In brain-dead potential heart donors, IV levothyroxine does not increase transplants
Key takeaways:
- Giving levothyroxine to hemodynamically unstable brain-dead heart potential heart donors did not result in more transplants.
- It also did not affect graft survival 30 days after transplant.
Giving IV levothyroxine to hemodynamically unstable brain-dead potential heart donors did not result in more transplants compared with placebo, researchers reported in The New England Journal of Medicine.
“Several large observational studies have suggested that more hearts and total organs are transplanted from donors who had received thyroid hormone,” Rajat Dhar, MD, FRCPC, professor of neurology at Washington University School of Medicine in St. Louis, and colleagues wrote. “These findings have led to widespread adoption of hormonal resuscitation as a cornerstone of deceased donor care, with the majority of organ procurement organizations administering thyroid hormone, predominantly levothyroxine (synthetic T4), to most or all organ donors, especially in the context of hemodynamic instability.
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“The few randomized trials that have evaluated administration of thyroid hormone to donors have focused on intermediate outcomes such as donor hemodynamics and were underpowered to evaluate organ utilization. ... The present clinical trial was designed to evaluate the hypothesis that intravenous levothyroxine would increase the rate of hearts transplanted from hemodynamically unstable brain-dead organ donors being considered for heart donation,” they wrote.
The researchers randomly assigned 838 hemodynamically unstable potential heart donors within 24 hours after declaration of death according to neurologic criteria to IV levothyroxine 30 µg per hour for at least 12 hours or placebo in the form of saline.
The primary outcome was transplantation of the donor heart. The primary recipient outcome was graft survival 30 days after transplant.
Dhar and colleagues found that transplantation of a donor heart occurred in 54.9% of the levothyroxine group and 53.2% of the saline group (adjusted RR = 1.01; 95% CI, 0.97-1.07; P = .57).
Graft survival 30 days after transplant occurred in 97.4% of hearts transplanted from donors in the levothyroxine group and in 95.5% of hearts transplanted from donors in the saline group (difference, 1.9 percentage points; 95% CI, –2.3 to 6; P for noninferiority at a margin of 6 percentage points < .001), according to the researchers.
There were no major differences between the groups in weaning from vasopressor therapy, left ventricular ejection fraction on echocardiography or organs transplanted per donor. However, the levothyroxine group had higher rates of severe hypertension (P < .001) and tachycardia (P = .003), Dhar and colleagues wrote.
“These results provide evidence that thyroid hormone administration does not improve donor stability or organ transplantation rates,” Dhar and colleagues wrote. “There remains a lack of high-quality evidence to guide donor interventions that aim to increase organs transplanted; our large multisite trial was able to rigorously evaluate a key aspect of hormonal resuscitation through collaboration among multiple organ procurement organizations across the United States. Our patient sample was representative of the target population, and we think these findings may be generalizable to hemodynamically unstable heart donors.”
Perspective
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Levothyroxine infusion is a therapy that has been used since I was managing donors in the late 1980s. This is a large well-controlled study that shows there was no real difference in the number of hearts transplanted or in the survival of those recipients who received a heart during this study.
The authors used a formula to assess the use of vasopressors published in the Journal of Cardiovascular Anesthesia in 2021 to compare the hemodynamic effects of levothyroxine infusions on donor hemodynamic stability. This is a fair and balanced method to assess inotrope/pressor use in the donor and recipient, and there was no significant difference in the groups.
The authors report no increased use of hearts in the levothyroxine group, which as they report, goes against the consensus belief that levothyroxine may be beneficial to increase heart donation from marginal donors. The study, however, incorporated a small number of hearts that many experts would consider as marginal. In fact, the authors chose 50% as the LVEF cut point between low and normal. Levothyroxine use has typically been used in donors with an initial EF of 35% or less, in an effort to expand the donor pool. The manuscript did not quantify the number of donors that initially had a low EF (35% or less).
There was an increased rate of tachycardia and hypertension in the recipients who were transplanted using a levothyroxine-infused donor. So while manageable, the use of this treatment is not without some clinical significance in the transplant recipient population.
Based on this manuscript, I believe the routine use of levothyroxine in donor management should be reconsidered, and standard management protocols that do not use thyroid hormone replacement be regarded as standard of care.
It would be interesting to look at donors with an initial EF of 30% to 35% to see if these more marginal hearts would benefit from a levothyroxine infusion, show an improved EF and subsequently be acceptable for transplantation.
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