AACN Clinical Issues Volume 12, Number 2, pp.

186201 2001, AACN

Care Before and After Lung Transplant and Quality of Life Research
Dorothy M. Lanuza, PhD, RN, FAAN,* and Mary A. McCabe, MS, RN

I Lung transplantation is a growing surgical

option for patients with end-stage lung and pulmonary vascular diseases. After completing an extensive evaluation and meeting the selection criteria, patients are listed for either single or bilateralsequential lung transplantation. Immediate postoperative management requires detailed attention to fluid management, monitoring for infection, reperfusion injury, pulmonary hygiene, and pain management. Length of stay depends on the patients condition before transplant and postoperative complications. Discharge from the hospital can be as early as 7 days after transplantation. Newer immunosuppressive medications offer more options for treating and preventing rejection. Advanced practice nurses, such as coordinators, case managers, nurse practitioners, and clinical nurse specialists, are uniquely positioned to play key roles in coordinating the care of transplant patients across settings and both before and after the transplant procedure. The perioperative needs of lung transplant patients and the impact of this complex procedure on the recipients and familys quality of life merit further investigation by clinicians and researchers. (KEYWORDS: lung transplantation, quality of life, perioperative care, transplant nurse coordinator, immunosuppressive medications)

Lung transplantation provides a last-resort therapy for selected individuals who have end-stage respiratory disease, a life expectancy of 3 years or less, and an unacceptable quality of life (QOL).1 The end-stage respiratory conditions may be the result of underlying diseases that can be classified under four major categories: suppurative (e.g., cystic fibrosis), obstructive (e.g., emphysema), restrictive (e.g., pulmonary fibrosis), and vascular (e.g., pulmonary hypertension). This article presents a brief historic overview of lung transplantation, describes care before and after lung transplant, and identifies nursing diagnoses2 that may be applicable for each stage of care. In addition, research on the quality of life of lung transplant patients is summarized, and implications for practice and research are discussed. The first lung transplant procedure was performed in 1963, and the patient survived only 18 days.3 It was not until after improvements in immunosuppressive medications (e.g., introduction of cyclosporine) and surgical techniques were achieved in the early 1980s that the number of lung transplant pro-

From *Niehoff School of Nursing, Loyola University of Chicago, and Nursing Department & Lung Transplant Program, Foster G. McGaw Hospital, Loyola University Medical Center, Maywood, Illinois. Reprint requests to: Dorothy M. Lanuza, PhD, RN, FAAN, Niehoff School of Nursing, Loyola University Medical Center, Building 105, Room 2859, 2160 S. First Avenue, Maywood, IL 60153. 186

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cedures increased markedly. Between 1988 and 1999, more than 7,033 transplant procedures were performed.4 Advances in surgical techniques, organ preservation methods, and immunosuppressive medications have led to significant improvements in lung transplant patients survival rates that average approximately 76%, 58%, and 44% for 1, 3, and 5 years after transplant, respectively.58 The early lung transplant procedures were primarily heartlung transplants (HLTs), which involved transplantation of a donor heart and both lungs, or double-lung transplants (DLTs), which involved transplantation of both donor lungs en block with a single tracheal anastomosis. The volume for HLT and DLT procedures peaked in 1989 because of improvements in surgical techniques and the development of new surgical procedures. Currently, most lung transplantations are either bilateralsequential lung transplants (BSLTs) or single-lung transplants (SLTs). The BSLT procedure involves two bronchial anastamoses and was shown to decrease the incidence of airway ischemia and bronchial complications associated with older surgical techniques (e.g., DLT using tracheal anastamoses).3 The BSLT procedure involves transplanting two donor lungs sequentially. First, one of the recipients native lungs is removed, followed immediately by transplantation of a donor lung; then the other native lung is explanted and the second donor lung is implanted. Each donor lung is anastomosed to the main stem bronchus.9 The SLT procedure is performed when the transplant team determines that one lung would be sufficient to provide the patient satisfactory pulmonary function.10 The SLT involves the replacement of one of the patients native lungs with a donor lung. It is used for patients with all types of lung disease, except septic lung diseases, such as cystic fibrosis and bronchiectasis.1 A bilateral lung transplantation is indicated for cystic fibrosis and bronchiectasis patients to avoid the risk of overwhelming infection that would occur if one of the recipients septic lungs were left in place.

Care Before Transplant

When patients with end-stage respiratory conditions are referred to transplant centers,

