Background

Transplantation of tissues and organs has been of interest to physicians and surgeons since the 18th century. Advances in our understanding of the immune system, development of immunosuppressive medications, and techniques such as cardiopulmonary bypass have provided the opportunity for successful organ transplants. In 1954, the first kidney was successfully transplanted. Other successful organ transplants include the first heart transplant in 1968, combined heart-lung transplant in 1981, and single-lung transplant in 1983.¹

Organ transplantation has become a viable alternative to medical treatment of many conditions. Because of the success rates, many types of transplants are no longer considered experimental but are considered appropriate treatment for organ failure. As a result of improved survival, long-term outcomes are as important as short-term outcomes as a measure of successful transplantation. The number of Medicare-approved medical centers that perform lung and heart-lung transplants has grown to 50 in the United States, and there are 110 certified heart transplant centers.² Over 2000 heart transplants and 1000 lung transplants have been performed annually since 2000. The 5-year survival rates for heart transplants of all status levels are reported as 70.9%; for lung transplants, 43.1%. Other national data on median waiting time and survival rates are presented in Table 40-1.

Issues Associated with Transplantation

There are many ethical, psychological, and social concerns surrounding organ transplantation. Ethical issues relate to increasing potential donor sources and distributing available organs. Psychological issues include stress due to an unknown waiting time, the potential of moving from one’s home to a location near a transplant center, and possible employment disruption. The transplant process affects not only the individual patient, but the patient’s social support systems as well. This is highly significant because adequate social support is a factor in long-term transplant success and quality of life.⁵

Physical Therapy Considerations

As important members of the transplant team, physical therapists need an understanding of the physiological components of both the pretransplant disease and posttransplant state, as well as knowledge of the influence of surgery, medications, or rejection on musculoskeletal structure and function. In addition, physical function may be decreased due to the primary cardiopulmonary condition and overall deconditioning. Knowledge of medical management, including medications, ventilatory support, and hemodynamic monitoring, assists the therapist in determining whether modifications are needed during rehabilitation.

Physical therapists have a role in the management of the transplant patient in all stages of transplant: before transplant, during the acute postoperative phase, and throughout the rehabilitation phase. The purpose of physical therapy before transplant is to identify baseline function and to screen for impairments that may limit rehabilitation goals. The pretransplantation period offers an opportunity to address limitations in strength and range of motion or endurance and to improve physical function. Because of the surgical intervention, bed mobility, ventilation, secretion management, range of motion, and pain control are important areas to address in the immediate postoperative phase. In the posttransplantation rehabilitation phase, physical therapy goals are to return the patient to the highest functional level. Upper and lower extremity muscle strength and range of motion are addressed, as well as posture, shoulder and trunk mobility, breathing pattern, breath sounds, and functional mobility.

Rehabilitation of the Transplant Patient

To assist in management of the patient with transplant, rehabilitation is categorized into the following four phases: (1) pretransplant, (2) surgery and the postoperative acute phase, (3) postoperative outpatient phase, and (4) community- or home-based phase. Although the ultimate goal of transplant rehabilitation is to improve the patient’s function and quality of life, each phase of rehabilitation has its own emphasis.

Lung Transplant and End-Stage Pulmonary Disease

Patients are referred for lung transplantation for end-stage pulmonary conditions. The primary diagnoses for adults requiring a lung transplant are severe chronic obstructive pulmonary disease (COPD) (44%), idiopathic pulmonary fibrosis (IPF) (17%), and cystic fibrosis (CF) (15%). Other conditions include pulmonary arterial hypertension (PAH). The guidelines for selection of patients for the lung transplant waiting list were updated by the ISHLT in 2006 and include specific criteria for the most common pulmonary conditions.14,15 Within the disease-specific listing criteria for COPD, the guidelines include a BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) score of 7-10. The BODE is more useful than measures of airflow obstruction in predicting mortality from COPD; higher scores are associated with increased mortality.¹⁶ Before 2005, patients who had accrued the most time on the waiting list were given priority for lung transplants. The change to a lung allocation score now gives priority for transplants to those patients who have a greater medical urgency for transplant. The lung allocation score is based on “(i) waitlist urgency measure (expected number of days lived without a transplant during an additional year on the waitlist), (ii) posttransplant survival measure (expected number of days lived during the first year posttransplant), and (iii) transplant benefit measure (posttransplant survival measure minus waitlist urgency measure).”¹⁷ The urgency and survival measures are based on factors that predict risk for death in patients with lung transplant and include functional status as well as physiological measures. This change has increased the number of transplants for patients with IPF and slowed the number of transplants for COPD.¹⁴

