Living lobar lung transplantation was developed as an alternative to cadaver lung transplantation because of the continuing shortage of acceptable donor organs.^1,2 In living lobar lung transplantation, two healthy donors are selected—one to undergo removal of the right lower lobe and the other removal of the left lower lobe. These lobes then are implanted in the recipient in place of whole right and left lungs. This technique has proved to be beneficial to a group of patients who otherwise would have succumbed to disease while awaiting lungs from a conventional deceased donor.³

GENERAL PRINCIPLES AND PATIENT SELECTION

Living lobar lung transplant candidates should meet the standard criteria for deceased donor lung transplantation and be listed on the Organ Procurement and Transplantation Network lung transplantation waiting list.⁴ The expectation for potential recipients should be that they will either die before a deceased (cadaver) donor lung becomes available or become too ill to undergo any sort of organ transplant procedure. In the United States, cystic fibrosis is the most common indication for living lobar lung transplantation. However, other indications include primary pulmonary hypertension, pulmonary fibrosis, bronchopulmonary dysplasia, obliterative bronchiolitis, lymphangioleiomyomatosis, and idiopathic interstitial pneumonia.^2,5

The goals of donor selection are to identify donors with excellent health, adequate pulmonary reserve for lobar donation, an emotional attachment to the recipient, and a willingness to accept the risks of donation without coercion. Our criteria for donation also include age between 18 and 55 years, no history of thoracic procedures on the side to be donated, and excellent general health. Donors taller than the recipient are favored over donors of the same or lesser height because they have the potential to provide larger lobes. Initially, only the mother and father of the recipient were considered as donors; however, lobes from siblings, extended family members, and unrelated individuals who can demonstrate an emotional attachment to the recipient are also presently considered. A psychosocial interview is conducted. Potential donors are interviewed both separately and with the potential recipient's family to ascertain interpersonal dynamics. Elements of the interview include the motivation to donate, pain tolerance, feelings regarding donation should the recipient expire, and the ability of the potential donor to be separated from family and career obligations. Since an element of coercion always can exist between a potential donor and the recipient and/or the recipient's family, any potential donor who discloses that he or she feels any pressure to donate after careful consultation and explanation of the procedure is denied for unspecified reasons, thus preventing untoward feelings between the family, recipient, and potential donor.

After the psychosocial evaluation, suitable potential donors undergo blood typing for compatibility as well as chest radiography and spirometry to assess lung size and function. This preliminary screening reduces costs because it allows for the evaluation of only a limited number of potential donors. A more thorough medical workup, including routine transplant serologies (i.e., HIV, VDRL, cytomegalovirus, Epstein-Barr virus, and hepatitis), electrocardiogram, echocardiogram, quantitative ventilation/perfusion scanning, and high-resolution chest CT scanning, is conducted after the preliminary screening is completed and found to be acceptable.

After identification of two suitable donors, one is chosen to undergo right lower lobectomy and the other, left lower lobectomy. The right lower lobe is usually selected from the larger donor, whereas the donor with the more complete fissure on the left is chosen to donate that side if the donors are of the same height. Occasionally, an acceptable donor will have a history of prior thoracic procedures, trauma, or infection. In this case, the contralateral side is chosen for donation. At our center, CT scanning and spirometry are used to estimate lung volume, although the optimal method of determining an appropriate size match between donor and recipient remains to be defined, and further improvements in this methodology are warranted. In children, care must be exercised to ensure that the lower lobe is not oversized. While human leukocyte antigen (HLA) matching is not required for donor selection, a prospective crossmatch to rule out the presence of anti-HLA antibodies is performed.

OPERATIVE TECHNIQUE

The performance of living lobar lung transplantation involves three simultaneous operations: two donor lobectomies and the recipient bilateral pneumonectomy and lobar implantation. The operative goals of living-donor lung transplantation are to avoid morbidity to the healthy volunteer lobe donor while providing adequate tissue margins for implantation in the recipient.⁶ The lobar vascular and bronchial anatomy of the right and left lower lobes are the most suitable for lobar transplantation.

