Transplant Trial Watch

Hemodynamic Effects of High-dose Levothyroxine and Methylprednisolone in Brain-dead Potential Organ Donors.

Van Bakel, A. B., et al.

Transplantation 2022 [record in progress].

The aim of this study was to examine whether high-dose levothyroxine, high-dose methylprednisolone, or a combination of the two hormones, when administered early in the course of donor management, would lead to improvements in donor hemodynamics, allowing significant reduction in vasopressor support.

Participants were randomly assigned to receive high-dose levothyroxine, high-dose methylprednisolone, a combination of both, or no hormonal therapy (control).

199 consecutive adult organ donors.

The primary outcome was the difference in vasopressor requirement to maintain goal hemodynamics among the four treatment groups. Secondary mechanistic outcomes included the assessment of thyroid hormone (TH) levels, cortisol levels and markers of inflammation (C-reactive protein [CRP] and multiple cytokines). Secondary clinical outcomes were the number, types, and proportion of organs procured versus consented, rate of transplantation of procured organs, and patient and graft outcomes of organ recipients exposed to the various treatments.

120 days

CET Conclusions
This donor intervention study randomised 199 deceased brain dead donors to 4 groups – levothyroxine, methylprednisolone, both or control. Primary outcome was the vasoactive inotropic score (VIS), a measure of inotropic requirement at various time points prior to procurement. Both per-protocol and ITT analyses are presented due to relatively high rates of crossover to the combination arm. VIS improved in the methylprednisolone and combination groups, and was worse in the levothyroxine alone group, suggesting that methylprednisolone is the main driver of improved donor stability. Importantly in a donor intervention study, the authors looked at organ utilisation and outcomes following transplantation. These outcomes did not differ significantly between groups, although the study is not powered to these outcomes. These findings are interesting and do question the role of levothyroxine in donor management. The one main caveat is the lack of blinding – this may have increased the crossover rate and impacted inotrope administration, introducing the potential for treatment bias.

Jadad score

Data analysis
Available case analysis

Allocation concealment

Trial registration - NCT04528797

Funding source
Non-industry funded