Idiopathic pulmonary fibrosis is characterized by scarring of lung parenchyma leading to decreased lung volumes and decreased diffusing capacity. Risk factors for mortality include the lung pathology, pulmonary function results, physical function from the 6-minute walk test, and respiratory failure.¹⁴ Criteria for listing of patients with IPF include a decrease in FVC of 10% or more during 6 months and pulse oximetry less than 88% during a 6-minute walk test.¹⁵ Patients with IPF waiting for lung transplant who walked less than 679 feet had higher mortality than those who walked longer distances.¹⁸

Recent advances in vasodilator therapy for patients with pulmonary artery hypertension and poor survival of patients with PAH after transplant have reduced the number of patients with PAH who receive lung transplants. The criteria for listing patients with PAH include an NYHA class III or IV status on the maximal vasodilator therapy and 6-minute walk test of less than 350 meters.¹⁵

In patients with cystic fibrosis, the predictors of mortality include declining FEV₁ and chronic infection. The current criteria for transplant include FEV₁ less than 30% of predicted, as well as other markers of declining pulmonary function.¹⁹

Pulmonary rehabilitation is an essential component of management of patients with chronic lung conditions even without transplant, and it is becoming an accepted requirement for patients awaiting lung transplantation. Clinical data from pulmonary rehabilitation programs suggest that patients with better physical function before transplant have improved posttransplantation outcomes.

The causes of exercise limitation in people with chronic lung conditions are both ventilatory and musculoskeletal. Muscle changes in pulmonary conditions include decreased muscle oxidative capacity and muscle weakness.²⁰ Reasonable goals for pretransplant rehabilitation include improvement in muscle strength in lower extremity musculature, functional upper extremity muscle strength and endurance, functional shoulder and chest wall range of motion, demonstration of coordinated diaphragmatic breathing with exercise and activities, and improved cardiovascular endurance. Because of the significant effect of immunosuppressive medications on muscle strength, a greater emphasis is placed on resistance training in a patient awaiting lung transplantation than in most typical pulmonary rehabilitation programs. An example of a preoperative pulmonary rehabilitation program is outlined in Table 40-3.

Patient Education

The pretransplant waiting period provides an ideal opportunity for patient education. Nursing generally provides much of the education regarding preoperative procedures, postoperative course, and medication. Rehabilitation teaching includes breathing training, airway clearance techniques, and activity progression.

Other Transplants

Patients awaiting other organ transplants may also be referred to physical therapy for treatment of musculoskeletal problems. Because of the level of metabolic abnormality in patients awaiting liver and kidney transplants, endurance training is difficult to perform. Other physical therapy interventions, however, may be used as appropriate (i.e., muscle strengthening, range of motion).

Surgical Implications

Surgical procedures have implications for the physical therapist in the areas of pain, abnormal hemodynamic responses, and movement patterns. The surgical approach for transplant is chosen to provide the surgeon the optimal working area and visual field. The choice of incision may affect patient comfort and function after surgery. Patients may experience pain in the area of the incision, and they may present with decreased muscle function and joint pain related to the muscles that were incised during surgery. The physical therapist should be familiar with the surgical incisions and their impact on rehabilitation. Other related complications from thoracic transplant include injury to the phrenic nerve, brachial plexus injury, and peroneal nerve injury secondary to prolonged positioning during surgery and recovery.

