Simultaneous Thoracic and Abdominal Transplantation
Simultaneous Thoracic and Abdominal Transplantation
Limited life-saving resources can be rationed according to different strategies, each with unique ethical quandaries. These strategies typically aim to strike balances between core principles that reflect society's values, but that may conflict with one another in particular scenarios. Deceased-donor organ allocation in the United States aims to balance the principles of justice and utility: The goal is to treat those with the greatest urgency, while maximizing benefit from available organs. The balance is not always even; for example, the allocation policies for some organs, particularly liver and heart, prioritize urgency as the primary determinant, and therefore emphasize justice over utility. STA is an example in which the principles of justice and utility could each suggest different allocation results, as two life-saving organs are allocated to one individual who is presumed to have a higher medical urgency. In the setting of a constrained resource and increasing number of STAs, this analysis explores STA in the context of the guiding principles of organ allocation, justice and utility, to determine if assumptions used to validate STA fulfill the objectives as outlined by the transplantation community.
STA recipients are allocated organs according to a UNOS policy, which states that once the candidate becomes eligible for the first organ, "the second required organ shall be allocated to the multiple organ candidate from the same donor if the donor is located with the same local organ distribution unit where the multiple organ candidate is registered." National policy therefore dictates that STA allocation should proceed according to the organ with greater priority. In practice, allocation schemes for each organ differ slightly, such that heart–liver allocation would involve a different geographical distribution depending upon whether it follows the heart or the liver. Additionally, the severity of illness for patients with multiple-organ failure may not be accurately described in single-organ models. These complexities may delay allocation, thereby contributing to longer wait-list times and higher mortality for STA candidates.
The principle of justice as rationale for STA assumes that STA candidates have a greater urgency than single-organ recipients, but the notion that patients with two failing organs would sustain a greater risk of death compared to patients with a single failing organ has not previously been addressed. As noted above, according to UNOS policy, a second organ is allocated to the STA candidate regardless of wait-list status for that second organ. For example, once an SHLi candidate with a relatively low MELD score has been allocated a heart, a liver is allocated from the same donor, thereby bypassing liver-only patients with greater MELD scores and associated risk of wait-list mortality. Similarly, SHK candidates who have been recently wait-listed and are not yet on dialysis may receive kidneys ahead of patients on chronic hemodialysis with substantially longer wait-list times.
These scenarios raise the possibility that the presumed difference in medical urgency between STA and non-STA patients is overstated. We therefore sought to determine whether the principle of justice truly applies to STA by examining wait-list outcomes. These analyses indicated that for multiple STA combinations—SHK, SHLi and SLuLi—survival on the wait-list is indeed markedly reduced when compared to candidates awaiting a single organ. From these data, one could argue that a more aggressive protocol for prioritizing STA patients on the wait-list is required in order to minimize wait-list death. Such a protocol would also need to consider the impact on the outcomes of single-organ candidates who are bypassed by STA allocation, an additional concern that is beyond the scope of this paper. Support for the continued practice of STA from our data is also provided by the demonstration of a clear survival benefit for transplantation among SHK, SHLi and SLuLi compared to remaining on the wait-list. It is notable that the survival benefit among SHK, SHLi and SLuLi is not too dissimilar to the survival benefit of a kidney after nonrenal transplant, a practice that like STA may not align with the goals of organ allocation.
Multiple organ transplantation in a single recipient cannot be easily defended on the merit of utility, at least when utility refers to the total number of lives saved. However, utility also considers efficacy, which includes measures such as patient or graft survival, total life-years saved or quality-of-life. An outcomes-based approach to utility has been applied to a range of scenarios including the debate over heart or liver retransplantation. As with STA, heart or liver retransplantation involves allocation of a second (or third, fourth, etc.) organ to a single patient while others wait for their first transplant. In a review of ethical considerations for retransplantation, Ubel et al. concluded that, while retransplantation is defensible on grounds of extreme medical urgency, these arguments ultimately rely on an assumption that outcomes are at least equivalent to primary transplantation. Since this is not the case—as a whole, retransplantation has inferior outcomes compared to the initial transplant—the authors reject the practice and recommend limitations to organ retransplantation.
It therefore stands to reason that STA can be justified for a selected group of patients as long as successful outcomes can be achieved. In this regard, STA differs importantly from retransplantation in that most of the published data available from single-centers ( Table 7 ) and multicenter/national reviews ( Table 8 ), though hindered by a limited number of subjects, support the notion that STA recipients survive at least as long as patients with single-transplants. Our findings are aligned with prior published data to the extent that we have shown equivalent survival for STA recipients and single-organ thoracic controls; however, we did not find that this equivalency extended to the abdominal organ, except in the scenario of SHLi.
