Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome.

Surgery is a major challenge for the immune system, but little is known about the immune response of geriatric patients to surgery. We therefore investigated the impact of surgery on the molecular signature of circulating CD14+ monocytes, cells implicated in clinical recovery from surgery, in older patients. We enrolled older patients having elective joint replacement (N = 19) or spine (N = 16) surgery and investigated pre- to postoperative expression changes in 784 immune-related genes in monocytes. Joint replacement altered the expression of 489 genes (adjusted p < 0.05), of which 38 had a |logFC| > 1. Spine surgery changed the expression of 209 genes (adjusted p < 0.05), of which 27 had a |logFC| > 1. In both, the majority of genes with a |logFC| > 1 change were downregulated. In the combined group (N = 35), 471 transcripts were differentially expressed (adjusted p < 0.05) after surgery; 29 had a |logFC| > 1 and 72% of these were downregulated. Notably, 21 transcripts were common across procedures. Thus, elective surgery in older patients produces myriad changes in the immune gene transcriptome of monocytes, with many suggesting development of an immunocompromised/hypoactive phenotype. Because monocytes are strongly implicated in the quality of surgical recovery, this signature provides insight into the cellular and molecular mechanisms of the immune response to surgery and warrants further study as a potential biomarker for predicting poor outcomes in older surgical patients.

Does the Association Between Psychosocial Factors and Opioid Use After Elective Spine Surgery Differ by Sex in Older Adults?

Purpose: Psychosocial disorders have been linked to chronic postoperative opioid use and the development of postoperative pain. The potential interaction between sex and psychosocial factors with respect to opioid use after elective spine surgery in the elderly has not yet been evaluated. Our aim was to assess whether any observed association of anxiety or depression indicators with opioid consumption in the first 72 hours after elective spine surgery varies by sex in adults ≥65 years. Patients and Methods: Secondary analysis of a retrospective cohort of 647 elective spine surgeries performed at Brigham and Women's Hospital, July 1, 2015-March 15, 2017, in patients ≥65. Linear mixed-effects models were used to test whether history of anxiety, anxiolytic use, history of depression, and antidepressant use were associated with opioid consumption 0-24, 24-48, and 48-72 post surgery, and whether these potential associations differed by sex. Results: History of anxiety, anxiolytic use, history of depression, and antidepressant use were more common among women (51.3% of the sample). During the first 24 hours after surgery, men with a preoperative history of anxiety consumed an adjusted mean of 19.5 morphine milligram equivalents (MME) (99.6% CI: 8.1, 31.0) more than men without a history of anxiety; women with a history of anxiety only consumed an adjusted mean 2.9 MME (99.6% CI: -3.1, 8.9) more than women without a history of anxiety (P value for interaction between sex and history of anxiety <0.001). No other interactions were detected between sex and psychosocial factors with respect to opioid use after surgery. Conclusion: Secondary analysis of this retrospective cohort study found minimal evidence that the association between psychosocial factors and opioid consumption after elective spine surgery differs by sex in adults ≥65.

Academic productivity and NIH funding for anesthesiology departmental chairs: A 15-year comparison.

