RESUMEN
INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.
Asunto(s)
Inhibidores de la Calcineurina , Funcionamiento Retardado del Injerto , Trasplante de Riñón , Donantes de Tejidos , Adulto , Femenino , Humanos , Masculino , Muerte Encefálica , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/uso terapéutico , Funcionamiento Retardado del Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Estudios Multicéntricos como Asunto , Ontario , Proyectos Piloto , Quebec , Ensayos Clínicos Controlados Aleatorios como Asunto , Tacrolimus/uso terapéutico , Tacrolimus/administración & dosificaciónRESUMEN
BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).
Asunto(s)
Paro Cardíaco , Corazón/fisiología , Pulso Arterial , Privación de Tratamiento , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Extubación Traqueal , Presión Sanguínea/fisiología , Muerte , Electrocardiografía , Femenino , Pruebas de Función Cardíaca , Humanos , Cuidados para Prolongación de la Vida , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
PURPOSE: Clinical researchers are now encouraged to include patient partners in all research projects. Nevertheless, published accounts of patient engagement in complex research projects, such as those involving critically ill and dying patients, are lacking. Whether this absence is due to the relatively new emergence of patient engagement research methods or fundamental challenges regarding family engagement in challenging research contexts is unclear. We describe our experiences with forming a researcher-family partnership in a deceased organ donation research project involving the prospective observation of potential and actual deceased organ donors dying in the intensive care unit. METHODS: We used the Guidance for Reporting Involvement of Patients and the Public evidence-based, consensus-informed reporting guidelines to organize our narrative. RESULTS: We were able to initiate and sustain a research consultant relationship with the mother of a deceased organ donor for over two years. Challenges faced included: constraints on money and time, communication preferences, and the emotional stress of participating in difficult conversations. Positive outcomes included: improvement of data collection tools, new opportunities for access to research populations, and motivation to include family partnership in future grant proposals. CONCLUSIONS: Family engagement in deceased organ donation research is feasible and contributes positively to study progress and outcomes. Patient and family engagement in challenging research contexts may require special attention to the emotional challenges of participation. We hope that our experience will encourage clinical researchers working in deceased organ donation and similarly complex domains to consider including patient partners in their projects.
RéSUMé: OBJECTIF: Les cliniciens sont maintenant encouragés à inclure les partenaires des patients dans tous leurs projets de recherche. Néanmoins, on ne dispose d'aucune publication sur la participation des patients et de leur famille dans des projets de recherche complexes tels que ceux impliquant des patients dans un état critique ou mourants. Savoir si cette absence est liée à l'émergence relativement récente des méthodes de recherche sur la participation des patients ou aux défis fondamentaux concernant la participation des familles dans un contexte de recherche difficile reste une question débattue. Nous décrivons nos expériences de la formation d'un partenariat chercheur-famille dans un projet de recherche sur le don d'organe impliquant l'observation prospective de donneurs d'organes potentiels ou décédés, décédant dans une unité de soins intensifs. MéTHODES: Nous utilisons le document intitulé Guidance for Reporting Involvement of Patients (conseils pour rendre compte de l'implication des patients) et les lignes directrices publiques basées sur des données probantes pour la publication fondées sur un consensus, pour organiser notre compte rendu. RéSULTATS: Nous avons pu instaurer et maintenir pendant plus de deux ans une relation de consultant en recherche avec la mère d'un donneur d'organe décédé. Les défis rencontrés étaient notamment les contraintes financières et de temps, les préférences en matière de communications et le stress émotionnel créé par la participation à des conversations sur des sujets difficiles. Les résultats positifs ont été, notamment l'amélioration des outils de collecte de données, les nouvelles possibilités d'accès à des populations de recherche et la motivation à inclure un partenariat avec la famille dans les futures propositions de subventions. CONCLUSIONS: La participation de la famille dans la recherche sur le don d'organe d'une personne décédée est faisable et contribue positivement à l'avancement et à l'aboutissement des études. La participation du patient et de sa famille dans un contexte de recherche difficile peut demander de porter une attention particulière aux défis émotionnels de cette participation. Nous espérons que notre expérience encouragera les cliniciens chercheurs qui travaillent sur le don d'organes de personnes décédées et d'autres domaines aussi complexes à envisager d'inclure les partenaires des patients dans leurs projets.