they undergo a thorough evaluation to determine whether they meet the selection criteria for lung transplantation (see Table 1). While the evaluation workup may vary from center to center, usually a complete history and physical examination, laboratory tests, and diagnostic procedures (especially of the heart, kidney, and lungs) are performed. In addition, a social worker or psychologist interviews the patient to assess the patients psychological, social (e.g., patients support system), and financial status. When the initial evaluations are completed, a multidisciplinary team (e.g., lung transplant surgeon, lung transplant pulmonary physician, transplant nurse coordinator, social worker, and dietician) meets to consider the findings and determine whether the patient qualifies as a candidate for lung transplantation. If the selection criteria are successfully met, than the patients name is added to the transplant waiting list and the individual becomes a lung transplant candidate. Since the demand for donor lungs far exceeds the supply, the waiting time for a suitable donor organ is increasing. As of September 1998, the median waiting time for candidates 18 to 64 years of age was 619 days.7 This prolonged waiting time currently results in a mortality rate of 11% before transplant.7 During the waiting period before the transplant, the goal is to provide the patient with optimal treatment for the underlying respiratory disease and any co-morbid medical conditions. If indicated, psychosocial conditions also should be addressed during this period. Anxiety and depression often are associated with end-stage respiratory conditions, such as chronic obstructive pulmonary disease (COPD).1116 Since the period before the transplant is laden with uncertainty and concerns about the future, it is not surprising that lung transplant candidates may experience anxiety and depression during this time. In one study, 21% of the lung transplant candidates (n = 57) developed a psychiatric disorder (e.g., an adjustment problem with anxious mood) while awaiting lung transplantation.17 Thus, care before transplant is aimed at treating the psychophysiological symptoms and complications of the patients underlying respiratory condition and existing co-morbidities. Referrals are made to psychologists, social workers, other health professionals, and community re-

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LANUZA AND MCCABE TABLE 1 International Guidelines for Selection of Lung Transplant Candidates22
Selection Criteria

AACN Clinical Issues

Patient has a diagnosis of end-stage chronic respiratory disease unresponsive to available medical or surgical treatment, declining function, and limited survival. Age: approximately 55 years for heartlung transplants; approximately 65 years for single lung transplant, and approximately 60 years for bilateral lung transplants. Has no dysfunction of other major organs besides the lung (e.g., renal dysfunction with creatinine clearance 50 mg/mL/min) Is not infected with human immunodeficiency virus Has no active malignancy within the past 2 years with the exception of basal cell and squamous cell carcinoma of the skin Does not have hepatitis B antigen positivity Does not have hepatitis C with biopsy-proven liver disease Has no progressive neuromuscular disease Relative Contraindications to Transplant Selection (candidates need to be considered on an individual basis) Medical condition without end-organ damage (e.g., hypertension, diabetes mellitus) Symptomatic osteoporosis Severe musculoskeletal disease affecting the thorax (e.g., kyphoscoliosis) Nutritional states 70% or 130% ideal body weight Not free of substance addiction (i.e., tobacco, street drugs, alcohol, etc.) for at least 6 months Poorly controlled major psychoaffective disorder Inability to comply with complex medical regimen or documented history of noncompliance Requires invasive ventilation Systemic disease (e.g., collagen vascular processes and diabetes mellitus) Colonization with fungi or atypical mycobacteria Note: The following are not considered contraindications for transplant: Active infection with systemic symptoms (e.g., Mycobacterium tuberculosis) Current use of corticosteroids, however, must attempt to discontinue these drugs or at least reduce the prednisolone or prednisone dosage to 20 mg/day64

sources, as necessary. In addition, the lung transplant candidate is encouraged to strive to achieve optimal nutritional and physical activity status within the limitations of his or her condition. Nursing diagnoses approved by the North American Nursing Diagnosis Association (NANDA) for lung transplant patients in the pretransplant period are listed in Table 2.
Nutrition

Nutrition can significantly impact immediate postoperative morbidity and mortality.

Malnutrition can increase the patients risk of developing airway infection through its adverse effect on the immune system.18,19 Poor nutrition can also unfavorably affect respiratory muscle function by reducing diaphragmatic muscle mass and strength.20,21 Thus, achieving an optimal nutritional status before transplant is considered critical to obtain a successful outcome after transplantation. In fact, a patient may be taken off the transplant waiting list and denied consideration for transplantation if his or her nutritional status does not meet the

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TABLE 2 Nursing Diagnoses for Lung Transplant Patients in Pretransplant Period*2

Risk for anxiety related to: threat of change in health status, role function, economic status Risk for impaired social interaction related to: impaired communication, impaired physical mobility Powerlessness related to: lifestyle of helplessness Risk for ineffective family coping: compromise related to inadequate or incorrect information or understanding by primary person; temporary family disorganization and role changes; other situational crises Impaired gas exchange related to: underlying respiratory disease or condition Activity intolerance related to: generalized deconditioning, dyspnea, poor oxygenation, etc. Altered nutrition related to: inability to ingest, digest, or absorb nutrients; insufficient or excessive nutritional intake related to metabolic needs Risk for activity intolerance related to: general weakness, sedentary lifestyle, imbalance between oxygen supply/demand, deconditioned status Care deficit related to: physical impaired mobility Self-C
*Approved by the North American Nursing Diagnosis Association.

transplant criteria. While the range may vary among transplant centers, many programs require lung transplant candidates to weigh between 70% and 130% of their ideal body weight (IBW) before they are eligible for transplantation.22 Therefore, a thorough nutritional assessment is part of the lung transplantation evaluation process. The initial assessment includes the determination of the patients nutritional history, anthropometric measurements, biochemical markers of nutritional status, as well as current and overall nutritional status. At the conclusion of this assessment, the dietitians recommendations and goals are reviewed with the patient, and target dates are set for attaining these goals. Subsequent assessments are conducted thereafter to evaluate the patients progress toward reaching the nutritional goals. For candidates who weigh less than 70% of IBW, nutritional interventions may include the placement of a feeding tube and a daily infusion of enteral feedings, as well as requiring the patient to record weekly weights and keep a daily nutritional log. For those candidates weighing greater than 130% of IBW, a weight-loss program with a goal to achieve weight loss of approximately 1 to 2 pounds per week is discussed. A target weight loss or gain must be achieved before the candidate will be listed for transplantation.

