Short-Term Graft Failure of Organs Procured from Drug-Related Deaths Compared with Other Causes of Death

Abstract

Background

A gap exists between the number of patients on the national organ transplant waiting list and the number of transplants performed. Victims of drug and overdose-related death are increasingly utilized as organ donors. We sought to evaluate the suitability of organs from drug and overdose-related death for organ transplantation. This study compares the proportion of short-term allograft failure of organs procured from patients with drug-related deaths with those without drug-related deaths.

Methods

Organ donations after drug-related deaths (DDD) were compared with organ donations from non-drug-related donations after brain deaths (DBD) and donations after circulatory deaths (DCD) utilizing the Gift of Hope Organ & Tissue Donor Network for a total of 15 months.

Results

Eighty-one donors were identified from each of the DDD, DBD, and DCD groups with 264, 234, and 181 organs transplanted, respectively. The proportions of short-term graft failures were 1.15% in the DDD group compared with 2.14% in the DBD group (p = NS) and 5.52% in the DCD group (p = 0.01). The US Public Health Service increased-risk features for transmission of infectious diseases were present in 70.3% of the DDD cases. Donors from the DDD group were younger on average than those in other groups (33 to 42 years).

Conclusions

The proportion of graft failures in the drug-related deaths (DDD) group was equal to or less than those from other causes of death on short-term follow-up. Drug-related death does not appear to be a contraindication for organ procurement despite increased risk features for infectious disease transmission.

Introduction

As of January 2019, there were over 113,000 patients in the United States’ national organ transplant waiting list [1]. In 2018, 36,528 organ transplants were performed, a figure that has been increasing since 2015 likely in part due to the ongoing opioid epidemic and organ donations resulting from opioid-related deaths [1, 2]. Despite the rising number of allograft transplants, a considerable gap exists between the number of patients on the waiting list and the number of organ transplants performed annually [3, 4]. As a result of this unmet need, 20 people die daily waiting for an organ transplant in the USA (1). Efforts to reduce this gap in the USA have included increased outreach to register potential organ donors, improvement in the relationships between healthcare facilities and organ procurement organizations, and increases in living organ donations (2).

As opioid-related and other drug-related deaths continue to rise, reaching 67,367 deaths in 2018 [5], a number of public health initiatives have aimed to combat these issues. Despite these efforts, the drug and opioid epidemics continue to lead patients to healthcare facilities. Victims of drug-related deaths, however, represent an increasingly utilized source of organ procurement, particularly from donors deceased from poisoning-related anoxic brain death [6–9]. From 2003 to 2014, drug overdoses contributed to the greatest relative increase in the mechanism of death of deceased organ donors [10, 11]. Because these organs may be procured from individuals engaging in high-risk behaviors, there is also some concern regarding the transmission of communicable infectious diseases including HIV and the viral hepatitis in organs procured from patients with drug-related deaths [12]. In this era of direct-acting antiviral therapy for the hepatitis C virus (HCV), however, many have advocated for increased transplantation of organs from donors which have tested positive for HCV [13, 14].

Previous research has shown that recipients of organs from drug overdose deaths have a similar 5-year survival to recipients of organs from trauma and medical deaths [6]. Survival of recipients of lungs specifically from drug intoxication death has also been shown to be similar to recipients of lungs from non-intoxication deaths [15]. The purpose of this study was to evaluate whether organs from patients with drug overdose deaths are suitable for organ transplantation. The primary objective of this study was to compare the proportion of short-term graft failures of all individual organs procured from patients who had a drug-related death compared with those specifically with brain death or circulatory deaths.

Materials and Methods

This was a retrospective cohort analysis of a regional organ donation registry utilizing the Gift of Hope Organ & Tissue Donor Network. Gift of Hope is one of the 58 not-for-profit organ procurement organizations that comprise the US organ procurement system. It services the states of Illinois and Indiana. De-identified registry data of organ transplants from September 2015 to March 2017 for organs procured from donors with “drug intoxication” listed as the primary mechanism of death were analyzed. The reported causes of drug-related death were identified through a combination of toxicology laboratory testing, historical report, and scene investigation at the time of death. A total of 692 organ donors were initially logged in the database, with 476 of these being non-drug-related donations after brain deaths (DBD), 135 non-drug-related donations after circulatory deaths (DCD), and 81 donations after drug-related deaths (DDD). Consecutive organ donations from 81 donors during the same study time period were compared across all three groups to optimize follow-up time. Subjects were followed according to standard transplant recipient follow-up time (TRF) periods for graft failure at 6 months, 1 year, and then annually thereafter—with the longest follow-up time period being 15 months at the time of our data analysis. Of note, the proportion of graft failures were initially reported by the Gift of Hope Organ & Tissue Network in TIEDI (Transplant Information Electronic Data Interchange), a standardized electronic data collection form developed by the United Network for Organ Sharing (UNOS); after which, this report was then de-identified for the purposes of our analysis.

