ORGAN TRANSPLANTATION IS ONE OF THE MOST complex surgical procedures in modern medicine. In 1954, Dr. Joseph Murray and Dr. David Hume of Brigham Hospital in Boston first successfully transplanted a human kidney from a living donor to his identical twin recipient. In 1967, Dr. Christiaan Barnard in Cape Town, South Africa, was the first to perform a human heart transplant. Notably, in the 1970s, Dr. Jean-Francois Borel discovered cyclosporine, a derivative of soil fungus that remains a key component in most transplant patients’ immunosuppressive therapy regimens today. These initial efforts did not have encouraging survival rates and over the next few decades, advances in immunosuppressant therapies and tissue typing helped to improve transplant procedure outcomes and prolong survival. Given that transplant patients are surviving longer, the ultimate goal of organ transplantation, recovery, and rehabilitation is to return these patients to the highest level of function and livelihood as possible.
Renal transplants are the most common organ transplant procedure performed in the United States, with over 16,000 procedures performed annually since 20101 (Fig. 86–1).
Renal transplants are followed by liver, heart, lung, pancreas, bowel, and multivisceral transplants. The most successful transplant procedures (kidney, heart, liver) have 5-year survival rates of around 70% to 80% (kidney, heart, liver; see Fig. 86–2). This is in contrast to the survival rates of other organs (lung, pancreas, intestine) whose survival rates are closer to 40% to 50%. Rehabilitation begins before a transplant occurs and continues through community reintegration.
This chapter will provide an overview of the role of Physical Medicine and Rehabilitation (PM&R) in the management and functional restoration of transplant patients. Organ-specific considerations and complications will be discussed, relevant to the patient’s course in both the immediate and long-term postoperative period. The chapter will track the phases of rehabilitation from before transplant through integration back into the community.
Preoperative rehabilitation (“prehab”) has received strong support in the literature with regard to management of a wide variety of conditions including solid organ transplants. This patient population is prone to muscle weakness, fatigue, extended hospitalizations, and decreased functional mobility. A recent meta-analysis2 demonstrated that a walking intervention prior to transplant improved cardiorespiratory fitness, self-reported physical function, and pain. Furthermore, a training exercise program for patients awaiting solid organ transplantation has been recommended based on evidence demonstrating improvement in physical condition and quality of life before and after transplant.3
Rehabilitation should begin as soon as possible. There are many barriers to post-transplant patients receiving early rehabilitation, particularly in the ICU. Deep sedation and unavailability of rehabilitation staff have been identified as major barriers to treatment. Early rehabilitation in the ICU by a multidisciplinary team should focus on reducing heavy sedation and making therapists available full-time. This strategy has been shown to increase the number of therapy sessions per patient and shorten ICU and overall hospital stay.4 Rehabilitation in the ICU helps to reduce pulmonary complications, preserve strength and range of motion, and prevent functional loss in the critically ill.5 This philosophy has been successfully applied to the transplant population.6
Postoperatively, many patients in the United States will benefit from a stay on an inpatient rehabilitation unit. For example, at our institution, roughly 50% of patients receiving kidney, liver, lung, or heart transplants undergo comprehensive inpatient rehabilitation. These patients require intensive therapy to improve mobility and self-care skills to transition home. An inpatient rehabilitation unit equipped with skilled medical, nursing, social work, and therapy staff is the most appropriate environment for medically complex patients including individuals recovering after transplant.
Transplant patients will commonly have decreased activity tolerance, multifactorial weakness, and active medical issues that require diagnostics and specialty visits. These can delay or interrupt therapy sessions unless they are scheduled around therapy time. Important psychosocial factors that influence patients’ participation in rehab include pain, fear of movement, symptom distress, and low physical self-efficacy.7
A small report done in Canada surveyed 113 transplant recipients for their opinions on pre- and postoperative rehabilitation. The majority of participants (n=58) viewed rehabilitation as beneficial to health and well-being, but only 54% (61 patients) actually attended post-transplant rehab. Interestingly, the most widely available rehab programs were for lung and heart recipients. Only one program was dedicated to liver recipients, and there were no programs available for kidney recipients.8
Due to improving survival rates, an increasing number of post-transplant patients return to the community and seek employment. For example, despite their complex courses, the majority of liver transplant patients are alive at 1-year post-transplant, having resumed their normal activities without restrictions.9 Vocational rehabilitation helps all patients affirm their professional self-efficacy and independence. A successful vocational rehabilitation program for transplant patients takes a multidisciplinary approach that addresses neurocognitive concerns, maintains mobility, and plans for workforce reintegration. A number of studies have been done on re-employment trends in the transplant population.