Rehabilitation

Pulmonary rehabilitation has been shown to prolong survival in patients with COPD.23 Thus, rehabilitation is started before transplantation to improve the transplant candidates overall physical condition, maximize activity tolerance, improve endurance, and decrease co-morbidities (e.g., obesity). Optimizing physical and emotional health through exercise also is thought to increase the potential for a positive outcome after transplantation.24 Although exercise programs do not necessarily change lung function, research findings indicate they improve patients abilities to carry out activities of daily living and increase their endurance.24 The duration and intensity of the exercise vary, depending on the patients severity of illness and motivation.24 Typically, a patient participates in a supervised exercise program three to five times a week, focusing on large muscle groups. In addition, portions of the exercise program are continued at home. The lung transplant candidates participation provides an indication of motivation, as well as the likelihood that he or she will participate in a rehabilitation program after transplantation.
Patient/Family Education

In addition to nutrition and physical therapy assessments before a transplant, a compre-

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TABLE 3 Topics Addressed During Teaching Sessions for Lung Transplant Candidates and Their Families
The procedure the candidate will follow when notified of the possibility that a suitable donor organ is available The possibility that the candidate will experience multiple admissions for potential transplantation before suitable donor lungs are found Potential and expected surgical and medical complications associated with lung transplantation The post transplant medications that are commonly used, including their names, dosages, administration frequency, and common side effects Expected hospital length of stay; the usual out-patient follow-up schedule; the frequency of scheduled transbronchial bronchoscopy and biopsies The potential need for in-patient rehabilitation and home care

hensive teaching session is conducted for the candidate and his or her significant other(s). During this educational session, many topics are addressed (Table 3). The oral presentation and discussion are reinforced with written patient education materials. In addition to patient teaching, the importance of strong family/social support systems also is stressed. Therefore, lung transplant candidates and the members of their support system are invited to attend and participate in group support meetings. At our institution, three support meetings are held each month; however, the frequency and format for support meetings vary at each transplant center.

Early Management After Transplant

As indicated earlier, before the recipient finally undergoes lung transplantation, he/she may experience multiple admissions for the procedure. It is not uncommon for transplant surgery to be cancelled after a patient is admitted to the hospital because the surgical team may determine that the donor lungs are unsuitable due to irreversible damage or poor function (e.g., multiple lung contusions, aspiration, or pneumonia). After patients undergo lung transplantation, they are usually transferred from the operating room to a private room in a surgical intensive care unit. Much of their immediate postoperative care is similar to other cardiothoracic surgical patients. The lung

transplant recipients require close monitoring of their overall fluid status throughout their hospitalization. The initial fluid assessment is done every 15 minutes along with continuous blood pressure monitoring, oxygen saturation monitoring, and heart rate and rhythm monitoring. The recipient may or may not have a pulmonary artery catheter in place, but he/she will have intravenous access via a large bore catheter that provides a route for the administration of fluid, blood products, and vasopressors, as needed. A Foley catheter will be in place so that hourly urine output can be determined, with the goal of keeping urine output at 30 mL/hour or more. Electrolytes will be monitored daily. The SLT recipient will have either a right or left posterolateral thoracotomy incision with two chest tubes on the side of the transplanted lung. The BSLT recipient will have an anterio-transverse thoracosternotomy with four chest tubes inserted, two on the left and two on the right side of the chest. The chest tubes will be connected to 20-cm water suction and monitored every 15 minutes for type and amount of drainage. If the chest drainage exceeds 100 mL/hr after the first 2 to 3 hours and is primarily sanguineous in nature, the surgeon is notified and the patients blood loss is closely monitored to determine whether the chest should be explored for bleeding. Table 4 lists nursing diagnoses for lung transplant patients in the postoperative period. Patients will be intubated and receive volume-controlled ventilation after the transplant procedure. The length of time patients

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TABLE 4 Nursing Diagnoses for Lung Transplant Patients in the Postoperative Period2
Risk for fluid volume imbalance related to: transplant surgical procedure Risk for fluid volume deficit related to: massive blood loss Risk for electrolyte imbalance related to: surgical procedure, altered fluid balance Potential for infection related to: surgical procedure, decrease respiratory ciliarys action, inadequate secondary defenses, chronic disease, invasive procedures Ineffective airway clearance of retained secretions related to: slowing of mucocilliary clearance Pain related to: surgical and diagnostic procedures, coughing and deep breathing Knowledge deficit related to: lack of recall, information misinterpretation, cognitive limits

