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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., (© 2023. The Author(s).)

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., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 International Anesthesia Research Society.)

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., (Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.)

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., Competing Interests: This paper/was presented at the 2019 Gerontological Society of America Annual Meeting as a poster presentation with interim findings entitled “The Association of a Frailty Index and Incident Delirium in Hospitalized Veterans”. The conference abstract was published in Innovations In Aging with DOI: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6845397/]. Dr Culley reports grants from NIGMS, during the conduct of the study; personal fees from American Society of Anesthesiology, personal fees from American Board of Anesthesiology, outside the submitted work. Dr. Arora reports an unrestricted educational grant from Pfizer Canada Inc. and honoraria from Abbott Nutrition, and honorarium from Edwards Lifesciences, outside the submitted work. Dr Rudolph reports being an unpaid board member of the American Delirium Society - a professional society dedicated to the advancement of delirium science. The authors report no other potential conflicts of interest for this work., (© 2020 Sillner et al.)

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.

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.

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.

Background: Dementia and delirium have been postulated to share common pathophysiologic mechanisms; however, identification of these unifying mechanisms has remained elusive. The inhalation anesthetic isoflurane has been shown to enhance beta-amyloid protein (Abeta) oligomerization and generation, to potentiate the cytotoxicity of Abeta, and to induce apoptosis. To address the molecular mechanisms of dementia and delirium associated with anesthesia and surgery, we assessed whether the Abeta fibrillar aggregation inhibitor Congo red can attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells overexpressing human beta-amyloid precursor protein (APP)., Methods: H4 human neuroglioma cells stably transfected to express human full-length wild-type APP were exposed to 2% isoflurane for 6 hours. The cells were harvested at the end of the treatment. Caspase-3 activation was measured with quantitative Western blotting., Results: We found that isoflurane induces cellular apoptosis in a dose-dependent manner, and that Congo red inhibits isoflurane-induced apoptosis in H4 human neuroglioma cells overexpressing APP. Interestingly, Congo red also inhibits staurosporine-induced apoptosis., Conclusion: The demonstration that isoflurane contributes to well-described mechanisms of Alzheimer's neuropathogenesis provides a plausible link between the acute effects of anesthesia, a well-described risk factor for delirium, and the more long-term sequelae of dementia. These findings suggest that isoflurane-induced Abeta oligomerization and apoptosis may contribute to the risk of postoperative cognitive dysfunction and provide a potential pathogenic link between delirium and dementia.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50-μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1-3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24-48h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2h after LPS but normalized by the time behavioral testing started 24h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further. [ABSTRACT FROM AUTHOR]

The article focuses on delirium and prolonged postoperative cognitive dysfunction, which are seen as the most common forms of perioperative morbidity in elders, affecting 8-74% of them. Delirium is defined as an acute brain disorder characterized in part by an altered level of consciousness, distorted environmental awareness, and a change in cognition or the development of perceptual disturbances that are not the result of a preexisting dementia.

Background. Dementia and delirium have been postulated to share common pathophysiologic mechanisms; however, identification of these unifying mechanisms has remained elusive. The inhalation anesthetic isoflurane has been shown to enhance β-amyloid protein (Aβ) oligomerization and generation, to potentiate the cytotoxicity of Aβ, and to induce apoptosis. To address the molecular mechanisms of dementia and delirium associated with anesthesia and surgery, we assessed whether the Aβ fibrillar aggregation inhibitor Congo red can attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells overexpressing human β-amyloid precursor protein (APP). Methods. H4 human neuroglioma cells stably transfected to express human full-length wild-type APP were exposed to 2% isoflurane for 6 hours. The cells were harvested at the end of the treatment. Caspase-3 activation was measured with quantitative Western blotting. Results. We found that isoflurane induces cellular apoptosis in a dose-dependent manner, and that Congo red inhibits isoflurane-induced apoptosis in H4 human neuroglioma cells overexpressing APP. Interestingly, Congo red also inhibits staurosporine-induced apoptosis. Conclusion. The demonstration that isoflurane contributes to well-described mechanisms of Alzheimer's neuropathogenesis provides a plausible link between the acute effects of anesthesia, a well-described risk factor for delirium, and the more long-term sequelae of dementia. These findings suggest that isoflurune induced Aβ oligomerization and apoptosis may contribute to the risk of postoperative cognitive dysfunction and provide a potential pathogenic link between delirium and dementia. [ABSTRACT FROM AUTHOR]

Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects. [ABSTRACT FROM AUTHOR]