Perioperative mental health intervention for depression and anxiety symptoms in older adults study protocol: design and methods for three linked randomised controlled trials.

INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients. METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem with similar methods. In each trial, 100 participants will be randomised to a remotely delivered perioperative behavioural treatment incorporating principles of behavioural activation, compassion and care coordination, and medication optimisation, or enhanced usual care with mental health-related resources for this population. The primary outcome is change in depression and anxiety symptoms assessed with the Patient Health Questionnaire-Anxiety Depression Scale from baseline to 3 months post surgery. Other outcomes include quality of life, delirium, length of stay, falls, rehospitalisation, pain and implementation outcomes, including study and intervention reach, acceptability, feasibility and appropriateness, and patient experience with the intervention. ETHICS AND DISSEMINATION: The trials have received ethics approval from the Washington University School of Medicine Institutional Review Board. Informed consent is required for participation in the trials. The results will be submitted for publication in peer-reviewed journals, presented at clinical research conferences and disseminated via the Center for Perioperative Mental Health website. TRIAL REGISTRATION NUMBERS: NCT05575128, NCT05685511, NCT05697835, pre-results.

Effect of electroencephalogram-guided anaesthesia administration on 1-yr mortality: follow-up of a randomised clinical trial.

BACKGROUND: Intraoperative EEG suppression duration has been associated with postoperative delirium and mortality. In a clinical trial testing anaesthesia titration to avoid EEG suppression, the intervention did not decrease the incidence of postoperative delirium, but was associated with reduced 30-day mortality. The present study evaluated whether the EEG-guided anaesthesia intervention was also associated with reduced 1-yr mortality. METHODS: This manuscript reports 1 yr follow-up of subjects from a single-centre RCT, including a post hoc secondary outcome (1-yr mortality) in addition to pre-specified secondary outcomes. The trial included subjects aged 60 yr or older undergoing surgery with general anaesthesia between January 2015 and May 2018. Patients were randomised to receive EEG-guided anaesthesia or usual care. The previously reported primary outcome was postoperative delirium. The outcome of the current study was all-cause 1-yr mortality. RESULTS: Of the 1232 subjects enrolled, 614 subjects were randomised to EEG-guided anaesthesia and 618 subjects to usual care. One-year mortality was 57/591 (9.6%) in the guided group and 62/601 (10.3%) in the usual-care group. No significant difference in mortality was observed (adjusted absolute risk difference, -0.7%; 99.5% confidence interval, -5.8% to 4.3%; P=0.68). CONCLUSIONS: An EEG-guided anaesthesia intervention aiming to decrease duration of EEG suppression during surgery did not significantly decrease 1-yr mortality. These findings, in the context of other studies, do not provide supportive evidence for EEG-guided anaesthesia to prevent intermediate term postoperative death. CLINICAL TRIAL REGISTRATION: NCT02241655.

Protocol for a proof-of-concept observational study evaluating the potential utility and acceptability of a telemedicine solution for the post-anesthesia care unit.

Introduction: The post-anesthesia care unit (PACU) is a clinical area designated for patients recovering from invasive procedures. There are typically several geographically dispersed PACUs within hospitals. Patients in the PACU can be unstable and at risk for complications. However, clinician coverage and patient monitoring in PACUs is not well regulated and might be sub-optimal. We hypothesize that a telemedicine center for the PACU can improve key PACU functions. Objectives: The objective of this study is to demonstrate the potential utility and acceptability of a telemedicine center to complement the key functions of the PACU. These include participation in hand-off activities to and from the PACU, detection of physiological derangements, identification of symptoms requiring treatment, recognition of situations requiring emergency medical intervention, and determination of patient readiness for PACU discharge. Methods and analysis: This will be a single center prospective before-and-after proof-of-concept study. Adults (18 years and older) undergoing elective surgery and recovering in two selected PACU bays will be enrolled. During the initial three-month observation phase, clinicians in the telemedicine center will not communicate with clinicians in the PACU, unless there is a specific patient safety concern. During the subsequent three-month interaction phase, clinicians in the telemedicine center will provide structured decision support to PACU clinicians. The primary outcome will be time to PACU discharge readiness determination in the two study phases. The attitudes of key stakeholders towards the telemedicine center will be assessed. Other outcomes will include detection of physiological derangements, complications, adverse symptoms requiring treatments, and emergencies requiring medical intervention. Registration: This trial is registered on clinicaltrials.gov, NCT04020887 (16 th July 2019).

Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis.

BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions: Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures: The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results: Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance: Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02241655.

Frailty Phenotypes and Relations With Surgical Outcomes: A Latent Class Analysis.

BACKGROUND: Frailty is an important concept in the care of older adults although controversy remains regarding its defining features and clinical utility. Both the Fried phenotype and the Rockwood deficit accumulation approaches cast frailty as a "burden" without exploring the relative salience of its cardinal markers and their relevance to the patient. New multifactorial perspectives require a reliable assessment of frailty that can validly predict postoperative health outcomes. METHODS: In a retrospective study of 2828 unselected surgical patients, we used item response theory to examine the ability of 32 heterogeneous markers capturing limitations in physical, functional, emotional, and social activity domains to indicate severity of frailty as a latent continuum. Eighteen markers efficiently indicated frailty severity and were then subject to latent class analysis to derive discrete phenotypes. Next, we validated the obtained frailty phenotypes against patient-reported 30-day postoperative outcomes using multivariable logistic regression. Models were adjusted for demographics, comorbidity, type and duration of surgery, and cigarette and alcohol consumption. RESULTS: The 18 markers provided psychometric evidence of a single reliable continuum of frailty severity. Latent class analyses produced 3 distinct subtypes, based on patients' endorsement probabilities of the frailty indicators: not frail (49.7%), moderately frail (33.5%), and severely frail (16.7%). Unlike the moderate class, severely frail endorsed emotional health problems in addition to physical burdens and functional limitations. Models adjusting for age, sex, type of anesthesia, and intraoperative factors indicated that severely frail (odds ratio, 1.89; 95% confidence interval, 1.42-2.50) and moderately frail patients (odds ratio, 1.31; 95% confidence interval, 1.03-1.67) both had higher odds of experiencing postoperative complications compared to not frail patients. In a 3-way comparison, a higher proportion of severely frail patients (10.7%) reported poorer quality of life after surgery compared to moderately frail (9.2%) and not frail (8.3%) patients (P < .001). There was no significant difference among these groups in proportions reporting hospital readmission (5.6%, 5.1%, and 3.8%, respectively; P = .067). CONCLUSIONS: Self-report frailty items can accurately discern 3 distinct phenotypes differing in composition and their relations with surgical outcomes. Systematically assessing a wider set of domains including limitations in functional, emotional, and social activities can inform clinicians on what precipitates loss of physiological reserve and profoundly influences patients' lives. This information can help guide the current discussion on frailty and add meaningful clinical tools to the surgical practice.

Achieving Milestones as a Prerequisite for Proceeding With a Clinical Trial.

BACKGROUND: Although the National Institutes of Health (NIH) invests $30 billion in research annually, many funded studies fail to generate results that can inform practice. The National Institutes of Health introduced a phased funding mechanism as one potential solution. Study-specific milestones are established for an initial pilot phase. We assess the utility of this phased approach through the ongoing Electroencephalography (EEG) Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) pragmatic clinical trial. The hypothesis of the trial is that EEG guidance of general anesthesia, through prevention of EEG suppression, can decrease postoperative delirium and its downstream negative sequelae. METHODS: In collaboration with study stakeholders, we identified critical milestones for the ENGAGES study, with themes common to many clinical trials. These themes include: regulatory tasks; enrollment targets; feasibility and impact of study intervention; primary outcome incidence; measurement reliability of primary outcome; and follow-up. Progress in achieving the milestones was assessed at regular intervals during the pilot phase by ENGAGES investigators, a National Institute on Aging program officer, and a nonpartisan research organization (Westat). RESULTS: Regulatory tasks, including institutional review board approval, infrastructure establishment, and trial registration, were completed on schedule. A total of 117 patients were randomized, exceeding the target by 51. The EEG-guided protocol was successfully implemented, and a relevant effect on anesthetic practice was demonstrated (decrease in median age-adjusted minimum alveolar anesthetic concentration from 0.93 to 0.78 [P < .001] and increase in median proportion of zero EEG suppression time from 87% to 94% [P < .01]). Nearly all patients (115 of 117, 98.3%) were assessed for delirium using the Confusion Assessment Method, and the delirium incidence was similar (28.1%; 95% CI, 20%-37%) to the estimate (25%) used for the sample size calculation. Good interrater reliability of delirium assessment was demonstrated (κ = 0.94 [95% CI, 0.86-1]). Finally, 1-month follow-up vital status data were obtained for 96.9% of patients, with 85.7% of patients completing at least 1 survey. CONCLUSIONS: With the ENGAGES trial, we demonstrated that key milestones can be identified and progressively assessed during a pilot phase. Success in attaining appropriate milestones hypothetically predicts meaningful completion of a study, and can provide justification for proceeding beyond a pilot phase. The impact of this phased approach on return on investment and scientific yield requires additional study.

Protocol for an observational study of delirium in the post-anaesthesia care unit (PACU) as a potential predictor of subsequent postoperative delirium.

INTRODUCTION: Postoperative delirium can be a serious consequence of major surgery, associated with longer hospital stays, readmission, cognitive and functional deterioration and mortality. Delirium is an acute, reversible disorder characterised by fluctuating course, inattention, disorganised thinking and altered level of consciousness. Delirium occurring in the hours immediately following anaesthesia and delirium occurring in the postoperative period of 1-5 days have been described as distinct clinical entities. This protocol describes an observational study with the aim of determining if delirium in the first hour following tracheal tube removal is a predictor of delirium in the 5 subsequent postoperative days. Improved understanding regarding the development of postoperative delirium would improve patient care and allow more effective implementation of delirium prevention measures. METHODS AND ANALYSIS: Patients enrolled to the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomised controlled trial will be eligible for this substudy. A validated delirium assessment method, the 3-min Diagnostic Confusion Assessment Method and the Richmond Agitation and Sedation Scale will be used to assess 100 patients for delirium at 30 min and 60 min following tracheal tube removal. Patients will also be assessed for delirium over postoperative days 1-5 using three validated methods, the Confusion Assessment Method (CAM), CAM for the Intensive Care Unit and structured chart review. Logistic regression analysis will then be performed to test whether immediately postoperative delirium independently predicts subsequent postoperative delirium. ETHICS AND DISSEMINATION: This observational substudy of ENGAGES has been approved by the ethics board of Washington University School of Medicine. Enrolment began in June 2016 and will continue until June 2017. Dissemination plans include presentations at scientific conferences and scientific publications. TRIAL REGISTRATION NUMBER: NCT02241655.

Changes in quality of life after elective surgery: an observational study comparing two measures.

PURPOSE: Our main objective was to compare the change in a validated quality of life measure to a global assessment measure. The secondary objectives were to estimate the minimum clinically important difference (MCID) and to describe the change in quality of life by surgical specialty. METHODS: This prospective cohort study included 7902 adult patients undergoing elective surgery. Changes in the Veterans RAND 12-Item Health Survey (VR-12), composed of a physical component summary (PCS) and a mental component summary (MCS), were calculated using preoperative and postoperative questionnaires. The latter also contained a global assessment question for quality of life. We compared PCS and MCS to the global assessment using descriptive statistics and weighted kappa. MCID was calculated using an anchor-based approach. Analyses were pre-specified and registered (NCT02771964). RESULTS: By the change in VR-12 scores, an equal proportion of patients experienced improvement and deterioration in quality of life (28% for PCS, 25% for MCS). In contrast, by the global assessment measure, 61% reported improvement, while only 10% reported deterioration. Agreement with the global assessment was slight for both PCS (kappa = 0.20, 57% matched) and MCS (kappa = 0.10, 54% matched). The MCID for the overall VR-12 score was approximately 2.5 points. Patients undergoing orthopedic surgery showed the most improvement in quality of life measures, while patients undergoing gastrointestinal/hepatobiliary or urologic surgery showed the most deterioration. CONCLUSIONS: Subjective global quality of life report does not agree well with a validated quality of life instrument, perhaps due to patient over-optimism.

Ability of preoperative falls to predict postsurgical outcomes in non-selected patients undergoing elective surgery at an academic medical centre: protocol for a prospective cohort study.

