Patel MS, Zatarain J, De La Cruz S, Sally MB, Ewing T, Crutchfield M, Enestvedt CK, Malinoski DJ. The Impact of Meeting Donor Management Goals on the Number of Organs Transplanted per Expanded Criteria DonorA Prospective Study From the UNOS Region 5 Donor Management Goals Workgroup. JAMA Surg. 2014;149(9):969-975. doi:10.1001/jamasurg.2014.967
The shortage of organs available for transplant has led to the use of expanded criteria donors (ECDs) to extend the donor pool. These donors are older and have more comorbidities and efforts to optimize the quality of their organs are needed.
To determine the impact of meeting a standardized set of critical care end points, or donor management goals (DMGs), on the number of organs transplanted per donor in ECDs.
Design, Setting, and Participants
Prospective interventional study from February 2010 to July 2013 of all ECDs managed by the 8 organ procurement organizations in the southwestern United States (United Network for Organ Sharing Region 5).
Implementation of 9 DMGs as a checklist to guide the management of every ECD. The DMGs represented normal cardiovascular, pulmonary, renal, and endocrine end points. Meeting the DMG bundle was defined a priori as achieving any 7 of the 9 end points and was recorded at the time of referral to the organ procurement organization, at the time of authorization for donation, 12 to 18 hours later, and prior to organ recovery.
Main Outcomes and Measures
The primary outcome measure was 3 or more organs transplanted per donor and binary logistic regression was used to identify independent predictors with P < .05.
There were 671 ECDs with a mean (SD) number of 2.1 (1.3) organs transplanted per donor. Ten percent of the ECDs had met the DMG bundle at referral, 15% at the time of authorization, 33% at 12 to 18 hours, and 45% prior to recovery. Forty-three percent had 3 or more organs transplanted per donor. Independent predictors of 3 or more organs transplanted per donor were older age (odds ratio [OR] = 0.95 per year [95% CI, 0.93-0.97]), increased creatinine level (OR = 0.73 per mg/dL [95% CI, 0.63-0.85]), DMGs met prior to organ recovery (OR = 1.90 [95% CI, 1.35-2.68]), and a change in the number of DMGs achieved from referral to organ recovery (OR = 1.11 per additional DMG [95% CI, 1.00-1.23]).
Conclusions and Relevance
Meeting DMGs prior to organ recovery with ECDs is associated with achieving 3 or more organs transplanted per donor. An increase in the number of critical care end points achieved throughout the care of a potential donor by both donor hospital and organ procurement organization is also associated with an increase in organ yield.
A shortage of organs available for transplantation continues with data from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipient 2011 Annual Report highlighting little change in supply accompanied by continued growth in demand.1 To date, from January 1995 to October 2013, approximately 125 000 patients have been removed from the organ transplant waiting list owing to death.2 In 2003, in an effort to increase the number of organ donations, the Organ Donation Breakthrough Collaborative began and focused on increasing the number of organs available, increasing the capacity of organ procurement organizations (OPOs) to manage donors and transplants, and expanding donor pools to include donations after cardiac death and expanded criteria donors (ECDs).3
With regard to organ supply, there are 2 types of organ donors: living and deceased. Currently, the majority of donors recovered in the United States are deceased donors. Among the deceased, there are donors after circulatory determination of death and donors after neurological determination of death. Of these 2 types of deceased donors, donors after neurological determination of death are more common and can be further categorized into standard criteria donors (SCDs) and ECDs. Generally, SCDs are healthier than ECDs, who are typically older donors with more significant comorbidities.
Since the efforts of the Organ Donation Breakthrough Collaborative, there has been a slight increase in the number of organs transplanted per donor in SCDs (3.71 in 2011 vs 3.60 in 2000) and ECDs (1.87 in 2011 vs 1.78 in 2000).1 However, there continues to be a large difference in the yield rates between these 2 types of donors. To increase the number of organs transplanted per donor, the US Department of Health and Human Services and the Health Resources and Services Administration have set goals for organ donation and transplantation through the Donation and Transplantation Community of Practice, which encouraged the use of preset critical care end points as donor management goals (DMGs). In brief, DMGs are physiologic parameters that reflect the normal hemodynamic, acid-base, cardiovascular, respiratory, endocrine, and renal status of the donor. In previous retrospective4 and prospective5 studies, SCDs were found to have a significantly greater number of organs transplanted per donor when meeting DMGs prior to donation.4,5 A subsequent study6 of renal transplant recipients showed that meeting DMGs at the time of consent of donors significantly decreased the risk of delayed graft function in recipients. Expanded criteria donors were evaluated in this latter study6 and, after accounting for age and creatinine level, were not found to be an independent predictor of delayed graft function.