The primary outcome was graft failure in the DDD, DBD, and DCD groups. Graft failure was defined using the United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network (OPTN) definitions [16]. For all organs other than the pancreas, graft failure was defined as when any one of the following conditions occur: the transplanted organ is removed, the recipient dies, or the recipient is placed on the chronic allograft support system. Pancreas graft failure was defined as when any one of the following conditions occur: the transplanted pancreas is removed, the recipient re-registers for a pancreas, the recipient registers for an islet transplant after receiving a pancreas transplant, the recipient’s total insulin use exceeds 0.5 units/kg/day for 90 consecutive days, or the recipient dies. The categorical outcome of graft failure was compared between groups using Fisher’s exact test due to the low number of graft failures. For the purposes of the primary analysis, double lung procurement and transplantation was counted as a single organ.

Secondary outcomes were for descriptive purposes only and included the number of organs donated per donor patient, reasons for not transplanting organs, reported causes of donor death, presence of US Public Health Service (PHS) increased-risk features for transmission of infectious diseases (HIV, HBV, HCV) [17], and testing for HBV and HCV in the DDD group. Organs transplanted to recipients lost to follow-up were also excluded. This exclusion applied across all 3 groups including DDD of all causes, DBD, and DCD. The research study was deemed exempt by the Institutional Review Board at our local institution.

Results

Over the study period, there were 81 organ donors with DDD and 264 individual organs were transplanted from these donors. These were compared with 81 donors each from the DBD and DCD groups which had 234 and 181 organs transplanted, respectively. The mean age of the donors with DDD was 33 years, compared with 42 years for donors with other causes of death.

The DDD group had 3 graft failures (1.15%) compared with 5 (2.14%) and 10 (5.52%) graft failures in the DBD and DCD groups, respectively. No difference in the proportion of graft failures was observed between the DDD and DBD groups (1.15 vs 2.14%, Fischer’s exact test p = 0.48) but a difference in the proportion of graft failures was observed between the DDD and DCD groups (1.15 vs 5.52%, Fischer’s exact test p = 0.01). The three graft failures in the DDD group were lung (1), kidney (1), and liver (1). The five graft failures from the DBD group were lung (3), liver (1), and pancreas (1). The ten graft failures from the DCD group were kidney (8) and liver (2). Total numbers of organ types transplanted and graft failures per group are shown in Table 1. The mean number of organs donated per donor patient was 3.3 organs (95% CI 2.9–3.6), 2.9 organs (95% CI 2.5–3.3), and 2.2 organs (95% CI 2.1–2.4) for the DDD, DBD, and DCD groups, respectively. Organ donation per individual donor by cause of death is shown in Table 2.

Table 1.

Types of organs transplanted by cause of donor death and graft failures.

	Kidney	Liver	Lung	Heart	Pancreas	Intestine	Total	Graft failure n (%)
Donation after drug-related death (DDD)	133	61	22	37	12	0	264	3 (1.15%)
Donation after brain death (DBD)	89	72	29	30	12	2	234	5 (2.14%)
Donation after circulatory death (DCD)	142	31	2	0	6	0	181	10 (5.2%)

Graft failure defined by the United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network (OPTN)

Table 2.

Organs donated per donor patient by organ type.

	DDD (n = 81)	DBD (n = 81)	DCD (n = 81)
Kidneys	1.6	1.1	1.8
Liver	0.8	0.9	0.4
Lung	0.3	0.4	0.0
Heart	0.5	0.4	NA
Pancreas	0.2	0.2	0.1
Total organs	3.3	2.9	2.2

All values are means. NA not applicable, heart donation not performed after circulatory deaths at time of study. DDD donations after drug-related death, DBD donations after brain death, DCD donations after circulatory death

Donations from Drug-Related Death Group

Overall, 42 donors (51.9%) had histories of intravenous drug use (IVDU) in the preceding 12 months. Eight donors tested positive for HCV and 3 were positive for HBV. A history of IVDU was reported in 7 (77.8%) of the hepatitis-positive cases. The US PHS increased-risk features were identified in 57 (70.3%) cases of DDD (Table 3). Additional reasons that organs were not accepted for transplantation included diseased organ (n = 29 organs), findings in the OR (n = 25), time constraints (n = 12), infection and/or hepatitis (n = 11), poor organ function (n = 11), no recipient location (n = 6), findings on the biopsy (n = 3), cardiac ejection fraction < 50% (n = 3), and restriction by the medical examiner (n = 3).

