There is a critical shortage of donor lungs for transplantation. We previously developed a parsimonious, highly discriminatory 9-variable Lung Donor (LUNDON) acceptability score. Here we assessed the utility of this score as a tool for improving lung recovery rates for transplantation.

We examined all brain-dead donors between 2014 and 2020 from 3 US organ procurement organizations and validated the score's predictive performance. We examined the trajectory of donors with low (<40) and high (>60) initial LUNDON scores, their corresponding lung recovery rates, factors contributing to score improvement using multivariable regression models, and 1-year post-transplant recipient survival.

Overall lung recovery was 32.4% (1410 of 4351). Validation of the LUNDON score in our cohort revealed a C statistic of 0.904 and required intercept calibration. Low initial LUNDON donors that improved to a high final score had an increase in lung recovery rate from 29.3% (1100 of 3765) to 86.8% (441 of 508), associated with lower body mass index, management in a specialized donor care facility (SDCF), and more bronchoscopies. Donors with high initial and final LUNDON scores had a lung recovery rate of 85.2% (98 of 115), associated with shorter length of hospital stay. One-year survival was similar in recipients of low-to-high versus high-to-high LUNDON score donors (0.89 vs 0.84; P = .2).

The LUNDON score performs well as a predictor of lung recovery in a contemporary cohort but may require organ procurement organization-specific calibration. SDCF care, increasing use of bronchoscopy, and decreasing the time from brain death to organ procurement may improve lung utilization. The LUNDON score can be used to guide donor management to expand the donor pool.

Optimizing the physiology of organ donors is a critical component of preserving the option for organ donation and addressing the shortage of organs available for transplantation. In this article, we review common physiologic alterations seen in organ donors with a focus on brain-dead organ donors. These physiologic alterations and recommended interventions to optimize the physiology of the brain-dead organ donor are discussed by organ system, providing a framework for trauma surgeons and intensivists involved in the care of organ donors.

To investigate whether recipient administration of thyroid hormone (liothyronine [T3]) is associated with reduced rates of primary graft dysfunction (PGD) after orthotopic heart transplantation.

Retrospective cohort study.

Single-center, university hospital.

Adult patients undergoing orthotopic heart transplantation.

A total of 609 adult heart transplant recipients were divided into 2 cohorts: patients who did not receive T3 (no T3 group, from 2009 to 2014), and patients who received T3 (T3 group, from 2015 to 2019). Propensity-adjusted logistic regression was performed to assess the association between T3 supplementation and PGD.

After applying exclusion criteria and propensity-score analysis, the final cohort included 461 patients. The incidence of PGD was not significantly different between the groups (33.9% no T3 group v 40.8% T3 group; p = 0.32). Mortality at 30 days (3% no T3 group v 2% T3 group; p = 0.53) and 1 year (10% no T3 group v 12% T3 group; p = 0.26) were also not significantly different. When assessing the severity of PGD, there were no differences in the groups' rates of moderate PGD (not requiring mechanical circulatory support other than an intra-aortic balloon pump) or severe PGD (requiring mechanical circulatory support other than an intra-aortic balloon pump). However, segmented time regression analysis revealed that patients in the T3 group were less likely to develop severe PGD.

These findings indicated that recipient single-dose thyroid hormone administration may not protect against the development of PGD, but may attenuate the severity of PGD.

Primary graft dysfunction (PGD) remains the main cause of early mortality following heart transplantation despite several advances in donor preservation techniques and therapeutic strategies for PGD. With that aim of establishing the aetiopathogenesis of PGD and the preferred management strategies, the new consensus definition has paved the way for multiple contemporaneous studies to be undertaken and accurately compared. This review aims to provide a broad-based understanding of the pathophysiology, clinical presentation and management of PGD.