As ECDs are becoming more commonly used as the source of organs for transplantation, it has become increasingly important to evaluate the impact of managing these donors on organ yield to identify factors that can further aid in improving the organ supply. Thus, the objectives of our study are to evaluate the impact of meeting DMGs at several points during the organ donation process on the number of organs transplanted per donor and to identify any factors that may significantly affect organ utilization rates with regard to ECDs. We hypothesize that meeting the DMG bundle in ECDs will be associated with increased organ transplantation rates.
Portions of our study method have been discussed in 2 previous reports5,6 that can be referenced for additional details. Our study was deemed to be nonhuman participants research by the Portland Veterans Affairs Medical Center Research and Development Committee.
In June of 2008 after the Canadian Council for Donation and Transplantation published recommendations for organ donor management, the representatives from the 8 OPOs in the United Network for Organ Sharing (UNOS) Region 5 (see the Additional Contributions section for the list of the OPOs) designed a bedside checklist of 9 DMGs intended to represent the critical care end points (Table 1). Note that specific end-point parameters for particular DMGs have evolved as the results from previous studies are analyzed, discussed, and incorporated.5,6
From February 2010 to July 2013, all donors after neurological determination of death managed by the 8 OPOs in UNOS Region were closely followed using 9 DMGs thought to represent normal critical care end points (Table 1) to optimize the function of all solid organs and to guide the resuscitation efforts of the bedside organ procurement coordinators. Specific donor management protocols used by the OPOs were aimed at achieving these specific end points. The 5 states in UNOS Region 5 are Arizona, California, Nevada, New Mexico, and Utah, and they represent the southwestern United States.
Among the donors after neurological determination of death managed were both SCDs and ECDs. Specifically, as previously defined,6 SCDs are those who were declared legally brain dead by use of hospital criteria for neurologic determination of death and were younger than 50 years or were 50 to 59 years of age with less than 2 of the following comorbidities: chronic hypertension, death resulting from a cerebral vascular accident, or a serum creatinine level of greater than 1.5 mg/dL (to convert to micromoles per liter, multiply by 88.4). Expanded criteria donors were those who were declared legally brain dead by use of hospital criteria for neurologic determination of death and were either 60 years of age or older or were 50 to 59 years of age with at least 2 of the previously listed comorbidities.1 Only ECDs were included in our study.
To evaluate the impact of meeting DMGs at several points during the organ donation process on the number of organs transplanted per donor in ECDs, a standardized checklist of these DMGs (Table 1) was prospectively implemented at the bedside of each donor. This checklist served as a data collection tool that was subsequently uploaded to the UNOS Region 5 web portal. Meeting the DMG bundle was defined a priori as achieving any 7 of the 9 end points. This definition of the DMG bundle being met is based on a statistical analysis conducted in a previous retrospective analysis.4 Data on whether the DMG bundle was met and on the specific number of individual DMG elements achieved were recorded at 4 points for each of the ECDs studied: at referral to reflect donor hospital intensive care unit care; at the time of authorization for donation, when the OPO assumes responsibility and begins targeting the DMGs; at 12 to 18 hours to reflect the approximate time when organ offers were being made and organs were being evaluated for acceptance by transplant centers; and immediately prior to organ recovery to reflect the end result of donor management. In addition, although thyroid hormone use was not considered a DMG, its impact on the number of organs transplanted per donor was also analyzed. Data collected for subsequent analyses also included donor age, serum creatinine levels, and the use of each organ.