Heart transplants are usually performed through a median sternotomy incision and require cardiopulmonary bypass.²¹ The native heart is excised, leaving a portion of the right atrium (atrial cuff), including the SA node. The left atrium of the donor heart is sutured to the recipient’s atrial cuff and the major vessels reattached, starting with the pulmonary arterial vessels and followed by the aorta. Drainage tubes are placed in the pleural and mediastinal spaces and an epicardial pacing wire is placed before closure of the sternum. Total heart ischemic time is minimized, with less than 4 hours recommended. Finally, the two halves of the sternum are wired together, the new heart defibrillated, cardiopulmonary bypass discontinued, and the patient awakened.

Lung transplantation surgical incisions depend on whether a single- or double-lung transplant is to be performed. Single-lung transplants are performed through a standard posterolateral thoracotomy incision, made through the fifth rib. The latissimus dorsi and lower trapezius muscles are incised, as are the intercostal muscles at this level. If the rib at the surgical level fractures, it is resected so that the bone ends do not rub or puncture the lung. The serratus anterior muscle is preserved if at all possible, but the lateral portion of the rhomboid may be cut to allow more access for the surgeon. Postoperative pain and impaired upper quarter movement patterns may present significant problems for patients.

Double-lung transplants are performed as two single-lung transplants, in a technique referred to as bilateral sequential lung transplantation. The surgical incision extends from the midaxillary line under the submammary fold to the other midaxillary line and may or may not use a transverse sternotomy.²² In this technique, called the clamshell incision, the pectoralis major is separated from the chest wall, and the serratus anterior may be incised.²³ Complications from this technique include sternal overlap if a transverse sternotomy is used.

Acute Phase Rehabilitation

The acute phase of rehabilitation begins in the intensive care unit and continues throughout the patient’s hospital stay. Interventions are focused on facilitating normal cardiovascular and pulmonary function and increasing functional abilities in self-care and ambulation.

Lung Transplant Acute Management

Postoperative management of the patient following lung transplantation begins in the intensive care unit. After lung transplantation, patients are generally mechanically ventilated for 24 to 72 hours. Often, paralytic agents are used in this period so that ventilation can be optimized. Chest tubes are likely in place, and patients are medicated for pain. Infection control is imperative; isolation rooms with negative-pressure ventilation are used, and respiratory isolation procedures are maintained.

Problems in the immediate lung transplantation period include ineffective airway clearance, poor gas exchange, and rejection. Hypotension and hypoxemia can lead to decreased blood flow at the site of anastomosis for the new lung, creating necrotic changes and impairment in airflow. Problems with airway clearance are related to the denervation of the transplanted lung, specifically the autonomic nervous system pathways. The lack of innervation leads to ineffective cough and ciliary clearance. Problems with gas exchange occur as a result of postoperative edema.

A common complication of organ transplantation is organ rejection. Acute rejection occurs within the first 6 months of transplantation, whereas chronic rejection remains a long-term problem. Rejection episodes are monitored closely, often with biopsy, and treated with a variety of immune suppressant medications.

Acute rejection is mediated by T cells. These T cells infiltrate the new organ allograft, and multiply, causing tissue destruction. Chronic rejection initially appears as hypertrophy of the intima in the transplanted organ and then progresses to fibrosis. In heart transplants, chronic rejection may also be seen as accelerated atherosclerosis. In lung transplants, chronic rejection appears in the airways as bronchiolitis obliterans. No effective treatment exists for chronic rejection.

Heart Transplant

After heart transplant, patients continue to experience decreased aerobic capacity and endurance, muscle atrophy, and decreased physical function. In addition, immune suppression increases the risk for infection and leads to loss of muscle and bone. Rejection remains a significant risk, and heart transplant patients are likely to acquire premature atherosclerosis. Despite these problems, aerobic capacity and physical function are amenable to rehabilitation.²⁷ Common long-term impairments are chest wall soreness, abnormal upper quarter movement patterns, and low back and knee pain from overuse. Once the patient leaves the hospital, rehabilitation looks much like phase II cardiac rehabilitation. The overall objective is to increase functional activity to within normal limits.