One cross-sectional study revealed that the majority of kidney transplant patients who were randomly selected and responded to a mailed questionnaire were interested in vocational rehabilitation and felt emotionally and physically ready to work after their transplant. Interestingly, employment rate decreased significantly, (68% pre- vs. 38% post-transplant) while retirement rates increased (8.3% pre- vs. 18% post-transplant).10
Transplant patients present with their own common set of functional impairments that differ from those patients with more traditional rehabilitation diagnoses. Whether as a consultant or primary provider, a physiatrist must incorporate complex medical history, physical exam findings, and deficits from baseline into a plan for functional progress. Below are a few deficits and functional impairments that are common to many transplant patients.
Delirium is a very common complication in the inpatient and postoperative period. For example, decreased perfusion pressure during lung transplantation operations is associated with increased incidence, duration, and severity of delirium.11 With any mental status change in a transplant patient, organ function should be evaluated in case of acute rejection or graft failure. Transplant pharmacists can be a key resource and caution should be taken with hepatotoxic and nephrotoxic medications and adjust doses accordingly. Medication administration schedules should be checked and centrally-acting medications should be avoided unless absolutely necessary.
Prolonged hospitalizations can result in mood disturbances for all solid organ transplant recipients and are not specific to any particular organ. Patient experiences are variable and depend on many factors. Although depression can occur, overall mood generally improves after transplantation. Anxiety regarding falls, shortness of breath, weakness, and pain are common.12–14
Transplant medications, neuropathy of critical illness, and cardiovascular complications can all contribute to sensory deficits that present as gait and balance abnormalities.15
Immobility and prolonged bed rest can lead to decreased strength and endurance. However, one should not assume that this is the exclusive cause of weakness in transplant patients.
Peripheral neuropathies: Transplant patients are at high risk for peripheral neuropathy because of the neurotoxic effects of some transplant medications. Additionally, medications such as Tacrolimus can lead to tremor.
Focal neuropathies: Single nerve injuries (axillary, radial, ulnar, median, peroneal, or femoral nerves) or even brachial plexus injuries are not uncommon. Injury can result from surgical positioning, invasive line placement, compression from immobility, or edema.
Myopathies: Frequently patients have significant proximal muscle weakness. Important potential contributors that should be considered are steroids, statins, transplant medications, and critical illness myopathy.
The ability to tolerate a full inpatient rehabilitation schedule may be challenging for this population. Many struggle with symptomatic orthostasis which can be due to a multitude of factors including severe deconditioning, autonomic dysfunction, cardiac insufficiency, fluid status, or polypharmacy.
Monitoring weight, input and output, is particularly important with cardiac, renal, and liver transplant patients due to cardiac output, renal clearance, or portal venous congestion. Rehabilitation patients that present with orthostasis and dysautonomia often require additional time for therapies and performing activities of daily living (ADL). Management options depend on the cause of orthostasis, but typically include a compression device or possibly medication management (e.g., midodrine, pyridostigmine, or fludrocortisone). Specialty services are often required due to complexity.16
Transplant patients often suffer from dysphagia or dysphonia, potential causes include injury to the superior and recurrent laryngeal nerve and/or vagus nerve, multiple or traumatic intubations and/or difficult airway due to varices, obesity, or dental considerations. Independence with feeding and tolerance of an adequate oral diet requires consultations from Speech and Language Pathology and occasionally with General Surgery or Otolaryngology for alternative routes of nutrition.
