Khan, Sikandar

Importance An estimated 70% to 80% of older adults develop delirium in the intensive care unit (ICU). Objective To determine if a slow-tempo music (60-80 beats/min) listening intervention decreases delirium duration, delirium severity, pain, or anxiety in older adults undergoing mechanical ventilation. Design, Setting, and Participants This multicenter randomized clinical trial with concealed outcomes assessments was conducted in older adults undergoing mechanical ventilation from February 2020 to December 2023. Patients were enrolled from the ICUs of 2 hospitals affiliated with the Indiana University School of Medicine and from the Mayo Clinic in Rochester, Minnesota. Intervention A music intervention comprising classical and contemporary tracks, delivered twice daily through noise-canceling headphones and tablets for up to 7 days, was compared to active control listening to a silence track delivered under identical conditions. Main Outcomes and Measures The primary outcome was delirium/coma-free days during the 7-day intervention period assessed by the Confusion Assessment Method for the ICU (CAM-ICU) and the Richmond Agitation-Sedation Scale. The secondary outcomes were delirium severity assessed by the CAM-ICU-7, pain assessed by the Critical Care Pain Observation Tool, and anxiety assessed by the visual analog scale for anxiety (VAS-A). Results A total of 158 patients were randomized (mean [SD] age, 68 (9.2) years; 72 [45.5%] female and 86 [54.4%] male). In an intention-to-treat analysis, no differences were found in the number of delirium/coma-free days in the music intervention group compared with control (median [IQR] days, 2.5 [0-5] vs 3 [0-5]; P = .66). There were also no statistically significant differences in the mean CAM-ICU-7 scores, mean pain scores, or mean VAS-A scores over the 7-day intervention period. By end of the 7-day period, both music intervention and control groups had similar mean (SD) CAM-ICU-7 scores (2.72 [2.80] vs 2.56 [2.72]), Critical Care Pain Observation Tool scores (0.20 [0.55] vs 0.61 [1.29]), and VAS-A scores (43.6 [24.7] vs 28.8 [38.4]). Conclusions and Relevance In this randomized clinical trial among older adults undergoing mechanical ventilation, a slow-tempo music intervention did not demonstrate a statistically significant decrease in delirium duration, delirium severity, pain, or anxiety symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04182334

Objectives: The delirium course of critically ill adults can be classified into trajectories based on the severity and duration of delirium as shown by a recent study. It is unknown whether these trajectories and associated outcomes are reproducible. We aimed to define delirium severity trajectories using the Intensive Care Delirium Screening Checklist (ICDSC) and delirium duration and evaluate the association of trajectory membership with clinical characteristics and 30-day post-discharge mortality. Design: Population-based retrospective cohort. Setting: Fourteen medical-surgical ICUs in Alberta, Canada from January 1, 2014, to December 21, 2019. Patients: We included adult patients (≥ 18 yr old) with an ICU length of stay of greater than or equal to 24 hours, an ICDSC score indicating delirium (≥ 4), and 30-day follow-up data were included. Group-based trajectory modeling identified trajectories over a 7-day period with SAS v9.4 (SAS Institute, Cary, NC). Interventions: None. Measurements and Main Results: Demographic (age, sex) and clinical data (2 × d ICDSC score, comorbidities, illness severity, admission reason, procedures, length of stay, in-hospital, and 30-d post-discharge mortality) were captured from electronic medical records. In total, 21,071 patients were included, with a median age of 59 years (interquartile range, 46–70 yr), 59% male (n = 12,547), and 3% died at 30 days (n = 541). The five-trajectory model was selected. These trajectories followed previously defined patterns: 1) Mild-Brief (19.4%); 2); Severe-Rapid Recovers (18.5%); 3) Severe-Slow Recovers (31%); 4) Mild-Accelerating (14.1%); and 5) Severe-Nonrecovers (16.9%). Trajectory membership was not significantly associated with 30-day post-discharge mortality; however, clinically relevant trends were observed. Conclusions: The current study substantiates the proof-of-concept model of five delirium severity trajectories. Trajectory membership did not predict 30-day post-discharge mortality. Further research is needed to understand the associations between trajectory membership, biological-based biomarkers, and patient-relevant outcomes.

