Long-term Outcomes with Spinal versus General Anesthesia for Hip Fracture Surgery: A Randomized Trial.

BACKGROUND: The effects of spinal versus general anesthesia on long-term outcomes have not been well studied. This study tested the hypothesis that spinal anesthesia is associated with better long-term survival and functional recovery than general anesthesia. METHODS: A prespecified analysis was conducted of long-term outcomes of a completed randomized superiority trial that compared spinal anesthesia versus general anesthesia for hip fracture repair. Participants included previously ambulatory patients 50 yr of age or older at 46 U.S. and Canadian hospitals. Patients were randomized 1:1 to spinal or general anesthesia, stratified by sex, fracture type, and study site. Outcome assessors and investigators involved in the data analysis were masked to the treatment arm. Outcomes included survival at up to 365 days after randomization (primary); recovery of ambulation among 365-day survivors; and composite endpoints for death or new inability to ambulate and death or new nursing home residence at 365 days. Patients were included in the analysis as randomized. RESULTS: A total of 1,600 patients were enrolled between February 12, 2016, and February 18, 2021; 795 were assigned to spinal anesthesia, and 805 were assigned to general anesthesia. Among 1,599 patients who underwent surgery, vital status information at or beyond the final study interview (conducted at approximately 365 days after randomization) was available for 1,427 (89.2%). Survival did not differ by treatment arm; at 365 days after randomization, there were 98 deaths in patients assigned to spinal anesthesia versus 92 deaths in patients assigned to general anesthesia (hazard ratio, 1.08; 95% CI, 0.81 to 1.44, P = 0.59). Recovery of ambulation among patients who survived a year did not differ by type of anesthesia (adjusted odds ratio for spinal vs. general, 0.87; 95% CI, 0.67 to 1.14; P = 0.31). Other outcomes did not differ by treatment arm. CONCLUSIONS: Long-term outcomes were similar with spinal versus general anesthesia.

Leg Length Discrepancy After Hip Fracture Repair is Associated With Reduced Gait Speed.

Introduction: A negative correlation exists between functional outcomes and leg length discrepancy (LLD) following hip fracture repair. We have assessed the effects of LLD following hip fracture repair in elderly patients on 3-meter walking time, standing time, activities of daily living (ADL), and instrumental activities of daily living (IADL). Methods: One hundred sixty-nine patients enrolled in the STRIDE trial were identified with femoral neck, intertrochanteric, and subtrochanteric fractures that were treated with partial hip replacement, total hip replacement, cannulated screws, or intramedullary nail. Baseline patient characteristics recorded included age, sex, body mass index Charlson comorbidity index (CCI) score. ADL, IADL, grip strength, sit-to-stand time, 3-meter walking time and return to ambulation status were measured at 1 year after surgery. LLD was measured on final follow-up radiographs by either the sliding screw telescoping distance or the difference from a trans-ischial line to the lesser trochanters, and was analyzed as a continuous variable using regression analysis. Results: Eighty eight patients (52%) had LLD <5 mm, 55 (33%) between 5-10 mm and 26 subjects (15%) >10 mm. Age, sex, BMI, Charlson score, and ambulation status had no significant impact on LLD occurrence. Type of procedure and fracture type did not correlate with severity of LLD. Having a larger LLD was not found to have a significant impact on post-operative ADL (P = .60), IADL (P = .08), sit-to-stand time (P = .90), grip strength (P = .14) and return to former ambulation status (P = .60), but did have a statistically significant impact on 3-meter walking time (P = .006). Discussion: LLD after hip fracture was associated with reduced gait speed but did not affect many parameters associated with recovery. Continued efforts to restore leg length after hip fracture repair are likely to be beneficial.

A Study of Physical Resilience and Aging (SPRING): Conceptual framework, rationale, and study design.

