Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors

Abstract

Background: Hemodynamic instability and myocardial dysfunction are major factors preventing the transplantation of hearts from organ donors after brain death. Intravenous levothyroxine is widely used in donor care, on the basis of observational data suggesting that more organs may be transplanted from donors who receive hormonal supplementation.

Methods: In this trial involving 15 organ-procurement organizations in the United States, we randomly assigned hemodynamically unstable potential heart donors within 24 hours after declaration of death according to neurologic criteria to open-label infusion of intravenous levothyroxine (30 μg per hour for a minimum of 12 hours) or saline placebo. The primary outcome was transplantation of the donor heart; graft survival at 30 days after transplantation was a prespecified recipient safety outcome. Secondary outcomes included weaning from vasopressor therapy, donor ejection fraction, and number of organs transplanted per donor.

Results: Of the 852 brain-dead donors who underwent randomization, 838 were included in the primary analysis: 419 in the levothyroxine group and 419 in the saline group. Hearts were transplanted from 230 donors (54.9%) in the levothyroxine group and 223 (53.2%) in the saline group (adjusted risk ratio, 1.01; 95% confidence interval [CI], 0.97 to 1.07; P = 0.57). Graft survival at 30 days occurred in 224 hearts (97.4%) transplanted from donors assigned to receive levothyroxine and 213 hearts (95.5%) transplanted from donors assigned to receive saline (difference, 1.9 percentage points; 95% CI, -2.3 to 6.0; P<0.001 for noninferiority at a margin of 6 percentage points). There were no substantial between-group differences in weaning from vasopressor therapy, ejection fraction on echocardiography, or organs transplanted per donor, but more cases of severe hypertension and tachycardia occurred in the levothyroxine group than in the saline group.

Conclusions: In hemodynamically unstable brain-dead potential heart donors, intravenous levothyroxine infusion did not result in significantly more hearts being transplanted than saline infusion. (Funded by Mid-America Transplant and others; ClinicalTrials.gov number, NCT04415658.).

Figure 1.. Subgroup Analyses of Hearts Transplanted (Primary Outcome).

Forest plots show analyses of prespecified subgroups for the primary outcome of transplantation of the donor heart. The trial was not powered and had no prespecified correction for multiple comparisons; the widths of the confidence intervals have not been adjusted for multiplicity and should not be used in place of hypothesis testing. LVEF denotes left ventricular ejection fraction.

Figure 2.. Kaplan–Meier Estimates of the Proportion of Donors Continuing to Receive Vasopressors.

Shown are survival curves in the intention-to-treat population for the time from initiation of levothyroxine or saline infusion until weaning from vasopressors and inotropes (excluding vasopressin at a dose of <1 unit per hour) in the two trial groups. The shaded bands represent 95% confidence intervals. The proportional-hazards assumption was satisfied.