INTRODUCTION: Falls are increasingly recognised for their ability to herald impending health decline. Despite the likely susceptibility of postsurgical patients to falls, a detailed description of postoperative falls in an unselected surgical population has never been performed. One study suggests that preoperative falls may forecast postoperative complications. However, a larger study with non-selected surgical patients and patient-centred outcomes is needed to provide the generalisability and justification necessary to implement preoperative falls assessment into routine clinical practice. The aims of this study are therefore twofold. First, we aim to describe the main features of postoperative falls in a population of unselected surgical patients. Second, we aim to test the hypothesis that a history of falls in the 6 months prior to surgery predicts postoperative falls, poor quality of life, functional dependence, complications and readmission. METHODS AND ANALYSIS: To achieve these goals, we study adult patients who underwent elective surgery at our academic medical centre and were recruited to participate in a prospective, survey-based cohort study called Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) (NCT02032030). Patients who reported falling in the 6 months prior to surgery will be considered 'exposed.' The primary outcome of interest is postoperative falls within 30 days of surgery. Secondary outcomes include postoperative functional dependence, quality of life (both physical and mental), in-hospital complications and readmission. Regression models will permit controlling for important confounders. ETHICS AND DISSEMINATION: The home institution's Institutional Review Board approved this study (IRB ID number 201505035). The authors will publish the findings, regardless of the results.

Preoperative Falls Predict Postoperative Falls, Functional Decline, and Surgical Complications.

BACKGROUND: Falls are common and linked to morbidity. Our objectives were to characterize postoperative falls, and determine whether preoperative falls independently predicted postoperative falls (primary outcome), functional dependence, quality of life, complications, and readmission. METHODS: This prospective cohort study included 7982 unselected patients undergoing elective surgery. Data were collected from the medical record, a baseline survey, and follow-up surveys approximately 30days and one year after surgery. RESULTS: Fall rates (per 100 person-years) peaked at 175 (hospitalization), declined to 140 (30-day survey), and then to 97 (one-year survey). After controlling for confounders, a history of one, two, and ≥three preoperative falls predicted postoperative falls at 30days (adjusted odds ratios [aOR] 2.3, 3.6, 5.5) and one year (aOR 2.3, 3.4, 6.9). One, two, and ≥three falls predicted functional decline at 30days (aOR 1.2, 2.4, 2.4) and one year (aOR 1.3, 1.5, 3.2), along with in-hospital complications (aOR 1.2, 1.3, 2.0). Fall history predicted adverse outcomes better than commonly-used metrics, but did not predict quality of life deterioration or readmission. CONCLUSIONS: Falls are common after surgery, and preoperative falls herald postoperative falls and other adverse outcomes. A history of preoperative falls should be routinely ascertained.

Preoperative Falls and Their Association with Functional Dependence and Quality of Life.

BACKGROUND: No study has rigorously explored the characteristics of surgical patients with recent preoperative falls. Our objective was to describe the essential features of preoperative falls and determine whether they are associated with preoperative functional dependence and poor quality of life. METHODS: This was an observational study involving 15,060 surveys from adult patients undergoing elective surgery. The surveys were collected between January 2014 and August 2015, with a response rate of 92%. RESULTS: In the 6 months before surgery, 26% (99% CI, 25 to 27%) of patients fell at least once, and 12% (99% CI, 11 to 13%) fell at least twice. The proportion of patients who fell was highest among patients presenting for neurosurgery (41%; 99% CI, 36 to 45%). At least one fall-related injury occurred in 58% (99% CI, 56 to 60%) of those who fell. Falls were common in all age groups, but surprisingly, they did not increase monotonically with age. Middle-aged patients (45 to 64 yr) had the highest proportion of fallers (28%), recurrent fallers (13%), and severe fall-related injuries (27%) compared to younger (18 to 44 yr) and older (65+ yr) patients (P < 0.001 for each). A fall within 6 months was independently associated with preoperative functional dependence (odds ratio, 1.94; 99% CI, 1.68 to 2.24) and poor physical quality of life (odds ratio, 2.18; 99% CI, 1.88 to 2.52). CONCLUSIONS: Preoperative falls might be common and are possibly often injurious in the presurgical population, across all ages. A history of falls could enhance the assessment of preoperative functional dependence and quality of life.