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Pulmonary transplantation: friend or foe?

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VOL: 98, ISSUE: 26, PAGE NO: 55

Helen Castle, BSc, RGN, is a clinician's assistant, Papworth Hospital, Cambridge

For patients with end-stage lung disease few options are available to relieve them of their increasing breathlessness and deteriorating quality of life. Transplantation is an option for some of them, but the length of time a patient must wait, once accepted on to the waiting list, before a suitable donor organ becomes available is unpredictable.

For patients with end-stage lung disease few options are available to relieve them of their increasing breathlessness and deteriorating quality of life. Transplantation is an option for some of them, but the length of time a patient must wait, once accepted on to the waiting list, before a suitable donor organ becomes available is unpredictable.

Given the dismal prognosis of many of these patients, it is imperative that they are referred early in the course of their disease to give them a chance of surviving to transplantation. This article serves as a general overview of lung transplantation to aid referring hospitals in the decision about whether to refer a patient for transplant.

Each patient will undergo an assessment period to ascertain their suitability to proceed to transplantation, as each centre has a responsibility to conserve scarce resources for those who can benefit. It is by no means an easy option, and the postoperative period can be fraught with difficulties.

The first lung transplant procedure was performed by James Hardy in 1963, but the patient survived for only 18 days (Blumenstock and Lewis, 1993). Although unsuccessful, his work inspired others to pursue the option of isolated lung transplantation. Reitz et al reported the first successful pulmonary transplant with a series of heart-lung transplantation procedures in 1982.

Closer to home, Papworth Hospital carried out its first heart-lung procedure in 1985. Although this patient went on to survive for 12 years, these first years were a steep learning curve in which immunosuppression was imprecise, as were the diagnosis and treatment of acute allograft rejection.

This situation changed with the evolution of technique, better graft preservation and adoption of transbronchial biopsy as the gold standard for the diagnosis of acute allograft rejection (Higenbottam et al, 1988). In addition, opportunistic infection, especially cytomegalovirus, has been much better controlled with the routine use of ganciclovir, acyclovir and newer antifungal agents (Meyers at al, 1999). Double lung and single lung transplants are now commonplace and, together with heart-lung transplantation, Papworth Hospital has now carried out over 530 pulmonary transplants.

The referral process
The current challenges facing clinical lung transplant programmes are no longer technical; rather they involve the critical shortage of suitable donor lungs (Meyers et al, 1999). There has to be a compromise between the patients who are most ill - who have the most to gain but for whom the overall outcome is poor (Bourge et al, 1993) - and those with no complications, for whom results can be excellent.

At a time when the organ donor rate is dropping, health professionals have a responsibility both to individual patients and to the larger pool of potential recipients to ensure the best possible outcome (Dark, 1989). The assessment of potential recipients is therefore paramount. It must ensure that patients are listed at a time when their disease is sufficiently advanced to justify the risks associated with transplantation but their condition has not deteriorated to the extent that they are unlikely to survive the transplant procedure (Sharples et al, 1994)

Referrals are usually made by GPs or physicians at a time when patients are no longer responsive to conventional therapy. Owing to an increasing number of referrals coming to Papworth, a proforma is sent out to the referring physician for any further information required. The relevant consultant physicians then make a provisional decision about each patient's suitability to proceed to a full transplant assessment, depending on the patient's age, presenting condition, concurrent disease and medical history (Mercer et al, 1986).

A wide range of lung diseases can be treated with transplantation (Box 1). However, a range of contraindications drawn up by the International Society for Heart and Lung Transplantation (Meyers et al, 1998) should also be considered when selecting patients for assessment (Box 2). The age limits are used as a generalised guideline, and some patients who are biologically very well 'preserved' are still considered for assessment.

If the consultant feels that assessment is appropriate, the patient's details are passed on the team of clinician's assistants (CAs). The CA role was developed at Papworth 10 years ago and utilises the skills of a specialist team of nurses predominantly with an intensive care background to see patients through the transplant process. This involves assessment, transplant coordination and postoperative care.

Often the patient's first point of contact with the transplant unit is via the CA. A telephone call to the patient confirms details received from the referring consultant and is often an opportunity to obtain additional background information - particularly about social circumstances and the patient's feelings about transplantation. Patients are given an explanation of the service, the tests they will undergo when they come in and the implications of assessment. Everything is done to try and alleviate fears and anxieties, but it is made clear that this is by no means a guarantee of a place on the active waiting list.

The assessment process
Patients are admitted for three days and undergo a variety of tests to assess the extent of their disease and to estimate the future course (Box 3).