remain intubated may vary among patients; however, attempts will be made to extubate all patients as soon as possible to prevent barotrauma. Barotrauma, which is caused by over-distension of alveoli with excessive ventilatory volume or pressures, can affect all transplant patients but is more likely to develop in patients with COPD who undergo SLT (i.e., the COPD patients native lung is especially vulnerable to barotrauma).25 Once the patient is successfully extubated, aggressive pulmonary hygiene is very important. The patient will need to actively participate in coughing and deep breathing to facilitate airway clearance and prevent atelectasis and pneumonia. These exercises will assist the patient in expectorating secretions and sputum, which are often thick and tenacious. Adequate pain management is essential if the patient is to fully engage in these activities. Epidural catheters or patient-controlled analgesia are frequently used to manage early postoperative pain. If pain or narcotic management is still needed after hospital discharge, the patient is referred to an outpatient pain management program.
Length of Stay

current trend of earlier hospital discharge protects the immunocompromised transplant recipient from the risk of nosocomial infections. An earlier hospital discharge also means that the costs related to the patients lung transplantation will be decreased.
Preparation for Discharge

The length of hospitalization is influenced by the patients overall condition before the transplant, underlying lung disease, cardiac function, nutritional status, age, type of transplant (SLT or BSLT), rehabilitation potential, perioperative complications, and support systems. An uncomplicated lung transplant recipient can be discharged from the hospital as early as 7 days after transplantation. The

To discharge patients early and provide continuity of care, a thorough, multidisciplinary discharge plan needs to be in place. For the plan to be successful, it is imperative to include the patient and family in the planning process. Good communication and coordination among the hospital transplant team, home healthcare agency, home intravenous provider, durable medical equipment agency, and the lung transplant recipient and his or her supporters are fundamental to the success of the plan. The anticipated date of discharge should be discussed with the patient and the patients supporters within the first 36 hours after the transplant procedure. This advanced notification will allow the healthcare team to make the necessary arrangements for the patients discharge and give the patient and members of his or her support system time to adjust to the idea of the patient going home. In addition, it provides the patients caregiver(s) time to make the necessary changes in their work schedules. An evaluation and a treatment plan for the patient are developed within 48 hours of the transplant procedure. Preparing the patient for discharge includes providing instructions about all postoperative medications that the patient will be taking at home

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TABLE 5 Signs and Symptoms Suggestive of Infection or Acute Rejection After Lung Transplant
Low grade fever41 Decrease in FEV1 10%41 Arterial blood gas values that indicate hypoxemia41 or decreased oxygen saturation63 Cough1, 41 Dyspnea1, 41 Presence of rales or wheezes41 Change in chest x-ray41 Reduced exercise tolerance41 New or increased fatigue63 Pleuritic chest pain New or increased productive sputum
FEV1=forced expiratory volume in 1 second.

cally kept in stock at most pharmacies. Usually, pharmacies, including major chains, require a 24-hour notice to place orders with their suppliers. During state, federal, or other recognized holidays, additional time may be needed to fill the order.
Transplant Nurse Coordinators

and the spirometry device the patient will use to monitor pulmonary function. In addition, the patients ability to monitor his or her blood pressure, temperature, and weight and to identify signs and symptoms that may be indicative of an infection or rejection (see Table 5) is reviewed. The recipient also is assessed to determine whether physical, occupational, or other skilled services will be needed after discharge from the hospital. The patients insurance case manager will need to be informed of the anticipated date of discharge as soon as possible. The inpatient transplant nurse coordinator (TNC) communicates with the insurance case manager to identify the appropriate home care agency, outpatient pharmacy, durable medical equipment, and intravenous provider. To find a home care agency that can meet the needs of the patient, it may be necessary for the TNC to seek a vendor not listed as a preferred provider of the patients insurance company. When this occurs, a letter of medical necessity may be required from the transplant center to support the referral. To ensure success with obtaining all prescribed medications, early communication with an outpatient pharmacy is essential, because many of the newer medications (e.g., mycophenolate mofetil [Cellcept, Roche Laboratories, Nutley, NJ] and sirolimus [Rapamune, Wyeth-Ayerst Laboratories, Philadelphia, PA]) are not typi-

The patients TNC plays a key role in coordinating the patients care among the many disciplines and healthcare providers. The role of the TNC varies among transplant centers. One TNC may be responsible for coordinating patient care for all phases of the transplantation, or the role may include two TNCs with responsibilities divided by inpatient versus outpatient or status before versus after transplantation. In any case, the TNC maintains close communication between the patient and the home care agency by way of daily telephone calls to the recipient and telephone calls from the visiting home care nurse. The TNC ensures that the lung transplant recipient, significant others, and home care nurse understand the process for obtaining 24-hour access to the hospital transplant team. The TNC is also responsible for reviewing laboratory results with the physician and notifying the patient of laboratory and/or bronchoscopy results. The TNC also coordinates the home care intravenous treatment that is prescribed if the laboratory tests or bronchoscopy results warrant intervention.
Long-Term

Management After Transplant

Home Care Nurse

Home care visits are part of the follow-up protocol of our institution, but this practice may vary among transplant centers. The home care nurse usually makes the initial home visit to the patient within 24 hours of a patients discharge from the hospital. The nurse conducts a standard patient and home assessment. In addition, a thorough pulmonary and cardiac assessment is performed and the surgical wound, chest tube site(s), and intravenous site are inspected. The nurse evaluates the patients fluid balance, pain status, understanding of medications, as

