Lung Transplantation

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69 Lung Transplantation

David Weill

image Historical Perspective

Lung transplantation evolved from heart-lung transplantation as a method by which donor organs could be used more efficiently. Heart-lung transplantation was first performed in 19811 and was initially the procedure of choice for diseases that are now more commonly treated by transplant using either bilateral sequential lung transplantation or single-lung transplantation. The appeal of developing the isolated lung transplant technique was improvement in donor organ utilization. Specifically, by using each of the three thoracic organs available from a single donor (i.e., two lungs and a heart), donor organ utilization can be maximized while achieving acceptable outcomes.

The double-lung transplant procedure, originally accomplished by en bloc replacement using a tracheal anastomosis, was first performed in 1983 in Toronto. The bilateral procedure is now performed as a sequential transplant using bilateral bronchial anastomoses. The bilateral sequential technique, as compared with the en bloc tracheal anastomotic technique, has been associated with fewer airway anastomotic complications, likely as a result of the superior blood supply from retrograde pulmonary artery flow.

Single-lung transplantation was first described in 1986.2 The advantage of the procedure is that it has allowed maximal donor utilization while being associated with good patient outcomes. The single-lung procedure has historically been accepted as the procedure of choice for common transplant indications such as emphysema and idiopathic pulmonary fibrosis and is currently performed as commonly as the bilateral procedure.3

image Survival and Demographics

Worldwide, 1200 to 1400 patients receive a lung transplant each year. Despite the yearly increase in patients on the transplant waiting list (recently nearly 4000 patients), the number of transplant procedures performed each year has been relatively stable over the past several years (Figure 69-1).3 Significant discussion and research regarding methods to expand the donor pool are ongoing,4 but until strategies to increase lung donor procurement are actually employed, the number of transplants performed each year will likely remain stable.

image

Figure 69-1 Number of lung transplants reported by year.

(Adapted from the International Society for Heart and Lung Transplantation [http://ishlt.org/]).

Long-term survival after lung transplantation is limited by the development of the bronchiolitis obliterans syndrome (BOS), which is commonly referred to as chronic rejection. BOS, defined by declining spirometry below the best postoperative level achieved, is variable in time to onset but increases in frequency as duration post transplant lengthens. Unfortunately, the etiology of BOS remains elusive, but it likely involves both immune and nonimmune mechanisms, including frequent early acute rejection episodes, infection with cytomegalovirus (CMV), severe early postoperative lung injury, and donor factors. Largely because the mechanism of BOS is unknown, satisfactory treatment is currently unavailable.

image Indications and Procedure Choice

Indications for lung transplant are listed in Table 69-1 according to the generally accepted procedure choice. Although there are many end-stage lung diseases that can potentially be amenable to lung transplantation, four diseases account for the vast majority of lung transplant recipients: emphysema (both cigarette-induced and due to alpha1-antitrypsin deficiency), cystic fibrosis, primary pulmonary hypertension, and idiopathic pulmonary fibrosis.3 Contraindications to transplant include evidence of extrapulmonary disease such as significant kidney, liver, or cardiac disease; poor nutritional or rehabilitation status; recent or current malignancy; and a poor psychosocial profile.

TABLE 69-1 Lung Transplant by Procedure Type (in Order of Frequency)

Single-Lung Transplant Double-Lung Transplant
Emphysema/chronic obstructive pulmonary disease (COPD) Cystic fibrosis
Idiopathic pulmonary fibrosis Emphysema/COPD
Alpha1-antitrypsin deficiency Alpha1-antitrypsin deficiency
Re-transplant Idiopathic pulmonary fibrosis
Primary pulmonary hypertension
Bronchiectasis

Generally the procedure of choice is the one that can be performed safely while utilizing the available donor organs most efficiently. Emphysema is the most common lung transplant indication and has consistently been associated with the best survival post transplant.3 While some controversy exists regarding the optimal procedure choice (single versus double) in this group of patients,5 most patients with emphysema who have undergone a lung transplant have received a single-lung transplant. Bilateral lung transplant has traditionally been reserved for suppurative lung diseases, such as cystic fibrosis, and other bronchiectatic disease where replacing as much infected lung tissue as possible is the primary goal. Patients with primary pulmonary hypertension generally receive a bilateral lung transplant because this prevents the potentially life-threatening situation that occurs when, in performing a unilateral transplant, nearly all cardiac output flows to the allograft, given its relatively lower vascular resistance compared to the native primary pulmonary hypertension lung. In the early transplant period when single lungs were transplanted for this indication, the result in most centers was profound unilateral pulmonary edema in the allograft.

