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.

Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network.

Delirium is a common, morbid, and costly syndrome that is closely linked to Alzheimer's disease (AD) and AD-related dementias (ADRD) as a risk factor and outcome. Human studies of delirium have advanced our knowledge of delirium incidence and prevalence, risk factors, biomarkers, outcomes, prevention, and management. However, understanding of delirium neurobiology remains limited. Preclinical and translational models for delirium, while challenging to develop, could advance our knowledge of delirium neurobiology and inform the development of new prevention and treatment approaches. We discuss the use of preclinical and translational animal models in delirium, focusing on (1) a review of current animal models, (2) challenges and strategies for replicating elements of human delirium in animals, and (3) the utility of biofluid, neurophysiology, and neuroimaging translational markers in animals. We conclude with recommendations for the development and validation of preclinical and translational models for delirium, with the goal of advancing awareness in this important field.

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.

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.

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.

Poor Performance on a Preoperative Cognitive Screening Test Predicts Postoperative Complications in Older Orthopedic Surgical Patients.

BACKGROUND: The American College of Surgeons and the American Geriatrics Society have suggested that preoperative cognitive screening should be performed in older surgical patients. We hypothesized that unrecognized cognitive impairment in patients without a history of dementia is a risk factor for development of postoperative complications. METHODS: We enrolled 211 patients 65 yr of age or older without a diagnosis of dementia who were scheduled for an elective hip or knee replacement. Patients were cognitively screened preoperatively using the Mini-Cog and demographic, medical, functional, and emotional/social data were gathered using standard instruments or review of the medical record. Outcomes included discharge to place other than home (primary outcome), delirium, in-hospital medical complications, hospital length-of-stay, 30-day emergency room visits, and mortality. Data were analyzed using univariate and multivariate analyses. RESULTS: Fifty of 211 (24%) patients screened positive for probable cognitive impairment (Mini-Cog less than or equal to 2). On age-adjusted multivariate analysis, patients with a Mini-Cog score less than or equal to 2 were more likely to be discharged to a place other than home (67% vs. 34%; odds ratio = 3.88, 95% CI = 1.58 to 9.55), develop postoperative delirium (21% vs. 7%; odds ratio = 4.52, 95% CI = 1.30 to 15.68), and have a longer hospital length of stay (hazard ratio = 0.63, 95% CI = 0.42 to 0.95) compared to those with a Mini-Cog score greater than 2. CONCLUSIONS: Many older elective orthopedic surgical patients have probable cognitive impairment preoperatively. Such impairment is associated with development of delirium postoperatively, a longer hospital stay, and lower likelihood of going home upon hospital discharge.

EARLY gestational exposure to isoflurane causes persistent cell loss in the dentate gyrus of adult male rats.

BACKGROUND: Our previous research showed that 4 h of maternal anesthesia with isoflurane during early gestation in pregnant rats leads to a deficit in spatial memory of adult male offspring. Because spatial memory is predominantly a hippocampally-mediated task, we asked the question if early gestational exposure to isoflurane affects development of the hippocampus in the offspring. FINDINGS: Previously behaviorally characterized adult male rats that were exposed to isoflurane during second trimester were sacrificed at 4 months of age (N = 10 and 13, control and isoflurane groups, respectively) for quantitative histology of hippocampal subregions. Sections were stained with cresyl violet and the total number of cells in the granular layer of the dentate gyrus and the pyramidal cell layer in the CA1 region were determined by a blinded observer using unbiased stereological principles and the optical fractionator method. Data were analyzed using Student's t test; P < 0.05 was accorded statistical significance. Stereological examination revealed 9% fewer cells in the granular layer of the dentate gyrus of isoflurane-exposed adult rats compared to controls (1,002,122 ± 84,870 vs. 1,091,829 ± 65,791, respectively; Mean ± S.D, *P = 0.01). In contrast, there were no changes in the cell number in the CA1 region, nor were there changes in the volumes of both regions. CONCLUSIONS: Our results show that maternal isoflurane anesthesia in rodents causes region-specific cell loss in the hippocampus of adult male offspring. These changes may, in part, account for the behavioral deficits reported in adult rats exposed to isoflurane in utero.

Preoperative Cognitive Stratification of Older Elective Surgical Patients: A Cross-Sectional Study.

