Substance use disorders in organ transplantation: perennial challenges and interprofessional opportunities : Current Opinion in Organ Transplantation

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PSYCHOSOCIAL AND ETHICAL ISSUES IN ORGAN TRANSPLANTATION: Edited by Sheila Jowsey-Gregoire

Substance use disorders in organ transplantation: perennial challenges and interprofessional opportunities

Winder, Gerald S.a,b,c; Clifton, Erin G.a; Mellinger, Jessica L.a,d

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Current Opinion in Organ Transplantation: December 2022 - Volume 27 - Issue 6 - p 495-500
doi: 10.1097/MOT.0000000000001026
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Abstract

INTRODUCTION

Substance use disorders (SUD) remain common contributors to advanced medical diseases and complicating factors during solid organ transplantation (SOT). There are many presentations and combinations of substance-related considerations and risks that teams encounter during routine clinical decision-making and treatment planning pre and post-SOT. Relevant considerations include the substance used, severity of clinical and social consequences, dose and delivery method, nature of a patient's medical disease, other pharmacotherapies, psychiatric comorbidities, and the urgency of SOT, among other factors. No single medical specialty could ever be adequately equipped to address substance use in SOT alone, obliging clinicians of all medical and psychosocial training backgrounds to increase their interprofessional curiosity and expertise to become more competent and efficient providers and colleagues. 

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Box 1:
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THE INTERPROFESSIONAL FOUNDATIONS OF SOLID ORGAN TRANSPLANTATION

Successful SOT requires the collaboration of multiple medical specialties and clinicians of diverse training backgrounds. Due to their nature and impact on patients and clinicians, psychosocial problems require particularly high-grade teamwork [1]. Despite its importance in the field, interprofessionalism, defined as the integration of multiple disciplines to improve patient care quality, is rarely the focus of published articles and research studies in SOT. Interprofessional teamwork in SOT is analogous to hand hygiene and surgical sterility. All clinicians recognize the hazards of dirty hands and contaminated instruments during patient care; fewer anticipate analogous threats to patient outcomes arising from poor team communication, interpersonal discord, weak professional relationships, insular specialty silos, and disparate clinical skillsets and knowledge bases.

SOT specialties vary widely in terms of clinical skills, knowledge bases, professional cultures, and personal relationships. After years of professional training within health system niches and specialty skillsets, clinicians naturally find themselves clustered personally and professionally with colleagues with whom they have more in common (Fig. 1). Perhaps there is no greater division among health professionals than between those focusing on biological versus psychological phenomena. Mind–body dualism is an archaic and inaccurate philosophy asserting mind and body are fundamentally distinct which still permeates modern medicine [2] and may contribute to natural divisions (dotted line in Fig. 1) among SOT specialties. Such relational asymmetry in SOT becomes increasingly important as clinical problems (such as SUD) requiring high-level interprofessional interactions become more common, severe, and impactful across clinical domains and organ systems. There are many such examples of SUD-related challenges in SOT presenting interprofessional opportunities and risks.

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FIGURE 1:
Asymmetric relational proximities and potential divisions among solid organ transplantation specialties.

LIVER TRANSPLANTATION IN SHORT SOBRIETY ALCOHOL-RELATED LIVER DISEASE

Alcohol use disorder (AUD) in liver transplantation is an archetype of SUD in SOT and represents the largest quantity of scientific literature on the topic. This issue rapidly rose in importance and urgency over the last decade as early liver transplantation for acute alcohol-associated hepatitis (AAH) became increasingly common and accepted since the seminal paper by Mathurin et al.[3]. Chief among the controversies of this practice is the allocation of a precious and scarce resource to a population with active SUD, short sobriety, and substantial psychiatric comorbidity. These risk factors are implicated in a recently published multicenter study finding more common post-liver transplantation rates of any alcohol use and heavy drinking in AAH patients when compared with patients with alcohol-related cirrhosis with at least 6 months of sobriety [4▪▪].

Though they are referred to separately, there is substantial histological and diagnostic overlap between AAH and alcohol-related cirrhosis [5,6] meaning that alcohol-related challenges in liver transplantation extend far beyond AAH. Indeed, acute presentations of all severe alcohol-related liver disease (ALD) with short alcohol sobriety represent a confluence of challenges requiring interprofessional experts: severe medical disease, urgent clinical timetables, active SUD, risk of altered mental status, and life-and-death decisions. Accordingly, innovative multimodal treatments and care models must play a pivotal role in ALD and liver transplantation [7,8▪] and consensus guidelines clearly emphasize the need for interprofessional care models [9,10].