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well as the patients and significant others ability to correctly measure blood pressure, temperature, and weight and to use the remote spirometer to measure pulmonary function. If small children are in the home, an inspection of where the medications will be stored also is done to ensure that the patients medications are kept safely out of reach. Blood samples for laboratory tests may need to be obtained within the first 72 hours of discharge. The laboratory tests may include a basic metabolic panel, magnesium level, complete blood count, and a trough tacrolimus or cyclosporine level. When trough blood levels are needed, the timing of the nursing visit is important because the blood sample will need to be obtained at least 30 to 60 minutes before the regularly scheduled morning immunosuppressive medication dose. The home care nurse visits the patient at least once, or as often as needed, until the patient is seen in the clinic by the transplant physician approximately 3 to 4 days after discharge. The frequency of subsequent home care visits is determined at that clinic visit.
Risks for Infection and Rejection

the transplant recipients treatment adherence, participation in physical rehabilitation, achievement of a good nutritional status, and a satisfactory QOL.
Self-Monitoring and Treatment Adherence

During the first 6 months after transplant, the greatest threat to survival is infection, especially bacterial, but also cytomegalovirus (CMV) infections.26,27 Patients with proven CMV pneumonitis were reported to be three times more likely to develop obliterative bronchiolitis than those who are CMV negative.28 Obliterative bronchiolitis is considered the most significant, long-term lung transplant complication, and the primary determinant of long-term survival.29 Frequent, severe episodes of acute rejection are considered among the most important risk factors that lead to the development of obliterative bronchiolitis; however, airway ischemia and CMV disease may also play a role.26,30 When obliterative bronchiolitis is detected early, it is more responsive to augmented immunosuppression medications.30 Thus, the aims of treatment after transplantation are to prevent or provide early treatment for infection and rejection episodes and treat existing co-morbid medical conditions and symptoms. In addition, it is important for healthcare workers to promote

To prevent infection and rejection episodes, the patient must assume the responsibility for carefully adhering to his or her transplant treatment regimen. It is crucial that the patient understands the importance of taking immunosuppressive medications as prescribed and discussing with the physician or nurses any difficulties they have adhering to the treatment regimen. Failure to take immunosuppressive medications can be life threatening. In addition, other drugs are prescribed to prevent or treat infections (e.g., antiviral, anti-fungal, antibiotics) and to treat pre-existing or new co-morbid medical conditions after transplantation (e.g., diabetes, hypertension). It is also critical that the patient and his or her significant other appreciate the need for regular, consistent, self-care monitoring (e.g., spirometry, blood pressure, temperature, and heart rate measurements), exercise, and good nutrition. The patient needs to be instructed to notify the physician of changes in the patterns and trends of the physiological measurements, problems with excessive weight gain or loss, and new, bothersome symptoms. Table 6 lists nursing diagnoses for long-term lung transplant patients.
Physical Activity

Physical activity is very important after transplantation. The aggressive rehabilitation program that was initiated before transplantation needs to be continued after transplantation until optimal recovery has been achieved. If the rehabilitation program is in a different setting, it is important for the physical therapist to try to determine what type of pulmonary rehabilitation program the lung transplant recipient participated in before transplantation and how the recipient responded to activity while in the acute care setting. An exercise program consisting of at least 30 minutes of continuous exercise four or five times a week is then developed for the patient, as toler-

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LANUZA AND MCCABE TABLE 6 Nursing Diagnoses for Long-Term Post-Lung Transplant Patients2

AACN Clinical Issues

Risk for body image changes related to: psychosocial, biophysical, cognitive/perceptual, illness, illness treatment, surgery Altered protection related to: immunosuppressive therapy Noncompliance related to: knowledge deficit, health beliefs, client value system Risk for opportunistic infection related to: abnormal immune function blood profiles, immunosuppressive medications Impaired health maintenance related to: long-term treatment after transplantation, diet, signs of rejection, use of medications Ineffective family coping: compromise related to inadequate or incorrect information or understanding by primary person; temporary family disorganization and role changes; other situational crises Risk for activity intolerance related to: deconditioned status Altered nutrition related to: inability to ingest, digest, or absorb nutrients; insufficient or excessive nutritional intake related to metabolic needs

ated.31 Limiting factors to exercise change after transplantation. It is no longer pulmonary, but rather peripheral factors, such as abnormal neuromuscular function and muscular deconditioning, that limit exercise performance.3234 Improvement in exercise capacity may continue throughout the first year after transplantation; however, usually the greatest improvement is manifested within the first 3 months.35,36 And yet, studies of lung transplant recipients aerobic and peak exercise capabilities in the first year were reported to be considerably less than untrained controls, but sufficient to allow moderate levels of work, exercise, and a comfortable lifestyle.32,37 Most transplant recipients undergo pulmonary rehabilitation within the first 3 months of their transplant. Recently, the effects of aerobic endurance training beyond the first 3 months after transplantation were investigated and the findings showed increases in the lung transplant recipients exercise capacity.38 Further studies are needed to determine whether longer periods of training would result in additional improvements.
Nutrition

ate enteral feedings, which may continue for 6 to 8 weeks after transplantation or until nutritional stability is attained. In contrast, the recipient may experience weight gain after transplantation without an increase in their caloric intake before transplantation. This could be due to the marked decrease in the patients work of breathing that decreases the need for the amount of calories before transplantation. Or, it could be that weight gain or loss after transplantation may be due, in part, to the excessive hunger or anorexia side effects of certain immunosuppressive medications. Strategies for achieving optimal nutritional status and weight management should be developed for lung transplant recipients as needed.

