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Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors
Rajat Dhar1, Gary F Marklin1, W Dean Klinkenberg1
1From the Department of Neurology, Section of Neurocritical Care (R.D.), and the Center for Biostatistics and Data Science (J.W., C.W.G.), Washington University School of Medicine, and Mid-America Transplant (G.F.M., W.D.K.) - both in St. Louis; the Department of Anesthesiology and Pain Medicine, University of Washington, Harborview Medical Center, Seattle, and LifeCenter Northwest, Bellevue - both in Washington (A.V.L.); LifeLink of Georgia, Norcross, and Piedmont Transplant Institute, Atlanta - both in Georgia (C.D.K.); Donor Alliance, Denver (P.A.L.); and Akron Children's Hospital, Akron, OH (D.J.L.).
Insights
Intravenous levothyroxine did not increase heart transplant rates in brain-dead donors. This hormonal therapy did not significantly improve organ transplantation outcomes compared to saline placebo.
Area of Science:
- Cardiology
- Transplantation Medicine
- Critical Care Medicine
Background:
- Hemodynamic instability and myocardial dysfunction are critical barriers to heart transplantation from brain-dead donors.
- Observational data suggest hormonal supplementation, including levothyroxine, may improve organ transplant rates.
Purpose of the Study:
- To evaluate the efficacy of intravenous levothyroxine in increasing heart transplant rates from hemodynamically unstable brain-dead donors.
Main Methods:
- A randomized trial was conducted across 15 US organ procurement organizations.
- Hemodynamically unstable brain-dead donors received either levothyroxine (30 μg/hour for ≥12 hours) or saline placebo.
- Primary outcome was heart transplantation; secondary outcomes included graft survival, vasopressor weaning, and ejection fraction.
Main Results:
- No significant difference in heart transplantation rates between levothyroxine (54.9%) and saline (53.2%) groups (aRR, 1.01; 95% CI, 0.97-1.07).
- Graft survival at 30 days was high and similar in both groups (97.4% vs. 95.5%).
- Levothyroxine group experienced more severe hypertension and tachycardia, with no significant differences in vasopressor weaning or ejection fraction.
Conclusions:
- Intravenous levothyroxine infusion did not significantly increase the rate of heart transplantation in hemodynamically unstable brain-dead donors compared to saline.
- The study found no significant benefit of levothyroxine on key secondary outcomes, but noted increased adverse events.
- Current evidence does not support the routine use of levothyroxine for improving heart transplant outcomes in this donor population.
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.).
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