Understanding the physiological basis of physical resilience to clinical stressors is crucial for the well-being of older adults. This article presents a novel framework to discover the biological underpinnings of physical resilience in older adults as part of the "Characterizing Resiliencies to Physical Stressors in Older Adults: A Dynamical Physiological Systems Approach" study, also known as The Study of Physical Resilience and Aging (SPRING). Physical resilience, defined as the capacity of a person to withstand clinical stressors and quickly recover or improve upon a baseline functional level, is examined in adults aged 55 years and older by studying the dynamics of stress response systems. The hypothesis is that well-regulated stress response systems promote physical resilience. The study employs dynamic stimulation tests to assess energy metabolism, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the innate immune system. Baseline characteristics influencing resilience outcomes are identified through deep phenotyping of physical and cognitive function, as well as of biological, environmental, and psychosocial characteristics. SPRING aims to study participants undergoing knee replacement surgery (n = 100), bone and marrow transplantation (n = 100), or anticipating dialysis initiation (n = 60). Phenotypic and functional measures are collected pre-stressor and at multiple times after stressor for up to 12 months to examine resilience trajectories. By improving our understanding of physical resilience in older adults, SPRING has the potential to enhance resilient outcomes to major clinical stressors. The article provides an overview of the study's background, rationale, design, pilot phase, implementation, and implications for improving the health and well-being of older adults.

Comparative Effectiveness Research on Spinal versus General Anesthesia for Surgery in Older Adults.

Comparative effectiveness research aims to understand the benefits and harms of different treatments to assist patients and clinicians in making better decisions. Within anesthesia practice, comparing outcomes of spinal versus general anesthesia in older adults represents an important focus of comparative effectiveness research. The authors review methodologic issues involved in studying this topic and summarize available evidence from randomized studies in patients undergoing hip fracture surgery, elective knee and hip arthroplasty, and vascular surgery. Across contexts, randomized trials show that spinal and general anesthesia are likely to be equivalent in terms of safety and acceptability for most patients without contraindications. Choices between spinal and general anesthesia represent "preference-sensitive" care in which decisions should be guided by patients' preferences and values, informed by best available evidence.

Outcomes with spinal versus general anesthesia for patients with and without preoperative cognitive impairment: Secondary analysis of a randomized clinical trial.

INTRODUCTION: The effect of spinal versus general anesthesia on the risk of postoperative delirium or other outcomes for patients with or without cognitive impairment (including dementia) is unknown. METHODS: Post hoc secondary analysis of a multicenter pragmatic trial comparing spinal versus general anesthesia for adults aged 50 years or older undergoing hip fracture surgery. RESULTS: Among patients randomized to spinal versus general anesthesia, new or worsened delirium occurred in 100/295 (33.9%) versus 107/283 (37.8%; odds ratio [OR] 0.85; 95% confidence interval [CI] 0.60 to 1.19) among persons with cognitive impairment and 70/432 (16.2%) versus 71/445 (16.0%) among persons without cognitive impairment (OR 1.02; 95% CI 0.71 to 1.47, p = 0.46 for interaction). Delirium severity, in-hospital complications, and 60-day functional recovery did not differ by anesthesia type in patients with or without cognitive impairment. DISCUSSION: Anesthesia type is not associated with differences in delirium and functional outcomes among persons with or without cognitive impairment.

Edmonton frailty scale score predicts postoperative delirium: a retrospective cohort analysis.