Optimal nutrition is critical to ongoing surgical and functional recovery. Poor nutrition can lead to a variety of impairments including activity tolerance, strength, cognition, and impaired healing. Careful caloric monitoring and working closely with a hospital nutritionist is critical to ensure adequate intake. In cases of poor oral intake, identifying the cause is important. Most patients will need nutritional supplements such as shakes and multivitamins. Nausea and constipation should be treated aggressively; bowel obstruction and intra-abdominal complications such as infection should be ruled out. If appetite is thought to be an issue, consider minimizing medications such as opioids and adding stimulants such as dronabinol or mirtazapine. In addition to following functional gains, labs such as pre-albumin electrolytes should be monitored regularly. Intestinal transplants will require close conversations with the primary transplant team.
The majority of pancreas transplantation (>90%) occurs simultaneously along with kidney transplantation, as this is the definitive cure for type 1 diabetes mellitus in end-stage renal disease (ESRD). These patients will likely have histories of ESRD as well as complications of hypertension and uremia (e.g., microvascular disease and retinopathy).
Neuro: Chronic kidney disease (CKD) and kidney transplant patients have decreased performance in verbal memory and executive functioning skills compared to healthy controls.12,17,18 A small prospective study demonstrated that poor performance in neuropsychology testing associated with ESRD can be quantifiably reversed at 6 months after kidney transplant. Another small, randomized prospective study concluded that a personalized multidisciplinary rehab program resulted in higher rates of adherence, glomerular filtration, quality of life (SF-36) scores, and employment rates when compared to a standard rehabilitation program at 1-year post-kidney transplant.19
Cardiovascular: Even when kidney transplant patients are free from atherosclerotic cardiovascular disease preoperatively, approximately 60% of patients can develop dyslipidemia after renal transplantation. It is important to ensure that these patients receive a heart-healthy diet tray and cholesterol-lowering medications if appropriate.20
Gastrointestinal and Nutrition: A recent systematic review and meta-analysis examined body mass index (BMI) and kidney transplantation outcomes. Both underweight and overweight/obese preoperative BMIs are associated with higher mortality in the renal transplant population.21
Early post-transplant, higher steroid doses increase protein requirements due to elevated catabolism. However, in maintenance and later phases of post-transplant recovery, excess dietary protein should be avoided in patients with chronic allograft nephropathy or insufficiency. Maintaining a dialogue with the dietitian team is critical for management of weight, cholesterol and protein intake, and diabetes.20
There is evidence that at 1-year post-renal transplant, up to 20% of patients will develop new onset diabetes, and this is not related to high doses of steroids patients may receive in the acute post-transplant phase. Of note, obesity, post-transplant weight gain, and choice of immunosuppressive regimen (particularly Tacrolimus) are known to be key modifiable risk factors for new onset diabetes.20
Musculoskeletal: There is evidence to suggest that even 3 years after kidney transplantation, a sizeable percentage of patients (40%) scored significantly lower in health-related quality of life measures. These lower scores were attributed to debility, muscular weakness, and anxiety.22
Due to their pre-existing conditions, kidney transplant patients are likely to have a history of chronic kidney disease, chronic steroid use, reduced calcium absorption, and/or hyperparathyroidism, which increases the risk of osteopenia and osteoporosis in this population. Renal osteodystrophy mostly affects dialysis-dependent patients. High-level evidence recommends daily supplementation with Calcitriol (vitamin D3) and calcium to preserve bone mineral density. These patients should be encouraged to participate in weight-bearing exercises as this promotes bone density. Bisphosphonate therapy should be considered.20
Rehabilitation Considerations: In kidney transplant recipients, therapists must consider the effects of exercise on blood glucose control, be mindful of extremity edema and neuropathy interfering with mobility, and focus on resistive exercises and osteoporosis precautions. It is also important to know the location of the transplanted kidney so that any belt or harness used for caregiving or therapy can be applied to the patient without disturbing the surgical site.
Liver transplant patients may have a history of nonalcoholic steatohepatitis (most common), hepatocellular carcinoma, hereditary liver disease, and alcohol or substance abuse. As a result of their illness, patients may be jaundiced, anemic, coagulopathic, and have a history of ascites, encephalopathy, multiple transfusions, multiple paracenteses, or prolonged hospitalizations.