STUDY OBJECTIVE: This study evaluated whether there were improvements in the number of departmental National Institutes of Health (NIH) training grants and the academic productivity of departmental chairs in terms of NIH research funding and PubMed-cited publications when compared to chairs of the same departments in 2006. DESIGN: Each chair was identified from the Society of Academic Associations of Academic Anesthesiology & Perioperative Medicine's Association of Academic Anesthesiology Chairs and entered into the NIH Research Portfolio Online Reporting Tools (RePORTER), PubMed, SCOPUS, and the National Provider Identifier Registry. MEASUREMENTS: The number and funding amounts of training grants awarded to the department in 2010, 2015, and 2020 were obtained as well as the department's national ranking and total dollar amount for NIH funding in 2020. For the current chair cohort, total publications and m-quotient (h-index corrected for active research years) were recorded along with each chair's history of NIH grant funding. These data were compared to a previous study of anesthesiology chairs that reviewed funding and publications through 2006. MAIN RESULTS: We analyzed data from 100 academic departments of anesthesiology and compared their scholarly activity relative to data gathered in 2006. In 2020, 52 of 100 departments of anesthesiology had evidence of NIH funding. There were not statistically significant (P > 0.05) differences in grants funding obtained by chairs between 2006 and 2020 with the exception that more chairs in 2006 had program or center grants. Median publications for chairs significantly increased from 35 in 2006 to 55 in 2021 (IRR = 1.5, 95% CI = 1.2-2.0, P = 0.003). Nineteen percent of chairs were female, which did not significantly differ from the proportion of women in the 2006 paper (15%, χ2 = 0.57, df = 1, P = 0.452). Of the male chairs, 90% were professors whereas 63% of female chairs were professors (χ2 = 8.8, df = 1, P = 0.003). Female chairs had fewer publications than male chairs (IRR = 1.8, 95% CI = 1.2-1.8, P = 0.002); however, m-quotients were not significantly different between men and women (P = 0.602). CONCLUSIONS: When compared to 2006, department of anesthesiology chairs had more publications in 2021; however, NIH funding rates remained unchanged. The specialty had 19% female chairs, and those chairs had fewer publications than their male counterparts, though sex differences were attenuated using metrics that account for disparities in career length.

Anesthetics inhibit phosphorylation of the ribosomal protein S6 in mouse cultured cortical cells and developing brain.

Introduction: The development and maintenance of neural circuits is highly sensitive to neural activity. General anesthetics have profound effects on neural activity and, as such, there is concern that these agents may alter cellular integrity and interfere with brain wiring, such as when exposure occurs during the vulnerable period of brain development. Under those conditions, exposure to anesthetics in clinical use today causes changes in synaptic strength and number, widespread apoptosis, and long-lasting cognitive impairment in a variety of animal models. Remarkably, most anesthetics produce these effects despite having differing receptor mechanisms of action. We hypothesized that anesthetic agents mediate these effects by inducing a shared signaling pathway. Methods: We exposed cultured cortical cells to propofol, etomidate, or dexmedetomidine and assessed the protein levels of dozens of signaling molecules and post-translational modifications using reverse phase protein arrays. To probe the role of neural activity, we performed separate control experiments to alter neural activity with non-anesthetics. Having identified anesthetic-induced changes in vitro, we investigated expression of the target proteins in the cortex of sevoflurane anesthetized postnatal day 7 mice by Western blotting. Results: All the anesthetic agents tested in vitro reduced phosphorylation of the ribosomal protein S6, an important member of the mTOR signaling pathway. We found a comparable decrease in cortical S6 phosphorylation by Western blotting in sevoflurane anesthetized neonatal mice. Using a systems approach, we determined that propofol, etomidate, dexmedetomidine, and APV/TTX all similarly modulate a signaling module that includes pS6 and other cell mediators of the mTOR-signaling pathway. Discussion: Reduction in S6 phosphorylation and subsequent suppression of the mTOR pathway may be a common and novel signaling event that mediates the impact of general anesthetics on neural circuit development.

Age-dependent differences and similarities in the plasma proteomic signature of postoperative delirium.

Delirium is an acute confusional state and a common postoperative morbidity. Prevalent in older adults, delirium occurs at other ages but it is unclear whether the pathophysiology and biomarkers for the condition are independent of age. We quantified expression of 273 plasma proteins involved in inflammation and cardiovascular or neurologic conditions in 34 middle-aged and 42 older patients before and one day after elective spine surgery. Delirium was identified by the 3D-CAM and comprehensive chart review. Protein expression was measure by Proximity Extension Assay and results were analyzed by logistic regression, gene set enrichment, and protein-protein interactions. Twenty-two patients developed delirium postoperatively (14 older; 8 middle-aged) and 89 proteins in pre- or 1-day postoperative plasma were associated with delirium. A few proteins (IL-8, LTBR, TNF-R2 postoperatively; IL-8, IL-6, LIF, ASGR1 by pre- to postoperative change) and 12 networks were common to delirium in both age groups. However, there were marked differences in the delirium proteome by age; older patients had many more delirium-associated proteins and pathways than middle-aged subjects even though both had the same clinical syndrome. Therefore, there are age-dependent similarities and differences in the plasma proteomic signature of postoperative delirium, which may signify age differences in pathogenesis of the syndrome.

