Pdcd1 deletion or intraventricular PD-1 blockade. Conversely, re-expression of Pdcd1 in PD-1-deficient hippocampal neurons suppresses memory and LTP. Exogenous PD-L1 suppresses learning/memory in mice and the excitability of mouse and NHP hippocampal neurons through PD-1. Notably, neuronal activation suppresses PD-L1 secretion, and PD-L1/PD-1 signaling is distinctly regulated by learning and TBI. Thus, conditions that reduce PD-L1 levels or PD-1 signaling could promote memory in both physiological and pathological conditions.

Amyloid beta and postoperative delirium: partners in crime or strangers in the dark?

Postoperative delirium is a particularly debilitating complication of surgery and perioperative care. Although the aetiology of postoperative delirium is not entirely understood, recent evidence suggests that Alzheimer's disease and related dementias pathology plays an important role in the development of postoperative delirium. A recent study evaluating postoperative changes in plasma beta amyloid (Aß) levels found increased Aß across the postoperative period, but the association with postoperative delirium incidence and severity was variable. These findings support the idea that Alzheimer's disease and related dementias pathology in combination with blood-brain barrier dysfunction and neuroinflammation may impart risk for postoperative delirium.

Perioperative changes in neurocognitive and Alzheimer's disease-related cerebrospinal fluid biomarkers in older patients randomised to isoflurane or propofol for anaesthetic maintenance.

BACKGROUND: Animal studies have shown that isoflurane and propofol have differential effects on Alzheimer's disease (AD) pathology and memory, although it is unclear whether this occurs in humans. METHODS: This was a nested randomised controlled trial within a prospective cohort study; patients age ≥60 yr undergoing noncardiac/non-neurological surgery were randomised to isoflurane or propofol for anaesthetic maintenance. Cerebrospinal fluid (CSF) was collected via lumbar puncture before, 24 h, and 6 weeks after surgery. Cognitive testing was performed before and 6 weeks after surgery. Nonparametric methods and linear regression were used to evaluate CSF biomarkers and cognitive function, respectively. RESULTS: There were 107 subjects (54 randomised to isoflurane and 53 to propofol) who completed the 6-week follow-up and were included in the analysis. There was no significant effect of anaesthetic treatment group, time, or group-by-time interaction for CSF amyloid-beta (Aß), tau, or phospho-tau181p levels, or on the tau/Aß or p-tau181p/Aß ratios (all P>0.05 after Bonferroni correction). In multivariable-adjusted intention-to-treat analyses, there were no significant differences between the isoflurane and propofol groups in 6-week postoperative change in overall cognition (mean difference [95% confidence interval]: 0.01 [-0.12 to 0.13]; P=0.89) or individual cognitive domains (P>0.05 for each). Results remained consistent across as-treated and per-protocol analyses. CONCLUSIONS: Intraoperative anaesthetic maintenance with isoflurane vs propofol had no significant effect on postoperative cognition or CSF Alzheimer's disease-related biomarkers within 6 weeks after noncardiac, non-neurological surgery in older adults. CLINICAL TRIAL REGISTRATION: NCT01993836.

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

Objective: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients. Methods: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR). Results: Of 207 patients (median age 68, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24-hours after surgery (median postoperative change 0.28, [IQR] [-0.48-1.24]; Wilcoxon p=0.001). Preoperative to 24-hour postoperative change in CPAR was greater among patients who developed delirium vs those who did not (median [IQR] 1.31 [0.004, 2.34] vs 0.19 [-0.55, 1.08]; p=0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24-hour postoperative change in CPAR was independently associated with delirium incidence (per CPAR increase of 1, OR = 1.30, [95% CI 1.03-1.63]; p=0.026) and increased hospital length of stay (IRR = 1.15 [95% CI 1.09-1.22]; p<0.001). Interpretation: Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay.

Awake Spinal Fusion Is Associated with Reduced Length of Stay, Opioid Use, and Time to Ambulation Compared to General Anesthesia: A Matched Cohort Study.