Neurologic: Liver cirrhosis has been associated with poor cognitive performance compared to healthy controls. Additionally, poor driving performance, increased number of motor vehicle crashes, and frontal brain dysfunction have been associated with hepatic encephalopathy. When retested after transplantation, cognitive scores improved significantly such that they matched healthy controls, which suggest cognitive deficits in cirrhosis are reversible.23–25
Signs and symptoms such as altered mental status, agitation, itching, and asterixis may be warning signs that graft function has been compromised and a patient is at risk of hepatic encephalopathy and potentially other dangerous toxicities due to decreased medication metabolism. It is important to alert the primary transplant team of any of these early signs of hepatic encephalopathy. Florid hepatic encephalopathy complicates bowel and bladder continence and increases aspiration risk by compromising airway support.
Gastrointestinal and Nutrition: Liver transplant patients will have hypoalbuminemia. They will have increased protein requirements that can be met with dietary supplements. In cases of hypovolemia, intravenous albumin can be used for acute but transient resuscitation.
Hematologic: Coagulopathies are frequently observed in the post-transplant period. Patients with history of liver disease or malignancy are particularly susceptible to deficiency or depletion of coagulation factors. A physiatrist’s threshold for ruling out deep vein thrombosis (DVT) or pulmonary embolism should be low. Close coordination with the surgical team is key, especially regarding DVT prophylaxis and therapeutic anticoagulation.
Musculoskeletal: Rapid bone loss is common during the first year after transplantation. There is strong evidence to support that bisphosphonate therapy in the acute post-transplant period can attenuate this process.26
The Model for End-Stage Liver Disease (MELD) is a reliable measure of mortality risk in patients with end-stage liver disease. It is used as a disease severity index to help prioritize allocation of organs for transplant. These models are for use by medical professionals.
Rehabilitation Considerations: Liver cirrhosis patients have impaired aerobic capacity that is correlated with severity of disease; the MELD score is a measure of mortality risk utilized by the transplant team to not only prioritize patients on the transplant list but to plan postoperative care.27 Liver transplant patients who undergo exercise training increase their distance walked and their resting energy expenditure, suggesting an increase in exercise and functional capacity compared to controls.28 The introduction of an intensive early rehabilitation program for liver transplant recipients has been found to be well tolerated and associated with a decreased length of stay in the ICU and hospital.6
Cardiovascular: Vagal and parasympathetic innervation of the heart is compromised in transplantation. As a result, heart transplant recipients tend to have a higher resting heart rate (90–100 bpm). Additionally, the heart’s response to and recovery from exercise is dependent only on circulating catecholamines, which take longer to influence heart rate. Rest breaks should be scheduled in between therapy sessions, as heart transplant patients have reduced exercise tolerance and require longer warm up and recovery time.
Vagal denervation also results in desensitivity to typical symptoms of angina or palpitations. Still, these symptoms are not common post-transplant given that the majority of donor hearts are free from cardiovascular disease.
Notably, cholesterol-lowering medications that are the staple of cardiovascular prevention are also metabolized by the liver (along with many other medications such as antihypertensives, antiretrovirals, and coumadin), along with cyclosporine and tacrolimus. These immunosuppressive medications are essential to graft survival. Despite the known benefits of these medications, if used concomitantly with statins, they elevate a patient’s risk of severe myalgia and myopathy.
Statins play a crucial role in cardiovascular health and are indicated postcardiac transplant. Their metabolism by the liver shares the same mechanism with drugs like cyclosporine and tacrolimus. Therefore, there is increased risk for side effects such as myalgias and myopathy.29
Even with a history of hyperlipidemia, heart transplant patients don’t develop coronary artery disease until well after the acute recovery phase {∼10 years).30
Rehab Considerations: Recent meta-analysis provides moderate evidence that post-transplant cardiac rehabilitation improves quality of life, morbidity, and mortality. Special considerations in this patient population include decreased exercise tolerance and sternal precautions.30 Despite this, a recent study encompassing all patients receiving Medicare coverage due to disability demonstrated that less than half (43%) of eligible heart transplant patients in 2008 (total 2,163 patients) participated in cardiac rehabilitation programs.31 For further details, please see the chapter on Cardiac Rehabilitation in this book.
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