BACKGROUND: Frailty has been associated with postoperative delirium (POD). Studies suggest that the Fried phenotype has a stronger association with POD than the Edmonton Frailty Scale (EFS) criteria. Although phenotypic frailty is recognized as a good predictor of delirium, the EFS has higher ratings for feasibility in the surgical setting. Thus, our aim was to determine the association between EFS-assessed vulnerability and POD in an elective surgical population of older adults. A secondary aim was to determine which domains assessed by the EFS were closely associated with POD. METHODS: After IRB approval was received, electronic medical records of surgical patients at our institution were downloaded from 12/1/2018 to 3/1/2020. Inclusion criteria included age ≥ 65 years, preoperative EFS assessment within 6 months of surgery, elective surgery not scheduled for intensive care unit (ICU) stay but followed by at least 1 day postoperative stay, and at least two in-hospital evaluations with the 4 A's test (arousal, attention, abbreviated mental test-4, acute change [4AT]) on the surgical ward. Vulnerability was determined by EFS score ≥ 6. Patients were stratified into two groups according to highest postoperative 4AT score: 0-3 (no POD) and ≥ 4 (POD). Odds of POD associated with EFS score ≥ 6 were evaluated by using logistic regression adjusted for potential confounders. RESULTS: The dataset included 324 patients. Vulnerability was associated with higher incidence of POD (p = 0.0007, Fisher's exact). EFS ≥6 was consistently associated with POD in all bivariate models. Vulnerability predicted POD in multivariable modeling (OR = 3.5, 95% CI 1.1 to 11.5). Multivariable analysis of EFS domains revealed an overall trend in which higher scores per domain had a higher odds for POD. The strongest association occurred with presence of incontinence (OR = 3.8, 95% CI 1.2 to 11.0). CONCLUSIONS: EFS criteria for vulnerability predict POD in older, non-ICU patients undergoing elective surgery.

Pain, Analgesic Use, and Patient Satisfaction With Spinal Versus General Anesthesia for Hip Fracture Surgery : A Randomized Clinical Trial.

BACKGROUND: The REGAIN (Regional versus General Anesthesia for Promoting Independence after Hip Fracture) trial found similar ambulation and survival at 60 days with spinal versus general anesthesia for hip fracture surgery. Trial outcomes evaluating pain, prescription analgesic use, and patient satisfaction have not yet been reported. OBJECTIVE: To compare pain, analgesic use, and satisfaction after hip fracture surgery with spinal versus general anesthesia. DESIGN: Preplanned secondary analysis of a pragmatic randomized trial. (ClinicalTrials.gov: NCT02507505). SETTING: 46 U.S. and Canadian hospitals. PARTICIPANTS: Patients aged 50 years or older undergoing hip fracture surgery. INTERVENTION: Spinal or general anesthesia. MEASUREMENTS: Pain on postoperative days 1 through 3; 60-, 180-, and 365-day pain and prescription analgesic use; and satisfaction with care. RESULTS: A total of 1600 patients were enrolled. The average age was 78 years, and 77% were women. A total of 73.5% (1050 of 1428) of patients reported severe pain during the first 24 hours after surgery. Worst pain over the first 24 hours after surgery was greater with spinal anesthesia (rated from 0 [no pain] to 10 [worst pain imaginable]; mean difference, 0.40 [95% CI, 0.12 to 0.68]). Pain did not differ across groups at other time points. Prescription analgesic use at 60 days occurred in 25% (141 of 563) and 18.8% (108 of 574) of patients assigned to spinal and general anesthesia, respectively (relative risk, 1.33 [CI, 1.06 to 1.65]). Satisfaction was similar across groups. LIMITATION: Missing outcome data and multiple outcomes assessed. CONCLUSION: Severe pain is common after hip fracture. Spinal anesthesia was associated with more pain in the first 24 hours after surgery and more prescription analgesic use at 60 days compared with general anesthesia. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Delirium detection methodologies: Implications for outcome measurement in clinical trials in postoperative delirium.

OBJECTIVE: Delirium is a common postoperative complication of hip fracture. Various methods exist to detect delirium as a reference standard. The goal of this study was to characterize the properties of the measures obtained in a randomized controlled trial, to document their relationship to the Diagnostic and Statistical Manual of Mental Disorders:Text Revision based diagnosis of postoperative delirium by a consensus panel, and to describe the method in detail to allow replication by others. METHODS: A secondary analysis of the randomized trial STRIDE (A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients) was conducted. Delirium assessments were performed in 200 consecutive hip fracture repair patients ≥65 years old. Assessors underwent extensive training in delirium assessment and the final delirium diagnosis was adjudicated by a consensus panel of three physicians with expertise in delirium assessment. RESULTS: A total of 680 consensus panel delirium diagnoses were completed. There were only 19 (2.8%, 19/678) evaluations where the delirium adjudication by the consensus panel differed from delirium findings by the Confusion Assessment Method (CAM). In 16 (84%, 16/19) of the cases, CAM was negative but the consensus panel diagnosed the patient as having delirium based on all of the available information including the CAM. CONCLUSION: The consensus panel diagnosis was more sensitive compared to CAM alone, however the magnitude of the difference was not large. When assessors are well trained and delirium assessments are closely supervised throughout the study, CAM may be adequate for delirium diagnosis in a clinical trial. Future studies are needed to test this hypothesis.