The Donor Lobectomy

The donors are placed in separate ORs, and epidural catheters are inserted for postoperative pain control. After induction of anesthesia, fiberoptic bronchoscopy is performed to exclude mucosal abnormalities or alterations in bronchial anatomy. The single-lumen endotracheal tube is replaced with a double-lumen tube, and the patient is positioned in the appropriate lateral decubitus position. Prostaglandin E₁ is administered intravenously to dilate the pulmonary bed, and the dosage is adjusted to maintain a systolic blood pressure of 90–100 mm Hg. There are important differences in performing a lobectomy for lobar transplantation in comparison with that for cancer or infection. The lobe must be removed with an adequate cuff of bronchus and pulmonary artery and vein to permit successful implantation into the recipient while allowing closure of these structures without compromise in the donor.

Donor Right Lower Lobectomy

The donor lung is deflated, and the chest is entered through a standard posterolateral thoracotomy through the fourth or fifth interspace. The lung is carefully inspected to exclude unsuspected pathology. Excellent exposure is mandatory, allowing dissection of hilar structures without excessive manipulation of the graft. The inferior pulmonary ligament is taken down, and the pleura is opened around the hilum. Dissection in the fissure characterizes anatomic variants and identifies the pulmonary arteries to the right lower and right middle lobes. The relationship between the superior segmental artery to the right lower lobe and middle lobe artery should be visualized (Fig. 96-1). Commonly, the middle lobe has two arteries, with the smaller artery having a more distal origin than the superior segmental artery to the lower lobe. In this case, the smaller artery may be ligated and divided. Ideally, there will be sufficient distance between the takeoff of the middle lobe artery and the superior segmental artery of the right lower lobe to permit placement of a vascular clamp distal to the middle lobe artery, thus enabling a sufficient vascular cuff for the pulmonary arterial anastomosis at implantation.

After confirming that the inferior pulmonary vein does not receive venous drainage from the right middle lobe, the pericardium surrounding the inferior pulmonary vein is incised. This dissection allows a vascular clamp to be placed on the left atrium and the inferior pulmonary vein to be cut with an adequate cuff on the donor lobe (Fig. 96-2). When the vascular dissections are complete, the fissures are stapled using a 75-mm nonvascular stapler or a 45-mm GIA thoracoscopic stapler. Between 5000 and 10,000 units of heparin and 500 mg methylprednisolone are administered intravenously, and the lung is reinflated and ventilated for 5–10 minutes to permit the drugs to circulate through the lung. The lung then is deflated. To avoid vascular congestion of the pulmonary allograft, a vascular clamp is placed first on the pulmonary artery and subsequently on the left atrial side of the inferior pulmonary vein, optimizing the length of the venous cuff for pulmonary venous anastomosis. The pulmonary artery is transected at a point that will leave an adequate vascular cuff for the anastomosis while leaving sufficient length to permit repair without compromising the remaining pulmonary arterial branches. The inferior pulmonary vein is transected with a small cuff of left atrium. The bronchus to the right lower lobe now should be exposed. Minimizing dissection around the bronchus preserves blood supply to both the donor lobe and the remaining lung. The right middle lobe bronchus is identified, and the bronchus to the lower lobe is transected tangentially. The incision begins in the bronchus intermedius above the bronchus to the superior segment of the right lower lobe and moves obliquely to a point just below the takeoff of the right middle lobe bronchus (Fig. 96-3).

Division of the pulmonary vessels and bronchus should be performed expeditiously to limit the warm ischemia time of the allograft. When separated, the donor lobe is wrapped in a cold, moist sponge and taken to a separate, sterile table for preservation. The donor pulmonary artery is repaired in two layers with a running polypropylene suture, and the pulmonary vein/left atrium is closed in a similar fashion. The bronchus is closed with interrupted polypropylene, being careful to avoid narrowing of the bronchus intermedius or infolding of the middle lobe carina. Resecting a small wedge of cartilage at the orifice of the middle lobe may facilitate closure. The bronchial suture line is covered with a pleural flap to separate the arterial and bronchial suture lines. Two chest tubes are placed in the pleural space, and the chest is closed in the standard fashion.

Donor Left Lower Lobectomy

The chest is opened using a standard posterolateral thoracotomy through the fourth or fifth interspace. The lung is examined in a similar fashion to that described for the right side. The inferior pulmonary ligament is taken down, and the pleura is opened around the hilum. Dissection in the fissure defines the vascular anatomy. The relationship between the superior segmental artery to the lower lobe and the anteriorly positioned lingular artery is evaluated (Fig. 96-4). The lingular artery may be ligated and divided if it is of small size and its origin is too far distal to the artery to the superior segment of the lower lobe. If the significance of this artery is uncertain, the anesthesiologist can inflate and deflate the lung while this artery is occluded. Dissection of the pulmonary artery to the lower lobe should enable placement of a vascular clamp proximal to the artery supplying the superior segment of the lower lobe. The pericardium around the inferior pulmonary vein is opened circumferentially, and the fissures are completed with a nonvascular stapler.