Blood tau-PT217 contributes to the anesthesia/surgery-induced delirium-like behavior in aged mice.

INTRODUCTION: Blood phosphorylated tau at threonine 217 (tau-PT217) is a newly established biomarker for Alzheimer's disease and postoperative delirium in patients. However, the mechanisms and consequences of acute changes in blood tau-PT217 remain largely unknown. METHODS: We investigated the effects of anesthesia/surgery on blood tau-PT217 in aged mice, and evaluated the associated changes in B cell populations, neuronal excitability in anterior cingulate cortex, and delirium-like behavior using positron emission tomography imaging, nanoneedle technology, flow cytometry, electrophysiology, and behavioral tests. RESULTS: Anesthesia/surgery induced acute increases in blood tau-PT217 via enhanced generation in the lungs and release from B cells. Tau-PT217 might cross the blood-brain barrier, increasing neuronal excitability and inducing delirium-like behavior. B cell transfer and WS635, a mitochondrial function enhancer, mitigated the anesthesia/surgery-induced changes. DISCUSSION: Acute increases in blood tau-PT217 may contribute to brain dysfunction and postoperative delirium. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.

The Relationship of Postoperative Pain and Opioid Consumption to Postoperative Delirium After Spine Surgery.

Purpose: To examine the relationship between postoperative pain and opioid use and the development of postoperative delirium (POD), with attention to the preoperative opioid use status of patients. Methods: This was a secondary analysis of data from a prospective observational study of patients (N = 219; ≥70 years old) scheduled to undergo elective spine surgery. Maximal daily pain scores (0-10) and postoperative morphine milligram equivalents per hour (MME/hr) were determined for postoperative days 1-3 (D1-3). POD was assessed by daily in-person interviews using the Confusion Assessment Method and chart review. Results: Patients who reported regular preoperative opioid use (n = 58, 27%) reported significantly greater maximal daily pain scores, despite also requiring greater daily opioids (MME/hr) in the first 3 days after surgery. These patients were also more likely to develop POD. Interestingly, while postoperative pain scores were significantly higher in patients who developed POD, postoperative opioid consumption was not significantly higher in this group. Conclusion: POD was associated with greater postoperative pain, but not with postoperative opioid consumption. While postoperative opioid consumption is often blamed for delirium, these findings suggest that uncontrolled pain may actually be a more important factor, particularly among patients who are opioid tolerant. These findings underscore the importance of employing multimodal perioperative analgesic management, especially among older patients who have a predilection to developing POD and baseline tolerance to opioids.

Odor Enrichment Attenuates the Anesthesia/Surgery-induced Cognitive Impairment.

OBJECTIVE: To determine the association between olfactory function and cognition in patients and rodents. BACKGROUND: Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR. METHODS: We performed a prospective observational cohort study to determine potential association between olfactory impairment and dNCR in patients. We assessed the effects of anesthesia/surgery on olfactory and cognitive function in mice using the block test and Barnes maze. We measured interleukin-6 (IL-6), olfactory mature protein, growth-associated protein 43, mature and premature olfactory neurons, postsynaptic density 95, and synaptophysin in blood, nasal epithelium, and hippocampus of mice. Odor enrichment, IL-6 antibody, and knockout of IL-6 were used in the interaction experiments. RESULTS: Patients with dNCR had worse odor identification than the patients without dNCR [preoperative: 7 (1.25, 9) vs 10 (8, 11), median (interquartile range), P <0.001; postoperative: 8 (2.25, 10) vs 10 (8, 11), P <0.001]. Olfactory impairment associated with dNCR in patients before and after adjusting age, sex, education, preoperative mini-mental state examination score, and days of the neuropsychological tests. Anesthesia/surgery induced olfactory and cognitive impairment, increased levels of IL-6 in blood and nasal epithelium, decreased amounts of olfactory receptor neurons and their markers in the nasal epithelium, and reduced amounts of synapse markers in the hippocampus of mice. These changes were attenuated by odor enrichment and IL-6 antibody. CONCLUSION: The anesthesia/surgery-induced olfactory impairment may contribute to dNCR in patients and postoperative cognitive impairment in mice. Odor enrichment could be a potential intervention.