Risk Factors for Nonresilient Outcomes in Older Adults After Total Knee Replacement.

BACKGROUND: Total knee replacement (TKR) is a common procedure in older adults. Physical resilience may be a useful construct to explain variable outcomes. We sought to define a simple measure of physical resilience and identify risk factors for nonresilient patient outcomes. METHODS: Secondary analysis of Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) cohort study, a prospective registry of total joint replacement. The analysis included 7 239 adults aged 60 or older who underwent TKR between 2011 and 2015. Measures included sociodemographic and health factors. Outcomes were categorized as physically resilient versus nonresilient based on the change from baseline to 1-year follow-up for 3 patient-reported outcomes: the physical component summary (PCS), bodily pain (BP), and vitality (VT) from the Short Form-36 subcomponent scores, at preop and 1-year postprocedure. Associations were expressed as relative risk (RR) of physically nonresilient outcomes using generalized linear regression models, with Poisson distribution and log link. RESULTS: Age, body mass index, and Charlson Comorbidity Index (CCI) were associated with increased risk of physically nonresilient outcomes across PCS, BP, and VT: age, per 5 years for PCS (RR = 1.18 [1.12-1.23]), BP (RR = 1.06 [1.01-1.11), and VT (RR = 1.09 [1.06-1.12]); body mass index, per 5 kg/m2, for PCS (RR = 1.13 [1.07-1.19]), BP (RR = 1.06 [1.00-1.11]), and VT (RR = 1.08 [1.04-1.11]); and CCI for PCS CCI = 1 (RR = 1.38 [1.20-1.59]), CCI = 2-5 (RR = 1.59 [1.35-1.88]), CCI ≥6 (RR = 1.55 [1.31-1.83]. Household income >$45 000 associated with lower risk for PCS (RR = 0.81 [0.70-0.93]), BP (RR = 0.80 [0.69-0.91]), and VT (RR = 0.86 [0.78-0.93]). CONCLUSIONS: We operationalized physical resilience and identified factors predicting resilience after TKR. This approach may aid clinical risk stratification, guide further investigation of causes, and ultimately aid patients through the design of interventions to enhance physical resilience.

Processed intraoperative burst suppression and postoperative cognitive dysfunction in a cohort of older noncardiac surgery patients.