When the dissection is complete, the lung is reinflated and ventilated for 5–10 minutes as described for the right side. Heparin and methylprednisolone are administered. The lung is subsequently deflated, and the pulmonary artery and vein are clamped and transected in the sequence described for the right lung. The exposed bronchus is followed upward until the lingular bronchus is identified. Care must be taken to avoid skeletonizing the bronchus because this may compromise healing in the recipient. The tangential transection begins at the base of the upper lobe bronchus and ends superiorly to the bronchus to the superior segment of the left lower lobe (Fig. 96-5). The donor lobe then is taken to a separate table for preservation and storage. The pulmonary vessels and bronchus are repaired in a manner similar to that described earlier.

Allograft Preservation

Preparation of the donor lobe begins at the start of the donor operation with a continuous prostaglandin infusion and meticulous attention to operative technique during the lobectomy. In contrast to standard deceased donor lung explantation, preservation of the lobe in a live donor does not permit in situ flushing and cooling of the graft with cold preservation solutions. Therefore, after the donor lobe is removed, it is taken to a separate, sterile table for cold preservation. The allograft is immersed in cold crystalloid solution. The pulmonary artery and vein are cannulated in an alternating fashion and flushed with 1–2 L of cold Perfadex (low potassium, dextran, and glucose) solution until the pulmonary venous and arterial effluents are clear and the parenchyma is blanched white. During perfusion, the lobe is gently ventilated with room air. A ventilation bag with different size endotracheal tubes should be available. Using an appropriately sized endotracheal tube permits an adequate seal to be formed while ventilating the bronchus and prevents potential damage to the bronchus caused by crushing or squeezing the bronchus in an effort to obtain an adequate seal. Depending on the length of the bronchus, it may be necessary to selectively intubate the superior segment bronchus separately with a smaller tube to ventilate that portion of the lobe. The superior segment artery may have to be perfused separately as well. Care must be taken to prevent the crystalloid bath or the preservation solution effluent from flooding the bronchus. In addition, a manometer is fastened to the ventilation apparatus, and the lobe is inflated to a pressure of 20–25 mm Hg, being careful to avoid overpressurizing the lung. After adequate perfusion and ventilation, a final tidal volume is administered to achieve approximately 75% maximum inflation, the endotracheal tube is quickly removed, and the bronchus is occluded with a noncrushing clamp. The donor lobe is placed in a sterile bag with cold storage solution and transported to the recipient OR in an ice-filled cooler.

Recipient Pneumonectomy

The recipient operation commences in a third OR while the donor operations are being performed. The patient is positioned supine and the arms padded and placed in an extended and abducted position on an overhead frame. The operation is performed through a transverse thoracosternotomy (clamshell) incision, which provides exposure for cardiac cannulation and adequate access to the pleural spaces. All the procedures at our center have been preferentially performed while on cardiopulmonary bypass, often because of the recipient's critical condition, as well as to minimize the risk of pulmonary edema while exposing one lobe to the entire cardiac output while the other lobe is implanted. Use of cardiopulmonary bypass prevents spillage of purulent secretions from the second native lung and allows simultaneous reperfusion of both lobes in a controlled fashion. Hilar dissection and lysis of adhesions are completed before heparinization and cardiopulmonary bypass. The pleural cavity of patients with cystic fibrosis is irrigated thoroughly with antibacterial and antifungal solutions. Dissection of the pulmonary artery and veins is performed as distally as possible to optimize cuff length for the anastomoses (Fig. 96-6). When the dissection is complete, cardiopulmonary bypass is initiated, and the pulmonary vasculature is divided. The pulmonary veins are divided between stapling devices while the pulmonary artery is doubly ligated and divided. The bronchus is divided with a stapling device at the level of the takeoff of the upper lobe bronchus. After the onset of bypass, the anesthesiologist suctions the lungs and removes the endotracheal tube.

