Evidence-Based Checklist to Delay Cardiac Arrest in Brain-Dead Potential Organ Donors: The DONORS Cluster Randomized Clinical Trial.

Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear. Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU). Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020. Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care. Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group. Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006). Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist. Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.

Statistical analysis plan for a cluster-randomised trial assessing the effectiveness of implementation of a bedside evidence-based checklist for clinical management of brain-dead potential organ donors in intensive care units: DONORS (Donation Network to Optimise Organ Recovery Study).

BACKGROUND: The quality of clinical care of brain-dead potential organ donors may help reduce donor losses caused by irreversible or unreversed cardiac arrest and increase the number of organs donated. We sought to determine whether an evidence-based, goal-directed checklist for donor management in intensive care units (ICUs) can reduce donor losses to cardiac arrest. METHODS/DESIGN: The DONORS study is a multicentre, cluster-randomised controlled trial with a 1:1 allocation ratio designed to compare an intervention group (goal-directed checklist for brain-dead potential organ donor management) with a control group (standard ICU care). The primary outcome is loss of potential donors due to cardiac arrest. Secondary outcomes are the number of actual organ donors and the number of solid organs recovered per actual donor. Exploratory outcomes include the achievement of relevant clinical goals during the management of brain-dead potential organ donors. The present statistical analysis plan (SAP) describes all primary statistical procedures that will be used to evaluate the results and perform exploratory and sensitivity analyses of the trial. DISCUSSION: The SAP of the DONORS study aims to describe its analytic procedures, enhancing the transparency of the study. At the moment of SAP subsmission, 63 institutions have been randomised and were enrolling study participants. Thus, the analyses reported herein have been defined before the end of the study recruitment and database locking. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03179020. Registered on 7 June 2017.

DONORS (Donation Network to Optimise Organ Recovery Study): Study protocol to evaluate the implementation of an evidence-based checklist for brain-dead potential organ donor management in intensive care units, a cluster randomised trial.

INTRODUCTION: There is an increasing demand for multi-organ donors for organ transplantation programmes. This study protocol describes the Donation Network to Optimise Organ Recovery Study, a planned cluster randomised controlled trial that aims to evaluate the effectiveness of the implementation of an evidence-based, goal-directed checklist for brain-dead potential organ donor management in intensive care units (ICUs) in reducing the loss of potential donors due to cardiac arrest. METHODS AND ANALYSIS: The study will include ICUs of at least 60 Brazilian sites with an average of ≥10 annual notifications of valid potential organ donors. Hospitals will be randomly assigned (with a 1:1 allocation ratio) to the intervention group, which will involve the implementation of an evidence-based, goal-directed checklist for potential organ donor maintenance, or the control group, which will maintain the usual care practices of the ICU. Team members from all participating ICUs will receive training on how to conduct family interviews for organ donation. The primary outcome will be loss of potential donors due to cardiac arrest. Secondary outcomes will include the number of actual organ donors and the number of organs recovered per actual donor. ETHICS AND DISSEMINATION: The institutional review board (IRB) of the coordinating centre and of each participating site individually approved the study. We requested a waiver of informed consent for the IRB of each site. Study results will be disseminated to the general medical community through publications in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT03179020; Pre-results.

Amiodarone for arrhythmia in patients with Chagas disease: A systematic review and individual patient data meta-analysis.

BACKGROUND: Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy. METHODOLOGY: We searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). PRINCIPAL FINDINGS: We included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11-0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0-91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61-34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71-35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77-21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17-13.7, 5 studies). Quality of evidence ranged from moderate to very low. CONCLUSIONS: Amiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making.

Study protocol to assess the effectiveness and safety of a flexible family visitation model for delirium prevention in adult intensive care units: a cluster-randomised, crossover trial (The ICU Visits Study).

INTRODUCTION: Flexible intensive care unit (ICU) visiting hours have been proposed as a means to improve patient-centred and family-centred care. However, randomised trials evaluating the effects of flexible family visitation models (FFVMs) are scarce. This study aims to compare the effectiveness and safety of an FFVM versus a restrictive family visitation model (RFVM) on delirium prevention among ICU patients, as well as to analyse its potential effects on family members and ICU professionals. METHODS AND ANALYSIS: A cluster-randomised crossover trial involving adult ICU patients, family members and ICU professionals will be conducted. Forty medical-surgical Brazilian ICUs with RFVMs (<4.5 hours/day) will be randomly assigned to either an RFVM (visits according to local policies) or an FFVM (visitation during 12 consecutive hours per day) group at a 1:1 ratio. After enrolment and follow-up of 25 patients, each ICU will be switched over to the other visitation model, until 25 more patients per site are enrolled and followed. The primary outcome will be the cumulative incidence of delirium among ICU patients, measured twice a day using the Confusion Assessment Method for the ICU. Secondary outcome measures will include daily hazard of delirium, ventilator-free days, any ICU-acquired infections, ICU length of stay and hospital mortality among the patients; symptoms of anxiety and depression and satisfaction among the family members; and prevalence of burnout symptoms among the ICU professionals. Tertiary outcomes will include need for antipsychotic agents and/or mechanical restraints, coma-free days, unplanned loss of invasive devices and ICU-acquired pneumonia, urinary tract infection or bloodstream infection among the patients; self-perception of involvement in patient care among the family members; and satisfaction among the ICU professionals. ETHICS AND DISSEMINATION: The study protocol has been approved by the research ethics committee of all participant institutions. We aim to disseminate the findings through conferences and peer-reviewed journals. TRIAL REGISTRATION: NCT02932358.