All patients have blood taken to confirm their blood group, virology status (including a hepatitis screen and HIV) and for tissue typing. In thoracic transplantation a prospective cross match with the donor blood is not usually required, and organs are matched on blood group and size only. However, some patients who have had previous surgery, blood transfusions or pregnancies may have developed antibodies, and in these situations a full cross match on the night of a transplant is imperative.

The assessment period also gives potential recipients a chance to learn as much about transplantation as possible. As well as all the tests they undergo they also meet the physiotherapist, dietitian and the social worker.

A close relationship between the CA and nurses from the transplant continuing care unit ensures that patients are given all the relevant information they need about their postoperative care. At this time they are informed of some of the possible complications associated with transplantation and the side-effects of the drugs they will be required to take for the rest of their lives. During the assessment period potential recipients and their family are given the opportunity to meet a patient who has already had a transplant and to visit the intensive care unit.

It is an extremely busy three days for these already compromised patients, and a variety of factors can affect their ability to accept and retain information given. To this end all patients are encouraged to have someone with them throughout their stay.

At the end of the assessment period the patient is met by the consultant physician and the surgeon to discuss treatment options. The timing of adding a patient to the list is crucial: if patients are too sick or deteriorating rapidly they may die before an organ becomes available or they become too unwell to survive the rigors of transplantation. If patients' condition has improved on conventional medical therapy or they have stabilised since referral then it is often thought inappropriate to place them on the waiting list, and they should be referred back if their condition deteriorates.

Alternatively, assessment may have uncovered contraindications to transplantation, making the risk unacceptably high, or indeed the patient may be too sick following a late referral. Other patients may require further investigations, for example, CT scan or coronary angiography, before a final decision is made. All patients over 50 with a history of smoking, high cholesterol or a positive family history of heart disease will require a coronary angiogram before listing, as coronary artery disease is a contraindication to lung transplantation.

Even if they are given the opportunity to go on the waiting list, not all patients take this up. Transplantation requires commitment from the whole family, and many patients need to go away and think about the information they have been given to make an informed decision. During their stay they will have been told about the short and long-term complications of transplantation in terms of survival and quality of life, and for many patients it is the first time they have confronted their own mortality.

The donor offer

Patients who are considered suitable for transplantation are added to the waiting list. While on this list they continue to be cared for by their local centre, with the emphasis on providing them with optimal care for their underlying disease and any co-morbid medical conditions. All patients are encouraged to remain as active as possible, and many potential lung transplant recipients try to keep up with a pulmonary rehabilitation programme.

Patients face an undetermined period of waiting and are encouraged to keep in regular contact with the transplant team and to keep them informed of any changes. This period is often laden with uncertainty and concerns about the future, and it is not surprising that patients may experience anxiety and depression during this time (Lanuza, 2001). Psychosocial problems associated with role adjustment, family stress, financial difficulty, change in body image, loss of physical or psychosocial control and feelings of bereavement are common and need to be dealt with sensitively (Hook et al, 1990).

When a donor becomes available the CA and consultant surgeon discuss the details of the donor and, if considered suitable, a potential recipient is chosen, depending on what organs are available, the blood group and size of the donor. The CA then contacts the chosen recipient and arranges for transfer to Papworth. Unfortunately, once they are inspected by our surgical team many organs are found to be unsuitable due to irreversible damage or poor function. In addition to the stress of being on the waiting list, patients also need to cope with these ' false alarms', and many experience numerous admissions before their transplant is actually performed.

Surgery
Lung transplantation can be performed using a variety of techniques, depending on what surgery is being performed and the surgeon's preferences. Single lung transplantation is performed for diseases such as pulmonary fibrosis or emphysema, when the transplant team has determined that one lung would be sufficient to give the patient satisfactory lung function (Cooper, 1987).

It is usually accomplished through a standard thoracotomy performed on the right or left side of the chest. Double lung transplantation, on the other hand, can be performed by either bilateral thoracotomies, median sternotomy or a transverse thoracosternotomy (clam shell) incision. This technique has evolved to allow better visualisation of the pleural space and the bilateral sequential replacement of the lungs, reducing operative time and the need for by-pass (Pasque et al, 1990).

Indications for bilateral transplantation include infective lung diseases such as cystic fibrosis or bronchiectasis, where if only one lung were replaced the transplanted lung would then become infected by the residual lung.