Music is one nonpharmacological intervention to reduce anxiety and stress for mechanically ventilated patients. Efficient delivery of a music listening intervention can be enhanced through digital tools such as a mobile application (app) loaded onto an electronic tablet device. The objective of this study is to describe the iterative development and deployment of a novel app (Soundese) to deliver, record, and retrieve data associated with a two-arm randomized, blinded clinical trial testing music listening intervention compared to control silence condition on delirium severity among critically ill intensive care unit (ICU) older adult patients receiving mechanical ventilatory support. The Soundese mobile app was developed to deliver either experimental music listening intervention or a silence control listening condition to a sample of older adults receiving mechanical ventilatory support in the ICU and retrieve all protocol data. The Soundese app was developed using the Swift software language and is compatible with all iOS devices. The Soundese app consists of two components: (1) a mobile app that delivers the assigned, blinded listening intervention from an iPad through headphones to each subject and automatically logs each listening session, its duration, the randomization arm, and uploads these data to a server, and (2) an analysis app that generates a spreadsheet with summarized data of the respective listening session, music details, and reports for further analyses. A Dropbox application programmer interface enabled the secure storage of files on a designated Dropbox account. After initial field testing and iterative development changes based on research staff feedback, the Soundese app delivers the assigned experimental listening condition or silence control condition when deployed remotely in the field. The app’s mobile nature allows for immediate and automatic data capture, which is summarized for statistical analysis. There is no need for any manual recording of any intervention data by busy ICU staff, including listening time or music selections. The Soundese mobile app efficiently delivers the research protocol with fidelity and collects the necessary data for an ICU-based clinical trial. The app may be useful in other clinical trials testing music listening interventions in various settings or for deploying other audio-based interventions.

OBJECTIVES: Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity. DESIGN: Retrospective, observational cohort study. SETTING: ICUs at two large, urban, academic referral hospitals. PATIENTS: All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17–2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02–1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14–1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08–2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04–1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14–2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03–1.79; p = 0.030) and delirium severity the next day (β = 0.30; se, 0.07; p ≤ 0.01). CONCLUSIONS: Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.

Abstract Background: Delirium is a highly prevalent and morbid syndrome in mechanically ventilated intensive care unit (ICU) patients. Music is a promising non-pharmacological intervention with beneficial effects on anxiety and stress, while its effects on delirium duration and severity are not well understood.Methods/design: Our study is a two-arm, randomized parallel-group, clinical trial to evaluate the efficacy of music intervention compared to a silence-track attention control on delirium/coma duration in mechanically ventilated critically ill older adults. One-hundred-sixty mechanically ventilated adults 50 years of age or older will be randomized to one of two arms within 72 hours of ICU admission: (1) one-hour music listening sessions twice daily through noise-cancelling headphones, or (2) one-hour sessions of a silence track twice daily through noise-cancelling headphones. Our primary aim is to compare delirium/coma free days after randomization during the 7-day study intervention phase using the Confusion Assessment Method for the ICU (CAM ICU) and the Richmond Agitation Sedation Scale (RASS) for delirium and coma. Secondary outcomes include pain and anxiety evaluated twice daily during the intervention phase and throughout the duration of ICU stay using the Critical Care Pain Observation Tool (CPOT) and Visual Analogue Scale-Anxiety (VAS-A). Enrolled participants will be followed after hospital discharge to further measure cognition as well as screening for depression and anxiety using the following telephone-based instruments: Indiana University Telephone-Based Assessment of Neuropsychological Status (IU TBANS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7).Discussion: This randomized clinical trial will measure the efficacy of a music listening intervention for delirium and coma duration early in the intensive care unit among older adults.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04182334

Background Management of delirium in intensive care units is challenging because effective therapies are lacking. Music is a promising nonpharmacological intervention. Objectives To determine the feasibility and acceptability of personalized music (PM), slow-tempo music (STM), and attention control (AC) in patients receiving mechanical ventilation in an intensive care unit, and to estimate the effect of music on delirium. Methods A randomized controlled trial was performed in an academic medical-surgical intensive care unit. After particular inclusion and exclusion criteria were applied, patients were randomized to groups listening to PM, relaxing STM, or an audiobook (AC group). Sessions lasted 1 hour and were given twice daily for up to 7 days. Patients wore noise-canceling headphones and used mp3 players to listen to their music/audiobook. Delirium and delirium severity were assessed twice daily by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the CAM-ICU-7, respectively. Results Of the 1589 patients screened, 117 (7.4%) were eligible. Of those, 52 (44.4%) were randomized, with a recruitment rate of 5 patients per month. Adherence was higher in the groups listening to music (80% in the PM and STM groups vs 30% in the AC group; P = .01), and 80% of patients surveyed rated the music as enjoyable. The median number (interquartile range) of delirium/coma-free days by day 7 was 2 (1-6) for PM, 3 (1-6) for STM, and 2 (0-3) for AC (P = .32). Median delirium severity was 5.5 (1-7) for PM, 3.5 (0-7) for STM, and 4 (1-6.5) for AC (P = .78). Conclusions Music delivery is acceptable to patients and is feasible in intensive care units. Further research testing use of this promising intervention to reduce delirium is warranted.