Among the different STA combinations, SHK is most commonly performed. Over a period of 14 years (1998–2011), nine different reports from single-centers compared SHK outcomes to those of single-heart transplants and six have shown statistically equivalent patient survival (1-year: 75–100%; 5-year: 55–92%). ( Table 7 ). Overall, these single-center findings agree with the body of multicenter data (UNOS, ISHLT and France). ( Table 8 ) There are fewer published comparisons between SHK and kidney-alone transplantation. Several prior single-center series reported equivalent patient survival; however, results from Gill et al. demonstrated a higher mortality rate for SHK recipients, particularly during the first year posttransplant.
Our findings are also in agreement with the available literature on SHLi recipients. In a series of SHLi recipients between 1992 and 2007, Raichlin et al. reported 1 and 5 years patient survival for SHLi (N = 15, 100%; 75%) that was not significantly different in comparison to heart (N = 258, 93%; 83%) and liver-alone recipients (N = 1201, 94%; 83%, p = 0.44). In a UNOS review (1987–2005), Te et al. found no difference in 1 and 5 years patient survival (N = 47, 85%; 75%) when compared to heart (86%; 72%) and liver-alone patients (88%; 74%). A recent followup by Cannon et al. reported similar values with a larger UNOS cohort (N = 97). All three of these reviews differ from our study in that they included triple-organ recipients in the survival analyses.
A single study by Barshes et al. has examined national outcomes for SLuLi, and found no difference in survival 1 and 5 years between SLuLi (N = 11, 79%, 63%) and liver-alone (N = 62 676, 83%, 71%, p = 0.59). This series did not include statistical analyses comparing SLuLi and lung-alone (1 year: 78%, 3 year: 60%) though they appeared comparable. There are no single-center series with associated control comparisons for SLuLi or SLuK. Couetil et al. reviewed an SLuLi experience of 10 patients with cystic fibrosis and reported 70% survival at 1 and 3 years. This was similar to Grannas et al., who reported a series of 13 SLuLi patients whose 1 and 3 years survivals were 69% and 62%.
Our study has several limitations. First, it is limited by the drawbacks inherent to retrospective cohort studies, namely a lack of granularity and the inability to control for key confounders. Small sample size, particularly for SLuK wait-list and transplant populations, may have also limited the utility of statistical testing. Inherently, the STA population with two dysfunctional organs is different from single-organ recipients. STA recipients are a highly selected group of patients whose clinical features may not closely match those of the single-transplant patients, and who carry a heavier burden of illness due to multiorgan failure. These baseline differences in STA versus abdominal-only transplant recipients limit our conclusions regarding posttransplant survival. The national STA cohorts are heterogeneous with respect to patient selection, surgical technique and specifics of clinical management, which can vary amongst institutions. An analysis of survival benefit assumes that the wait-list and transplant populations are similar, aside from the treatment effect of transplantation. However the process of spending time as a candidate and being selected as a suitable recipient may in fact actually represent differentiation between the two cohorts, a limitation that has been recognized by other authors utilizing this modeling technique.
In summary, our results indicate that (1) patients wait-listed for SHK, SHLi and SLuLi (but not SLuK) transplantation have a greater risk of wait-list removal than candidates awaiting only one organ and a significant survival benefit if transplanted; (2) posttransplant STA recipient survival is equivalent to thoracic-alone transplantation in all groups; (3) SHK, SLuLi and SLuK recipient survival is less than abdominal-alone transplantation; (4) SHLi recipient survival is equivalent to both thoracic and abdominal organ controls. Combined with a lower survival rate experienced on the wait-list, the benefit of transplantation, at least when compared to thoracic recipients, is greater for STA patients. Put another way, these patients simply do not have the same luxury of time while waiting for organs but have potential to experience similar results if they survive to transplant. Criteria for prioritizing STA candidates, including modifications to the current allocation protocols, may need to be considered in order to reduce disparity in wait-list survival. On the other hand, these data raise ethical questions about whether distribution of deceased kidney and liver allografts to certain STA groups (SHK, SLuLi, SLuK) is truly the most efficacious use of these scarce resources, because it leads to inferior outcomes compared to single abdominal organ transplantation. In this regard SHLi transplantation appears uniquely justifiable, with encouraging results at least supporting SHLi transplant as an effective option to a select group of patients.
