Prehab to Prepare Living Liver Donors for Enhanced Recovery

Living donor liver transplantation (LDLT) is an established treatment for end-stage liver disease.1 Preserving health and quality of life are priorities of care for living liver donors (LLD) as they receive no direct medical benefit from their donation.1,2 Unfortunately, recent research demonstrates that LLDs experience significant postoperative pain, dysfunction, and adverse psychosocial outcomes that may persist up to several years.3-5 Given the risks and postoperative sequalae associated with LDLT, potential LLDs must undergo a comprehensive and interdisciplinary screening and selection process, including a medical history, laboratory assessments, and physical and psychosocial/psychiatric examinations.1 Yet, despite widely established thresholds for organ donation candidacy, research demonstrates that living liver or kidney donors with lower pre-donation physical and mental health (e.g., higher BMI, fatigue, less physical activity, smoking, mood and anxiety disturbance) are at higher risk for worse physical and mental health, and health-related quality of life up to 12 months after donation.6-8 Moreover, some potential donors may lose donation candidacy for a variety of reasons, including changes in health, increasing anxiety and ambivalence related to the donation, or insufficient support.1,9 Strategies aimed at optimizing the mental and physical health for potential LLDs are therefore appropriate for both the minimization of surgical risks and preservation of candidate pools, but also, are in keeping with the priorities of LDLT - that is, preservation of health and quality of life for LLDs.

Over the last fifteen years, prehabilitation (or 'prehab') has emerged and grown as a feasible, safe, and efficacious strategy to improve preoperative health and contribute to reductions in surgical complications and adverse postoperative outcomes. Prehab has been examined in numerous surgical settings, including oncology10, cardiology11,12, and among solid organ transplant recipients.13-16 Prehab research and clinical application have generally focused on high-risk surgical candidates in the interest of efficient resource allocation given the likelihood for clinically meaningful improvements in outcomes (e.g., reduced surgical complications).17-20 To date, living organ donors have not been targeted recipients of prehab given their relatively low surgical risk due to health screening and selection. However, this is at odds with the philosophy of care for living donors (i.e., to protect against adverse effects) and undervalues the decrement in quality of life that many donors endure. Accordingly, research examining the role and effect of prehab for LLDs has important health and ethical implications.

Given that there have been no studies examining the effect of prehab for LLDs, much uncertainty remains about whether LLDs will enroll, adhere, and be retained in the intervention. Further, while we may surmise what the ideal components of prehab may be for LLDs, this has yet to be examined. Finally, there are no studies assessing the feasibility of conducting a large scale randomized controlled trial (RCT) of prehab for LLDs that could help establish sample sizes, recruitment strategies, and intervention and measurement design elements. Thus, in this trial protocol entitled "PRehab tO PreparE Living Liver Donors for Enhanced Recovery" (PROPELLER), we propose a feasibility RCT of prehab vs usual care for LLDs who are scheduled for LDLT.