image Candidate Selection

Because of the rigors of a major thoracic surgery such as lung replacement, an extensive evaluation process occurs in all potential lung transplant recipients. The majority of the preoperative testing is directed toward excluding significant extrapulmonary disease, particularly those diseases that would lessen the chances of survival in the immediate postoperative period or make tolerance of the commonly used postoperative immunosuppression difficult. Occult coronary artery disease or malignancies are commonly uncovered as the evaluation proceeds, particularly in those patients who have significant cigarette-smoking histories. Other important goals of the evaluation process are to determine the likelihood of compliance with the complicated postoperative medical regimen and the existence of a solid support system to help with medical care once the patient leaves the hospital.

image Waiting List Considerations

Time on Waiting List

Waiting times for lung transplant recipients are highly unpredictable and vary considerably geographically. Waiting list priority is strictly according to time, or “seniority,” on the list. Currently there is no waiting list status system, although there likely will continue to be significant efforts to give priority to those on the waiting list who are more ill and who are most likely to do well post transplant. Unfortunately, devising such a system for lung allocation is problematic, primarily owing to the lack of compelling data correlating likelihood of waiting list mortality among the various disease groups with the highest probability of survival after transplantation. At most centers, as the numbers of patients referred for transplant increase and the length of the waiting list increases, waiting times continue to lengthen, and the mortality rate for patients on the waiting list will increase as well.

Care of Patients on Waiting List

Management of patients on the lung transplant waiting list involves close interaction with the referring physician. Treatment is directed toward the underlying disease process and is not generally affected by the patient’s waiting list status. However, clinical activities that may affect transplant outcome should form prominent aspects of the medical care plan. For instance, enrollment and participation in a cardiopulmonary rehabilitation program is of paramount importance so waiting patients can develop or maintain the best cardiovascular fitness possible. Furthermore, weight management is often an important issue, and regular exercise can help avoid excessive weight gain, which is associated with poor outcomes after transplantation. Conversely, in patients with cystic fibrosis, weight maintenance can be achieved by regular consultation with nutritional support personnel familiar with patients in whom specific dietary needs exist. Other considerations requiring the attention of the transplant team include substantial increases in corticosteroid use, which although never definitively linked to poor outcomes post transplant, remain a theoretical concern in terms of bronchial anastomotic and wound healing. As lung transplant waiting lists grow at most centers, regular outpatient clinic visits to monitor patients on the waiting list will likely become more important so that clinical issues that may affect transplant success can be detected and addressed.

An important development in donor lung allocation occurred in 2005 with the institution of the Lung Allocation Score (LAS). Traditionally, lungs had been allocated using a time-based system governed by how long a patient had been on the lung transplant waiting list. However, the new LAS system is based on two factors: (1) expected mortality on the waiting list for a given patient and (2) expected survival following lung transplant. These two factors are influenced by a number of clinical parameters that are measured by individual transplant centers and used to assign a score. The highest scores are assigned to patients with relatively high waiting list mortality (due to severity of illness) and an adequate or better chance of survival following lung transplantation. Familiarity with this system is particularly important for the ICU physician, who may encounter a patient with a high urgency score.

image Donor Criteria

The expansion of lung transplantation as a therapy for end-stage lung disease is not limited by the number of potential recipients but rather by the availability of suitable donor organs. The standard, or “classic,” lung donor criteria are well known, if not closely followed, among lung transplant practitioners. Although some of these criteria certainly make good sense (i.e., a clear chest radiograph, no bronchoscopic evidence of aspiration), nearly all the others are controversial, often ignored, and not based on convincing research data.4 The standard or classic lung donor criteria are listed in Table 69-2. Whereas certain geographic regions in the United States, some countries in Europe, and Australia have adopted more aggressive donor management strategies that have resulted in more donor lungs, many areas with lung transplant programs have fewer than expected lung donors.

TABLE 69-2 Standard Lung Transplant Donor Criteria

Age <55 years
ABO blood group compatibility
Clear chest radiograph
PaO2 > 300 mm Hg on fractional inspired oxygen of 1.0 and positive end-expiratory pressure = 5 cm H2O
Less than 20-pack-year smoking history
Absence of chest trauma
No aspiration or sepsis
Gram stain shows sputum sample free of bacteria, fungus, and significant number of white blood cells

image Postoperative Care

Early postoperative care of lung transplant recipients can be divided into four general categories: (1) hemodynamic management, (2) respiratory management, (3) initiation of an immunosuppression regimen, and (4) infectious disease prophylaxis. Although many basic critical care principles apply to the care of lung transplant recipients, certain special considerations apply.