Postoperative cognitive dysfunction (POCD) is a decline in cognitive test performance which persists months after surgery. There has been great interest in the anesthesia community regarding whether variables generated by commercially available processed EEG monitors originally marketed to prevent awareness under anesthesia can be used to guide intraoperative anesthetic management to prevent POCD. Processed EEG monitors represent an opportunity for anesthesiologists to directly monitor the brain even if they have not been trained to interpret EEG waveforms. There is continued equipoise regarding whether any of the variables generated by the machines' interpretation of raw data are associated with POCD. Most literature has focused on the depth of anesthesia number, however recent studies have shown that processed depth may not be accurate in older age groups due to reduced alpha band power. Burst suppression is an encephalographic pattern of high voltage activity alternating with periods of electrical silence and is another marker of depth which can be obtained from commercial processed EEG monitors. We performed a prospective cohort study to determine whether burst suppression and burst suppression ratio as measured by the BIS Monitor (Bispectral Index, BIS Medtronic, Boulder CO), is associated with cognitive dysfunction 3 months after surgery. We recruited 167 elective surgery patients, 65 years of age and older, anticipated to require at least 2 day inpatient admission. Our main outcome measure was cognitive decline in composite z-score on the Alzheimer's Disease Research Center UDS Battery of at least 1 standard deviation 3 months after surgery relative to preoperative baseline. 14% experienced POCD, this group was older (72 [70, 74] versus 70 [67, 75] years), and had frailty scores as measured by the FRAIL Scale (2 [0, 3] versus 1 [0, 2]) and lower baseline z-scores (- 0.2 [- 0.6, 0.5] versus 0.1 [- 0.3, 0.5]). There was a univariable association between suppression ratio > 10 (SR > 10) and POCD (4.8 [0, 37.3] versus 15.4 [4.0-142.4] min), p = .038. However, after adjustment this relationship did not persist, only anesthetic technique, age, and pain remained in the model. In our cohort of older elective noncardiac surgery patients we found a marginal association between processed burst suppression (total burst suppression p = .067, SR > 5 p = .052, SR > 10.038) which did not persist in a multivariable model. Patients with POCD had almost twice the number of minutes of burst suppression, and three times the amount of time for SR > 5 and > 10. Our finding may be a limitation of the monitor's ability to detect burst suppression. The consistent trend towards more intraoperative burst suppression in patients who developed POCD suggests that future studies are needed to investigate the relationship of raw intraoperative burst suppression and POCD.Trial registry Clinical trial number and registry URL: Optimizing Postoperative Cognitive Dysfunction in the Elderly-PRESERVE, Clinical Trials Gov# NCT02650687; https://clinicaltrials.gov/ct2/show/NCT02650687 .

Spinal Anesthesia with Targeted Sedation based on Bispectral Index Values Compared with General Anesthesia with Masked Bispectral Index Values to Reduce Delirium: The SHARP Randomized Controlled Trial.

BACKGROUND: Reducing depth of anesthesia and anesthetic exposure may help prevent delirium, but trials have been conflicting. Most studies were conducted under general anesthesia or in cognitively impaired patients. It is unclear whether reducing depth of anesthesia beyond levels consistent with general anesthesia reduces delirium in cognitively intact patients. The authors' objective was to determine whether a bundled approach to reduce anesthetic agent exposure as determined by Bispectral Index (BIS) values (spinal anesthesia with targeted sedation based on BIS values) compared with general anesthesia (masked BIS) reduces delirium. METHODS: Important eligibility criteria for this parallel-arm randomized trial were patients 65 yr or greater undergoing lumbar spine fusion. The intervention group received spinal anesthesia with targeted sedation to BIS greater than 60 to 70. The control group received general anesthesia (masked BIS). The primary outcome was delirium using the Confusion Assessment Method daily through postoperative day 3, with blinded assessment. RESULTS: The median age of 217 patients in the analysis was 72 (interquartile range, 69 to 77). The median BIS value in the spinal anesthesia with targeted sedation based on BIS values group was 62 (interquartile range, 53 to 70) and in the general anesthesia with masked BIS values group was 45 (interquartile range, 41 to 50; P < 0.001). Incident delirium was not different in the spinal anesthesia with targeted sedation based on BIS values group (25.2% [28 of 111] vs. the general anesthesia with masked BIS values group (18.9% [20 of 106]; P = 0.259; relative risk, 1.22 [95% CI, 0.85 to 1.76]). In prespecified subgroup analyses, the effect of anesthetic strategy differed according to the Mini-Mental State Examination, but not the Charlson Comorbidity Index or age. Two strokes occurred among patients receiving spinal anesthesia and one death among patients receiving general anesthesia. CONCLUSIONS: Spinal anesthesia with targeted sedation based on BIS values compared with general anesthesia with masked BIS values did not reduce delirium after lumbar fusion.

Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults.

BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.).

The Association of Preoperative Frailty and Postoperative Delirium: A Meta-analysis.

