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.

Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the AMIB, ABTO, BRICNet, and the General Coordination of the National Transplant System.

OBJECTIVE: To contribute to updating the recommendations for brain-dead potential organ donor management. METHOD: A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, joined a task force formed by the General Coordination Office of the National Transplant System/Brazilian Ministry of Health (CGSNT-MS), the Brazilian Association of Intensive Care Medicine (AMIB), the Brazilian Association of Organ Transplantation (ABTO), and the Brazilian Research in Intensive Care Network (BRICNet). The questions were developed within the scope of the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors. The topics were divided into mechanical ventilation, hemodynamic support, endocrine-metabolic management, infection, body temperature, blood transfusion, and use of checklists. The outcomes considered for decision-making were cardiac arrest, number of organs recovered or transplanted per donor, and graft function/survival. Rapid systematic reviews were conducted, and the quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Two expert panels were held in November 2016 and February 2017 to classify the recommendations. A systematic review update was performed in June 2020, and the recommendations were reviewed through a Delphi process with the panelists between June and July 2020. RESULTS: A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong (lung-protective ventilation strategy, vasopressors and combining arginine vasopressin to control blood pressure, antidiuretic hormones to control polyuria, serum potassium and magnesium control, and antibiotic use), 11 as weak (alveolar recruitment maneuvers, low-dose dopamine, low-dose corticosteroids, thyroid hormones, glycemic and serum sodium control, nutritional support, body temperature control or hypothermia, red blood cell transfusion, and goal-directed protocols), and 1 was considered a good clinical practice (volemic expansion). CONCLUSION: Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak. The observed lack of robust evidence on the topic highlights the importance of the present guideline to improve the management of brain-dead potential organ donors.

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.

Positive impact of a clinical goal-directed protocol on reducing cardiac arrests during potential brain-dead donor maintenance.

BACKGROUND: The disproportion between the large organ demand and the low number of transplantations performed represents a serious public health problem worldwide. Reducing the loss of transplantable organs from deceased potential donors as a function of cardiac arrest (CA) may contribute to an increase in organ donations. Our purpose was to test the hypothesis that a goal-directed protocol to guide the management of deceased donors may reduce the losses of potential brain-dead donors (PBDDs) due to CA. METHODS: The quality improvement project included 27 hospitals that reported deceased donors prospectively to the Transplant Center of the State of Santa Catarina, Brazil. All deceased donors reported prospectively between May 2012 and April 2014 were analyzed. Hospitals were encouraged to use the VIP approach checklist during the management of PBDDs. The checklist was composed of the following goals: protocol duration 12-24 hours, temperature > 35 °C, mean arterial pressure ≥ 65 mmHg, diuresis 1-4 ml/kg/h, corticosteroids, vasopressin, tidal volume 6-8 ml/kg, positive end-expiratory pressure 8-10 cmH2O, sodium < 150 mEq/L, and glycemia < 180 mg/dl. A logistic regression model was used to identify predictors of CA. RESULTS: There were 726 PBDD notifications, of which 324 (44.6) were actual donors, 141 (19.4 %) CAs, 226 (31.1 %) family refusals, and 35 (4.8 %) contraindications. Factors associated with CA reduction included use of the checklist (odds ratio (OR) 0.43, p < 0.001), maintenance performed inside the ICU (OR 0.49, p = 0.013), and vasopressin administration (OR 0.56, p = 0.04). More than three interventions had association with less CAs (OR 0.19, p < 0.001). After 24 months, CAs decreased from 27.3 % to 14.6 % (p = 0.002), reaching 12.1 % in the following two 4-month periods (p < 0.001). Simultaneous increases in organ recovered per donor and in actual donors were observed. CONCLUSIONS: A quality improvement program based on education and the use of a goal checklist for the management of potential donors inside the ICU is strongly associated with a decrease in donor losses and an increase in organs recovered per donor.

The effect of brain death protocol duration on potential donor losses due to cardiac arrest.

BACKGROUND: The severe inflammatory reaction that occurs after brain death (BD) tends to amplify over time, contributing to cardiovascular deterioration and occurrence of cardiac arrest (CA). Our purpose is to evaluate the effect of BD protocol duration (BDPD) on potential donor losses due to CA. METHODS: This retrospective analysis included potential donors reported during the period from May 2012 to April 2014. The risk of losses due to CA was analyzed to identify the chronological threshold at which the probability of loss due to CA increases. RESULTS: Three hundred and eighty-four potential donors were analyzed. There was a greater chance of CA after a 30-hour threshold (OR 1.67, 95% CI: 1.38-1.83), and the lowest risk of was identified for the range from 12 to 30 hours (OR 0.32, 95% CI: 0.19-0.52). Multivariate analysis identified the following variables as being associated with lower occurrence of CA: BDPD between 12 and 30 hours, management of a potential donor inside the intensive care unit, and the adherence to a goal-directed protocol. CONCLUSION: A long duration between the first clinical test for BD diagnosis and the procurement of organs may be an important risk factor for the occurrence of cardiac arrest in deceased potential donors.

Brazilian Sepsis Epidemiological Study (BASES study).

INTRODUCTION: Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome METHODS: This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used. RESULTS: For the whole cohort, median age was 65.2 years (49-76), median length of stay was 2 days (1-6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract. CONCLUSION: Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate.