Single-lung transplantation (SLT) is performed for obstructive nonsuppurative lung disease, such as emphysema resulting from tobacco use or α₁-antitrypsin deficiency. It is also indicated for fibrotic lung diseases such as idiopathic pulmonary fibrosis (29%), familial pulmonary fibrosis, drug- or toxin-induced lung disease, occupational lung disease, sarcoidosis, limited scleroderma, lymphangioleiomyomatosis, eosinophilic granuloma, and other disorders resulting in end-stage fibrotic lung disease [1].

The most frequent indications for bilateral lung transplantation (BLT) are suppurative pulmonary lung disease, cystic fibrosis and bronchiectasis (31%) and severe chronic obstructive pulmonary disease (COPD) resulting from tobacco use (26%), or α₁-antitrypsin deficiency (8%). In addition, more than 90% of transplant centers prefer to perform BLT when patients have idiopathic pulmonary hypertension (5%) [1].

Heart–lung transplantation (HLT) is performed at only a few transplantation centers and should be reserved for patients who cannot be treated by LT alone. The most frequent indications for HLT are Eisenmenger syndrome with a cardiac anomaly that cannot be corrected surgically and severe end-stage lung disease with concurrent severe heart disease. HLT is discussed in more detail in Chapter 183.

There has been a revision of the original consensus-based guidelines for the selection of lung transplant candidates [2]. Any patient with end-stage pulmonary or cardiopulmonary disease with the capacity for rehabilitation can be considered for transplantation. The patient should have untreatable end-stage pulmonary disease, no other significant medical illness, have a limited life expectancy, and be psychologically stable and compliant.

Until the spring of 2005, as established by the United Network of Organ Sharing, lungs were allocated primarily by time on the waiting list, and not by necessity. In the spring of 2005, the system for donor allocation for lungs was revised, and assigned priority for lung offers became based on a benefit or need-based Lung Allocation Score [7]. The LAS is calculated using the following measures: (1) waitlist urgency measure (i.e., the expected number of days lived without a transplant during an additional year on the waitlist); (2) posttransplant survival measure (i.e., the expected number of days lived during the first year posttransplant); and (3) the transplant benefit measure (i.e., the posttransplant survival measure minus waitlist urgency measure) [8]. Although it is still too early to determine the long-term effects that this new allocation system will have on LT, it appears that many of the goals of the system (decreased waiting list deaths, and times, prioritizing patients by urgency rather than time on the list) are being accomplished, with comparable survival rates except in those with the very high LAS scores (> 46 in one study) [9,10]. There appears to be a stepwise decline in posttransplant survival as the LAS score increases. In patients with high LAS scores there was also higher morbidity including requirements for dialysis, infections, and longer lengths of stay [11]. Since the implementation of the LAS, the distribution of patient diagnoses on the list, and those transplanted, has also shifted from a majority of COPD patients to an increasing number of patients with pulmonary fibrosis. In addition, sicker patients are being transplanted.

Donor lungs are first distributed locally, then regionally, and finally nationally. Currently, the average time spent on the waiting list is approximately 18 to 24 months, and therefore close management of the listed transplant patient is required. Despite this close attention, a small percentage of patients die while awaiting transplantation.

A shortage of donor organs remains the primary factor limiting the number of LTs performed. Contributing to this shortage is the estimate that lungs for transplantation are procured from only 19% of multiorgan donors [12]. The vast majority of transplanted lungs are from brain-dead donors. A small number of LT procedures involving living related donors and non–heart-beating lung donors (also called donation after cardiac death [DCD]) have been performed at institutions specializing in these procedures [13]. In a small group of DCD donors lung transplant recipients, rates of PGD, acute rejection, bronchiolitis obliterans, and 2-year survival rates were comparable to those of lung transplant recipients from cadaveric donors during the same period. Graft function was better preserved in the DCD recipients [14].

