A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors

Background Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy. Methods This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography. Discussion This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management. Trial registration ClinicalTrials.govNCT04415658. Registered on June 4, 2020

Perioperatives Management der postmortalen Organspende

Zusammenfassung Hintergrund Die Anzahl postmortal gespendeter Organe ist in Deutschland weit geringer als der Bedarf. Dies unterstreicht die Wichtigkeit einer optimalen Versorgung während des gesamten Prozesses der Organspende. Fragestellung Es existieren internationale Leitlinien und nationale Empfehlungen zu intensivmedizinischen organprotektiven Maßnahmen beim Organspender. Für das anästhesiologische Management fehlen evidenzbasierte Empfehlungen. Ziel dieser Übersichtsarbeit ist es, anhand der vorhandenen Evidenz die pathophysiologischen Veränderungen des irreversiblen Hirnfunktionsausfalls zu rekapitulieren und sich kritisch mit den empfohlenen Behandlungsstrategien und therapeutischen Zielgrößen auseinanderzusetzen. Auch auf ethische Aspekte der Betreuung des postmortalen Organspenders wird eingegangen. Methode Diese Übersichtsarbeit basiert auf einer selektiven Literaturrecherche in PubMed (Suchwörter: „brain dead donor“, „organ procurement“, „organ protective therapy“, „donor preconditioning“, „perioperative donor management“, „ethical considerations of brain dead donor“). Internationale Leitlinien und nationale Empfehlungen wurden besonders berücksichtigt. Ergebnisse Insgesamt ist die Evidenz für optimale intensivmedizinische und perioperative organprotektive Maßnahmen beim postmortalen Organspender sehr gering. Nationale und internationale Empfehlungen zu Zielwerten und medikamentösen Behandlungsstrategien unterscheiden sich teilweise erheblich: kontrollierte randomisierte Studien fehlen. Der Stellenwert einer Narkose zur Explantation bleibt sowohl unter pathophysiologischen Gesichtspunkten als auch aus ethischer Sicht ungeklärt. Schlussfolgerungen Die Kenntnisse über die pathophysiologischen Prozesse im Rahmen des irreversiblen Hirnfunktionsausfalls und die organprotektiven Maßnahmen sind ebenso Grundvoraussetzung wie die ethische Auseinandersetzung mit dem Thema postmortale Organspende. Nur dann kann das Behandlungsteam in dieser herausfordernden Situation sowohl dem Organempfänger als auch dem Organspender und seinen Angehörigen gerecht werden.

Outcome Measures in Solid Organ Donor Management Research - a Systematic Review

BackgroundTo systematically review published outcome measures across randomised controlled trials (RCTs) of donor management interventions. MethodsThe systematic review was conducted in accordance with recommendations by the Cochrane Handbook and PRISMA statement. We searched MEDLINE, EMBASE, CENTRAL, Web of Science as well as trial databases from 1980 to December 2019 for RCTs of donor management interventions. ResultsTwenty-two RCTs (n = 3432 donors) were included in our analysis. Fourteen RCTs (63.6%) reported a primary outcome relating to a single organ only. Eight RCTs primarily focused on aspects of donor optimisation in critical care. Thyroid hormones and methylprednisolone were the most commonly evaluated interventions (five and four studies, respectively). Only two studies, focusing on single organs (e.g. kidney), evaluated outcomes relating to other organs. The majority of studies evaluated physiological or biomarker-related outcomes. No study evaluated recipient health-related quality of life. Only one study sought consent from potential organ recipients. ConclusionsThe majority of RCTs evaluating donor management interventions only assessed single organ outcomes or effects on donor stability in critical care. There is a need for an evaluation of patient-centred recipient outcomes, and standardisation and reporting of outcome measures for future donor management RCTs. PROSPERO RegistrationCRD42018109487

