Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium is common among older cardiac surgery patients. Often difficult to predict and address prophylactically, delirium complicates the postoperative course by increasing morbidity and mortality as well as prolonging both hospital and intensive care unit (ICU) lengths of stay. Based on our pilot trial, we intend to study the effect of scheduled 6-hourly acetaminophen administration for 48 hours post-cardiac surgery with cardiopulmonary bypass (CPB) on the incidence of in-hospital delirium and long-term neurocognitive outcomes. Additionally, effect on duration and severity of delirium, rescue analgesic consumption, acute and chronic pain scores and lengths of hospital and ICU stay will also be explored. METHODS AND ANALYSIS: This multicentre, randomised, placebo-controlled, quadruple-blinded trial will include 900 older (>60 years) cardiac surgical patients requiring CPB. Patients meeting the inclusion criteria and not meeting any exclusion criteria will be enrolled at seven centres across the USA with Beth Israel Deaconess Medical Center (BIDMC), Boston, as the central coordinating centre. Additional sites may be included to broaden or speed accrual. The primary outcome measure is the incidence of in-hospital delirium till day 30. Secondary outcomes include the duration and severity of in-hospital delirium, hospital and ICU lengths of stay, postoperative pain scores, postoperative rescue analgesic consumption, postoperative cognitive function and chronic sternal pain. Creation of a biorepository and the use of intraoperative-blinded electroencephalogram (EEG) and cerebral oximetry data will support exploratory endpoints to determine mechanistic predictors of postoperative delirium. ETHICS AND DISSEMINATION: This trial is approved and centrally facilitated by the Institutional Review Board at BIDMC. An independent Data Safety and Monitoring Board is responsible for maintaining safety oversight. Protocol # 2019 P00075, V.1.4 (dated 20 October 2020). TRIAL REGISTRATION NUMBER: NCT04093219.

Reliability and accuracy of delirium assessments among investigators at multiple international centres.

INTRODUCTION: Delirium is a common, serious postoperative complication. For clinical studies to generate valid findings, delirium assessments must be standardised and administered accurately by independent researchers. The Confusion Assessment Method (CAM) is a widely used delirium assessment tool. The objective was to determine whether implementing a standardised CAM training protocol for researchers at multiple international sites yields reliable inter-rater assessment and accurate delirium diagnosis. METHODS: Patients consented to video recordings of CAM delirium assessments for research purposes. Raters underwent structured training in CAM administration. Training entailed didactic education, role-playing with intensive feedback, apprenticeship with experienced researchers and group discussions of complex cases. Raters independently viewed and scored nine video-recorded CAM interviews. Inter-rater reliability was determined using Fleiss kappa. Accuracy was judged by comparing raters' scores with those of an expert delirium researcher. RESULTS: Twenty-seven raters from eight international research centres completed the study and achieved almost perfect agreement for overall delirium diagnosis, kappa=0.88 (95% CI 0.85 to 0.92). Agreement of the four core CAM features ranged from fair to substantial. The sensitivity and specificity for identifying delirium were 72% (95% CI 60% to 81%) and 99% (95% CI 96% to 100%), considering an expert rater's scores as the reference standard (delirious, n=3; non-delirious, n=6). Delirium severity ratings were tightly clustered, with most scores within 5% of the median. CONCLUSION: Our results demonstrate that, with appropriate training and ongoing scoring discussions, researchers at multiple sites can reliably detect delirium in postsurgical patients. These results support the premise that methodologically rigorous multi-centre studies can yield standardised and accurate determinations of delirium.

The SAGES telephone neuropsychological battery: correlation with in-person measures.