Immunosuppressive Medications
Many of the symptoms experienced by patients after transplantation are thought to be due to the side effects of their immunosuppressive medications. The following section briefly discusses the current and new immunosuppressive and antiviral medications prescribed to prevent organ rejection. Advances in the development of immunosuppressive medications have played a key role in improving survival rates. These medications can be divided into the following categories: corticosteroids, calcineurin inhibitors, antimetabolites, and monoclonal

Good nutrition is encouraged after transplantation, but it is not usually as serious a concern as it is before transplantation. If the lung transplant recipient is considered undernourished, it may be necessary to initi-

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and polyclonal antibodies (Table 7). These agents are prescribed in several different combinations to achieve a rejection-free state. The combination of these therapies is as much an art as it is a science. The drug regimen varies based on the type of rejection the recipient experiences, whether drug tolerance develops, and the recipients response to alternate therapies. Although each transplant center follows center-specific protocols for initiating and adjusting immunosuppressive regimens, most centers follow similar guidelines as outlined in this article. Examples of triple maintenance immunosuppressive medications regimens are shown in Table 7.
Steroids

Corticosteroids (anti-inflammatory steroids) have been a mainstay in transplantation to augment immunosuppression by inhibiting the production of T-cell lymphokines.39,40 Methylprednisolone (Pharmacia and Upjohn, Inc., Peapack, NJ) and prednisone are used both intraoperatively and after transplantation (see Table 7). The intraoperative dose of methylprednisolone is given after the anastomosis of the first bronchus. It is also indicated as treatment for acute rejection diagnosed either clinically or by tissue biopsy. Prednisone (Table 7) is initiated on the second postoperative day (if the patient is able to take oral medications) and given every 12 hours, then gradually reduced to daily at the time of discharge. There are many potential side effects associated with this drug (Table 7), and patients need to be informed about what to expect. Since the side effects are usually dose-dependent, as the dose decreases so should the side effects.
Calcineurin Inhibitors

tivation and proliferation by connecting to Tcellbinding proteins, preventing the synthesis of IL-239,41 and inhibiting cell-mediated immunity.42 Tacrolimus has been shown to significantly decrease the incidence of acute rejection41 and may be more effective than CSA in some instances. Hausen and Morris42 report that the standard triple-drug immunosuppressive regimen (CSA, azathioprine, and prednisone) has failed to prevent acute and chronic rejection episodes in many lung transplant recipients, resulting in incidence rates that are higher for lung transplant recipients than for any other solid organ transplant group. Currently, there is an increasing trend to replace CSA with tacrolimus because the latter drug produces significant reductions in acute and chronic rejection episodes and decreases the incidence of infection. Although research has shown that the survival rates did not differ significantly between lung transplant recipients receiving CSA or tacrolimus, the development of obliterative bronchiolitis was significantly (P = 0.025) less in the tacrolimus group.43,44
Antimetabolites

Antimetabolites (see Table 7) such as azathioprine (Imuran), methotrexate (Barr Laboratories, Inc., Pomona, NY), and mycophenolate mofetil (Cellcept) promote immunosuppression by interfering with DNA and RNA synthesis, which results in the inhibition of the proliferation of both T and B lymphocytes.39 In the past, azathioprine, which may cause liver dysfunction, was the most frequently used antimetabolite. More recently, there is a growing interest in mycophenolate mofetil, which is reported to decrease the risk of first rejection by 50% and have only minor toxicity.39
Monoclonal Antibodies

Cyclosporine (CSA) and tacrolimus (FK506, Prograf) are examples of immunosuppressant medications that prevent organ rejection by inhibiting calcineurin activity and thus interfering with the function of interleukin-2 (IL-2) (Table 7). Cyclosporine blunts the activation of lymphocytes and inhibits the production and release of IL-2.39,41 Tacrolimus, a fungal macrolide, has an action similar to CSA, in that it also impairs T lymphocyte ac-

Monoclonal antibodies, including muromanab-CD3 (Orthocolne OKT 3, Ortho Biotech, Inc., Raritan, NJ), basiliximab (Simulect, Novartis, Summit, NJ), daclizumab (Zenapax, Roche Laboratories, Nutley, NJ), and sirolimus (Rapamune) are relatively new medications, and they are used at some transplant centers as induc-

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TABLE 7 Triple Immunosuppressive Therapy

Common Adverse Effects
No clinically significant interactions

Drug

Dose*

Drug Interactions

LANUZA AND MCCABE

Arrhythmias, bruising, confusion, cushingnoid changes, edema, electrolyte imbalance, fragile skin, hirsutism, hyperglycemia, hyperlipidemia, hypertension, hunger, gastrointestinal irritation, impaired wound healing, infection, weight gain, osteoporosis, steroid myopathy, psychiatric disturbances (steroid psychosis, mood changes), insomnia, cataracts/glaucoma, fluid and electrolyte imbalance, diabetes mellitus, neurotoxicity (tremors, seizures, headache), trouble concentrating Cyclosporine The amount needed to Edema, electrolyte imbalance, elevated creatinine, gastrointestinal (Neoral, achieve a whole-blood disturbance (nause and vomiting, diarrhea, constipation) hirsutism, hypertension, hyperlipidemia, hepatotoxicity, Sandimmune) trough level of 250350 tremor, seizures, ng/ml in the first year after infection, nephrotoxicity, neurotoxicity (t headache), malignancies, pain, skin changes, stomatitis transplantation and a trough level of 200250 ng/mL thereafter.