Background: Low levels of the active thyroid hormone triiodothyronine (T3) in cardiac patients are associated with worse outcomes. The aim of this analysis was to assess if T3 treatment is beneficial and safe in patients undergoing cardiac surgery or those with cardiovascular diseases in whom there is observed or expected reduction in serum T3 levels. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed as per the PRISMA guidelines. Pubmed, EMBASE, and Web of Science databases were searched for RCTs published between January 1, 1960 and March 30, 2022 that evaluated the effects of T3 therapy in patients undergoing cardiac surgery or with cardiovascular diseases. The primary outcomes were measures of cardiac function. Weighted mean difference (MD) or relative risk was calculated using a random effects model. PROSPERO registration number CRD42020211966. Results: Of the 3181 full-text articles screened, 34 studies with 2547 participants (number ranging between 13 and 223, mean ages between 0.5 and 73 years, mean percentage of women between 7% and 64%) were included. In 12 RCTs with 1093 adults undergoing cardiac surgery T3 therapy was associated with improvement in cardiac index (MD [95% confidence interval], 0.24 [0.08 to 0.40] L/min/m², I² = 74%). The quality of evidence was high to moderate. In 3 RCTs with 188 children undergoing cardiac surgery, 3 RCTs with 131 adult cardiac donors, 3 RCTs with 83 adult patients with heart failure, and 2 RCTs with 89 adults with acute myocardial infarction, T3 therapy did not improve cardiac index or left ventricular function; the quality of evidence ranged from high (pediatric cardiac surgery) to low (other groups). No detrimental effect of T3 therapy was observed on heart rate, risk of in-hospital atrial fibrillation, or mortality. Conclusions: Short-term T3 therapy is safe and trials in adults undergoing cardiac surgical procedures to evaluate longer term clinical endpoints are required. Current data do not support the routine use of T3 therapy in children undergoing cardiac surgery or in cardiac donors. Adequately designed trials are required to determine if T3 therapy improves cardiac function and clinical outcomes in patients with heart failure or acute myocardial infarction.

Donor hearts and lungs are more susceptible to the inflammatory physiologic changes that occur after brain death. Prior investigations have shown that protocolized management of potential organ donors can rehabilitate donor organs that are initially deemed unacceptable. In this review we discuss advances in donor management models with particular attention to the specialized donor care facility model. In addition we review specific strategies to optimize donor thoracic organs and improve organ yield in thoracic transplantation.

We performed a literature review by searching the PubMed database for medical subject heading terms associated with organ donor management models. We also communicated with our local organ procurement organization to gather published and unpublished information first-hand.

The specialized donor care facility model has been shown to improve the efficiency of organ donor management and procurement while reducing costs and minimizing travel and its associated risks. Lung protective ventilation, recruitment of atelectatic lung, and hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) are associated with improved lung utilization rates. Stroke volume-based resuscitation is associated with improved heart utilization rates, whereas studies evaluating hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) have shown variable results.

Lack of high-quality prospective evidence results in conflicting practices across organ procurement organizations, and best practices remain controversial. Future studies should focus on prospective, randomized investigations to evaluate donor management strategies. The specialized donor care facility model fosters a collaborative environment that encourages academic inquiry and is an ideal setting for these investigations.

There is a critical shortage of deceased human donor organs for transplantation. The need is perhaps most acute in neonates and infants with life-threatening congenital heart disease, in whom mechanical support devices are largely unsuccessful. If orthotopic (life-supporting) heart transplantation (OHTx) were consistently successful in the genetically engineered pig-to-nonhuman primate (NHP) model, a clinical trial of bridging with a pig heart in such patients might be justified. However, the results of pig OHTx in NHPs have been mixed and largely poor. We hypothesise that a factor is the detrimental effects of the inflammatory response that is known to develop (a) during any surgical procedure that requires cardiopulmonary bypass, and (b) immediately after an NHP recipient is exposed to a pig xenograft. We suggest that the combination of these two inflammatory responses has a direct detrimental effect on pig heart graft function, but also, and possibly of more importance, on recipient baboon pulmonary function, which further impacts survival of the pig heart graft. In addition, the inflammatory response almost certainly adversely impacts the immune response to the graft. If our hypothesis is correct, the potential steps that could be taken to reduce the inflammatory response or its effects (with varying degrees of efficacy) include (a) white blood cell filtration, (b) complement depletion or inactivation, (c) immunosuppressive therapy, (d) high-dose corticosteroid therapy, (e) cytokine/chemokine-targeted therapy, (f) ultrafiltration or CytoSorb hemoperfusion, (g) reduction in the levels of endogenous catecholamines, (h) triiodothyronine therapy and (i) genetic engineering of the organ-source pig. Prevention of the inflammatory response, or attenuation of its effects, by judicious anti-inflammatory therapy may contribute not only to early survival of the recipient of a genetically engineered pig OHTx, but also to improved long-term pig heart graft survival. This would open the possibility of initiating a clinical trial of genetically engineered pig OHTx as a bridge to allotransplantation.

Primary graft dysfunction is an important cause of morbidity and mortality after cardiac transplantation. Donor brain stem death (BSD) is a significant contributor to donor heart dysfunction and primary graft dysfunction. There remain substantial gaps in the mechanistic understanding of peritransplant cardiac dysfunction. One of these gaps is cardiac metabolism and metabolic function. The healthy heart is an "omnivore," capable of utilizing multiple sources of nutrients to fuel its enormous energetic demand. When this fails, metabolic inflexibility leads to myocardial dysfunction. Data have hinted at metabolic disturbance in the BSD donor and subsequent heart transplantation; however, there is limited evidence demonstrating specific metabolic or mitochondrial dysfunction. This review will examine the literature surrounding cardiometabolic and mitochondrial function in the BSD donor, organ preservation, and subsequent cardiac transplantation. A more comprehensive understanding of this subject may then help to identify important cardioprotective strategies to improve the number and quality of donor hearts.