Cardiac and Respiratory Physiology in Heart Transplant

After transplantation, functional capacity is about 50% of the capacity of control subjects; abnormalities in heart rate, blood pressure, and ventilatory abnormalities also exist during this period. In posttransplant patients, peak heart rate is lower than in controls (156 versus 168 beats/minute),²⁸ although heart rate kinetics are not different.²⁹ In regard to long-term effects of heart transplantation on heart rate, some children who have received heart transplantation do acquire a normal heart rate response to exercise.³⁰ The ventilatory response to exercise is abnormal, as demonstrated by a decreased diffusing capacity.³¹ However, there may be some peripheral limitations that contribute to decreased functional capacity; these include decreased capillary density in muscle.³² A summary of how cardiac variables are affected by heart transplant is shown in Table 40-6.

Table 40-6

Effect of Heart Transplant on Selected Cardiovascular Variables As Compared with Normal Age-Predicted Values

	Heart Rate	Stroke Volume	Blood Pressure
Rest	Lower than normal	Lower than normal with little change when shifting positions	+	NA
Exercise	Lower (approximately 15 beats less)	Decreased and late onset	+	May approximate normal with exercise training program

Signs of Rejection

The primary signs and symptoms of rejection are flu-like symptoms, including low-grade fever and muscle aches. Dysrhythmias and bradycardia below 60 or relative bradycardia (decreased compared with patient’s normal resting heart rate) are significant and should be reported to the physician immediately. Rejection episodes are monitored by biopsy. Exercise can continue if the rejection episode is mild or moderate as determined by biopsy.

Exercise and the Heart Transplant Patient

Exercise training is important for reversing the physiological abnormalities observed after heart transplant, returning patients to improved functional status, and preventing disability incurred from the immunosuppressant regimen. The outpatient phase of rehabilitation resembles phase II cardiac rehabilitation, which generally continues for 8 to 12 weeks, at which time the patient is encouraged to continue exercise on his or her own or at a fitness facility. ISHLT guidelines for care address health-related issues for patients after heart transplant. Hypertension after heart transplant should be treated to achieve the same goals as the general population, and lifestyle modifications are the same as for others with cardiac risk factors.²⁵Aerobic exercise and resistance training are recommended. Guidelines for exercise for the posttransplant cardiac patient are shown in Box 40-2.

Box 40-2   Summary Guidelines for Posttransplant Cardiac Rehabilitation

 Use cardiac rehabilitation phase II protocols

 Heart rate is not best indicator of exercise intensity

 Increase warm-up and cool-down to 10 to 15 minutes

 RPE in conjunction with other physiological monitoring (e.g. RPP)

 No exercise when patient is in acute rejection episode (biopsy needed)

 Continue exercise in mild rejection

After heart transplantation, there is no direct innervation to the heart to control heart rate response during exercise. Heart rate and stroke volume increase due to the effect of increased preload and through circulation of catecholamines. There is evidence that some sympathetic re-innervation can occur 1-2 years after transplant.³³ For the patient in phase II cardiac rehabilitation, this means that the warm-up and cool-down portions of exercise should be slowly increased to 10 to 15 minutes. Exercise intensity should not be determined by heart rate alone, because of the effects of denervation. In addition, rating of perceived exertion (RPE) scales remain an unreliable method for determining exercise intensity after heart transplant, because large inter-individual variations occur in the relationship of RPE and maximal oxygen consumption.³⁴ Although there is no strong clinical consensus about the optimal method for prescribing and monitoring exercise intensity for patients following heart transplant, ventilatory threshold, rate-pressure product (RPP), or a combination of RPE and physiological monitoring is recommended. Evidence suggests that patients with heart transplants can exercise at high intensity and achieve better functional outcomes than sedentary individuals without transplant.³⁵ Intensity set at 10% below anaerobic threshold produced significant increases in aerobic capacity.³⁶ Endurance and strength exercise can be performed in this rehabilitation stage, although upper extremity strengthening should not be started until after the sternum has healed. Treadmill, bike, arm ergometry, and indoor cross-country ski equipment are all appropriate choices.³⁷