Prednisone

0.25 mg/kg twice daily immediately posttransplant followed by tapering of the dose to 0.15 mg/kg/day Maintenance dose: 7.510 mg, mid-morning every or every other day

OR

Tacrolimus (Prograf FK506)

The amount needed to achieve a whole-blood trough level of 1020 ng/mL during the first year post transplant and 714 ng/mL thereafter.

Acne, abdominal distention, alopecia, anxiety, body weight changes, cardiac arrhythmias, chills, confusion, cough, cushingnoid changes, depression, dyspnea, edema, electrolyte imbalance, elevated creatinine, fever, nausea and vomiting, diarrhea, constipation, hallucinations, hirsutism, hypertension, hyperlipidemia, hyperglycemia, hepatotoxicity infection, insomnia, impaired wound healing, malignancies, muscle weakness, nephrotoxicity, neurotoxicity (t tremor , seizures, headache), osteoporosis, pain, psychosis, skin changes, stomatitis

Blood levels are increased by: macrolide antibiotics, azole antifungal agents, calcium-channel blockers, sirolimus, methylprednisolone, allopurinol, danazol, bromocriptine, HIV-protease inhibitors, and grapefruit and grapefruit juice. Blood levels are decreased by: anticonvulsant drugs, rifampin, nafcillin, carbamazeprine, phenobarbital, octreitide, ticlopidine, and possibly rifabutin. Blood levels are increased by: macrolide antibiotics, azole antifungal agents, calcium-channel blockers, sirolimus, methylprednisolone, cimetidine, mycophenolate mofetil, cyclosporine, danazol, cisapride, metoclopramide, HIV-protease inhibitors, bromocriptine. Blood levels are decreased by: Tegretol, isoniazid, phenobarbital, anticonvulsant drugs, rifampin, and rifabutin.
(continues)

AACN Clinical Issues

TABLE 7 Triple Immunosuppressive Therapy (Continued)

Common Adverse Effects Drug Interactions

Vol. 12, No. 2 May 2001

Drug

Dose*

Azathioprine (Imuran)

Dose is the same intravenously Alopecia, myelosuppression (e.g., leukopenia, anemia or orally 22.5 mg/kg/day thrombocytopenia), hepatotoxicity, infection, gastrointestinal disturbance (nausea, vomiting, diarrhea), malignancy

OR

Mycophenolate mofetil (Cellcept)

250 mg twice daily. Increase the dose by 250 mg twice daily every 3 days until a goal of 10001500 mg twice daily is reached.

Acne, anxiety, artrhythmias, abdominal pain, body weight changes confusion, cough, depression, dyspnea, edema, electrolyte imbalance, elevated creatinine, depression, fever, nausea, vomiting, constipation, diarrhea, hepatotoxicity, hyperlipidemia, hyperglycemia, hypertension, hypotension, infection, insomnia, muscle weakness, myelosuppression (e.g., leukopenia, anemia), nephrotoxicity, neurotoxicity (tremors, seizures, headache,), skin changes, pain

When given with allopurinol a marked reduction in azothioprine doseage is needed. May lead to anemia and leukopenia when given with ACE inhibitors; synergistic with other bone marrow suppressants. No clinically significant interactions. If renal impairment is present and/or if patient is on either acyclovir or gancyclovir, the drug concentrations of mycophenolate mofetil and these drugs may increase. Avoid drugs (e.g., cholestyramine) which interfere with enterohepatic cirulation and antacids with magnesium and aluminum hydroxide which may decrease absorption.

ACE = angiotensin-converting enzyme.

*Drug dose lung transplant protocol used at Loyola University Medical Center, Maywood, Illinois. Dose range may vary across transplant centers.

Sources: Pirsch et al.39 and drug insert information from the following: Cyclosporine (Neoral, Sandimmune), Novartis, Summit, NJ, 1998; Tacrolimus (FK506, Prograf), Fujisawa, Deerfield, IL, 1998; Azathioprine (Imuran), Faro Pharmaceuticals, Inc., Bedminster, NJ, 2000; Prednisone, Roxane Laboratories, Columbus, OH, 2000; Mycophenolate mofetil (Cellcept), Roche Laboratories, Nutley, NJ, 1999.

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symptoms are symptoms most frequently reported.