A recent 6-year multicenter study of early liver transplantation in AAH demonstrated that pretransplantation medical therapy nonresponders can be successful recipients thus satisfying the ethical principles of urgency, utility, and benefit [11▪▪]. The study's strict pre-liver transplantation selection of AAH candidates was performed by an interprofessional team including a SUD specialist, psychologist, and psychiatrist. Working alongside medicine and surgery, post-liver transplantation follow-up (n = 16) was carried out by an SOT-embedded psychosocial team with expertise in psychology, toxicology, psychometrics, neuropsychology, and psychopharmacology. Mirroring previous similar studies [3], the study identified a significantly higher survival rate in transplanted patients than those denied liver transplantation and those responding to medical therapy. With a median post-liver transplantation follow-up of 53.5 months, recurrent drinking was detected in two patients correlating with immunosuppressant nonadherence and loss of follow-up. Both relapsing patients received specialty psychological counseling and one regained sobriety.

As a notable and encouraging study finding, the authors highlight their interprofessional ‘close collaboration’ with psychosocial specialists who are themselves ‘transplant-dedicated’ and specifically trained for the assessment of AUD in SOT. They clearly credit the study teams’ interprofessionalism (i.e., SOT expertise in psychosocial specialists and alcohol-related training in hepatology) with successful candidate selection and favorable clinical outcomes. Integration strategies and myriad benefits of interprofessional evaluation and treatment of AUD in hepatology and liver transplantation and integration strategies have been documented elsewhere [1,12–14].

MEDICATION-ASSISTED OPIOID USE DISORDER TREATMENT

Medication-assisted addiction treatment (MAT) with methadone or buprenorphine is a mainstay in the treatment of opioid use disorder (OUD). These medications extinguish cravings, prevent withdrawal, lower rates of relapse and mortality, and resolve other OUD symptoms. Although overdose tragedies during the opioid crisis supplied a substantial percentage of donor organs in recent years (drug intoxication comprised 16.2% of donor deaths in 2021 as compared with 1.4% in 2001) [15], ironically OUD patients themselves face several unfortunate challenges as prospective SOT candidates [16]. SOT centers have highly variable policies regarding MAT and oftentimes written policies do not exist [17,18]. Overall, 37.7% of surveyed liver transplantation centers found MAT a relative contraindication for SOT with 16.6% of these centers recommending weaning pretransplantation; 1.6% of centers deemed MAT an absolute contraindication for SOT [18]. When compared with OUD patients not in treatment, methadone reduces mortality rates in OUD from 36.1 to 11.3 per 1000 patient years and buprenorphine reduces mortality rates from 9.5 to 4.3 per 1000 patient-years [19]. Discontinuing MAT raises relapse and mortality risks [19] and, if done without clinical justification in the context of the numerous baseline medical and psychological trials of advanced medical disease and SOT, culminates in highly adverse circumstances for OUD patients unlikely to be ethically defensible [16]. Methadone has no discernible effect on liver transplantation patients and graft survival rates [20].

A recent article details crucial strategies for MAT integration into SOT [21▪▪]. Although all clinicians must be aware of a patients’ MAT, particularly their likely opioid tolerance requiring larger than average doses for adequate analgesia, SUD-oriented specialists’ awareness of prescribing details may help ensure interprofessional maintenance of adequate OUD care. Full agonist MAT (methadone) dosing should be once daily and adjusted if CYP2C19, CYP3A4, and CYP2D6 inhibitors, characteristics of many post-SOT antimicrobial agents, are used to avoid oversedation. Partial agonist MAT (buprenorphine) exhibits high receptor binding affinity displacing other opioids from receptors and precipitating withdrawal. At doses at or greater than 16 mg, 95% of receptors will be occupied. OUD patients taking buprenorphine can be continued on lower doses of the drug perioperatively allowing for concurrent full agonist opioids to be added for pain control; hydromorphone, morphine, and fentanyl are preferred due to their ability to compete at the receptor. Alongside prescribing guidance, the authors tout the importance of interprofessionalism in terms of careful history taking, candidate selection, treatment planning, and post-SOT care continuity.

CANNABINOID USE

Cannabinoids are among the most controversial topics that SOT clinicians encounter [22] as their use continues to rapidly gain widespread legal and societal acceptance. Use is similarly increasing among liver transplantation patients with 12-month cannabis use rates in candidates at 11.0% and recipient rates of active cannabis use of 23.8% and rates of active cannabidiol use of 21.0% [23,24▪]. Cannabinoid data in SOT exist primarily in liver and kidney populations and less is known about their effects in heart and lung candidates and recipients.

Cannabis has not been significantly associated with liver transplantation recipient survival, rates of complications, and hospital readmissions or length of stay [23,25–28]. Cannabis users, however, have elevated scores on the Stanford Integrated Psychosocial Assessment for Transplant scale and higher rates of alcohol and polysubstance use, past SUD treatment, and use of psychiatric medications which may correlate with longer time-to-listing [23]. Similar psychosocial complexity and risk are also documented in the kidney population [29–32] where approximately 3% of patients have cannabis use disorder (CUD) [33] a condition defined by the Diagnostic and Statistical Manual of Mental Disorders 5 criteria [34]. Cannabis does not affect kidney recipient all-cause graft failure or patient mortality but increases death-censored graft failure (odds ratio 1.72, confidence interval 1.13–2.60) according to meta-analysis [35].