OBJECTIVE: There is increasing interest in performing awake spinal fusion under spinal anesthesia (SA). Evidence supporting SA has been positive, albeit limited. The authors set out to investigate the effects of SA versus general anesthesia (GA) for spinal fusion procedures on length of stay (LOS), opioid use, time to ambulation (TTA), and procedure duration. METHODS: The authors performed a retrospective review of a single surgeon's patients who underwent lumbar fusions under SA versus GA from June of 2020 to June of 2022. SA patients were compared to demographically matched GA counterparts undergoing comparable procedures. Analyzed outcomes include operative time, opioid usage in morphine milligram equivalents, TTA, and LOS. RESULTS: Ten SA patients were matched to 10 GA counterparts. The cohort had a mean age of 66.77, a mean body mass index of 27.73 kg/m2, and a median American Society of Anesthesiologists Physical Status Score of 3.00. LOS was lower in SA versus GA patients (12.87 vs. 50.79 hours, P = 0.001). Opioid utilization was reduced in SA versus GA patients (10.76 vs. 31.43 morphine milligram equivalents, P = 0.006). TTA was reduced in SA versus GA patients (7.22 vs. 29.87 hours, P = 0.022). Procedure duration was not significantly reduced in SA patients compared to GA patients (139.3 vs. 188.2 minutes, P = 0.089). CONCLUSIONS: These preliminary retrospective results suggest the use of SA rather than GA for lumbar fusions is associated with reduced hospital LOS, reduced opioid utilization, and reduced TTA. Future randomized prospective studies are warranted to determine if SA usage truly leads to these beneficial outcomes.

Awake spinal anesthesia facilitates spine surgery in poor surgical candidates: A case series.

BACKGROUND: Annually, hundreds of thousands of patients undergo surgery for degenerative spine disease (DSD). This represents only a fraction of patients that present for surgical consideration. Procedures are often avoided due to comorbidities that make patients poor candidates for general anesthesia (GA) and its associated risks. With increasing interest in awake surgery under spinal anesthesia (SA), the authors have observed that SA may facilitate spine surgery in patients with relative contraindications to GA. With this in mind, the authors set out to summarize the outcomes of a series of highly comorbid patients who received surgery under SA. METHODS: Case logs of a single surgeon were reviewed, and patients undergoing spine surgery under SA were identified. Within this group, patients were identified with relative contraindications to GA, such as advanced age and medical comorbidities. For these patients, for whom surgery was facilitated by SA, the medical records were consulted to report demographic information and patient outcomes. RESULTS: Ten highly comorbid patients were identified who received lumbar spine surgery for DSD under SA. Comorbidities included octogenarian status, obesity, and chronic health conditions such as heart disease. The cohort had a mean age of 75.5 and a mean American Society of Anesthesiologists Physical Status (ASA-PS) score of 3.1. The patients were predicted to have a 2.74-fold increase of serious complications compared to the average patient. There were no adverse events. CONCLUSION: For patients with symptomatic, refractory DSD and relative contraindications to GA, SA may facilitate safe surgical intervention with excellent outcomes.

Outcomes of Nonoperative vs Operative Management of Acute Appendicitis in Older Adults in the US.

Importance: Although the incidence of acute appendicitis among adults 65 years and older is high, these patients are underrepresented in randomized clinical trials comparing nonoperative vs operative management of appendicitis; it is unclear whether current trial data can be used to guide treatment in older adults. Objective: To compare outcomes following nonoperative vs operative management of appendicitis in older adults and assess whether they differ from results in younger patients. Design, Setting, and Participants: This retrospective cohort study used US hospital admissions data from the Agency for Healthcare Research and Quality's National Inpatient Sample from 2004 to 2017. Of 723 889 adult patients with acute uncomplicated appendicitis, 474 845 with known procedure date who survived 24 hours postprocedure and did not have inflammatory bowel disease were included (43 846 who were treated nonoperatively and 430 999 with appendectomy) were included. Data were analyzed from October 2021 to April 2022. Exposures: Nonoperative vs operative management. Main Outcomes and Measures: The primary outcome was incidence of posttreatment complications. Secondary outcomes included mortality, length of stay, and inpatient costs. Differences were estimated using inverse probability weighting of the propensity score with sensitivity analysis to quantify effects of unmeasured confounding. Results: The median (IQR) age in the overall cohort was 39 (27-54) years, and 29 948 participants (51.3%) were female. In patients 65 years and older, nonoperative management was associated with a 3.72% decrease in risk of complications (95% CI, 2.99-4.46) and a 1.82% increase in mortality (95% CI, 1.49-2.15) along with increased length of hospitalization and costs. Outcomes in patients younger than 65 years were significantly different than in older adults, with only minor differences between nonoperative and operative management with respect to morbidity and mortality, and smaller differences in length of hospitalization and costs. Morbidity and mortality results were somewhat sensitive to bias from unmeasured confounding. Conclusions and Relevance: Nonoperative management was associated with reduced complications in older but not younger patients; however, operative management was associated with reduced mortality, hospital length of stay, and overall costs across all age groups. The different outcomes of nonoperative vs operative management of appendicitis in older and younger adults highlights the need for a randomized clinical trial to determine the best approach for managing appendicitis in older patients.