What's Your Perspective?

  • Opioids and The Transplant Surgeon

    Vinayak S. Rohan, MDVinayak S. Rohan, MD
    Assistant Professor of Surgery
    Medical University of South Carolina

    One need only to see the statistics to realize the gravity of the current opioid epidemic; >115 people are dying of overdoses daily, equating to an economic burden of 78.5 billion dollars /year.

    With more than 42,000 annual deaths attributed to opiates, a surge in the number of organs available for transplant is inevitable. In fact, there has been a 24-fold rise in organ transplants available from overdose deaths, a national tragedy earning the morose moniker of the “Grim Silver Lining.”

    How did we get here?

    Not surprisingly, opiates have been known to humans as long as the existence of recorded history. A reference to ‘Hulgul’ or joyplant was seen as early as 3400 BCE from Mesopotamia.

    In the U.S., the 1990s saw an increase in the use of opiates for a variety of pain-control regimens, driven and pushed by pharmaceutical companies. Marketing budgets swelled to more than $200 million a year. Extended release formulations also began to appear, and doctors, nurses and pain societies advocated for these “non-addicting” opioids.

    By 1994, 4 million people (2% of the population) were using prescription medications non-medically. Additionally, after JCAHO incorporated pain as the 5th vital sign, there was a doubling of the opioid abuse/misuse in one decade.

    Opioids and transplant

    Opiate overdose contributed to 1.1% of all donors in 2000. In 2017, it was 13.4%, an increase of 17% per year. At the same time, the discard rate for these organs is much higher than for donors from trauma, due to 56% of donors from overdose being deemed as PHS high risk (especially due to Hepatitis C.)

    We in the transplant world are acutely aware of the perpetual shortage of organs with more than 100,000 people on the waiting list. Every transplant is balancing the risk with the benefit. With the advent of new Hepatitis C drugs with excellent cure rates, trials have shown the feasibility and benefit of transplanting Hepatitis C–negative patients with Hepatitis C–positive kidneys. It is time for us as a community to adopt it in wider practice and decrease the discard rates of these organs.

    The other face of the coin is more humbling. We have to contemplate how we, as surgeons, have contributed to this epidemic and how our actions affect transplant outcomes.

    Opioids are intended for short-term treatment of surgical pain. For far too long we have prescribed opioids without seriously considering the long-term consequences. The best predictor of misuse was the number of post-discharge prescriptions, with an additional refill increasing the misuse by 44%.

     Alarmingly, 80% of heroin users first used prescription opioids. The fact is that 67% to 92% of patients have unused opiates left with them after surgery, forming an important reservoir available for abuse.

    Although the transplant rates have increased with the epidemic, outcomes have been adversely affected. Recent articles looking at the single center studies and national data have shown that graft loss and mortality are both increased in liver and kidney transplant patients who are chronic opioid users.

    As we continue to focus our energies on increasing the organ utilization, the education of patients and the prescriber regarding opioid use should not be neglected. We took the easy route in treating pain; fixing the problem is not going to be pain free. A concerted effort amongst all of us is required for the development of multimodality and alternative pain control strategies in transplantation and beyond…from my perspective.
    Go comment!
  • HCV Positive Allografts: A Solution for… Most?

    Dr. Ryan HelmickRyan A. Helmick, MD
    University of Tennessee Health Science Center
    Methodist University Hospital

     

    As the transplant community continues to search for a solution to the available organ shortfall, xenotransplantation remains a far-off promise and tissue engineered organs are in the earliest stages of research. Despite these challenges, the number of deceased donors has been increasing in recent years, due in large part to the opioid crisis. Between the years of 2010 and 2016, the number of deceased donors has increased overall by about 26%, while the number of donors who have died of a drug overdose has increased by 277%.1 Often these donors are classified as PHS increased risk, and many have recent or long term infection from Hepatitis B virus (HBV) or Hepatitis C virus (HCV).