Being that the national average number of organs transplanted per ECD is only 2, our primary outcome measure was having 3 or more organs transplanted per ECD. Secondary outcomes included the overall number of organs transplanted per donor and individual organ utilization rates. Using SPSS version 22 (IBM Corp), we initially performed a univariate analysis to identify variables that had an association with our primary outcome measure. Those variables with P < .05 were included in a binary logistic regression analysis to determine independent predictors of achieving 3 or more organs transplanted per donor, with separate models being used for inherently related variables. Variables with P < .05 on multivariate analysis were considered statistically significant. The concordance index (C statistic) and the Hosmer-Lemeshow goodness-of-fit test were calculated to assess the discrimination and acceptability, respectively, of each model. The impact of meeting the bundle as a whole was the chosen outcome rather than meeting each DMG individually, for 2 main reasons: (1) the intervention implemented was the use of a standardized checklist rather than specific protocols to reach each end point, and (2) many of the end points are inherently related and trying to achieve one could affect the ability of achieving another.
Over the nearly 3.5-year study period from February 2010 to July 2013, there were 671 ECDs with a mean (SD) number of 2.1 (1.3) organs transplanted per donor. The majority of donors were men, and 43% achieved the primary outcome of having 3 or more organs transplanted per donor. Of these ECDs, 10% had met the DMG bundle at referral, 15% at the time of authorization, 33% at 12 to 18 hours, and 45% prior to organ recovery.
With regard to analyses, the results of the univariate analysis of continuous and categorical data associated with having 3 or more organs transplanted per donor are presented in Table 2 and Table 3, respectively. As can be seen, donors who were younger and had a lower creatinine level prior to organ recovery were significantly more likely to have 3 or more organs transplanted per donor. Although the impact of meeting specific DMGs on organs transplanted per donor was intentionally not analyzed, both the number of DMGs met at different points and the changes of the number of DMGs met over the 4 points were analyzed to get closer to causation rather than just association. After analysis, we found that there were significantly more DMGs met at 12 to 18 hours, as well prior to organ recovery, for those with 3 or more organs transplanted per donor. This supported the finding that a significantly higher number of ECDs obtained this outcome measure when the DMG bundle was met 12 to 18 hours later, as well as prior to organ recovery. With regard to changes over time, the relative changes in DMGs from referral to prior to organ recovery and from authorization to prior to organ recovery were both significant. Of note, thyroid hormone use was not significantly different for those ECDs with 3 or more organs transplanted per donor.
Taking into account the results of the univariate analysis, we included variables with P < .05 in the multivariable analysis, with the results presented in Table 4. Older age and an increased serum creatinine level were associated with a significantly lower odds of having 3 or more organs transplanted per donor, whereas having met DMGs prior to organ recovery was associated with a 90% higher chance of obtaining 3 or more organs transplanted per donor. In addition, when separate models were run in order to account for related variables, the change in the number of DMGs from referral to prior to organ recovery as well as from authorization to prior to organ recovery were found to be significant predictors of having 3 or more organs transplanted per donor.
Lastly, the impact of meeting DMGs in ECDs at each time point on specific organ utilization rates was studied (Table 5). In terms of specific organ utilization rates, kidneys and livers were the most commonly transplanted organs, followed by lungs and then hearts and pancreata. When the DMGs were met prior to authorization, 12 to 18 hours later, and prior to organ recovery, it was found that there were generally more thoracic organs transplanted, specifically more lungs. The heart was transplanted more when DMGs were met prior to organ recovery and the impact on kidneys was significant 12 to 18 hours later and prior to recovery.
To our knowledge, this is the first study to prospectively report the impact of meeting DMGs at several time points in the donation process on the number of organs transplanted per donor from ECDs. We found that after adjusting for age and creatinine levels, meeting DMGs prior to organ recovery was associated with achieving 3 or more organs transplanted per ECD. In addition, larger increases in the number of individual DMGs achieved throughout the organ donation process, by both the donor hospital and the OPO, are also associated with higher organ utilization rates. The impact of meeting the DMG bundle appears to have its greatest effect on thoracic organ acceptance rates, with more lungs and hearts being transplanted when the DMG bundle is met in ECDs.
