A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors.

RATIONALE: Brain-dead (BD) organ donors frequently exhibit hemodynamic instability and/or reversible cardiac dysfunction. Retrospective studies have suggested that thyroid hormone may stabilize hemodynamics and enhance myocardial recovery. Intravenous levothyroxine (T4) is most frequently utilized but studies have suggested that triiodothyronine (T3) may be superior. We performed a randomized comparative-effectiveness trial to address this uncertainty in donor management. METHODS: All heart-eligible donors managed at a single OPO underwent standardized fluid resuscitation. If not weaned off vasopressors, donors underwent echocardiography (within 12 hours of BD) and were randomized to T3 or T4 infusion for eight hours. RESULTS: A total of 37 BD donors were randomized (16 T3 vs 21 T4). Baseline ejection fraction (EF) was comparable (median 38% vs 45%, P = 0.87) as was vasopressor dosage (6 vs 12 µg/min of norepinephrine, NE, P = 0.12). Reduction in NE dose and proportion weaned off vasopressors was similar and LVEF improved in both groups (repeat EF: 50% vs 52.5%, P = 0.38) with almost half attaining EF ≥55%. Although more hearts were transplanted in the T3 group (10/16 vs 6/21, P = 0.04), this difference did not persist after adjusting for baseline imbalances in age and PF ratio. CONCLUSIONS: Infusion of T3 does not appear to confer significant hemodynamic or cardiac benefits over T4 for hemodynamic unstable BD organ donors.

Characteristics of human donor lungs utilized for research.

Introduction: Many fundamental discoveries have occurred using primary cells from deceased donor lungs. These cells respond differently to injury when there are underlying co-morbidities like diabetes mellitus, hypertension, aging and exposures to cigarette smoke, cocaine and chronic alcohol use. However, the prevalence of these characteristics in donor lungs utilized for research is currently unknown. Methods: This retrospective cohort study procured data of lung transplant donors from Mid-America Transplant from January 2017 until July 2023. The donors were characterized based on lung utilization into three groups - lungs used for research, lungs used for transplant, and lungs not recovered from donors for either research or transplantation. Results: The mean age of donors whose lungs were utilized for research was 41±18 years. 25% of them were expanded criteria donors (ECD) while 10% of the donors in the transplant cohort were ECD. 14% of the donors whose lungs were utilized for research had history of diabetes compared to 8% of donors whose lungs were transplanted. A quarter of the research donor population had positive history of cigarette use within the preceding 20 years. At least 40% of donors had a positive history of non-intravenous drug use, of whom a majority had a history of continued non-intravenous drug use. Conclusions: No strict selection criteria or protocols exist when human donor lungs are obtained for ex-vivo research. There is a high prevalence of diabetes mellitus, history of smoking and non-intravenous drug use along with older age distribution in donors whose lungs used are for research.

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

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.

A Randomized Controlled Trial of Naloxone for Optimization of Hypoxemia in Lung Donors After Brain Death.

BACKGROUND: Persistent hypoxemia is the principal reason lungs from otherwise eligible brain dead (BD) organ donors are not transplanted. Experimental models and retrospective studies have suggested that naloxone attenuates neurogenic pulmonary edema and reverses hypoxemia after brain death. We undertook a multisite, randomized, placebo-controlled trial to evaluate whether naloxone is able to improve oxygenation in BD donors with hypoxemia. METHODS: BD organ donors at 4 organ procurement organizations were randomized in a blinded manner to naloxone 8 mg or saline placebo if lung were being considered for allocation but exhibited hypoxemia (partial pressure of oxygen in arterial blood to fraction of inspired oxygen ratio [PFR] below 300 mm Hg). The primary outcome was change in PFR from baseline to final arterial blood gas. Secondary outcomes included early improvement in PFR and proportion of lungs transplanted. RESULTS: A total of 199 lung-eligible BD donors were randomized to naloxone (n = 98) or placebo (n = 101). Groups were comparable at baseline. Both groups exhibited similar improvements in oxygenation (median improvement in PFR of 81 with naloxone versus 80 with saline, P = 0.68), with 37 (39%) versus 38 (40%) exhibiting reversal of hypoxemia. There was no difference in the rate of lungs transplanted (19% in both groups, P = 0.97) although it was significantly higher in those with reversal of hypoxemia (32/69 versus 2/111, P < 0.001). CONCLUSIONS: Naloxone does not improve oxygenation more than placebo in hypoxemic organ donors. However, reversal of hypoxemia was a powerful predictor of lung utilization regardless of drug therapy. Further organ procurement organization-led research is needed to assess optimal interventions to improve oxygenation in BD donors with hypoxemia.