Cardiac rehabilitation can result in substantial increases in aerobic capacity with patients able to improve 20% to 50% over prerehabilitation levels. The mechanisms that contribute to increased aerobic capacity include increased maximal heart rate, improved ventilatory capacity, and improved peripheral muscle function.³⁸ Supervised exercise programs lead to greater increases in aerobic capacity than do home exercise programs (49% versus 18% improvement, respectively).²⁷ Resistance training has been used in patients following heart transplantation as an essential component of cardiac rehabilitation to improve physical function and prevent losses of muscle strength associated with corticosteroid use. Resistance training does appear to increase bone mineral density to nearly pretransplant levels.³⁹ Resistance training increases oxidative capacity of muscles⁴⁰ and also prevents adverse effects of corticosteroids and immune therapy on skeletal muscle.

Despite the evidence that cardiac rehabilitation is beneficial in increasing aerobic capacity and exercise capacity, scant literature exists to suggest that exercise training prevents transplant atherosclerosis. Early studies of patients after renal transplant, however, show promising results of exercise in preventing atherosclerosis.⁴¹

Community- or Home-Based Rehabilitation

Patients are generally followed at the transplant center until the medical staff is satisfied with patient progress. Return to home can occur at this point in time, whether or not rehabilitation goals have been met. For patients who have left their home community to wait for transplant, the transition to home frequently occurs at 3 months after transplant. The major goal of community-based rehabilitation is a return to normal function with minimal limitations. Therapists in rural settings and community hospitals may be involved with a transplant patient’s plan of care in this phase. Therapists should be comfortable treating patients in many settings, skilled in addressing the common complications, and vigilant in watching for signs of rejection. In the initial stages of posttransplant rehabilitation, a supervised program is recommended. Hospital-based phase III cardiac rehabilitation programs are appropriate, or patients may elect to exercise independently in a fitness facility. Some follow-up by the transplant center is important to encourage compliance in exercise programs. Once patients reach their desired level of fitness, a community-based program is appropriate for maintaining endurance, aerobic capacity, strength, and flexibility. Patients who participate in training can attain high levels of exercise performance, with an appropriate training regimen.⁴⁵

Although transplants prolong life, some health professionals believe that patients are merely exchanging one set of problems for another. For transplants to be successful, recipients must remain on powerful immunosuppressive drugs for the remainder of their lives. Some of these medications have crippling side effects. The effects of long-term prednisone are well known: osteoporosis, muscle weakness, and glucose intolerance. The long-term effects of cyclosporine and azathioprine affect the patient’s ability to fight infection. Patients also need to manage medication side effects on a daily basis. It is these medications, however, that make for impressive survival rates.

Osteoporosis remains a prevalent and disabling problem for patients following organ transplantation surgery. Before transplant, the prevalence of osteoporosis is 37% in patients awaiting lung transplantation.⁴⁶ In the first year after transplant, a high incidence of vertebral and other atraumatic fractures occurs (between 8% and 65%), which can significantly limit physical function and complicate the posttransplantation rehabilitation course. Physical therapists have a role in identifying the physical limitations of osteoporosis and in prescribing appropriate exercise programs. Osteoporosis medications are considered essential components of care, and the addition of resistance exercise to a medication regimen does improve bone mineral density.³⁹

Quality of Life

Although quality of life generally improves after heart and/or lung transplantation, many factors may influence that quality of life. Generally, patients report improved physical function, general health, and social functioning.⁴⁹ Despite these improvements, a decline in quality of life eventually occurs in long-term survivors. It is unclear whether this downturn is due to declines in physical condition or other social or psychological factors. Patients with lung transplantation generally have increased quality of life until the onset of bronchiolitis obliterans, which then causes a decline in quality of life.

Summary

Physical therapy has an important role in maintaining and improving functional levels of patients both before and after organ transplantation. Knowledge of cardiovascular and pulmonary physiology, along with the ability to analyze movement and function, allows rehabilitation professionals to maximize a patient’s quality of life. The exciting field of organ transplant is growing quickly. New advances in long-term management of transplant recipients mean that rehabilitation professionals need to continue to develop and evaluate evolving approaches to care.