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.

Ketamine for postoperative avoidance of depressive symptoms: the K-PASS feasibility randomised trial.

Background: Surgical patients with previous depression frequently experience postoperative depressive symptoms. This study's objective was to determine the feasibility of a placebo-controlled trial testing the impact of a sustained ketamine infusion on postoperative depressive symptoms. Methods: This single-centre, triple-blind, placebo-controlled randomised clinical trial included adult patients with depression scheduled for inpatient surgery. After surgery, patients were randomly allocated to receive ketamine (0.5 mg kg-1 over 10 min followed by 0.3 mg kg-1 h-1 for 3 h) or an equal volume of normal saline. Depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale. On post-infusion day 1, participants guessed which intervention they received. Feasibility endpoints included the fraction of patients approached who were randomised, the fraction of randomised patients who completed the study infusion, and the fraction of scheduled depression assessments that were completed. Results: In total, 32 patients were allocated a treatment, including 31/101 patients approached after a protocol change (31%, 1.5 patients per week). The study infusion was completed without interruption in 30/32 patients (94%). In each group, 7/16 participants correctly guessed which intervention they received. Depression assessments were completed at 170/192 scheduled time points (89%). Between baseline and post-infusion day 4 (pre-specified time point of interest), median depressive symptoms decreased in both groups, with difference-in-differences of -1.00 point (95% confidence interval -3.23 to 1.73) with ketamine compared with placebo. However, the between-group difference did not persist at other time points. Conclusions: Patient recruitment, medication administration, and clinical outcome measurement appear to be highly feasible, with blinding maintained. A fully powered trial may be warranted. Clinical trial registration: NCT05233566.

User-Centered Design of a Machine Learning Dashboard for Prediction of Postoperative Complications.

BACKGROUND: Machine learning models can help anesthesiology clinicians assess patients and make clinical and operational decisions, but well-designed human-computer interfaces are necessary for machine learning model predictions to result in clinician actions that help patients. Therefore, the goal of this study was to apply a user-centered design framework to create a user interface for displaying machine learning model predictions of postoperative complications to anesthesiology clinicians. METHODS: Twenty-five anesthesiology clinicians (attending anesthesiologists, resident physicians, and certified registered nurse anesthetists) participated in a 3-phase study that included (phase 1) semistructured focus group interviews and a card sorting activity to characterize user workflows and needs; (phase 2) simulated patient evaluation incorporating a low-fidelity static prototype display interface followed by a semistructured interview; and (phase 3) simulated patient evaluation with concurrent think-aloud incorporating a high-fidelity prototype display interface in the electronic health record. In each phase, data analysis included open coding of session transcripts and thematic analysis. RESULTS: During the needs assessment phase (phase 1), participants voiced that (a) identifying preventable risk related to modifiable risk factors is more important than nonpreventable risk, (b) comprehensive patient evaluation follows a systematic approach that relies heavily on the electronic health record, and (c) an easy-to-use display interface should have a simple layout that uses color and graphs to minimize time and energy spent reading it. When performing simulations using the low-fidelity prototype (phase 2), participants reported that (a) the machine learning predictions helped them to evaluate patient risk, (b) additional information about how to act on the risk estimate would be useful, and (c) correctable problems related to textual content existed. When performing simulations using the high-fidelity prototype (phase 3), usability problems predominantly related to the presentation of information and functionality. Despite the usability problems, participants rated the system highly on the System Usability Scale (mean score, 82.5; standard deviation, 10.5). CONCLUSIONS: Incorporating user needs and preferences into the design of a machine learning dashboard results in a display interface that clinicians rate as highly usable. Because the system demonstrates usability, evaluation of the effects of implementation on both process and clinical outcomes is warranted.

Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial.

INTRODUCTION: Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA. METHODS AND ANALYSIS: This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described. ETHICS AND DISSEMINATION: This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT05346588.

Perioperative mental health intervention bundle for older surgical patients: protocol for an intervention development and feasibility study.

INTRODUCTION: The perioperative period is high risk for older adults. Depression and anxiety are common perioperative problems, frequently coexisting with cognitive impairment. Older patients with these conditions are more likely than younger patients to experience postoperative delirium, long hospital stays, poor quality of life and rehospitalisation. These experiences can, in turn, exacerbate anxiety and depressive symptoms. Despite these risks, little is known about how to treat perioperative anxiety and depression among older adults. METHODS AND ANALYSIS: We designed a feasibility study of a perioperative mental health intervention bundle to improve perioperative mental health, specifically depression and anxiety. The overarching goals of this study are twofold: first, to adapt and refine an intervention bundle comprised of behavioural activation and medication optimisation to meet the needs of older adults within three surgical patient populations (ie, orthopaedic, oncological and cardiac); and second, to test the feasibility of study procedures and intervention bundle implementation. Quantitative data on clinical outcomes such as depression, anxiety, quality of life, delirium, falls, length of stay, hospitalisation and pain will be collected and tabulated for descriptive purposes. A hybrid inductive-deductive thematic approach will be employed to analyse qualitative feedback from key stakeholders. ETHICS AND DISSEMINATION: The study received approval from the Washington University Institutional Review Board. Results of this study will be presented in peer-reviewed journals, at professional conferences, and to our perioperative mental health advisory board. TRIAL REGISTRATION NUMBER: NCT05110690.

Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial.

Background: Postoperative depressive symptoms are associated with pain, readmissions, death, and other undesirable outcomes. Ketamine produces rapid but transient antidepressant effects in the perioperative setting. Longer infusions confer lasting antidepressant activity in patients with treatment-resistant depression, but it is unknown whether a similar approach may produce a lasting antidepressant effect after surgery. This protocol describes a pilot study that will assess the feasibility of conducting a larger scale randomized clinical trial addressing this knowledge gap. Methods: This single-center, double-blind, placebo-controlled pilot trial involves the enrollment of 32 patients aged 18 years or older with a history of depression scheduled for surgery with planned intensive care unit admission. On the first day following surgery and extubation, participants will be randomized to an intravenous eight-hour infusion of either ketamine (0.5 mg kg -1 over 10 minutes followed by a continuous rate of 0.3 mg kg -1 h -1) or an equal volume of normal saline. Depressive symptoms will be quantified using the Montgomery-Asberg Depression Rating Scale preoperatively and serially up to 14 days after the infusion. To detect ketamine-induced changes on overnight sleep architecture, a wireless headband will be used to record electroencephalograms preoperatively, during the study infusion, and after infusion. The primary feasibility endpoints will include the fraction of patients approached who enroll, the fraction of randomized patients who complete the study infusion, and the fraction of randomized patients who complete outcome data collection. Conclusions: This pilot study will evaluate the feasibility of a future large comparative effectiveness trial of ketamine to reduce depressive symptoms in postsurgical patients. Registration: K-PASS is registered on ClinicalTrials.gov: NCT05233566; registered February 10, 2022.

Protocol for the perioperative outcome risk assessment with computer learning enhancement (Periop ORACLE) randomized study.

Background: More than four million people die each year in the month following surgery, and many more experience complications such as acute kidney injury. Some of these outcomes may be prevented through early identification of at-risk patients and through intraoperative risk mitigation. Telemedicine has revolutionized the way at-risk patients are identified in critical care, but intraoperative telemedicine services are not widely used in anesthesiology. Clinicians in telemedicine settings may assist with risk stratification and brainstorm risk mitigation strategies while clinicians in the operating room are busy performing other patient care tasks. Machine learning tools may help clinicians in telemedicine settings leverage the abundant electronic health data available in the perioperative period. The primary hypothesis for this study is that anesthesiology clinicians can predict postoperative complications more accurately with machine learning assistance than without machine learning assistance. Methods: This investigation is a sub-study nested within the TECTONICS randomized clinical trial (NCT03923699). As part of TECTONICS, study team members who are anesthesiology clinicians working in a telemedicine setting are currently reviewing ongoing surgical cases and documenting how likely they feel the patient is to experience 30-day in-hospital death or acute kidney injury. For patients who are included in this sub-study, these case reviews will be randomized to be performed with access to a display showing machine learning predictions for the postoperative complications or without access to the display. The accuracy of the predictions will be compared across these two groups. Conclusion: Successful completion of this study will help define the role of machine learning not only for intraoperative telemedicine, but for other risk assessment tasks before, during, and after surgery. Registration: ORACLE is registered on ClinicalTrials.gov: NCT05042804; registered September 13, 2021.

Association of bleeding with serotonergic antidepressants in patients receiving left ventricular assist device support.

STUDY OBJECTIVE: This study sought to determine whether SA use is associated with bleeding in patients receiving CF-LVAD support. DESIGN: A retrospective cohort analysis was conducted of all adult patients who received CF-LVAD implantation at our institution. SETTING: Barnes-Jewish Hospital between July 1, 2009, and October 1, 2018. PATIENTS: Patients at least 18 years of age who received a HVAD™ (HeartWare Corp.), HeartMate II™ (St. Jude Medical), or HeartMate 3™ (St. Jude Medical) CF-LVAD and survived for at least 30 days postoperatively were included. INTERVENTION: Patients who received SAs (n = 203) were compared to those who did not (n = 391) from 30 days to 18 months following implantation. The primary outcome was the incidence of first bleeding events including gastrointestinal bleed (GIB), epistaxis, or intracerebral hemorrhage (ICH). MEASUREMENTS AND MAIN RESULTS: During follow-up, 219 patients had bleeding events: 93 of 203 (45.8%) in the SA group versus 126 of 391 (32.2%) in the control group (p = 0.001). After adjustment for age, angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) use, history of bleeding events, history of smoking, and CF-LVAD type, SA use remained associated with bleeding (adjusted odds ratio: 1.75, 95% confidence interval: 1.22-2.51, p = 0.002). HeartMate 3™ patients experienced less bleeding than HeartMate II™ patients (adjusted odds ratio 0.46, 95% confidence interval: 0.23-0.90, p = 0.024). CONCLUSIONS: In this single-center, retrospective cohort of patients supported with CF-LVADs, SA use was associated with the incidence of first bleeding events, primarily driven by GIB. Further studies are needed to assess any differential risk of bleeding among SA agents and to assess the utility of altering antithrombotic strategies.