Table 3.

US PHS increased-risk features for transmission of HIV, HBV, and HCV in drug-related death donor group [17].

US PHS increased-risk feature	Number of DDD donors (%)
Non-medical intravenous, intramuscular, or subcutaneous injection in the preceding 12 months	42 (51.9%)
Sex in preceding 12 months with increased-risk population or with a person known or suspected to have HIV/HBV/HCV	20 (24.7%)
Incarceration for greater than 72 hours within the preceding 12 months	17 (21.0%)
Hemodialysis within the preceding 12 months	9 (11.1%)
Engaged in sex in exchange for money or drugs in preceding 12 months	5 (6.2%)
Men who have sex with men (MSM), or women who have had sex with a man with a history of MSM in the preceding 12 months	2 (2.5%)
New diagnosis or treatment for syphilis, gonorrhea, chlamydia, or genital ulcers in the preceding 12 months	2 (2.5%)
Exposure to known or suspected HIV-infected blood through percutaneous inoculation or through contact with an open wound, non-intact skin, or mucous membrane in the preceding 12 months	1 (1.2%)
No. of US PHS increased-risk features	24 (29.6%)

Total donors in DDD group = 81

Discussion

The gap between patients awaiting organ transplants and the number of transplants performed annually in the USA continues to claim lives. In the present study, organs procured from donors who died of drug-related causes resulted in a similar proportion of short-term allograft failures compared with organs procured from those who died of brain death. However, the proportion of graft failures was less than that of organs procured from those who died of circulatory death. These data are consistent with previous studies showing similar proportions of 5-year survival in patients receiving organs from donors who died of overdose death, trauma death, and medical death [6] although the groups chose for comparison in the present study were different.

Because patients who die from drug-related deaths tend to be younger than those who die from other causes of death commonly resulting in organ procurement, their organs appear to do well during short-term follow-up. The relative youth of this population of donors, however, must be balanced with the risk of communicable infectious diseases such as HIV, HBV, and HCV, which were commonly found in this study. In fact, the US PHS increased-risk features were identified in 70.3% of donors who died from drug-related causes in our study, which is a sharp increase from the 26.3% baseline prevalence of increased-risk features reported in all deceased organ donors in 2017 [12]. The significance of individual infectious concerns may also change as new treatments become available, as in the case of HCV where curative treatment has advanced to the point where HCV may no longer be considered a contraindication to organ transplantation in many clinical settings [18–20]. While several of the donors in the current study tested positive for HCV, organ transplantation was still undertaken and successful during the follow-up period.

The total number of organs procured and transplanted from a deceased organ donor is likely affected by the cause of death. For example, in the present study, there were no heart transplants from donors who died from circulatory death. Although some transplant centers are increasingly using DCD hearts for transplant, this practice is not universal [21]. Among DDD organs, some organs may not be transplanted due to concerns about specific organ damage caused by the substance involved in death [22]. In circumstances where there is concern about organ viability for transplantation following a toxic exposure, consultation with a medical toxicologist by the transplant team is warranted.

The current study was limited by its retrospective nature, non-randomized cohort design, and sample size. As only short-term follow-up (with the longest follow-up duration being 15 months) data were analyzed, we cannot draw conclusions on the long-term graft failures of organs procured from donors who died of drug-related causes. Also, the categorization of patients in the drug-related death category was determined by the Gift of Hope Registry and not by our study’s data abstractors. This categorization was based upon historical data provided at the time of death as well as laboratory testing. Given the limitations of historical reports and laboratory drug test results, some patients might have been misclassified as drug-related deaths. Additionally, there is regional variability in drug-use which may limit the generalizability of these data to populations in other countries or areas of the USA.

Conclusion

Utilizing existing organ procurement and transplantation methods, organs procured from patients with drug-related deaths appear to have a similar proportion of graft failure compared with those from non-drug brain deaths and a decreased graft failure proportion compared with those from non-drug circulatory deaths. The total number of organs donated per donor patient in our study was greatest in the drug-related death group. The population of patients with drug-related deaths can represent an underutilized pool of suitable organ donors, and healthcare providers caring for these patients should be aware of organ transplantation as an option should other management options fail to lead to survival.

Authors’ Contribution

Participated in research design: Kim, Chhabra, Weech, and Leikin

Participated in the writing of the paper: Kim, Chhabra, Weech, and Leikin

Participated in the performance of the research: Kim, Chhabra, Weech, and Leikin

Contributed new reagents or analytic tools: Weech

Participated in data analysis: Kim and Chhabra

Funding Information

None

Compliance with Ethical Standards

All authors attest to meeting the International Committee of Medical Journal Editors (ICMJE) requirements for authorship.

Conflict of Interest

None