Academic achievement and gender among adult critical care program directors.

PURPOSE: Accreditation Council for Graduate Medical Education (ACGME) program director (PD) qualifications includes scholarly activity with demonstrated academic productivity and dissemination. Our hypothesis: academic productivity among adult critical care medicine (CCM) fellowship PDs is affected by gender with women having lower productivity. MATERIALS AND METHODS: PDs in 39 institutions with CCM fellowships in anesthesiology, surgery, and pulmonary medicine were analyzed using data from ACGME website, PubMed, and NIH Research Portfolio Online Reporting Tools. Primary outcomes were total publications and h-index. Secondary outcomes included NIH funding and past five year publications. Independent variables and covariates included gender, academic rank, year appointed as program director, years certified in CCM, and specialty. RESULTS: PDs who were women had fewer total publications (median: 13 vs: 20, p = 0.030), past 5 years publications (median: 6 vs median: 9; p = 0.025), and less NIH funding (12% vs 32%; p = 0.046) compared to men. In exploratory analyses stratified by rank, assistant professor ranked women had fewer total (p = 0.027) and recent publications (p = 0.031) compared to men. CONCLUSIONS: Women who were PDs had fewer publications and less NIH funding compared to men with differences in publications more prominent in early career faculty.

Association Among Preoperative Cognitive Performance, Regional Cerebral Oxygen Saturation, and Postoperative Delirium in Older Portuguese Patients.

BACKGROUND: Postoperative delirium is common among older patients and preoperative identification of high-risk patients is widely recommended. The aim of this study was to assess whether preoperative cognitive performance using brief screening tools or regional cerebral oxygen saturation (Scto2) was associated with the development of postoperative delirium in older Portuguese patients undergoing elective surgery. METHODS: Prospective observational cohort study where preoperative cognitive screening tools (Mini-Cog, Mini-Mental State Examination, verbal fluency) and Scto2 (INVOS 5100C; Medtronic, Ireland) were assessed in 238 patients ≥65 years old undergoing elective surgery between July 2017 and May 2019 at a tertiary academic center in Portugal. The primary outcome was postoperative delirium detected by the 3D-Confusion Assessment Method. Data were analyzed by univariate analysis and multivariable logistic regression. RESULTS: Delirium was identified in 53 patients (22%); 162 patients (68%) had completed only 4 years of education. On multivariable analysis, probable cognitive impairment tested by the Mini-Cog (odds ratio [OR] = 1.57; 95% confidence interval [CI], 0.70-3.53; corrected P value >.999), by the Mini-Mental State Examination (OR = 2.75; 95% CI, 1.23-6.13; corrected P value = .052), and by the animal verbal fluency test (OR = 1.24; 95% CI, 0.49-3.16; corrected P value >.999) were not significantly associated with the development of postoperative delirium. In contrast, lower preoperative Scto2 (OR = 1.08; 95% CI, 1.02-1.14; corrected P value = .024 for each point decrease in Scto2) was associated with postoperative delirium. CONCLUSIONS: We did not find enough evidence to suggest that poor preoperative cognitive performance was significantly associated with the development of postoperative delirium in an older Portuguese surgical population with an overall low level of formal education, but rather that preoperative Scto2 may be helpful in identifying patients at risk for delirium.

The Association of a Frailty Index and Incident Delirium in Older Hospitalized Patients: An Observational Cohort Study.