The usual donor selection criteria are age younger than 60 to 65 years, no history of clinically significant lung disease, normal results from a sputum Gram stain, and a limited history of smoking (less than 20 pack-years). In addition, the lung fields should be clear as demonstrated by chest radiograph, and gas exchange should be adequate as demonstrated by a partial pressure of arterial oxygen (PaO₂) more than 300 mm Hg, while receiving fractional inspired oxygen (FIO₂) equal to 1, or a PaO₂/FIO₂ ratio of more than 300 with a positive end expiratory pressure (PEEP) of 5 cm H₂O. Bronchoscopy is also
part of the evaluation of the donor. The main goal of the endobronchial evaluation is to rule out gross aspiration or purulent secretions in the distal airways.

Lungs from extended donors (i.e., those who do not meet all of the criteria listed earlier) are now more frequently being transplanted in an attempt to expand the donor pool [15,16,17,18], and some centers are actively engaged in developing protocols for optimizing marginal donor lungs, thereby rendering them transplantable. By instituting a protocol including educational and donor management interventions, and changing donor classification and selection criteria, a single-organ procurement organization was able to increase the percentage of lungs procured from 11.5% to 22.5% with an increase in the number of procedures performed, without adverse recipient outcomes [15].

Donors are excluded from potential lung donation if there is evidence of active infection, human immunodeficiency virus, hepatitis, or malignancy. Donor and recipient compatibility is assessed by matching A, B, and O blood types and chest wall size. Human leukocyte antigen (HLA) matching is not routinely performed in LT except in patients with history of preformed donor-specific antibodies.

Initially, double-lung transplantation was the procedure of choice; the anastomosis was placed at the level of the trachea. However, the rate of ischemic airway complications was prohibitive. Now, SLT or BLT (essentially sequential SLT) with anastomoses at the level of the mainstem bronchi is the preferred surgical technique. At the time of cardiac harvest, the donor lung is usually removed through a median sternotomy. The pulmonary veins are detached from the heart with a residual 5-mm cuff of left atrium. The pulmonary artery is transected from the main pulmonary trunk, and the mainstem bronchus is transected between two staple lines. During transportation to the recipient site, the partially inflated donor lung graft is placed into preservation solution, usually a low-potassium dextran solution with extracellular electrolyte composition or a modified Euro-Collins solution with an intracellular electrolyte composition at 4°C.

For SLT, the recipient surgery is performed through a posterolateral thoracotomy or sternotomy, or vertical axillary muscle-sparing minithoracotomy. Most centers start with the bronchial anastomosis, without a vascular anastomosis of the bronchial circulation of the recipient and donor lungs. Initially, most transplant procedures involved an end-to-end anastomosis, which was wrapped with a piece of omentum or pericardial fat with an intact vascular pedicle for assistance in bronchial revascularization. Subsequently, a telescoping technique was recommended, with the recipient and donor bronchi overlapping by approximately one cartilaginous ring. This procedure allowed the recipient’s intact bronchial circulation to supply the donor bronchus. More recently, most anastomoses are performed with an end-to-end single suture in the membranous portion and a single or continuous suture in the cartilaginous portion, without omental wrap, and telescoping is performed when the donor and recipient bronchi differ in size and there is a natural, unforced telescoping of both bronchi [19,20].

After the bronchial anastomosis has been performed, the donor pulmonary veins are anastomosed end-to-end to the recipient’s left atrium, and the pulmonary arteries are attached with an end-to-end anastomosis.

BLT is usually performed through a transverse thoracosternotomy (clamshell incision) or a median sternotomy followed by sequential single-lung procedures. Cardiopulmonary bypass may be required for patients with pulmonary hypertension or those who cannot tolerate single-lung ventilation or perfusion and who experience marked hypoxemia or hemodynamic instability. Although center specific, an increasing number of cases (nearly 50% of LT procedures at some institutions) are performed with the use of cardiopulmonary bypass.