OBJECTIVE: Neuropsychological test batteries are administered in person to assess cognitive function in both clinical and research settings. However, in-person administration holds a number of logistical challenges that makes it difficult to use in large or remote populations or for multiple serial assessments over time. The purpose of this descriptive study was to determine whether a telephone-administered neuropsychological test battery correlated well with in-person testing. METHODS: Fifty English-speaking patients without dementia, over 70 years old, and part of a cohort of patients in a prospective cohort study examining cognitive outcomes following elective surgery were enrolled in this study. Five well-validated neuropsychological tests were administered by telephone to each participant by a trained interviewer within 2-4 weeks of the most recent in-person interview. Tests included the Hopkins Verbal Learning Test-Revised, Digit Span, Category Fluency, Phonemic Fluency, and Boston Naming Test. A General Cognitive Performance composite score was calculated from individual subtest scores as a Z-score. RESULTS: Mean age was 74.9 years (SD = 4.1), 66% female, and 4% non-White. Mean and interquartile distributions of telephone scores were similar to in-person scores. Correlation analysis of test scores revealed significant correlations between telephone and in-person results for each individual subtest, as well as for the overall composite score. A Bland-Altman plot revealed no bias or trends in scoring for either test administration type. CONCLUSIONS: In this descriptive study, the telephone version of a neuropsychological test battery correlated well with the in-person version and may provide a feasible supplement in clinical and research applications. Copyright © 2016 John Wiley & Sons, Ltd.

Detection of Delirium in Hospitalized Older General Medicine Patients: A Comparison of the 3D-CAM and CAM-ICU.

BACKGROUND: Delirium is common in older hospitalized patients and is associated with poor outcomes, yet most cases go undetected. The best approach for systematic delirium identification outside the intensive care unit remains unknown. OBJECTIVE: To conduct a comparative effectiveness study of the Confusion Assessment Method for the ICU (CAM-ICU) and the newly developed 3-minute diagnostic assessment for delirium using the Confusion Assessment Method (3D-CAM) in general medicine inpatients. DESIGN: Cross-sectional comparative effectiveness study. SETTING: Two non-intensive care general medicine units at a single academic medical center. PARTICIPANTS: Hospitalized general medicine patients aged ≥75 years. MEASUREMENTS: Clinicians performed a reference standard assessment for delirium that included patient interviews, family interviews, and review of the medical record. An expert panel determined the presence or absence of delirium using DSM-IV criteria. Two blinded research assistants administered the CAM-ICU and the 3D-CAM in random order, and we determined their diagnostic test characteristics compared to the reference standard. RESULTS: Among the 101 participants (mean age 84 ± 5.5 years, 61 % women, 25 % with dementia), 19 % were classified as delirious based on the reference standard. Evaluation times for the 3D-CAM and CAM-ICU were similar. The sensitivity [95 % confidence interval (CI)] of delirium detection for the 3D-CAM was 95 % [74 %, 100 %] and for the CAM-ICU was 53 % [29 %, 76 %], while specificity was >90 % for both instruments. Subgroup analyses showed that the CAM-ICU had sensitivity of 30 % in patients with mild delirium vs. 100 % for the 3D-CAM. CONCLUSIONS: In this comparative effectiveness study, we found that the 3D-CAM had substantially higher sensitivity than the CAM-ICU in hospitalized older general medicine patients, and similar administration time. Therefore, the 3D-CAM may be a superior screening tool for delirium in this patient population.

Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture.

OBJECTIVES: To determine whether donepezil hydrochloride can reduce the prevalence and severity of delirium in older adults undergoing hip fracture repair. DESIGN: Pilot double-masked randomized placebo-controlled trial. SETTING: Large academic medical center. PARTICIPANTS: Sixteen individuals aged 70 and older with hip fracture. INTERVENTION: Donepezil 5 mg or placebo was randomly allocated and initiated within 24 hours of surgery, preoperatively or postoperatively. Daily treatment was continued for 30 days or until side effects or the clinical situation required termination. MEASUREMENTS: All outcomes were ascertained masked to treatment status. Information on drug tolerability and safety was obtained from the participant, nurse, and medical record. Delirium presence and severity were measured during daily hospital interviews and at 2, 4, and 6 weeks after surgery after a standardized assessment using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS). RESULTS: Participants in the donepezil and placebo arms had similar baseline characteristics. Participants in the donepezil arm experienced significantly more side effects. In longitudinal models, there were no significant differences between the donepezil and placebo arms with regard to delirium presence over time (odds ratio = 0.9, 95% confidence interval (CI) = 0.4-2.3) or delirium severity over time (effect size = -0.2 on 30-point MDAS scale, 95%CI = -1.5-1.2). CONCLUSION: Participants randomized to donepezil had no significant improvement in delirium presence or severity but experienced more side effects. Overall, sufficient evidence was not found from this pilot study to warrant a definitive Phase III trial.