BACKGROUND: Both frailty and postoperative delirium (POD) are common in elective surgical patients 65 years of age and older. However, the association between preoperative frailty and POD remains difficult to characterize owing to the large number of frailty and POD assessment tools used in the literature, only a few of which are validated. Furthermore, some validated frailty tools fail to provide clear score cutoffs for distinguishing frail and nonfrail patients. We performed a meta-analysis to estimate the relationship between preoperative frailty and POD. METHODS: We searched several major databases for articles that investigated the relationship between preoperative frailty and POD in patients with mean age ≥65 years who were undergoing elective, nonemergent inpatient surgery. Inclusion criteria included articles published in English no earlier than 1999. Both preoperative frailty and POD must have been measured with validated tools using clear cutoff scores for frailty and delirium. Articles were selected and data extracted independently by 2 researchers. Risk of bias (ROBINS-I) and presence of confounders were summarized. Odds ratios (ORs) for POD associated with frailty relative to nonfrailty were computed with adjusted ORs when available. Original estimates were pooled by random effects analysis. Statistical significance was set at 2-sided P < .05. RESULTS: Nine studies qualified for meta-analysis. The Fried score or a modified version of it was used in 5 studies. Frailty prevalence ranged from 18.6% to 56%. Delirium was assessed with the Confusion Assessment Method (CAM) or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in 7 studies, Delirium Observation Scale in 1 study, and Intensive Care Delirium Screening Checklist in 1 study. The incidence of POD ranged from 7% to 56%. ROBINS-I risk of bias was low in 1 study, moderate in 4 studies, serious in 3 studies, and critical in 1 study. Random effects analysis (n = 794) of the OR for POD in frail versus nonfrail patients based on adjusted OR estimates was significant with an OR of 2.14 and a 95% confidence interval of 1.43-3.19. The I2 value was in the low range at 5.5, suggesting small variability from random effects. Funnel-plot analysis did not definitively support either the presence or absence of publication bias. CONCLUSIONS: This meta-analysis provides evidence for a significant association between preoperative frailty and POD in elective surgical patients age 65 years or older.

Association of Depressive Symptoms With Postoperative Delirium and CSF Biomarkers for Alzheimer's Disease Among Hip Fracture Patients.

OBJECTIVES: While there is growing evidence of an association between depressive symptoms and postoperative delirium, the underlying pathophysiological mechanisms remain unknown. The goal of this study was to explore the association between depression and postoperative delirium in hip fracture patients, and to examine Alzheimer's disease (AD) pathology as a potential underlying mechanism linking depressive symptoms and delirium. METHODS: Patients 65 years old or older (N = 199) who were undergoing hip fracture repair and enrolled in the study "A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" completed the 15-item Geriatric Depression Scale (GDS-15) preoperatively. Cerebrospinal fluid (CSF) was obtained during spinal anesthesia and assayed for amyloid-beta (Aß) 40, 42, total tau (t-tau), and phosphorylated tau (p-tau)181. RESULTS: For every one point increase in GDS-15, there was a 13% increase in odds of postoperative delirium, adjusted for baseline cognition (MMSE), age, sex, race, education and CSF AD biomarkers (OR = 1.13, 95%CI = 1.02-1.25). Both CSF Aß42/t-tau (ß = -1.52, 95%CI = -2.1 to -0.05) and Aß42/p-tau181 (ß = -0.29, 95%CI = -0.48 to -0.09) were inversely associated with higher GDS-15 scores, where lower ratios indicate greater AD pathology. In an analysis to identify the strongest predictors of delirium out of 18 variables, GDS-15 had the highest classification accuracy for postoperative delirium and was a stronger predictor of delirium than both cognition and AD biomarkers. CONCLUSIONS: In older adults undergoing hip fracture repair, depressive symptoms were associated with underlying AD pathology and postoperative delirium. Mild baseline depressive symptoms were the strongest predictor of postoperative delirium, and may represent a dementia prodrome.

Effects of Ramelteon on the Prevention of Postoperative Delirium in Older Patients Undergoing Orthopedic Surgery: The RECOVER Randomized Controlled Trial.