Allograft Implantation

The first allograft is placed on a cooling jacket within the pleural space, and the exposed lung is wrapped in iced, saline-soaked sponges. The bronchial anastomosis is performed with running 4-0 polypropylene suture. Care is taken to limit the amount of peribronchial dissection. The bronchial anastomosis places the donor lobar vein in close approximation to the superior pulmonary vein of the recipient, and the venous anastomosis is performed in a running fashion with 5-0 polypropylene suture. The short length of the donor vein makes anastomosis directly to the left atrium difficult and underscores the importance of leaving an adequate length of recipient pulmonary vein during pneumonectomy. The pulmonary artery anastomosis is performed end to end with 5-0 polypropylene suture (Fig. 96-7). A similar procedure is performed for the second allograft.

After completing the bilateral implantations, the arterial vascular clamp is slowly removed. The preservation perfusate is permitted to egress from the venous anastomosis before tying the venous sutures, and ventilation is begun gently. Continuous nitric oxide starting at 20 ppm and intermittent aerosolized bronchodilator therapy are both administered via the anesthesia circuit. Blood volume is returned gradually, allowing increased cardiac ejection and pulmonary blood flow to occur with subsequent weaning from cardiopulmonary bypass. At completion of implantation, transesophageal echocardiography to evaluate for patency of the one pulmonary vein on each side draining into the left atrium and bronchoscopy to assess the bronchial anastomoses and for pulmonary toileting are performed. Four chest tubes then are placed, the clamshell incision is closed, and the patient is transported directly to the ICU.

POSTOPERATIVE MANAGEMENT

Donor Management

The donors are transported to the recovery room with epidural catheters in place after the lobectomy. Chest tubes are required until all evidence of air leak has ceased, chest tube output is acceptable, and the remaining lung tissue fills the hemithorax with no significant pneumothorax. Donors receive low-dose enoxaparin and sequential compression devices postoperatively to prevent thromboembolic complications. Oral analgesics are administered on removal of the chest tubes and are continued for a short time at home. Standard postthoracotomy management includes incentive spirometry and physical therapy exercises.

Recipient Management

While immunosuppression, antibiotic therapy and prophylaxis, and long-term management of the lobar recipient are very similar to those for standard deceased-donor lung transplantation, the perioperative management is different given the physiology of lobar transplantation.

The lobar physiology of the recipient presents unique challenges compared with whole-lung transplantation because the entire cardiac output is flowing through two relatively undersized lobes. In an attempt to decrease atelectasis and optimize expansion of the lobes, the recipient is kept sedated and ventilated through a single-lumen endotracheal tube with positive end-expiratory pressures of 5–10 cm H₂O for at least 48 hours. Additionally, efforts are undertaken to decrease pulmonary artery pressures and minimize the risk of reperfusion injury and pulmonary edema. This is accomplished by maintaining the recipient in a relatively hypovolemic state, the use of nitroglycerin infusion, and the use of aerosolized nitric oxide for the first 48–72 hours.

Another unique aspect of managing the lobar recipient in the perioperative period is chest tube control. Depending on the degree of size mismatch between the donor lobe and the recipient pleural cavity, conventional chest tube suction in the postoperative period can result in impaired deflation mechanics. This can lead to air trapping with increasing airway pressures, a rise in pulmonary vascular resistance, and subsequently, an acute rise in pulmonary arterial pressure. This problem is exaggerated as the discrepancy between the size of the lobe and the thoracic cavity increases. To avoid this problem, suction is applied at low levels (10 cm H₂O) to each tube sequentially for 1-hour intervals in a rotational fashion for the first 24 hours postoperatively. Subsequently, each of the four chest tubes is placed on continuous suction that is increased gradually to 20 cm H₂O over the next 48 hours. Chest tube output can be much greater than that seen after deceased-donor whole-lung implantation because there is an obligatory space-filling of the pleural cavity with fluid, which can be exacerbated by greater topographic mismatches. The question of whether these tubes can be removed despite these higher than normal outputs is unclear. However, because of concerns of lobe compression by the pleural fluid, the chest tubes are left in place for 2–3 weeks, which is significantly longer than for conventional transplantation. Residual air leaks typically resolve in this time period as well.

Management of the lobar recipient in regard to immunosuppression, antibiotic therapy and prophylaxis, and long-term follow-up is very similar to that for standard lung allograft recipients. In all recipients, pulmonary function testing and chest roentgenography are performed with each clinic visit; however, bronchoscopy is performed only when clinically indicated by symptoms, radiography, or a decrease in spirometric results. Transbronchial biopsy is performed sparingly because of a perceived increased risk of bleeding in the lobar recipient.