Hemodynamic Management

Fluid Administration

In the early postoperative period, proper fluid management may be the most important aspect of lung transplant care. Because the lymphatic drainage is disrupted during surgery, the transplanted lung has a propensity toward pulmonary edema, and this tendency is exacerbated by several conditions. First, owing to the procurement and reimplantation process, lung allografts suffer lung injury that is characterized by a diffuse capillary leak. This process, commonly referred to as ischemia-reperfusion injury or the reimplantation response, is usually mild and treated easily with supportive measures. This type of injury is characterized by diffuse pulmonary infiltrates radiographically and varying degrees of oxygenation impairment. In cases of severe injury, the pulmonary edema may be profound and require more aggressive measures such as independent lung ventilation, inhaled nitric oxide, and in extreme cases, extracorporeal membrane oxygenation (ECMO). Second, because intraoperative and early postoperative hypotension occurs commonly, overexuberant resuscitation with crystalloid solutions sometimes occurs and worsens the pulmonary edema. In some circumstances, hypotension or decreased urine output has been treated with starch solutions that, because of the large molecules they contain, results in passage of even greater amounts of fluid through the dilated capillary channels.

Especially in the first 72 hours after surgery, judicious use of intravenous fluids should be exercised, and efforts should be made to minimize fluid administration while maintaining adequate urine output. Use of pulmonary artery catheters is standard in the early postoperative care of transplant recipients and helps guide fluid management. Low central venous pressures (0–5 mm Hg) are the objective. Also, careful attention to input and output measurements provides additional information regarding volume status and is a reminder to administer only essential fluids. Generally, if renal function allows, an appropriate goal is to keep the patient 1 L negative for the first 3 postoperative days. This is best achieved with liberal use of loop diuretics and limiting extra fluid infusions.

Hypotension is common after lung transplantation. Not only is the patient (by design) intravascularly volume depleted but he or she is also receiving medications that cause hypotension: paralytics, sedatives, and analgesics. As a result, during the early postoperative period, patients typically will have episodes of hypotension that need to be addressed. Another important consideration is the effect of positive-pressure ventilation on the hemodynamics of a recent lung transplant recipient, particularly in those receiving a single-lung transplant for emphysema, owing to discrepancies in native lung and allograft compliance characteristics. These discrepancies, coupled with many recipients who not only have preoperative right ventricular dysfunction but also in whom postoperative intravascular volume depletion is intentionally achieved, can result in overinflation of the native lung. The concept of native lung hyperinflation is covered in more detail later in Ventilator and Respiratory Management, but one must consider whether early postoperative hypotension is best treated with ventilator management strategies that address overdistention of the native lung.

During periods where hypotension is found to be the result of profound intravascular volume depletion, fluid resuscitation should ideally include solutions that have the greatest tendency to remain in the vascular space and not simply migrate through the dilated pulmonary capillary channels. Colloid solutions such as albumin and packed red blood cells (RBCs) are ideal in this setting, as is replacement with clotting factors, particularly in the patient who has postsurgical consumption of these factors. Generally, in hypotensive patients with hemoglobin less than 10 g, use of packed RBCs is the treatment of choice. If a patient has very little postoperative bleeding, albumin infusions provide a temporary solution to intravascular volume depletion and can be given in conjunction with a loop diuretic to achieve a more brisk diuresis by transiently increasing effective renal blood flow. This effect is likely short lived but nonetheless provides a temporary increase in oncotic pressure that may lessen the development of pulmonary edema.

Ventilator and Respiratory Management

Initial care of early postoperative lung transplant recipients is directed toward ventilatory stability. Selection of a ventilator mode is generally dictated by the patient’s level of consciousness in the early postoperative period. For example, patients who are deeply sedated and/or under the influence of paralytic agents will obviously require full control of ventilation. The assist-control mode meets this requirement and is generally the preferred ventilatory modality in the immediate postoperative period. However, because an effort is made at many programs to extubate patients soon after surgery, use of less sedation and avoidance of paralytic agents are being employed. In such patients, less ventilatory control is required; patients usually do well with intermittent mandatory ventilation until early extubation is achieved. In patients with poor early graft function—for example, those with primary graft failure—ventilatory strategies that limit barotrauma are most efficacious and usually include pressure-control modalities. Certainly, with pressure-control ventilation, the use of sedation and paralytics is warranted, recognizing the potential deleterious neuromuscular effects of the latter when used in combination with high doses of corticosteroids and, in some instances, aminoglycoside antibiotics.

Use of Positive End-Expiratory Pressure

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