BACKGROUND: Preexisting cognitive impairment is emerging as a predictor of poor postoperative outcomes in seniors. We hypothesized that preoperative cognitive screening can be performed in a busy preadmission evaluation center and that cognitive impairment is prevalent in elective geriatric surgical patients. METHODS: We approached 311 patients aged 65 years and older presenting for preoperative evaluation before elective surgery in a prospective, observational, single-center study. Forty-eight patients were ineligible, and 63 declined. The remaining 200 were randomly assigned to the Mini-Cog (N =100) or Clock-in-the-Box [CIB; N = 100)] test. Study staff administered the test in a quiet room, and 2 investigators scored the tests independently. Probable cognitive impairment was defined as a Mini-Cog ≤ 2 or a CIB ≤ 5. RESULTS: The age of consenting patients was 73.7 ± 6.4 (mean ± SD) years. There were no significant differences between patients randomly assigned to the Mini-Cog and CIB test in age, weight, gender, education, ASA physical status, or Charlston Index. Overall, 23% of patients met criteria for probable cognitive impairment, and prevalence was virtually identical regardless of the test used; 22% screened with the Mini-Cog and 23% screened with the CIB scored as having probable cognitive impairment (P = 1.0 by χ analysis). Both tests had good interrater reliability (Krippendroff α = 0.86 [0.72-0.93] for Mini-Cog and 1 for CIB). CONCLUSIONS: Preoperative cognitive screening is feasible in most geriatric elective surgical patients and reveals a substantial prevalence of probable cognitive impairment in this population.

Isoflurane Ameliorates Acute Lung Injury by Preserving Epithelial Tight Junction Integrity.

BACKGROUND: Isoflurane may be protective in preclinical models of lung injury, but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. The authors hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome. METHODS: Wild-type mice were treated with isoflurane 1 h after exposure to nebulized endotoxin (n = 8) or saline control (n = 9) and then allowed to recover for 24 h before mechanical ventilation (MV; tidal volume, 15 ml/kg, 2 h) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane 1 h after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo. RESULTS: Mice treated with isoflurane following exposure to inhaled endotoxin and before MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice after treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e., zona occludens 1) that was rescued by isoflurane treatment. CONCLUSIONS: Isoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein.

Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3ß activation in young mice.

BACKGROUND: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane is a commonly used anesthetic in children. Tau phosphorylation contributes to cognitive dysfunction. The authors therefore assessed the effects of sevoflurane on Tau phosphorylation and the underlying mechanisms in young mice. METHODS: Six-day-old wild-type and Tau knockout mice were exposed to sevoflurane. The authors determined the effects of sevoflurane anesthesia on Tau phosphorylation, levels of the kinases and phosphatase related to Tau phosphorylation, interleukin-6 and postsynaptic density protein-95 in hippocampus, and cognitive function in both young wild-type and Tau knockout mice. RESULTS: Anesthesia with 3% sevoflurane 2 h daily for 3 days induced Tau phosphorylation (257 vs. 100%, P = 0.0025, n = 6) and enhanced activation of glycogen synthase kinase 3ß, which is the kinase related to Tau phosphorylation in the hippocampus of postnatal day-8 wild-type mice. The sevoflurane anesthesia decreased hippocampus postsynaptic density protein-95 levels and induced cognitive impairment in the postnatal day-31 mice. Glycogen synthase kinase 3ß inhibitor lithium inhibited the sevoflurane-induced glycogen synthase kinase 3ß activation, Tau phosphorylation, increased levels of interleukin-6, and cognitive impairment in the wild-type young mice. Finally, the sevoflurane anesthesia did not induce an increase in interleukin-6 levels, reduction in postsynaptic density protein-95 levels in hippocampus, or cognitive impairment in Tau knockout young mice. CONCLUSIONS: These data suggested that sevoflurane induced Tau phosphorylation, glycogen synthase kinase 3ß activation, increase in interleukin-6 and reduction in postsynaptic density protein-95 levels in hippocampus of young mice, and cognitive impairment in the mice. Future studies will dissect the cascade relation of these effects.

Academic productivity of directors of ACGME-accredited residency programs in surgery and anesthesiology.