Cannabinoids are common contributors to hyperemesis and cyclic vomiting syndromes [36] which may adversely impact SOT patients. Rare, severe pulmonary aspergillosis has also been documented in immunocompromised patients where the implicated infection source was contaminated cannabis products [37]. There is limited research on cannabinoids’ interactions with immunosuppressant medications. Cannabinoids induce and inhibit cytochrome p450 enzymes and inhibit p-glycoprotein [38▪]. Clinically significant tacrolimus-related toxicity due to supratherapeutic serum levels secondary to CYP3A4 inhibition has been documented [39–41]. SOT pharmacists are often challenged by cannabinoids’ pharmacological interactions given their patients’ complex medication regimens and the unpredictable levels of cannabinoids resulting from variable formulations and use frequencies.

Similar to AUD and MAT, cannabinoid use in SOT requires an interprofessional approach since the self-reported reasons for patient use overlap significantly across recreational, psychiatric, and medicinal categories [24▪] and may require standardized scales [42] or expert examination to characterize use as part of selection and treatment planning. Furthermore, the incentive to qualify for SOT motivates the concealment of substance use. A careful, interprofessional, case-by-case clinical approach to cannabinoid use was recommended in a recently published white paper from the Canadian Society of Transplantation which also provides a thorough ethical analysis [43]. Several US transplantation psychiatry clinicians also recently published mental health-related and SUD-related recommendations regarding cannabinoid use [38▪]. Increasing the difficulty of this matter further, there are no proven pharmacological treatments for CUD [44], effective psychotherapies may not be immediately available to SOT clinicians, and multimodal treatment may be most effective [45] which SOT centers may not have ready access to.

RECURRENT SUBSTANCE USE DISORDERS AND RETRANSPLANTATION

Increasing SOT access for patients with SUD alongside teams’ ability to diagnose them and monitor for recurrence, the question inevitably arises regarding retransplantation in a patient with post-SOT SUD recurrence, particularly when the SUD was implicated in the pathophysiology of the patient's advanced medical disease. The United Network of Organ Sharing mandates that SOT teams produce the greatest good but permissible policy exceptions may be made according to teams’ policy interpretations along with individual patient factors [46▪].

A recent article explored the pros, cons, and ethical implications of this controversy using tobacco smoking relapse after lung transplantation [46▪]. Using a hypothetical case, the article effectively depicts active and remission phases of a patient's SUD intersecting with SOT including the ‘vehement disagreement’ among selection committee members as they consider retransplantation. These circumstances and controversies are applicable to the question of retransplantation in other recurrent substance use patterns in SOT patients [38▪,47].

Arguments in favor of retransplantation assert that SOT clinicians must see a larger, nuanced clinical context, obliging them to view patients’ SUD relapses as simply another psychosocial facet of complex clinical presentations rather than binary ‘rights’ or ‘wrongs.’ SUD relapses are equivalent to the recurrence of any other chronic disease which may not uniformly preclude retransplantation. Counterfactual arguments contend that donor organs are scarce; principles of beneficence, utility, and justice, must be extended to wait-listed patients; relapses often harm transplanted organs and should call into question patients’ level of overall adherence and risk; and ethical problems arise when patients with unhealthy behaviors and questionable adherence access a second organ before other patients receive their first.

Recurrent SUD in SOT represent intricately intertwined biology, habit, psychology, and biography requiring an interprofessional approach since individual clinicians and specialties are unlikely to possess adequate perspective and expertise for ethical and therapeutic decision-making. Retransplantation decision-making should involve the careful analysis of several clinical domains including the substance used (i.e., intravenous methamphetamine or heroin may be viewed differently than inhaled nicotine or cannabis), length and severity of the slip or relapse, any graft damage or medical consequences incurred, how the recurrent use was discovered (i.e., patient-offered disclosure, clinician-elicited disclosure, toxicology), any patient or family deception, recurrence of other SUD-related behaviors, number of substances used, reactions of social support persons, new or worsening of psychiatric comorbidity, reengagement with SUD treatment and clinical response, and the state of the patient's substance-related insight.

CONCLUSION

SUD remain a permanent and prominent aspect of SOT. They are chronic and recurrent problems with complex biological, psychological, and social components requiring the expertise of multiple clinicians and specialties. Regardless of the substance used or the organ transplanted, SUD in SOT require an interprofessional approach to selection and treatment planning. Such a blended and coordinated approach will not appear on its own or persist indefinitely; it must be intentionally formed and maintained.

Acknowledgements

None.

Financial support and sponsorship

None.

Conflicts of interest

J.L.M. is supported by an NIAAA K23 AA026333 Career Development Award. The remaining authors have no conflicts of interest.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

▪ of special interest

▪▪ of outstanding interest

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Keywords:

addiction; interprofessional; substance use disorder; transplantation

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