OBJECTIVES: Postoperative delirium, associated with negative consequences including longer hospital stays and worse cognitive and physical outcomes, is frequently accompanied by sleep-wake disturbance. Our objective was to evaluate the efficacy and short-term safety of ramelteon, a melatonin receptor agonist, for the prevention of postoperative delirium in older patients undergoing orthopedic surgery. DESIGN: A quadruple-masked randomized placebo-controlled trial (Clinical Trials.gov NCT02324153) conducted from March 2017 to June 2019. SETTING: Tertiary academic medical center. PARTICIPANTS: Patients aged 65 years or older, undergoing elective primary or revision hip or knee replacement. INTERVENTION: Ramelteon (8 mg) or placebo MEASUREMENTS: Eighty participants were randomized to an oral gel cap of ramelteon or placebo for 3 consecutive nights starting the night before surgery. Trained research staff conducted delirium assessments for 3 consecutive days starting on postoperative day (POD) 0, after recovery from anesthesia, and on to POD2. A delirium diagnosis was based upon DSM-5 criteria determined by expert panel consensus. RESULTS: Of 80 participants, five withdrew consent (one placebo, four ramelteon) and four were excluded (four ramelteon) after randomization. Delirium incidence during the 2 days following surgery was 7% (5 of 71) with no difference between the ramelteon versus placebo: 9% (3 of 33) and 5% (2 of 38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% confidence interval: 0.21-7.93; z-value 0.27; p-value = 0.79). Adverse events were similar between the two groups. CONCLUSION: In older patients undergoing elective primary or revision hip or knee replacement, ramelteon was not efficacious in preventing postoperative delirium.

Does Postoperative Cognitive Decline Result in New Disability After Surgery?

OBJECTIVE: Establish whether POCD is associated with new disability after surgery, which would inform whether POCD impacts patient-centered outcomes. BACKGROUND: POCD is a decline in neuropsychiatric tests scores from presurgical baseline which occurs in approximately 15% of older patients 3 months after surgery. POCD is a research construct meant to investigate patient and family reports of older adults who were "never the same after surgery." However, many patients with POCD do not perceive difficulty with thinking and memory, and the question remains whether POCD impacts patient function. METHODS: We performed a prospective cohort study of 167 older adults undergoing major noncardiac surgery (requiring at least a 2-day hospital stay). Exclusion criteria were: history of dementia, cardiac or intracranial procedure, inability to consent for themselves, or emergency surgery. We administered formal neuropsychiatric testing (Alzheimer Disease Research Center UDS battery), basic and instrumental activities of daily living (Alzheimer Disease Research Center IADLs), pain (geriatric pain measure), and depression screening (hospital depression and anxiety scale) before and 3 months after surgery. We recorded all patient refined diagnostic related groups codes, blood pressure, anesthetics and narcotics administered, surgical and anesthesia duration, and measured complications and severity, length of stay, and readmissions. RESULTS: Patients with POCD (21/167, 14.1%) had twice the proportion of new impairment in IADL as compared to those without POCD (57% vs 27%, P = .01). The most common areas of decline were social activities, ability to find items around the house, remember appointments, shop and pay for items, do laundry, drive a car/use public transport, and do housework. Predictors of IADL change after surgery included POCD, presurgical cognition, presurgical function, postoperative depression, and the development of postoperative complications. CONCLUSIONS: Patients with POCD experience a much higher incidence of new disability after surgery. Baseline cognitive or functional limitations are also risk factors for new disability. Many patients are not aware of their limitations before surgery. Future study is needed to identify practical ways to routinely screen patients and reduce risk. Patients need to be informed of their risk for new disability after surgery to inform their medical decision making.

Kidney Function Modifies the Effect of Intraoperative Opioid Dosage on Postoperative Delirium.