BACKGROUND: Scholarly activity is expected of program directors of Accreditation Council for Graduate Medical Education (ACGME)-accredited residency training programs. Anesthesiology residency programs are cited more often than surgical programs for deficiencies in academic productivity. We hypothesized that this may in part reflect differences in scholarly activity between program directors of anesthesiology and surgical trainings programs. To test the hypothesis, we examined the career track record of current program directors of ACGME-accredited anesthesiology and surgical residency programs at the same institutions using PubMed citations and funding from the National Institutes of Health (NIH) as metrics of scholarly activity. METHODS: Between November 1, 2011 and December 31, 2011, we obtained data from publicly available Web sites on program directors at 127 institutions that had ACGME-accredited programs in both anesthesiology and surgery. Information gathered on each individual included year of board certification, year first appointed program director, academic rank, history of NIH grant funding, and number of PubMed citations. We also calculated the h-index for a randomly selected subset of 25 institution-matched program directors. RESULTS: There were no differences between the groups in number of years since board certification (P = 0.42), academic rank (P = 0.38), or years as a program director (P = 0.22). However, program directors in anesthesiology had less prior or current NIH funding (P = 0.002), fewer total and education-related PubMed citations (both P < 0.001), and a lower h-index (P = 0.001) than surgery program directors. Multivariate analysis revealed that the publication rate for anesthesiology program directors was 43% (95% confidence interval, 0.31-0.58) that of the corresponding program directors of surgical residency programs, holding other variables constant. CONCLUSIONS: Program directors of anesthesiology residency programs have considerably less scholarly activity in terms of peer-reviewed publications and federal research funding than directors of surgical residency programs. As such, this study provides further evidence for a systemic weakness in the scholarly fabric of academic anesthesiology.

Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory.

OBJECTIVE: There are approximately 8.5 million Alzheimer disease (AD) patients who need anesthesia and surgery care every year. The inhalation anesthetic isoflurane, but not desflurane, has been shown to induce caspase activation and apoptosis, which are part of AD neuropathogenesis, through the mitochondria-dependent apoptosis pathway. However, the in vivo relevance, underlying mechanisms, and functional consequences of these findings remain largely to be determined. METHODS: We therefore set out to assess the effects of isoflurane and desflurane on mitochondrial function, cytotoxicity, learning, and memory using flow cytometry, confocal microscopy, Western blot analysis, immunocytochemistry, and the fear conditioning test. RESULTS: Here we show that isoflurane, but not desflurane, induces opening of mitochondrial permeability transition pore (mPTP), increase in levels of reactive oxygen species, reduction in levels of mitochondrial membrane potential and adenosine-5'-triphosphate, activation of caspase 3, and impairment of learning and memory in cultured cells, mouse hippocampus neurons, mouse hippocampus, and mice. Moreover, cyclosporine A, a blocker of mPTP opening, attenuates isoflurane-induced mPTP opening, caspase 3 activation, and impairment of learning and memory. Finally, isoflurane may induce the opening of mPTP via increasing levels of reactive oxygen species. INTERPRETATION: These findings suggest that desflurane could be a safer anesthetic for AD patients as compared to isoflurane, and elucidate the potential mitochondria-associated underlying mechanisms, and therefore have implications for use of anesthetics in AD patients, pending human study confirmation.

Sevoflurane anesthesia in pregnant mice induces neurotoxicity in fetal and offspring mice.

BACKGROUND: Each year, over 75,000 pregnant women in the United States undergo anesthesia care. The authors set out to assess the effects of the anesthetic sevoflurane on neurotoxicity in pregnant mice and on learning and memory in fetal and offspring mice. METHODS: Pregnant mice (gestational day 14) and mouse primary neurons were treated with 2.5% sevoflurane for 2 h and 4.1% sevoflurane for 6 h, respectively. Brain tissues of both fetal and offspring mice (P31) and the primary neurons were harvested and subjected to Western blot and immunohistochemistry to assess interleukin-6, the synaptic markers postsynaptic density-95 and synaptophysin, and caspase-3 levels. Separately, learning and memory function in the offspring mice was determined in the Morris water maze. RESULTS: Sevoflurane anesthesia in pregnant mice induced caspase-3 activation, increased interleukin-6 levels (256 ± 50.98% [mean ± SD] vs. 100 ± 54.12%, P = 0.026), and reduced postsynaptic density-95 (61 ± 13.53% vs. 100 ± 10.08%, P = 0.036) and synaptophysin levels in fetal and offspring mice. The sevoflurane anesthesia impaired learning and memory in offspring mice at P31. Moreover, interleukin-6 antibody mitigated the sevoflurane-induced reduction in postsynaptic density-95 levels in the neurons. Finally, environmental enrichment attenuated the sevoflurane-induced increases in interleukin-6 levels, reductions of synapse markers, and learning and memory impairment. CONCLUSIONS: These results suggest that sevoflurane may induce detrimental effects in fetal and offspring mice, which can be mitigated by environmental enrichment. These findings should promote more studies to determine the neurotoxicity of anesthesia in the developing brain.

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.

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.