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tion therapy and also to treat refractory chronic rejection of transplanted organs. Induction therapy, an additional step that is taken to prevent organ rejection, involves the administration of non-maintenance immunosuppressive medication for a specific number of doses, with the first dose given before implantation. Monoclonal antibodies prevent rejection of transplanted organs and promote immunosuppression by interfering with antigen recognition and with the IL-2 receptor alpha chain of activated T lymphocytes.39 Although sirolimus is classified as a macrolide antibiotic, it has a structure similar to tacrolimus but its mode of action is different.39,45 When sirolimus was given with CSA, phase II clinical trials showed that the addition of sirolimus led to a decrease in acute rejection rates from 40% to less than 10%.45
Polyclonal Antibodies

Antithymocyte globulins, which are derived from either equine (ATGAM, Pharmacia and Upjohn) or rabbit (Thymoglobulin, SangStat, Fremont, CA) sources, are polyclonal antibodies. These medications are used prophylactically to delay the first onset of acute rejection and for the reversal of acute rejection. They produce a decrease in T lymphocytes through the interaction of antibodies with antigens.39

Quality of Life
As the preceding discussion indicates, it is clear that lung transplantation is effective in improving survival in certain patients with end-stage respiratory disease.4 Yet, there is very little information on the impact of this procedure on the quality of the recipients life and function. A review of QOL studies (19882000)4658 conducted on lung transplant candidates and recipients indicates that lung transplant recipients generally report a significantly better QOL than lung transplant candidates.59 However, only seven of the QOL studies used a longitudinal design,4749,53,55,58,60 following the same subjects prospectively from before to after transplantation. In one50 of the three studies50,53,61 that examined symptoms of

lung transplant patients, shortness of breath (SOB) with activity was reported to be a frequently occurring and distressing symptom by one third of the 48 subjects. Since some patients may not anticipate that some respiratory symptoms, such as SOB with activity, may still exist after transplantation, these findings need to be shared with them. It is very likely that the SOB with activity and exercise after transplantation limitations are due primarily to general deconditioning rather than to centrally impaired respiratory function.34 When the symptoms of the total sample were examined, general muscle weakness, fatigue, changed facial and bodily appearance, overeating, and hirsutism also were reported to be frequently occurring and distressing symptoms. Lung transplant patients are a heterogeneous group. Subgroup differences (i.e., gender, underlying diagnosis, type of transplant procedure) in mortality rates4 and symptom experiences have been reported.50,62 Yet, only one62 of the three studies that examined symptoms of lung transplant patients reported subgroup findings. While many symptoms were common across the subgroups, in general female lung transplant recipients reported more symptoms to be frequently occurring and distressing than males (e.g., changed facial appearance, excessive hair growth, tremors, and heart palpitations). Men, on the other hand, reported more distress associated with sexual problems. Patients who underwent SLT reported more symptom frequency and distress (e.g., SOB with activity, bruising, fever) than those who underwent BSLT procedures. Finally, patients with conditions other than cystic fibrosis as their underlying respiratory condition reported more frequently occurring and distressing symptoms (e.g., SOB with activity, muscle weakness, fatigue). Virtually all the reported symptoms may be related to the side effects associated with the immunosuppressive medications (Table 7).62 A review of the QOL lung transplant literature indicates that many conceptual and methodological limitations exist that make comparison of findings across studies difficult and weaken the credibility of some of the studies findings (e.g., the lack of a com-

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mon definition of QOL4648,50,53,5557 the great variety of instruments used to measure QOL, etc.).59 In addition, only three studies examined the symptom experiences of lung transplant recipients50,53,61 and just a few studies included physiological variables.53,54,60 Knowledge of the symptom experiences of lung transplant recipients is necessary to provide the patients and their families a clear understanding of the potential risks and benefits associated with the transplant procedure and the patients lifelong follow-up care. Furthermore, to teach patients what to expect during and after transplantation, we need to learn about the experiences, concerns, and symptoms of lung transplant candidates and recipients. The lung transplant population is heterogeneous, and this must be taken into consideration when planning patient care. For example, subgroup differences (i.e., according to underlying respiratory diagnosis, gender, and type of transplant procedure) were found for symptoms,62 and, thus, there is a need to individualize symptom management strategies to meet the needs of the individual patient.

excellent communication and coordination among the healthcare teams and with the lung transplant patient and family to be successful. Although research has shown that transplant recipients report a higher QOL and better functional status than candidates, the number of studies that have been conducted on this patient population are very few and mostly cross-sectional. Additional prospective, longitudinal research is needed that further examines the needs and concerns of these patients and the impact of the transplant procedure on their everyday lives.
Acknowledgments

The authors thank Gabriella A. Farcas for her computer assistance in the preparation of this article.

References
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Summary
In summary, the development and implementation of care management strategies require basic knowledge about the needs and treatment requirements of lung transplant patients before and after transplantation in both the hospital and home settings. Advanced practice nurses (e.g., clinical nurse specialists, TNCs, nurse practitioners) are uniquely positioned to play a key role on the health team in coordinating the care of transplant patients across settings, both before and after the transplant procedure. Identification of potential nursing diagnoses that may develop during the various stages of the transplant process can guide patient care. Providing thorough patient and family teaching so that the patient and members of their support system understand and are able to do what is required as part of the patients treatment and monitoring regimen is crucial to achieving positive transplant outcomes. After discharge from the hospital, follow-up care management will require

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