Donor thyroid hormone (TH) supplementation therapy is widely used. Recent reports suggested an increased risk of graft dysfunction in heart transplant (HTx) recipients not receiving TH supplementation. Our aim was to determine the effect of a donor TH supplementation in a large contemporary HTx cohort.

We analyzed data reported to the International Society for Heart and Lung Transplantation Registry on adult HTx recipients transplanted from 2006 to 2016. Early graft loss (EGL) was defined as death or retransplant because of graft failure within 48 hours of transplant. Logistic regression and propensity score analyses were performed.

There were 23,002 adult HTx recipients transplanted during the study period for whom data on the use of donor TH supplementation were provided to the Registry. There were 15,821 recipients whose donors had received TH supplementation, and 7,181 who had not. Multivariable analysis showed donor TH therapy to be associated with an increased risk for EGL (odds ratio, 1.51; 95% CI, 1.13-2.06; p < 0.001). Long-term survival was similar, irrespective of donor TH supplementation. Recipients whose donors had received TH supplementation exhibited a lower 8-year incidence of vasculopathy (hazard ratio, 0.90; 95% CI, 0.85-0.97; p = 0.003). These results remained consistent in a propensity-matched analysis.

Donor TH therapy is independently associated with an increased risk of EGL. Whether this is a result of the donor allograft intrinsic characteristics related to the reasons why TH was used or whether this is a result of a TH withdrawal effect, which could be mitigated by administration of TH to the recipient, should be further studied.

Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.

Heart transplantation (HT) is uniquely associated with the potential impact of thyroid hormone therapy at three intersecting levels-donor, operation, and recipient. We aimed to study the effect of thyroid hormone therapy of the donor on primary graft dysfunction (PGD).

A retrospective cohort study was conducted on 209 HT recipients assessed from 1997 to 2018; for 33 of the recipients, the donors had received T4 (DT4 group), and for 176, the donors had not (NoDT4 group). The primary endpoint was PGD defined according to the International Society for Heart and Lung consensus statement.

Both the incidence (58% vs 35%, P = .022) and the severity of PGD (42% vs 25% moderate/severe, P = .007) were significantly higher in the DT4 recipients. Multivariable analysis showed donor T4 therapy to be independently associated with a ~3.5-fold increased risk for PGD (OR = 3.44, 95% CI 1.26-9.86). These results remained consistent after propensity score analysis.

Donor thyroid hormone therapy is independently associated with an increased risk of PGD. Hypothesizing a "withdrawal effect" as the cause, we suggest that administration of thyroid hormone to the recipient at time of reperfusion could counter this negative effect. Prospective studies are needed to validate this hypothesis-generating study.

Primary graft dysfunction (PGD) remains the leading cause of early mortality post-heart transplantation. Despite improvements in mechanical circulatory support and critical care measures, the rate of PGD remains significant. A recent consensus statement by the International Society of Heart and Lung Transplantation (ISHLT) has formulated a definition for PGD. Five years on, we look at current concepts and future directions of PGD in the current era of transplantation.

There is a national shortage of organs available for transplantation, and utilization rates for thoracic organs are less than 40%. In addition, the optimal method of assessing cardiovascular status during donor management is uncertain. FloTrac is a noninvasive hemodynamic technique that measures cardiac output and fluid responsiveness. Our objective was to measure the impact of using this technique to guide management on fluid balance, vasopressor usage, thyroid hormone usage, and pulmonary function. We hypothesized that FloTrac guidance will increase thoracic organs transplanted per donor (OTPD).

Data were prospectively collected on a convenience sample of 38 donors after neurologic determination of death. Organs transplanted, net fluid balance, dosage of vasopressors, dosage of thyroid hormone, and Pao₂:Fio₂ were compared between treatment and control groups.

The treatment group had greater thoracic OTPD (1.3 [1.0] vs 0.4 [0.6], P = .004) and overall OTPD (4.3 [1.5] vs 2.7 [1.5], P = .002). Donors in the treatment group maintained a neutral fluid balance, had more thyroid hormone used, and had an improvement in oxygenation.

The implementation of this technology to aid providers may help ameliorate the shortage of thoracic and overall organs available for transplantation.