The change in the characteristics of donors to include a growing number of older patients with comorbid conditions and the continuing need to expand the donor pool are 2 important factors that led to the concept of ECDs in the early 1990s.7 Expanded criteria donors, also known as extended criteria donors or marginal donors, have generally been defined as donors who are associated with a higher risk of posttransplant dysfunction for the recipient. In efforts to establish a more objective definition of ECD that could be used for the graft allocation decision-making process, donor characteristics that were found to lead to a greater than 1.7 times risk of graft loss in renal transplant recipients were determined, and donors with these characteristics were termed ECDs.8,9 Using this method, we defined ECDs as donors who were legally declared dead by neurologic criteria and were 60 years of age or older or 50 to 59 years of age with 2 of the following comorbidities: chronic hypertension, stroke as a cause of death, or a serum creatinine level greater than 1.5 mg/dL.8 Note that despite this definition of ECD being based on the outcomes of renal allografts from such donors, it is applied in the present study to all donors because it is the only Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipient definition of expanded donors.1 It should be noted that to assess the impact of donor age in the ECD population, this variable was independently added into the final multivariable analysis and found to be significant (Table 4). In other words, independent of the presence of comorbidities in the ECD population, having 3 or more organs transplanted per donor was significantly less likely as donor age increased.
Among the strategies for increasing the quantity of organs available for transplantation, optimizing the care of ECDs may present a potential opportunity. As already mentioned, previous retrospective and prospective studies4,5 by our group have evaluated the impact of meeting the DMG bundle and noted a significant increase in the number of organs transplanted per donor. However, these studies4,5 were limited to SCDs. In addition, a retrospective review of the UNOS Region 11 by Franklin et al10 included ECDs in its study population but did not conduct a subgroup analysis of this population. In a separate study presenting the efforts of UNOS Region 10, Hagan et al11 evaluated the effect of attaining specific DMGs on the number of organs transplanted per donor in all donors and also included a subgroup analysis of ECDs. In this study,11 although the ECDs meeting DMGs had a greater number of organs transplanted per donor than the ECDs not meeting the DMGs (2.16 vs 1.57; P = .30), a statistically significant difference was not noted. However, their study11 was limited in that data were only collected prior to organ recovery (thus, the impact of meeting DMGs over time could not be discerned) and were analyzed in a univariate fashion, limiting its ability to account for confounders. Of note, the list of DMGs used in the present study included slightly different critical care end-point target ranges as well as 3 additional goals (ejection fraction, urine output, and glucose level), which may account for the statistical differences noted in the study by Hagan et al.11 In terms of thyroid hormone use, and similar to a previous report5 on SCDs, using thyroid hormone did not appear to significantly affect the ability to achieve 3 or more organs transplanted per donor.
It should be mentioned that, with regard to achieving DMGs, each OPO had its own donor management protocols aimed to meet these specific critical care end points. These particular protocols could not be identified given the availability and limitations of the data used in our study, which also made it difficult to note differences between OPO performance and management techniques used. An example of such a technique that has been adopted by many hospitals to help guide the management of patients with significant neurology injury include catastrophic brain injury guidelines, which are often in the form of pathways or processes. Although a causal relationship is difficult to delineate, hospitals with catastrophic brain injury guidelines have been found to have significantly more organ donors per trauma admissions.12
Given that the primary outcome measure of the present study was the number of organs transplanted per donor, it is limited in being able to make conclusions regarding the ultimate impact of meeting DMGs in ECDs on graft function. However, a previous report6 by our group that included both SCDs and ECDs found that meeting the DMG bundle in the donor was associated with significantly lower odds of developing delayed renal graft function in the recipient. Metzger et al9 noted that the 1-year and 5-year survival rates of patients with ECD transplants were 90.6% and 69.9%, respectively, compared with 94.5% and 81.2% for patients with non-ECD grafts.9 Despite this, it has been shown that there is an approximate 5-year increase in life expectancy for recipients of marginal donor kidneys compared with candidates undergoing dialysis on the waiting list who do not receive a transplant.13 Furthermore, in a retrospective review14 of patients receiving ECD livers, it was noted that the use of ECD grafts could lead to a significant decrease in waiting times for those willing to except an ECD liver, with patient and graft survival rates that were comparable to those from standard donors. Thus, increasing the organ supply from ECDs may have a substantial impact on a select group of those wait-listed for transplantation.