After LT, patients usually remain intubated, require mechanical ventilation, and are transferred to the ICU. Most patients are ventilated in a volume-control mode, although in recent years some transplant centers have changed to pressure-control ventilation, or airway pressure release ventilation. In general, low tidal volume ventilation strategies are used. Airway pressures are kept as low as possible so that barotrauma and anastomotic dehiscence can be avoided. Many institutions use routine pharmacologic sedation. Patients are generally maintained with tidal volumes of 6 to 8 mL per kg postoperatively. At most institutions, a low level of PEEP (5.0 to 7.5 cm H₂O) is applied immediately after lung expansion in the operating room and is continued after transplantation. Early extubation is one of the main goals after LT, and lung transplant recipients who do not experience complications are extubated within the first 12 to 24 hours postoperatively if they meet the commonly accepted weaning criteria. Some centers may attempt to extubate immediately postoperatively [21]. Both postural drainage and chest physiotherapy can be routinely employed without concern for mechanical complications at the anastomosis, and patients should perform incentive spirometry soon after extubation.

Certain patient populations require special ventilator management. Most patients with idiopathic pulmonary hypertension undergo BLT; however, at a few centers some patients undergo SLT for pulmonary hypertension with an increased risk of reperfusion pulmonary edema because nearly all of the perfusion is going to the newly implanted lung.

Patients with obstructive lung disease can encounter problems if the delivered tidal volume or the required levels of PEEP are high. Occasionally, clinically significant acute native lung hyperinflation can occur and can compromise the newly transplanted lung and lead to hypotension and hemodynamic instability. To reduce this problem, some transplant centers avoid PEEP for patients undergoing SLT for obstructive disease. However, the problem is magnified when patients experience reperfusion injury or pneumonia after transplantation; in such cases the compliance of the transplanted lung is decreased and higher PEEP is required for maintaining oxygenation. As a consequence, the more compliant emphysematous lung becomes overexpanded and can herniate toward the contralateral hemithorax [22]. Attempts to prevent this possible complication by using selective independent ventilation with a double-lumen endotracheal tube have been tried. Lung hyperinflation is associated with a significantly longer stay in the intensive care unit (ICU), a longer duration of mechanical ventilation, and a trend toward higher mortality [23].

Pain control is usually provided by opiates, usually fentanyl, administered intravenously or morphine sulfate via an epidural catheter with a patient-regulated pain-control system.

Because many patients are nutritionally depleted before transplantation as a result of their underlying disease, postoperative nutrition is important. Ideally, enteral nutrition should be provided as soon as tolerated.

Antibiotics are routinely administered for the first 48 to 72 hours after transplantation. Antibiotic regimens include broad-spectrum antibiotic coverage for both Gram-negative
and Gram-positive bacteria. Most centers advocate empiric anaerobic coverage. Gram stains and cultures of sputum from the donor and the recipient may be used when available to guide the choice of appropriate antibiotics. Many centers routinely use antifungal agents such as inhaled amphotericin B, voriconazole, or itraconazole postoperatively. Most transplantation programs administer ganciclovir and, more recently, valganciclovir for CMV prophylaxis if either the patient or the donor is CMV-positive before surgery.

Immunosuppression is begun preoperatively with tacrolimus or cyclosporine and corticosteroids. Corticosteroids are administered in the operating room as intravenous methylprednisolone 0.5 to 1 g (usually administered at the time of reperfusion) and then at doses of 1 to 3 mg per kg daily for the next 3 days, followed by 0.8 mg per kg daily and then conversion to an equivalent oral dose. In the past, lympholytic medications, such as intravenous antithymocyte globulin (ATG) at 1.5 mg per kg daily for 3 to 5 days or muromonab-CD3 (Orthoclone OKT3) at 5 mg per day for the first 5 to 10 days, were used as induction therapy after transplantation; however, more recently the use of these medications has been limited. Some centers currently use interleukin (IL)-2 receptor blockers (e.g., basiliximab) for induction. A retrospective registry analysis of the impact of induction therapy on survival following LT showed a survival advantage with the use of interleukin-2- receptor antagonists in both SLT and BLT recipients and in BLT recipients treated with ATG [24]. After the transplantation procedure, most patients begin a triple immunosuppression protocol with a combination of prednisone, a calcineurin agent, tacrolimus or cyclosporine, and a cell cycle inhibiting agent, mycophenolate mofetil or azathioprine [25].