A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function

Prog Transplant. 2020 Mar;30(1):48-55 doi: 10.1177/1526924819893295.
Abstract
RATIONALE:

Brain death (BD) precipitates cardiac dysfunction impairing the ability to transplant hearts from eligible organ donors. Retrospective studies have suggested that thyroid hormone may enhance myocardial recovery and increase hearts transplanted. We performed a randomized trial evaluating whether intravenous thyroxine (T4) improves cardiac function in BD donors with impaired ejection fraction (EF).

METHODS:

All heart-eligible donors managed at a single-organ procurement organization (OPO) underwent protocolized fluid resuscitation. Those weaned off vasopressors underwent transthoracic echocardiography (TTE) within 12 hours of BD and, if EF was below 60%, were randomized to T4 infusion or no T4 for 8 hours, after which TTE was repeated.

RESULTS:

Of 77 heart-eligible donors, 36 were weaned off vasopressors. Ejection fraction was depressed in 30, of whom 28 were randomized to T4 (n = 17) vs control (n = 11). Baseline EF was comparable (45%, interquartile range [IQR] 42.5-47.5 vs 40%, 40-50, P = .32). Ejection fraction did not improve more with T4 (10%, IQR 5-15 vs 5%, 0-12.5, P = .24), although there was a trend to more hearts transplanted (59% vs 27%, P = .14). This difference appeared to be accounted for by more donors with a history of drug use in the T4 group, who exhibited greater improvements in EF (15% vs 0% without drug use, P = .01) and more often had hearts transplanted (12 of 19 vs 1 of 9, P = .01).

CONCLUSIONS:

In this small randomized study of BD donors with impaired cardiac function, T4 infusion did not result in greater cardiac recovery. A larger randomized trial comparing T4 to placebo appears warranted but would require collaboration across multiple OPOs.

CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This small study from a single organ procurement organization in the US investigated the use of thyroxine in the management of DBD donors with an ejection fraction less than 60%. In the 28 potential donors randomized to T4 or control, no changes were seen in ejection fraction or donation rates between the groups. The study is limited by its small size – of the 28 patients recruited, around 40% did not receive the full treatment with T4 or undergo repeat echo. The lack of power means that no firm conclusion can be made. However, it does nicely demonstrate feasibility, as well as the challenges to recruitment in a study such as this. Ultimately a larger, definitive study is still needed.
Methodological quality
Jadad score 3
Allocation concealment YES
Data analysis INTENTION TO TREAT
Study Details
Aims: The primary objective of this pilot study was to examine if cardiac function in brain dead (BD) donors exhibiting impaired ejection fraction (EF) could be improved by the infusion of thyroxine (T4).
Interventions: Donors were randomly assigned to either the T4 group or the placebo group.
Participants: 28 brain-dead organ donors from 18 to 50 years of age were included in the study.
Outcomes: The primary outcome included improvements in the left ventricular ejection fraction (LVEF) with thyroxine infusion versus no treatment, evaluated using thoracic echocardiogram (TTE) immediately after infusion. The secondary outcome was the porportion of successfully transplanted hearts.
Follow Up: 2.5 years
Metadata
Funding: No funding was received for this study
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Organ: Kidney; Pancreas; Liver; Simultaneous Kidney/Pancreas; Heart; Heart/Lung; Lung; Intestine; Various
Language: Engish
Author email: dharr@wustl.edu
MeSH terms: Adult; Brain Death; Female; Heart Transplantation; Humans; Infusions, Intravenous; Male; Middle Aged; Thyroxine; Tissue Donors; Tissue and Organ Procurement; Treatment Outcome; Ventricular Function, Left; Young Adult; Q51BO43MG4 (Thyroxine); Kidney Transplantation; Heart-Lung Transplantation; Lung Transplantation; Liver Transplantation; Pancreas Transplantation