INTRODUCTION/BACKGROUND: Frailty identifies patients that have vulnerability to stress. Acute illness and hospitalization are stressors that may result in delirium and further accelerate the negative consequences of frailty. PURPOSE: The purpose of this study was to determine whether frailty, identified at hospital admission and as measured by a frailty index, is associated with incident delirium. METHODS: A retrospective, observational, cohort study was done at a Veterans hospital between January 2013 and March 2014. English-speaking patients over 55 years were eligible. Exclusion criteria included inability to complete baseline assessments due to pre-existing cognitive impairment, emergent surgery; and/or admission from a nursing home, pre-existing delirium, and those with psychiatric disease or substance use disorder. MAIN OUTCOMES AND MEASURES: Frailty index (FI) variables included cognitive screening, physical function and comorbidities. The FI was calculated as a proportion of possible deficits (range 0 to 1; higher scores indicate increased frailty). Incident delirium was measured daily by an expert clinician interview. RESULTS: A total of 247 patients were admitted and 218 met inclusion/exclusion criteria, with a mean age of 71.54 years (SD = 9.53 years) and were predominantly white (92.7%) and male (91.7%). Participants were grouped using FI ranges as non-frail (FI <0.25, n=56 (26%)), pre-frail (FI =0.25-0.35, n=86 (39%)), and frail (FI >0.35, n=76 (35%)). Pre-frailty and frailty were associated with incident delirium (non-frail: 3.6% vs pre-frail: 20.9% vs frail: 29.3%, p=0.001) and total delirium days (mean day =non-frail 0.04 vs pre-frail 0.35 vs frail 0.57, p=0.003). After adjustment for sociodemographic factors, pre-frail (adjusted OR=5.64, 95% CI: 1.23, 25.99) and frail status (adjusted OR=6.80, 95% CI: 1.38, 33.45) were independently associated with delirium. CONCLUSION: This study demonstrates that a frailty index is independently associated with incident delirium and suggests that admission assessments for frailty may identify patients at high risk of developing delirium.

First-Year Results of the American Board of Anesthesiology's Objective Structured Clinical Examination for Initial Certification.

In 2018, the American Board of Anesthesiology (ABA) became the first US medical specialty certifying board to incorporate an Objective Structured Clinical Examination (OSCE) into its initial certification examination system. Previously, the ABA's staged examination system consisted of 2 written examinations (the BASIC and ADVANCED examinations) and the Standardized Oral Examination (SOE). The OSCE and the existing SOE are now 2 separate components of the APPLIED Examination. This report presents the results of the first-year OSCE administration. A total of 1410 candidates took both the OSCE and the SOE in 2018. Candidate performance approximated a normal distribution for both the OSCE and the SOE, and was not associated with the timing of the examination, including day of the week, morning versus afternoon session, and order of the OSCE and the SOE. Practice-based Learning and Improvement was the most difficult station, while Application of Ultrasonography was the least difficult. The correlation coefficient between SOE and OSCE scores was 0.35 ([95% confidence interval {CI}, 0.30-0.39]; P < .001). Scores for the written ADVANCED Examination were modestly correlated with scores for the SOE (r = 0.29 [95% CI, 0.25-0.34]; P < .001) and the OSCE (r = 0.15 [95% CI, 0.10-0.20]; P < .001). Most of the candidates who failed the SOE passed the OSCE, and most of the candidates who failed the OSCE passed the SOE. Of the 1410 candidates, 77 (5.5%) failed the OSCE, 155 (11.0%) failed the SOE, and 25 (1.8%) failed both. Thus, 207 (14.7%) failed at least 1 component of the APPLIED Examination. Adding an OSCE to a board certification examination system is feasible. Preliminary evidence indicates that the OSCE measures aspects of candidate abilities distinct from those measured by other examinations used for initial board certification.

Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery.