BACKGROUND: There are few studies demonstrating how kidney function affects the risk of developing delirium in older adult surgical patients administered opioids. This study determined whether baseline kidney function influences the relationship between morphine equivalent dose and the development of delirium on postoperative day (POD) 2 in patients with hip fracture. METHODS: This retrospective study analyzed emergency department (ED) estimated glomerular filtration rate (eGFR), perioperative serum creatinine, intravenous morphine equivalents, and POD2 delirium assessment by the Confusion Assessment Method in 652 patients aged 65 years or older without preoperative delirium. ED eGFR was used to divide subjects into groups by presence or absence of chronic kidney disease (CKD), and associations of opioid dose with POD2 delirium were compared using multivariable logistic regression. RESULTS: POD2 delirium incidence was 29.8% (N = 194). Intraoperative and postanesthesia care unit (PACU) morphine equivalent dosage as well as ED eGFR were similar comparing patients with and without POD2 delirium. Age, American Society of Anesthesiologists status, and dementia were associated with delirium on POD2. The odds of POD2 delirium increased significantly with increase of intraoperative opioid in patients with CKD (odds ratio = 1.6; 95% confidence interval = 1.2-2.2), but not in patients without CKD (P-interaction = .04). PACU or POD1 opioid doses were not associated with POD2 delirium after covariate adjustment. CONCLUSION: This study suggests that incremental increases in intraoperative opioids combined with CKD increase odds of POD2 delirium after hip fracture repair, compared with patients without CKD.

Preoperative Evaluation of the Frail Patient.

Perioperative management of older adults is a complex field that is heavily influenced by the clinical heterogeneity of older adults. Frailty-a geriatric syndrome in which a patient is more vulnerable to stressors due to decreases in physical function and reserve-has been indicative of adverse postoperative outcomes. Many tools have been developed to measure frailty that incorporate a variety of factors including physical and cognitive function, comorbidities, self-reported measures of health, and clinical judgment. Most of these frailty assessment tools are able to identify a subset of patients at risk of adverse outcomes including postoperative complications, longer hospital length of stay, discharge to a higher level of care, and mortality. Frailty assessment before surgical interventions can also guide discussions among patients, their families, anesthesiologists, and surgeons to tailor operative plans for patients to mitigate this increased risk. Studies are ongoing to identify interventions in frail patients that can improve postoperative outcomes, but high-quality data in the form of randomized controlled trials are lacking at this time.

Frailty Is Associated With Postoperative Delirium But Not With Postoperative Cognitive Decline in Older Noncardiac Surgery Patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) and delirium are the most common perioperative cognitive complications in older adults undergoing surgery. A recent study of cardiac surgery patients suggests that physical frailty is a risk factor for both complications. We sought to examine the relationship between preoperative frailty and postoperative delirium and preoperative frailty and POCD after major noncardiac surgery. METHODS: We performed a prospective cohort study of patients >65 years old having major elective noncardiac surgery with general anesthesia. Exclusion criteria were preexisting dementia, inability to consent, cardiac, intracranial, or emergency surgery. Preoperative frailty was determined using the FRAIL scale, a simple questionnaire that categorizes patients as robust, prefrail, or frail. Delirium was assessed with the Confusion Assessment Method for the intensive care unit (CAM-ICU) twice daily, starting in the recovery room until hospital discharge. All patients were assessed with neuropsychological tests (California Verbal Learning Test II, Trail Making Test, subtests from the Wechsler Adult Intelligence Scale, Logical Memory Story A, Immediate and Delayed Recall, Animal and Vegetable verbal fluency, Boston Naming Test, and the Mini-Mental Status Examination) before surgery and at 3 months afterward. RESULTS: A total of 178 patients met inclusion criteria; 167 underwent major surgery and 150 were available for follow-up 3 months after surgery. The median age was 70 years old. Thirty-one patients (18.6%) tested as frail, and 72 (43.1%) prefrail before surgery. After adjustment for baseline cognitive score, age, education, surgery duration, American Society of Anesthesiologists (ASA) physical status, type of surgery, and sex, patients who tested frail or prefrail had an estimated 2.7 times the odds of delirium (97.5% confidence interval, 1.0-7.3) when compared to patients who were robust. There was no significant difference between the proportion of POCD between patients who tested as frail, prefrail, or robust. CONCLUSIONS: After adjustment for baseline cognition, testing as frail or prefrail with the FRAIL scale is associated with increased odds of postoperative delirium, but not POCD after noncardiac surgery.