The present study evaluates the impact of meeting DMGs at several time points in the donation process and has found that meeting the DMG bundle prior to organ recovery is an independent predictor of 3 or more organs transplanted per donor in ECDs. To further understand this finding, a subsequent analysis found that donors who had a significant change in the number of individual DMGs met over the entire care spectrum (ie, from referral to prior to organ recovery) were more likely to yield more than 3 organs transplanted per donor. This finding suggests that improvement in a donor’s condition during the donor management process affects organ yield. It still remains possible that the improved condition may be due to a donor’s underlying condition rather than active management aimed at achieving preset critical care end points. Regardless of whether or not improved outcomes are caused by the active use of the DMG checklist or just the donor’s underlying condition, the statistical association may help inform OPO and transplant center staff about the condition of a particular donor and the quality of his or her organs. Identifying the optimal critical care targets is necessary before future studies can be conducted that will investigate which interventions are more likely to lead to a critical care end point being met, as well as investigate organ transplantation rates and graft outcomes.
Additional limitations to our study should be noted. As already mentioned, using the number of organs transplanted per donor as an outcome measure does not necessarily provide insight into graft quality and patient survival. Furthermore, the exact reasons for an organ being accepted for transplantation or not by transplant centers is not known and the exact role that ECD status played in that decision-making process cannot be identified through our data set. Lastly, the relative impact of meeting each of the individual critical care end points contained within the DMG bundle cannot be determined from this analysis. This was by design, for implementing the entire bundle was the specific intervention examined in our study, and aiming to achieve one element could affect the ability to meet another. Future studies could be aimed at investigating the optimal ranges for each end point, as well as the ideal therapeutic strategies for achieving each DMG.
In conclusion, our study found that meeting the DMG bundle was an independent predictor of more organs being transplanted per ECD. Because care provided throughout the donation process is important, as opposed to at only 1 particular point, the use of a checklist method for implementation of a DMG bundle may be effective. The utility of such standardization of care may be particularly beneficial in the management of ECDs, whose physiology is in need of optimization and less likely to tolerate variation. Such efforts may help lessen the shortage of organs available for transplantation by increasing both the quantity and the quality of grafts from ECDs.
Accepted for Publication: April 7, 2014.
Corresponding Author: Darren J. Malinoski, MD, Surgical Critical Care Section, Portland Veterans Affairs Medical Center, PO Box 1034, P3SURG, Portland, OR 97207 (email@example.com).
Published Online: July 23, 2014. doi:10.1001/jamasurg.2014.967.
Author Contributions: Dr Malinoski had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Patel, Zatarain, De La Cruz, Sally, Malinoski.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Patel, Zatarain, Sally, Crutchfield, Malinoski.
Critical revision of the manuscript for important intellectual content: Patel, Zatarain, De La Cruz, Sally, Ewing, Enestvedt, Malinoski.
Statistical analysis: Patel, Zatarain, De La Cruz, Sally, Crutchfield, Malinoski.
Obtained funding: Malinoski.
Administrative, technical, or material support: Zatarain, Ewing, Crutchfield, Malinoski.
Study supervision: Zatarain, Enestvedt, Malinoski.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C and grant R380T10586.
Role of the Sponsor: The funding agency had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
Previous Presentation: This paper was presented at the 85th Annual Meeting of the Pacific Coast Surgical Association; February 15, 2014; Dana Point, California.
Additional Contributions: We thank all of the members of the UNOS Region 5 DMGs Workgroup and the donors, recipients, staff, and leadership of the 8 OPOs in Region 5 for their support of this study and for aid in the collection and management of data: Jennifer Muriett, BSN, CPTC (Donor Network of Arizona in Phoenix); Ricardo Elizondo, RN, BSN (California Transplant Donor Network in Oakland); David Fox, BA (Golden State Donor Services in Sacramento, California); Scott Buntin, RRT, CPTC, Melissa Friedman, MSN, and Tom Mone, BA, MS (OneLegacy in Los Angeles, California); William Snyder, CTP (Lifesharing in San Diego, California); Rene Maldonado, BA, and Galyn Schoenstein, BS, CTBS, CPTC (Nevada Donor Network in Las Vegas); and Craig Myrick, RN, CPTC, and Mike Ingraham, RN, CPTC (Intermountain Donor Services in Salt Lake City, Utah). The Health Resources and Services Administration provided funding for the contributors’ participation.
Correction: This article was corrected on August 22, 2014, to fix a typographical error in Table 2.