BACKGROUND: Frailty and cognitive impairment are associated with postoperative delirium, but are rarely assessed preoperatively. The study was designed to test the hypothesis that preoperative screening for frailty or cognitive impairment identifies patients at risk for postoperative delirium (primary outcome). METHODS: In this prospective cohort study, the authors administered frailty and cognitive screening instruments to 229 patients greater than or equal to 70 yr old presenting for elective spine surgery. Screening for frailty (five-item FRAIL scale [measuring fatigue, resistance, ambulation, illness, and weight loss]) and cognition (Mini-Cog, Animal Verbal Fluency) were performed at the time of the preoperative evaluation. Demographic data, perioperative variables, and postoperative outcomes were gathered. Delirium was the primary outcome detected by either the Confusion Assessment Method, assessed daily from postoperative day 1 to 3 or until discharge, if patient was discharged sooner, or comprehensive chart review. Secondary outcomes were all other-cause complications, discharge not to home, and hospital length of stay. RESULTS: The cohort was 75 [73 to 79 yr] years of age, 124 of 219 (57%) were male. Many scored positive for prefrailty (117 of 218; 54%), frailty (53 of 218; 24%), and cognitive impairment (50 to 82 of 219; 23 to 37%). Fifty-five patients (25%) developed delirium postoperatively. On multivariable analysis, frailty (scores 3 to 5 [odds ratio, 6.6; 95% CI, 1.96 to 21.9; P = 0.002]) versus robust (score 0) on the FRAIL scale, lower animal fluency scores (odds ratio, 1.08; 95% CI, 1.01 to 1.51; P = 0.036) for each point decrease in the number of animals named, and more invasive surgical procedures (odds ratio, 2.69; 95% CI, 1.31 to 5.50; P = 0.007) versus less invasive procedures were associated with postoperative delirium. CONCLUSIONS: Screening for frailty and cognitive impairment preoperatively using the FRAIL scale and the Animal Verbal Fluency test in older elective spine surgery patients identifies those at high risk for the development of postoperative delirium.

Incidental Durotomy Is Associated With Increased Risk of Delirium in Patients Aged 65 and Older.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the impact of incidental durotomy during spine surgery on the development of delirium in patients aged 65 and older. SUMMARY OF BACKGROUND DATA: Delirium after spine surgery has been shown to increase the risk of adverse events, including morbidity and readmissions. Durotomy has previously been postulated to influence the risk of delirium, but this has not been explored in patients 65 and older, the demographic at greatest risk of developing delirium. METHODS: We obtained clinical data on 766 patients, including 182 with incidental durotomy, from the Partners healthcare registry (2012-2019). Patients had their medical records abstracted and age, biologic sex, body mass index, smoking status, preoperative diagnosis, use of a fusion-based procedure, and number of comorbidities were recorded. Our primary outcome was the development of delirium. Our primary predictor was incidental durotomy. We used logistic regression techniques to adjust for sociodemographic and clinical confounders. We performed propensity score matching as a sensitivity test. We hypothesized that elderly patients would be at increased risk of delirium following durotomy. RESULTS: Delirium was identified in 142 patients (19%). Among patients with an incidental durotomy, 26% were diagnosed with delirium. The incidence of delirium was 16% in the control group. Following adjusted analysis, the likelihood of delirium was significantly greater in patients with a durotomy (odds ratio [OR] 1.91; 95% confidence interval [CI] 1.27, 2.88). After propensity score matching, durotomy remained significantly associated with delirium in multivariable adjusted analyses (OR 1.90; 95% CI 1.07, 3.39). CONCLUSION: This investigation is among the first to specifically evaluate an association between durotomy and delirium in elderly patients undergoing spine surgery. The increased association between durotomy and delirium in this cohort should prompt increased surveillance and interventions designed to minimize the potential for cognitive deterioration or impairment during postoperative management of a durotomy. LEVEL OF EVIDENCE: 3.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Delirium Prevention.

Postoperative delirium is a geriatric syndrome that manifests as changes in cognition, attention, and levels of consciousness after surgery. It occurs in up to 50% of patients after major surgery and is associated with adverse outcomes, including increased hospital length of stay, higher cost of care, higher rates of institutionalization after discharge, and higher rates of readmission. Furthermore, it is associated with functional decline and cognitive impairments after surgery. As the age and medical complexity of our surgical population increases, practitioners need the skills to identify and prevent delirium in this high-risk population. Because delirium is a common and consequential postoperative complication, there has been an abundance of recent research focused on delirium, conducted by clinicians from a variety of specialties. There have also been several reviews and recommendation statements; however, these have not been based on robust evidence. The Sixth Perioperative Quality Initiative (POQI-6) consensus conference brought together a team of multidisciplinary experts to formally survey and evaluate the literature on postoperative delirium prevention and provide evidence-based recommendations using an iterative Delphi process and Grading of Recommendations Assessment, Development and Evaluation (GRADE) Criteria for evaluating biomedical literature.