RESULTS

We have now performed 141 living lobar lung transplants through April 2005 on 136 patients at the University of Southern California and Children's Hospital of Los Angeles.² Ninety recipients were adults (mean age 27 ± 7 years), and 46 were pediatric patients (mean age 14 ± 3 years). The main indication for transplantation was cystic fibrosis (86%); the remaining 14% of recipients had a variety of other diagnoses, including primary pulmonary hypertension, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, and obliterative bronchiolitis. At the time of transplantation, many of the patients were critically ill, with 67% hospital-bound and 20% ventilator-dependent—including three on jet ventilation and one patient on extracorporeal membrane oxygenation.

Overall recipient actuarial 1-, 3-, and 5-year survival rates are 73%, 58%, and 48%, respectively. There has been no difference in actuarial survival between adult or pediatric recipients. These actuarial survivals are not statistically different from the results of the International Society for Heart and Lung Transplantation registry data, which report 1-, 3-, and 5-year survival rates of 74%, 58%, and 47%.⁷ Mean follow-up is 3.6 ± 3.3 years (range 0-11.8 years). Deaths occurring within 30 days of transplantation have been largely due to infection and primary graft failure. Deaths occurring between 30 days and 1 year after transplantation usually have been due to infectious etiologies. Late death (>1 year after transplantation) has been predominantly due to infection and bronchiolitis obliterans syndrome.

The predominant infections seen have presented as sepsis and/or pneumonia from Pseudomonas spp., Staphylococcus spp., and Aspergillus spp. As opposed to standard double-lung transplantation, in which rejection almost always presents in a bilateral fashion, rejection episodes in the lobar recipients have been predominantly unilateral (72%), whereas only 28% presented bilaterally. In adult recipients, overall freedom from bronchiolitis obliterans syndrome is 98%, 82%, and 76% at 1, 3, and 5 years, respectively. Age, gender, etiology, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, -B, and -DR typing did not influence survival or rejection. Patients undergoing retransplantation had an elevated risk of death, whereas those patients on ventilators preoperatively had significantly worse outcomes (odds ratio for death at 1 year 4.9, p = 0.0015; overall odds ratio 3.06, p = 0.03).

Analysis of pulmonary function after both living lobar and bilateral deceased-donor lung transplantation showed that both groups of recipients demonstrated improvement during the first year after transplantation and that pulmonary function was equivalent between the groups by 6 months after transplantation.⁸ Exercise capacities also were comparable in the lobar and conventional lung transplant recipients when assessed by exercise stress testing.

Donor Outcome

There has been no perioperative or long-term mortality in the total cohort of 279 lobar donors. In a detailed study of the first 253 donors, 80.2% had no perioperative complications.³ Fifty (19.8%) of the 253 donors had one or more perioperative complications. Overall length of stay was 9.4 ± 4.8 days. Right-sided donors were more likely to have a perioperative complication than left-sided donors, likely secondary to right lower and middle lobe anatomy.

SUMMARY

A constant awareness of the risk to the living donors must be maintained with any live-donor organ transplantation program, and comprehensive short- and long-term follow-up should be strongly encouraged to maintain the viability of these potentially lifesaving programs. Despite the high-risk patient group, this alternative procedure has been lifesaving in severely ill patients who would either die or become unsuitable recipients before deceased-donor lungs became available. Although conventional transplantation is preferable owing to the risk to the donors, living lobar lung transplantation should continue to be used under properly selected circumstances. While there have been no deaths in the donor cohort, a risk of death of between 0.5% and 1% should be quoted pending further data. Loss of lung function should be considered an expected aspect of this procedure and is explained as such to the potential donor during the process of obtaining informed consent. The results reported by our group and others are important if this procedure is to be considered as an option at more pulmonary transplant centers in view of the institutional, regional, and intra- and international differences in the philosophical and ethical acceptance of the use of live organ donors for transplantation.^9,10

EDITOR'S COMMENT

Lobar transplantation highlights (1) the difference between lung volume and lung function, and (2) the absence of convincing compensatory growth in the lung. After pneumonectomy, the remaining lung can dramatically enlarge to fill the chest. Despite the increase in volume, lung function is rarely greater than 50% of the predicted baseline. Similarly, an adult lobe may expand its volume in a recipient patient, but there is no convincing evidence for an adaptive increase in lung function. Adaptive regeneration of the lung is an area of active biologic research that has many potential disease applications—none more important than lobar lung transplantation.

–SJM

REFERENCES