Chronic Postsurgical Pain After Solid Organ Transplantation: A Dreaded Complication in Recipients and Living Donors

Chronic postsurgical pain (CPSP) must be distinguished from acute postoperative pain and is defined by the International Association for the Study of Pain as pain that develops after a surgical procedure and persists for at least 3 mo after surgery, excluding all other causes of pain or preexisting pain problems.¹ CPSP varies in intensity from discomfort to functional limitation and could be persistent or intermittent. Anxiety, surgical trauma, stress, side effects of drugs (mostly in relation to opioid use), and an underestimation of the magnitude of the problem by physicians, family, and relatives complicate the management.²

Merely 2% to 10% of individuals undergoing surgery will develop severe persisting pain leading to chronic physical disability and psychosocial distress.² After solid organ transplantation (SOT), the prevalence of CPSP is estimated to be 20% but varies according to the type of organ transplant.³ CPSP has been reported after heart and lung transplantation with a prevalence of 54% and 18%, respectively, after kidney (25.8%) and liver (35% in nonusers of opioids before transplant, 10% were severe CPSP), mainly occurring in recipients on opioids or benzodiazepines before transplant.^4-6

CSP has a striking psychological burden when occurring in the context of a living donation from a healthy donor. Holtzman et al⁷ reported CPSP after the hepatectomy in 31% and 27% of the donors, respectively, at 6 and 12 mo of follow-up. The prevalence of CPSP following living donor laparoscopic nephrectomy was 5.7% in the series by Bruintjes et al⁸ and 41% in a prospective cohort of living donor nephrectomy reported by Fleishman et al.⁹ This substantial variation might be related to the definition of CPSP, the design of the study, and various pain tool assessment.

Management of CPSP consists of the use of single or combination drugs, mainly paracetamol, non–steroidal anti-inflammatory drugs, and tramadol, but often requires the need for opioids. Several reports evaluated chronic opioid consumption before and after transplantation and its impact on mortality.^4-6

Chuan et al¹⁰ performed a retrospective analysis of 140 SOT patients followed by a transitional pain service (TPS) at the Toronto General Hospital that provides a multidisciplinary care pathway preoperatively and postoperatively. Opioid consumption calculated in milligram morphine equivalent (MME) per day was the main outcome measure. The TPS used 6 well-known various screening tools, scores, or questionnaires to quantify and assess the various physical, psychological, and social consequences of CPSP (Neuropathic Pain Screening Tool, Brief Pain Inventory, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, Sensitivity to Pain Traumatization Scale, and Short-form McGill Pain Questionnaire) at the first and last TPS visits. The authors showed that self-reported total pain, the use of opioid medication, opioid dosing consumption, and rating of intensity and quality of pain decreased from the first TPS visit to the last TPS visit. The main significant changes over the treatment at the TPS were the reduction of opioid dose consumption and improvement in total pain traumatization score.

The study by Chuan et al¹⁰ has the merit to address the beneficial issue on transplant patients of a long follow-up by a specialized pain care service. Despite that, currently, some centers have a pain care referent or department, often run by an anesthesiologist or addictologist, and few are dedicated to long-term follow-up of SOT recipients. Nevertheless, some points deserve to be elucidated. This was a very select cohort of 140 patients in a large organ transplant center performing merely 700 transplants per year. In this cohort, 35% of the patients had a history of addiction, 53% had a history of mental health difficulties, and 67% were on opioid medication at the pretransplant visit. It is well known that these factors, in addition to a few others, including patient characteristics, comorbidities, and alterations in central pain processing, are the main risk factors of posttransplant opioid consumption.^4,5,7,11 This must be distinguished from CPSP and opioid use acquired after transplant surgery, considering both patient and medical team perception, in which technical issues related to surgery (previous surgery, severe acute postoperative pain, tissue adhesions, nerve injury) might influence the development of CPSP.

Several reports highlighted an association between chronic opioid consumption, the daily dose of opioid consumption, before organ transplant or during the first year posttransplant, and increased morbidity and mortality.^5,11,12 Data from the US kidney transplant registry showed an association between long-term opioid prescription doses of ≥90 MME/d and mortality (adjusted hazard ratio 1.61; 95% CI, 1.24-2.10) and graft loss (adjusted hazard ratio 1.33; 95% CI, 1.05-1.67).¹² Similar data were reported after a heart transplant.¹¹ In the study of Chuan et al,¹⁰ 34% of the patients were on an opioid dose prescription of >50 MME/d posttransplant, and the management by the TPS led to a significant reduction in the daily dose. Nevertheless, the tools used by the TPS in terms of management, interventions and medications, and the patient willingness to integrate such programs are not elucidated. Finally, whether the benefit of opioid reduction or discontinuation improved long-term patient and graft survival is worth evaluating.

High-dose opioid consumption appears as a marker, possibly reflecting underlying conditions, comorbidities, and behaviors. The Centers for Disease Control guidelines recommend specific caution and careful reassessment of individual benefits and risks when considering increasing dosages to ≥50 MME/d.¹³

In summary, a multidisciplinary approach involving anesthesiologist, psychiatrists, psychologists, addictologists, physiotherapists, and referent nursing personnel is often required for the long-term follow-up of patients with CPSP. Targeted evaluation of high-risk patients at time of transplant, by the transplant team and a TPS, is mandatory. Chronic opioid consumption before transplant is a major risk factor for posttransplant consumption and might affect long-term morbidity and mortality. A specialized multidisciplinary pain care team might help improve pre- and postoperative pain management in transplant centers and long-term outcomes.