    Utilization of organs from donors that are seropositive for HBV core antibody has long been considered acceptable at many centers, given the available therapies including Hepatitis B immunoglobulin as well as the antiretrovirals with a long history of successful HBV prevention. The lack of effective therapies for HCV has long limited organs from these donors only to patients who already have HCV. Some have reported positive results by utilizing the narrow subset of donors that are HCV antibody positive and RNA negative.2 Yet in the current age of highly effective direct acting antiviral therapy, this way of thinking needs to be re-evaluated. The utilization of HCV positive organs for negative patients necessitates many ethical, financial, and medical questions be addressed in a thorough fashion, ideally by the entire transplant community.

    The biggest hurdle in the utilization of HCV mismatch organs may relate to the ethical questions that arise from such transplants. Our medical school oath to “do no harm,” and the thought of knowingly “giving” someone HCV causes great hesitation; however, the transmission of cytomegalovirus (CMV) or Epstein Barr virus (EBV) in a seronegative recipient is rarely given a second thought. Treatment of CMV tissue invasive disease can be a significant though manageable challenge with severe cases causing morbidity and prolonged hospitalizations. Less frequently, EBV causes lymphomas necessitating chemotherapy and reductions in immunosuppression that can place the transplanted organs at risk of rejection. With the current state of treatment for HCV, patients receive a 12- to 24-week course of oral therapy that is often well tolerated with minimal side effects. De novo HCV infection almost never causes severe liver dysfunction, and with treatment response rates reported at 99-100% depending on the chosen direct acting antiviral regimen, post-transplant HCV should be a rather benign and easily treatable issue, especially when compared to PTLD or aggressive CMV. Given the treatability of HCV in the current era, use of these organs should flow from the basic tenets of medical ethics; with adequate informed consent, autonomous patients should have the option to proceed with these transplants.

    The next tenet of medical ethics, beneficence, may be a trickier ethical question to address. The framing of the question should not merely revolve around “should this patient get an HCV+ allograft or not?” Rather, the issue is “should this recipient get an HCV+ kidney or remain on dialysis for another year or two?” or “should this low MELD recipient take an HCV+ liver or not get transplanted at all?” Bowring et al recently described the risks to kidney recipients who decline kidneys labeled as “PHS Increased Risk” in terms of delays in transplantation.3 What further gains might patients be able to realize in terms of decreases in dialysis time by opting for a HCV mismatched organ and going through treatment after transplant?

    Once a program, surgeon, and patient are comfortable with the ethical issues regarding HCV mismatch, there are financial considerations to consider. While the early direct acting antiviral (DAA) therapies were reported to cost as much as $100,000, newer regimens are coming down in cost with estimates in the $25,000-35,000 range. When we compare these costs to the yearly costs associated with dialysis, earlier transplantation of kidney recipients might result in overall cost savings compared to waiting on dialysis for an HCV negative organ. Patients who are willing to accept HCV+ kidneys may be able to avoid dialysis altogether and realize the benefits of pre-emptive kidney transplant. As newer and more effective HCV therapies come to market and innovation and competition drive drug prices down, this will continue to be a more financially competitive option compared to years on dialysis.

    Utilization of HCV mismatch organs is not likely to be a one-size-fits-all solution as it relates to medical suitability, including long wait times and donor shortages. Does it make sense to give a 30-year-old who has not yet started dialysis an HCV+ kidney? Would it make sense if the average wait time in that recipient’s region was eight years and he was not expected to do well on dialysis? What if instead he had steatosis and grade 2 fibrosis? There are certainly patients where HCV mismatch makes a great deal of sense; older diabetic patients without living donors in regions with long waiting times are prime candidates to use HCV+ kidneys. Similarly, patients with persistently low MELD scores can benefit from liver transplant with HCV mismatch livers and DAA therapy afterwards.  

    The great efficacy that new DAA therapies for HCV have demonstrated has ushered in new opportunities for organ utilization. Given the rapidly increasing numbers of donors who are dying of drug overdose and who have HCV exposures, the transplant community has the opportunity and responsibility to utilize these organs for patients in dire need of lifesaving transplantation.