Discussion
Limited life-saving resources can be rationed according to different strategies, each with unique ethical quandaries. These strategies typically aim to strike balances between core principles that reflect society's values, but that may conflict with one another in particular scenarios. Deceased-donor organ allocation in the United States aims to balance the principles of justice and utility: The goal is to treat those with the greatest urgency, while maximizing benefit from available organs. The balance is not always even; for example, the allocation policies for some organs, particularly liver and heart, prioritize urgency as the primary determinant, and therefore emphasize justice over utility. STA is an example in which the principles of justice and utility could each suggest different allocation results, as two life-saving organs are allocated to one individual who is presumed to have a higher medical urgency. In the setting of a constrained resource and increasing number of STAs, this analysis explores STA in the context of the guiding principles of organ allocation, justice and utility, to determine if assumptions used to validate STA fulfill the objectives as outlined by the transplantation community.
Complexities in STA allocation
STA recipients are allocated organs according to a UNOS policy, which states that once the candidate becomes eligible for the first organ, "the second required organ shall be allocated to the multiple organ candidate from the same donor if the donor is located with the same local organ distribution unit where the multiple organ candidate is registered." National policy therefore dictates that STA allocation should proceed according to the organ with greater priority. In practice, allocation schemes for each organ differ slightly, such that heart–liver allocation would involve a different geographical distribution depending upon whether it follows the heart or the liver. Additionally, the severity of illness for patients with multiple-organ failure may not be accurately described in single-organ models. These complexities may delay allocation, thereby contributing to longer wait-list times and higher mortality for STA candidates.
Justice: STA Candidates Have a Greater Medical Urgency Than Single-Organ Candidates
The principle of justice as rationale for STA assumes that STA candidates have a greater urgency than single-organ recipients, but the notion that patients with two failing organs would sustain a greater risk of death compared to patients with a single failing organ has not previously been addressed. As noted above, according to UNOS policy, a second organ is allocated to the STA candidate regardless of wait-list status for that second organ. For example, once an SHLi candidate with a relatively low MELD score has been allocated a heart, a liver is allocated from the same donor, thereby bypassing liver-only patients with greater MELD scores and associated risk of wait-list mortality. Similarly, SHK candidates who have been recently wait-listed and are not yet on dialysis may receive kidneys ahead of patients on chronic hemodialysis with substantially longer wait-list times.
These scenarios raise the possibility that the presumed difference in medical urgency between STA and non-STA patients is overstated. We therefore sought to determine whether the principle of justice truly applies to STA by examining wait-list outcomes. These analyses indicated that for multiple STA combinations—SHK, SHLi and SLuLi—survival on the wait-list is indeed markedly reduced when compared to candidates awaiting a single organ. From these data, one could argue that a more aggressive protocol for prioritizing STA patients on the wait-list is required in order to minimize wait-list death. Such a protocol would also need to consider the impact on the outcomes of single-organ candidates who are bypassed by STA allocation, an additional concern that is beyond the scope of this paper. Support for the continued practice of STA from our data is also provided by the demonstration of a clear survival benefit for transplantation among SHK, SHLi and SLuLi compared to remaining on the wait-list. It is notable that the survival benefit among SHK, SHLi and SLuLi is not too dissimilar to the survival benefit of a kidney after nonrenal transplant, a practice that like STA may not align with the goals of organ allocation.
Utility: Patient Survival After STA and Non-STA
Multiple organ transplantation in a single recipient cannot be easily defended on the merit of utility, at least when utility refers to the total number of lives saved. However, utility also considers efficacy, which includes measures such as patient or graft survival, total life-years saved or quality-of-life. An outcomes-based approach to utility has been applied to a range of scenarios including the debate over heart or liver retransplantation. As with STA, heart or liver retransplantation involves allocation of a second (or third, fourth, etc.) organ to a single patient while others wait for their first transplant. In a review of ethical considerations for retransplantation, Ubel et al. concluded that, while retransplantation is defensible on grounds of extreme medical urgency, these arguments ultimately rely on an assumption that outcomes are at least equivalent to primary transplantation. Since this is not the case—as a whole, retransplantation has inferior outcomes compared to the initial transplant—the authors reject the practice and recommend limitations to organ retransplantation.
It therefore stands to reason that STA can be justified for a selected group of patients as long as successful outcomes can be achieved. In this regard, STA differs importantly from retransplantation in that most of the published data available from single-centers ( Table 7 ) and multicenter/national reviews ( Table 8 ), though hindered by a limited number of subjects, support the notion that STA recipients survive at least as long as patients with single-transplants. Our findings are aligned with prior published data to the extent that we have shown equivalent survival for STA recipients and single-organ thoracic controls; however, we did not find that this equivalency extended to the abdominal organ, except in the scenario of SHLi.