Heart-lung transplantation, performed for diseases such as Eisenmenger's and pulmonary hypertension (primary or secondary), is accomplished by median sternotomy on cardiopulmonary by-pass. Alternatively it may be performed in patients who are also suitable for double lung transplantation - for instance, those with cystic fibrosis - and if deemed suitable their heart can be used for an isolated cardiac transplant. This procedure is known as a domino transplant and ensures that two recipients still benefit from a single donor.

Postoperative care
Following surgery, patients are transferred to the intensive care unit sedated and ventilated. Haemodynamic status is closely monitored, together with the maintenance of a strict fluid balance. If volume is required, colloids are preferable to crystalloid, due to the permeability of the lungs and the risk of reperfusion oedema following their period of ischaemia (Hoyos and Meyers, 1992). Once it has been established that the patient is not bleeding and has good gaseous exchange, sedative agents are usually stopped, with the aim of extubating the patient as soon as possible to prevent the risk of barotrauma caused by positive pressure ventilation.

Adequate pain control is imperative at this point to enable the patient to expectorate easily and to allow early ambulation. In transplants where cardiopulmonary bypass has not been used, an epidural is often inserted pre-operatively or just before extubation.

Once patients are cardiovascularly stable, with acceptable arterial blood gases and good urine output, they are transferred back to the ward.

Infection remains a leading cause of morbidity and mortality following transplantation (White-Williams, 1995). Antibiotic therapy is directed at organisms in the sputum of the recipient and the donor. In recipients with infective lung disease sputum specimens are routinely analysed both pre- and post-transplantation so that the appropriate antibiotic therapy can be instituted in the early postoperative period.

Until results are obtained, broad-spectrum antibiotics are used. Current policy is the use of cefotaxime/vancomycin in lung transplant recipients with a non-infective cause. For patients with recurrent infections a regimen of ceftazidime/vancomycin and tobramycin is used. Unfortunately it is never quite this simple, as many patients with long-term infective illness - for example, cystic fibrosis - develop a resistance or allergy to many commonly used antibiotics. Multiresistant organisms are not a complete contraindication against transplantation but need to be seriously considered when the patient is put on the waiting list, and a strategy formed for post-operative management

Rejection
Acute rejection remains the most important clinical problem in the first year after transplantation. Patients are loaded with immunosuppressive drugs to suppress the immune response while they are still in the anaesthetic room and must continue to take these for the rest of their lives. One of the most important aspects of nursing transplant patients is teaching them about the use of their drugs. Unless they are willing and able to understand the medical regimen and are compliant, the latest techniques and drugs are useless (Hook, 1990).

The Papworth transplant team currently uses a triple therapy maintenance regimen of cyclosporin, azathioprine or mycophenolate mofetil and prednisolone. Many of these medications have adverse side-effects, and alternative agents are now being used and developed to offer alternatives to patients who find these unacceptable - for instance, tacrolimus and rapamycin (Table 1).

Before discharge nurses educate patients on what signs and symptoms to look out for concerning both rejection and infection. Temperature, weight and spirometry are recorded daily and patients are encouraged to contact the unit if they are unsure of their symptoms. Rejection can be symptomless, so surveillance biopsies are taken on a regular basis in this first year.

In lung transplant patients it can be difficult to distinguish between infection or rejection, and bronchoalveolar lavage and transbronchial biopsy has to be obtained by fibre-optic bronchoscopy, usually under sedation or general anaesthesia. Both conditions can present with pyrexia, dyspnoea, cough and comparable signs of both crackle and wheeze. Rejection in either case is treated with three doses of methylprenisolone (500mg or 1,000mg, depending on body weight) with a dramatic improvement in clinical findings usually evident within eight to 12 hours after administration (Meyers et al, 1999)

Long-term complications
In lung transplant patients the main cause of morbidity and mortality is that of obliterative bronchiolitis. This is an inflammatory disorder of the small airways that leads to the obstruction of the bronchioles. The airways become thickened and narrow, which is believed to be the result of damage by the immune system, and acute rejection seems to be the strongest risk factor for the subsequent development of this process (Paradis, 1998). Newer immunosuppressive drugs have been developed, which are believed to slow the progression of obliterative bronchiolitis, but multicentre studies are needed to assess the efficacy of these new agents. Table 2 shows the long-term survival of lung transplantation as issued by the International Heart-Lung Registry.

Conclusion
Transplantation remains an option for patients whom conventional medical therapy is failing. With the support and help from a dedicated multidisciplinary team they can be supported and encouraged to come to terms with the scars, weight gain and the side-effects of drugs following transplantation, and quite soon patients report improvement in health with increasing endurance and physical condition. Unfortunately their long-term outlook remains uncertain, and intense investigation into chronic rejection is required to increase long-term survival.

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