    References

    1. Chute DF, Sise ME. Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010-2016. Am J Nephrol. 2018;47(2):84-93. doi:10.1159/000486516
    2. Nowak KM, Witzke O, Sotiropoulos GC, et al. Transplantation of Renal Allografts From Organ Donors Reactive for HCV Antibodies to HCV-Negative Recipients: Safety and Clinical Outcome. Kidney Int Rep. 2017;2(1):53-59. doi:10.1016/j.ekir.2016.09.058
    3. Bowring Mary G., Holscher Courtenay M., Zhou Sheng, et al. Turn down for what? Patient outcomes associated with declining increased infectious risk kidneys. Am J Transplant. 2017;18(3):617-624. doi:10.1111/ajt.14577

     

    1 Comment
  • The National Living Donor Assistance Center: A Valuable Tool for Living Donors and Transplant Programs

    Dr. Amith MathurAmit K. Mathur, MD, MS
    Consultant, Division of Transplant Surgery, Mayo Clinic in Arizona
    Assistant Professor of Surgery, Mayo Clinic School of Medicine
    Program Evaluation Specialist, National Living Donor Assistance Center

    As transplant professionals engaged in living donor transplantation, we come across the same story every day. We evaluate and list a transplant candidate, who begins the long wait on the deceased donor waiting list because they do not have a living donor. We are all too familiar with the risk of waitlist mortality – to our patients and our programs. Even more frustrating than the lack of a living donor is watching a perfectly good living donor be ruled out, or maybe never even come forward. Many of these individuals are fit enough to donate, want to donate, but are unable to do so because they lack the resources to be evaluated, to subsist after surgery, and struggle with even getting to the transplant center. The associated costs are often uncovered by recipient insurance. Without financial assistance to support living donors, we are often caught offering patients a less optimal therapy than they could have availed through a living donor transplant.

    One of the most helpful resources to help potential living donors is The National Living Donor Assistance Center (NLDAC). NLDAC provides financial support for travel and subsistence costs to support living donor evaluation, surgery, and after care for up to two years. NLDAC has been continuously supported by federal funds awarded by the Division of Transplantation, Healthcare Systems Bureau, Health Resources and Services Administration (HRSA). The program is cooperatively administered by the ASTS and the University of Arizona, owing to the tireless efforts of our dedicated program staff working with potential donors. The program is also supported through the efforts of individuals from a consortium of institutions including Arbor Research Collaborative for Health, Washington University in Saint Louis, and the Mayo Clinic.

    NLDAC celebrated its 10th anniversary in 2017. Since its inception (as of November 2017), NLDAC has received nearly 8,000 applications, has provided more than $14.3 million dollars, which has culminated in 4,156 living donor transplants.

    NLDAC now supports nearly 10% of all living donors in the United States.

    Based on surveys of donors who have used NLDAC, 75% state that they could not have donated without financial assistance from NLDAC. This is quite astounding, given that the average amount spent per application received is $1,737.

    96% of transplant centers have filed applications on behalf of living donors, but there is tremendous variation in the use of the program among centers. Here is an outline of the NLDAC program, how it works, and how your program can access these resources for living donors.

    What is the legal basis for NLDAC?

    The funds issued by NLDAC do not constitute payment for profit. The National Organ Transplant Act of 1984 (NOTA) and the Organ Donation and Recovery Improvement Act of 2004 (ODRIA) are the federal legal precedents that have established many of the regulations surrounding transplant and organ donation activity in the United States. NOTA specifically prohibits individuals from receiving “valuable consideration” for donating organs, i.e. people cannot profit specifically for donating an organ. However, expenses incurred related to travel, subsistence, and other non-medical expenses can be provided. This is specifically authorized in ODRIA, and is the basis for the NLDAC program and funds provided to a potential living donor through NLDAC do not constitute a profit for that individual. More information on this is available at http://www.livingdonorassistance.org.

