07 Jul The Role of Opioids in Transplant Patient Outcomes
Candidates for transplantation undergo evaluation of the severity of end-stage organ failure, comorbid conditions, overall fitness for surgery, and psychosocial status including risk factors for poor adherence after transplant. The goal of evaluation is to select candidates with acceptable anticipated risks of perioperative and longer-term complications who are expected to benefit from organ transplant. Pharmaceutical care as indicated by the medication list is often reviewed to identify health problems, assess special care needs, and identify possible drug interactions that might occur after transplant. Until recently, use of pharmaceutical fill records to quantitatively inform expectations for clinical outcomes after liver transplant has not been described.
Opioid analgesics serve an important role in management of both acute and chronic pain, but recognition of an “epidemic” of complications related to the misuse, abuse, and inherent potential toxicity of prescription opioids is growing.1-3 Concerns about opioid-related toxicity are even greater in patients with end-stage organ failure due to altered drug protein binding, metabolism, and excretion, leading to accumulation of parent agents and potentially toxic metabolites. Patients who use high levels of opioids may also have increased risk of nonadherence with prescribed care.
In a recent study published as a ‘cover article’ in the journal Liver Transplantation, this author, along with collaborators including Mark Schnitzler and David Axelrod, report that the use of opioid pain medications may play a significant role in patient outcomes following liver transplantation.4 Based on an analysis of linked national transplant and pharmacy fill records for nearly 30,000 patients undergoing liver transplantation in the United States between 2008 and 2014, elevated death and organ loss rates in the first five years after transplantation among recipients with the highest use of opioid pain medications while on the waiting list was noted.
Overall, 9.3% of recipients filled opioids on the waiting list. After ranking use quantified by morphine equivalents into four levels, compared to no use, level 3 and level 4 opioid use during listing were associated with significantly increased mortality over 5 years posttransplant. Similar patterns occurred for graft failure. Higher risks mainly emerged after the first transplant anniversary, a pattern that may in part reflect sustained opioid use. Sixty-five percent of those with the highest level of opioid use on the waiting list continued moderate-to-high level use in the first year after transplantation. Opioid use in the first-year post-transplant also had graded associations with subsequent death and graft loss >1 to 5 years post-transplant.
This new work extends recent findings by the research team that prescription opioid fills predict increased risk of complications after kidney transplant, and higher readmission rates after living donor nephrectomy.5-7
Importantly, the SRTR center performance equations do not adjust for chronic pain or pre-transplant opioid use as risk factors for posttransplant death or graft failure. While more work is needed to identify underlying mechanisms of mortality, determine the impact of decreasing opioid use before transplant, and design pain management strategies that improve patient outcomes, centers performing transplants in patients who require opioid analgesics before transplant should be aware of associated risk that is not recognized by SRTR.
The study authors conclude that “transplant candidates who require high levels of opioids warrant careful evaluation of pain management strategies, perhaps by a multidisciplinary team including a pain management specialist, as well as focused monitoring of clinical status after transplant.”
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- Degenhardt L, Larney S, Kimber J, et al. The impact of opioid substitution therapy on mortality post-release from prison: retrospective data linkage study. Addiction. 2014;109(8): 1306-1317.
- Falkowski C. The rampant abuse of prescription pain medications. Minnesota medicine.2013;96(3): 38-41.
- Manchikanti L, Helm S, 2nd, Fellows B, et al. Opioid epidemic in the United States. Pain physician. 2012;15(3 Suppl): ES9-38.
- Randall HB, Alhamad T, Schnitzler MA, et al. Survival implications of opioid use before and after liver transplantation. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2017;23(3): 305-314.
- Lentine KL, Yuan H, Tuttle-Newhall JE, et al. Quantifying prognostic impact of prescription opioid use before kidney transplantation through linked registry and pharmaceutical claims data. Transplantation. 2015;99(1): 187-196.
- Lentine KL, Lam NN, Xiao H, et al. Associations of pre-transplant prescription narcotic use with clinical complications after kidney transplantation. American journal of nephrology.2015;41(2): 165-176.
- Lentine KL, Lam NN, Schnitzler MA, et al. Predonation Prescription Opioid Use: A Novel Risk Factor for Readmission After Living Kidney Donation. American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2017;17(3): 744-753.