Prior Reported Outcomes
Among the different STA combinations, SHK is most commonly performed. Over a period of 14 years (1998–2011), nine different reports from single-centers compared SHK outcomes to those of single-heart transplants and six have shown statistically equivalent patient survival (1-year: 75–100%; 5-year: 55–92%). ( Table 7 ). Overall, these single-center findings agree with the body of multicenter data (UNOS, ISHLT and France). ( Table 8 ) There are fewer published comparisons between SHK and kidney-alone transplantation. Several prior single-center series reported equivalent patient survival; however, results from Gill et al. demonstrated a higher mortality rate for SHK recipients, particularly during the first year posttransplant.
Our findings are also in agreement with the available literature on SHLi recipients. In a series of SHLi recipients between 1992 and 2007, Raichlin et al. reported 1 and 5 years patient survival for SHLi (N = 15, 100%; 75%) that was not significantly different in comparison to heart (N = 258, 93%; 83%) and liver-alone recipients (N = 1201, 94%; 83%, p = 0.44). In a UNOS review (1987–2005), Te et al. found no difference in 1 and 5 years patient survival (N = 47, 85%; 75%) when compared to heart (86%; 72%) and liver-alone patients (88%; 74%). A recent followup by Cannon et al. reported similar values with a larger UNOS cohort (N = 97). All three of these reviews differ from our study in that they included triple-organ recipients in the survival analyses.
A single study by Barshes et al. has examined national outcomes for SLuLi, and found no difference in survival 1 and 5 years between SLuLi (N = 11, 79%, 63%) and liver-alone (N = 62 676, 83%, 71%, p = 0.59). This series did not include statistical analyses comparing SLuLi and lung-alone (1 year: 78%, 3 year: 60%) though they appeared comparable. There are no single-center series with associated control comparisons for SLuLi or SLuK. Couetil et al. reviewed an SLuLi experience of 10 patients with cystic fibrosis and reported 70% survival at 1 and 3 years. This was similar to Grannas et al., who reported a series of 13 SLuLi patients whose 1 and 3 years survivals were 69% and 62%.
Study Limitations and Conclusions
Our study has several limitations. First, it is limited by the drawbacks inherent to retrospective cohort studies, namely a lack of granularity and the inability to control for key confounders. Small sample size, particularly for SLuK wait-list and transplant populations, may have also limited the utility of statistical testing. Inherently, the STA population with two dysfunctional organs is different from single-organ recipients. STA recipients are a highly selected group of patients whose clinical features may not closely match those of the single-transplant patients, and who carry a heavier burden of illness due to multiorgan failure. These baseline differences in STA versus abdominal-only transplant recipients limit our conclusions regarding posttransplant survival. The national STA cohorts are heterogeneous with respect to patient selection, surgical technique and specifics of clinical management, which can vary amongst institutions. An analysis of survival benefit assumes that the wait-list and transplant populations are similar, aside from the treatment effect of transplantation. However the process of spending time as a candidate and being selected as a suitable recipient may in fact actually represent differentiation between the two cohorts, a limitation that has been recognized by other authors utilizing this modeling technique.
In summary, our results indicate that (1) patients wait-listed for SHK, SHLi and SLuLi (but not SLuK) transplantation have a greater risk of wait-list removal than candidates awaiting only one organ and a significant survival benefit if transplanted; (2) posttransplant STA recipient survival is equivalent to thoracic-alone transplantation in all groups; (3) SHK, SLuLi and SLuK recipient survival is less than abdominal-alone transplantation; (4) SHLi recipient survival is equivalent to both thoracic and abdominal organ controls. Combined with a lower survival rate experienced on the wait-list, the benefit of transplantation, at least when compared to thoracic recipients, is greater for STA patients. Put another way, these patients simply do not have the same luxury of time while waiting for organs but have potential to experience similar results if they survive to transplant. Criteria for prioritizing STA candidates, including modifications to the current allocation protocols, may need to be considered in order to reduce disparity in wait-list survival. On the other hand, these data raise ethical questions about whether distribution of deceased kidney and liver allografts to certain STA groups (SHK, SLuLi, SLuK) is truly the most efficacious use of these scarce resources, because it leads to inferior outcomes compared to single abdominal organ transplantation. In this regard SHLi transplantation appears uniquely justifiable, with encouraging results at least supporting SHLi transplant as an effective option to a select group of patients.
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