Cost Evaluation of a Donation after Cardiac Death Program: How Cost per Organ Compares to Other Donor Types.

BACKGROUND: Donation after cardiac death (DCD) is one method of organ donation. Nationally, more than half of evaluated DCD donors do not yield transplantable organs. There is no algorithm for predicting which DCD donors will be appropriate for organ procurement. Donation after cardiac death program costs from an organ procurement organization (OPO) accounting for all evaluated donors have not been reported. STUDY DESIGN: Hospital, transportation, and supply costs of potential DCD donors evaluated at a single OPO from January 2009 to June 2016 were collected. Mean costs per donor and per organ were calculated. Cost of DCD donors that did not yield a transplantable organ were included in cost analyses resulting in total cost of the DCD program. Donation after cardiac death donor costs were compared with costs of in-hospital donation after brain death (DBD) donors. RESULTS: There were 289 organs transplanted from 264 DCD donors evaluated. Mean cost per DCD donor yielding transplantable organs was $9,306. However, 127 donors yielded no organs, at a mean cost of $8,794 per donor. The total cost of the DCD program was $32,020 per donor and $15,179 per organ. Mean cost for an in-hospital DBD donor was $33,546 and $9,478 per organ transplanted. Mean organ yield for DBD donors was 3.54 vs 2.21 for DCD donors (p < 0.0001), making the cost per DBD organ 63% of the cost of a DCD organ. CONCLUSIONS: Mean cost per DCD donor is comparable with DBD donors, however, individual cost of DCD organs increases by almost 40% when all costs of an entire DCD program are included.

Organ Donor Recovery Performed at an Organ Procurement Organization-Based Facility Is an Effective Way to Minimize Organ Recovery Costs and Increase Organ Yield.

BACKGROUND: A new era in organ donation with national redistricting is being proposed. With these proposals, costs of organ acquisition are estimated to more than double. Traditionally, organ recoveries occur in the donor hospital setting, incurring premium hospital expenses. The aim of the study was to determine organ recovery costs and organ yield for donor recoveries performed at an organ procurement organization (OPO) facility. STUDY DESIGN: In 2001, we established an OPO facility and in 2008 began transferring the donor expeditiously when brain death was declared. The OPO donor and hospital costs on a per donor basis were calculated. Donation after cardiac death donors cannot be transferred and were included in the hospital cost analysis. RESULTS: From January 2009 to December 2014, nine hundred and sixty-three donors originating in our OPO had organs recovered and transplanted. Seven hundred and sixty-six (79.5%) donors were transferred to the OPO facility 8.6 hours (range 0.6 to 23.6 hours) after declaration of brain death. Donor recovery cost was 51% less when donors were transferred to the OPO facility ($16,153 OPO recovery vs $33,161 hospital recovery; p < 0.0001). Organ yield was 27.5% better (3.43 organs) from OPO-recovered donors vs an organ yield of 2.69 from hospital-recovered donors (p < 0.0001). Standard criteria donor organ yield from our OPO was 6% higher than the national average (3.92 vs 3.7 nationally; p = 0.012) and expanded criteria donor organ yield was 18% higher (2.2 vs 1.87 nationally; p = 0.03). CONCLUSIONS: An OPO facility for donor organ recovery increases efficiency and organ yield, reduces costs, and minimizes organ acquisition charge. As we face new considerations with broader sharing, increased efficiencies, cost. and organ use should be considered.