    Who is eligible for financial support from NLDAC?

    NLDAC categoriesThe program is designed to be a payer of last resort. If other public or private programs (or funds from the recipients) are accessible to potential donors to help support travel and subsistence costs, those should be used.

    If no other funds exist, NLDAC has specific eligibility guidelines based primarily on recipient income relative to the federal poverty guidelines (Figure 1). Donor and recipient income verification is performed as a part of the application process. Since funds are limited for the program on an annual basis, the priority for funding follows Preference Categories. These Preference Categories are centered on where donor and recipient household income (not personal income) fall relative to the 300% threshold of the federal poverty line. The Preference Categories are shown in the Figure. NLDAC is not currently accepting Preference Category 2 applications.

    Based on these eligibility guidelines, NLDAC has found that both recipient and donor household average approximately $27,000 - $35,000 per year.

    What if the donor and recipient live above the 300% federal poverty line but would still have considerable financial hardship in the donor evaluation process?

    These applications will be considered in NLDAC Preference Category 4. There is a portion of the application process for providing proof of financial hardship. These applications are reviewed on an individual basis by the HRSA project officer. Historically, this preference category was underutilized, but now constitutes more than 20% of NLDAC applications.

    What expenses qualify for reimbursement? Is there a cap on funds? Is there a cap on donors per recipient?

    Currently, NLDAC reimburses travel, lodging, meals, and incidental expenses incurred by the potential donor and an accompanying person as a part of donor evaluation, hospitalization for the living donor surgical procedure, and followup appointments for up to 2 years. The program will pay for a total of five trips, three for the donor and two for the accompanying person. This can be modified if additional visits are required by the transplant center.

    The cap on NLDAC funds for a particular donor and accompanying individual is $6000.00. Kidney recipients may have one donor evaluated at a time, with a maximum of three donors total. Liver recipients operate similarly, with a maximum of five donors. Lung recipients may have two donors at a time, with a maximum of six donors total.

    Does NLDAC work with paired exchange donors?

    NLDAC does operate with paired exchange donors, and the eligibility criteria are based on the originally intended recipient. NLDAC is currently exploring options for non-directed donors.

    How quickly are applications processed? How do living donors receive funds from NLDAC?

    NLDAC applications are typically initiated by transplant center personnel and directed to us. Once applications are received by NLDAC, the average time for an application decision and to contact the applicant is 5.7 days.

    NLDAC issues funds prospectively to potential living donors through a Control Value Card (CVC), administered by American Express. This card resembles a credit card that potential donors can use to purchase airline tickets, pay for gas, hotels, food at restaurants or grocery stores, and other vendors. It takes less than a week to receive the CVC from NLDAC.

    How can donors at my center access NLDAC?

    NLDAC application forms are available on our website (http://www.livingdonorassistance.org). Educational videos are also available there to help potential donors understand if they qualify and how to apply. Questions can also be directed to NLDAC@livingdonorassistance.org or by calling 1-888-870-5002. You can also follow NLDAC on social media on Facebook, Twitter (@NLDAC_ASTS), and Instagram (@NLDAC)

    How does NLDAC help my transplant center?

    208 transplant centers have used NLDAC for their potential donors. Utilization of the NLDAC program varies greatly by transplant centers. Transplant center staff may request a report of their activity by completing an electronic request form. Some centers have filed more than 400 applications, and some as few as one application. We would love to see this change, and encourage centers to contact us to help answer questions about eligibility, assistance with applications, or other issues. The NLDAC team holds monthly webinars for transplant professionals to learn about the application process and will provide a webinar for your transplant team on request.

    NLDAC is a relatively untapped tool at many centers, and can help centers evaluate more living donors and potentially see growth in their living donor transplant programs.

    Summary

    NLDAC is valuable resource for potential living donors by providing financial assistance for expenses that go uncovered by recipient insurance. Greater awareness of this program may help transplant candidates receive a timely living donor transplant at even greater rates in the future.

    Go comment!