Outcome Measures in Solid Organ Donor Management Research - a Systematic Review

BackgroundTo systematically review published outcome measures across randomised controlled trials (RCTs) of donor management interventions. MethodsThe systematic review was conducted in accordance with recommendations by the Cochrane Handbook and PRISMA statement. We searched MEDLINE, EMBASE, CENTRAL, Web of Science as well as trial databases from 1980 to February 2021 for RCTs of donor management interventions. ResultsTwenty-two RCTs (n = 3432 donors) were included in our analysis. Fourteen RCTs (63.6%) reported a primary outcome relating to a single organ only. Eight RCTs primarily focused on aspects of donor optimisation in critical care. Thyroid hormones and methylprednisolone were the most commonly evaluated interventions (five and four studies, respectively). Only two studies, focusing on single organs (e.g. kidney), evaluated outcomes relating to other organs. The majority of studies evaluated physiological or biomarker-related outcomes. No study evaluated recipient health-related quality of life. Only one study sought consent from potential organ recipients. ConclusionsThe majority of RCTs evaluating donor management interventions only assessed single organ outcomes or effects on donor stability in critical care. There is a need for an evaluation of patient-centred recipient outcomes, and standardisation and reporting of outcome measures for future donor management RCTs. PROSPERO Registration CRD42018109487

Outcome Measures in Solid Organ Donor Management Research - a Systematic Review

BackgroundTo systematically review published outcome measures across randomised controlled trials (RCTs) of donor management interventions. MethodsThe systematic review was conducted in accordance with recommendations by the Cochrane Handbook and PRISMA statement. We searched MEDLINE, EMBASE, CENTRAL, Web of Science as well as trial databases from 1980 to December 2019 for RCTs of donor management interventions. ResultsTwenty-two RCTs (n = 3432 donors) were included in our analysis. Fourteen RCTs (63.6%) reported a primary outcome relating to a single organ only. Eight RCTs primarily focused on aspects of donor optimisation in critical care. Thyroid hormones and methylprednisolone were the most commonly evaluated interventions (five and four studies, respectively). Only two studies, focusing on single organs (e.g. kidney), evaluated outcomes relating to other organs. The majority of studies evaluated physiological or biomarker-related outcomes. No study evaluated recipient health-related quality of life. Only one study sought consent from potential organ recipients. ConclusionsThe majority of RCTs evaluating donor management interventions only assessed single organ outcomes or effects on donor stability in critical care. There is a need for an evaluation of patient-centred recipient outcomes, and standardisation and reporting of outcome measures for future donor management RCTs. PROSPERO RegistrationCRD42018109487

Donor organ management

Organ transplantation is the standard treatment modality for end-stage organ disease in selected cases. Two types of potential organ donors can be identified: the brain-dead 'heart-beating donors', referred to as DBD (donation after brain death), and the warm ischaemic 'non-heart-beating donors', referred to as DCD (donation after circulatory death). Brain death induces several physiological changes in the DBD donor. An autonomic storm is characterized by massive catecholamine release, followed by autonomic depletion during a vasoplegic phase. This is associated with several hormonal changes (suppression of vasopressin, the hypothalamic-pituitary-adrenal axis, and the hypothalamic-pituitary-thyroid axis) and an inflammatory response. These physiological changes form the basis of organ donor management, including cardiovascular stabilization and hormonal therapy (including vasopressin and analogues, thyroid hormone, and cortisol). Donor management is the continuation of critical care, with a shift towards individual organ stabilization. An aggressive approach to maximize organ yield is recommended; however, many treatment strategies need further investigation in large randomized trials. DCD donors have now evolved as a valid alternative to increase the potential donor pool and challenge the clinician with new questions. Optimal donor comfort therapy and end-of-life care are important to minimize the agonal phase. A strict approach towards the determination of death, based on cardiorespiratory criteria, is prerequisite. Novel strategies have been developed, using ex situ organ perfusion as a tool, to evaluate and recondition donor organs. They might become more important in the future to further optimize organ quality.