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Lung transplantation

Paula Moreno

HISTORY

James Hardy performed the first lung transplantation (LT) in a human in 1963. The patient, a 58-year-old prisoner diagnosed with a squamous cell carcinoma in his left main bronchus, underwent single left LT. ¹ Despite the initial success, the patient developed renal failure and died on postoperative day 18. Nearly 40 additional procedures were done worldwide in the following 15 years, all of them unsuccessful as a result of primary graft failure, airway complications, and multiorgan failure. The advent of cyclosporine and the refinement in surgical technique heralded clinical success. In 1981, the Stanford Group led by Norman Shumway performed the first human heart-lung transplantation (HLT). ² The first successful single lung transplantation (SLT) was performed in 1983 by Joel Cooper and colleagues from Toronto. ³ Three years later, the same group reported the first en bloc double lung transplantation (DLT) through a median sternotomy using full cardiopulmonary bypass (CPB). ⁴ The introduction of the clamshell incision allowed for superb exposure of the pleural cavity, while providing adequate access for performing the left atrial anastomosis. ⁵

PRINCIPLES

Indications for LT include any chronic end-stage pulmonary disease, refractory to maximal medical therapy or for which no medical therapy exists. Currently, chronic obstructive pulmonary disease (COPD) is the leading indication for LT, followed by idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), emphysema due to alpha-1 antitrypsin deficiency, and idiopathic pulmonary arterial hypertension (IPAH). For septic lung diseases and certain pulmonary hypertensive disorders, the extent of disease mandates the removal of both lungs. During the early years of LT, this was achieved with combined heart-DLT. This technique was first replaced by en bloc DLT using CPB and a tracheal anastomosis, and finally by bilateral sequential LT through a clamshell incision. ⁴ , ⁵ The procedure involves three major anastomoses: (1) bronchus, (2) pulmonary artery (PA), and (3) left atrium (LA). Bronchial artery revascularization is not routinely per-formed. Brain-dead donors remain the main source of lung grafts for transplantation. However, only 20% of potential donors, even those whose other organs are perfectly suitable, provide lungs that are usable for transplantation.

DONOR LUNG PROCUREMENT

Donor selection criteria

The lung is especially vulnerable to being damaged as a result of trauma, aspiration, ventilator-related pneumonia, or fluid overload. Moreover, brainstem death itself may cause lung injury, which may be worsened in the posttransplant period as a result of primary graft dysfunction (PGD). The standard criteria for choosing an ideal donor lung are shown in Table 24.1. ⁶ However, many of these clinical criteria were chosen arbitrarily in the early years of LT. Indeed, the use of less than optimal or marginal donor lungs has not been associated with poorer outcomes and the use of such lungs has allowed for expansion of the donor pool.

Operation

DONOR LUNG PROCUREMENT

The donor chest is opened by median sternotomy, extending the incision inferiorly to the pubis, to permit extraction of the abdominal organs. Thymic remnants are dissected until the innominate vein is identified. The pericardium is widely opened in an inverted T fashion and the heart is exposed and examined. Both pleurae are incised along the reflection and the lungs are examined, looking for areas of atelectasis, edema, or contusion. A compliance test is performed by disconnecting the ventilator at end inspiration, and should result in a prompt deflation of the lungs.

1. The intrapericardial superior vena cava (SVC) is isolated and encircled with two No. 2 silk ligatures, and the inferior vena cava (IVC) is encircled with a single No. 2 silk ligature. The SVC is retracted to the left to allow the right main PA to be dissected away from the SVC and the ascending aorta (AA). The AA and main PA are dissected free from one another and each encircled with an umbilical tape. A 4-0 polypropylene suture is placed in the distal main PA in purse-string fashion for the pulmoplegia cannula and a 2-0 purse-string suture is placed in the AA for the cardioplegia cannula. The posterior pericardium between the aorta and the SVC is incised and the distal trachea is exposed. Once the thoracic dissection is completed, the donor is given a systemic dose of heparin (300 units/kg). The AA is cannulated for cardiac preservation and the proximal main PA is cannulated with a 14 mm bullet-tipped perfusion cannula. A 500 mcg bolus of prostaglandin E1 (PGE1) is injected directly into the PA. Close attention should be paid to the systemic blood pressure, as this bolus may result in systemic hypotension. Shortly after, the SVC is doubly ligated and the IVC is divided above the clamp to decompress the right heart. After three or four heartbeats, the heart empties of blood, the AA is cross-clamped, and cardioplegia is initiated. The tip of the left atrial appendage is generously incised to decompress the left heart, and the lung flush is initiated. Perfadex, 60 mL/kg at 4°C, is used as preservation solution. The pericardial sac and both pleural spaces are topically cooled with ice slush saline, while gentle ventilation of both lungs is continued. Toward the end of lung perfusion, the effluent should run almost clear. After completion of the cardioplegia and the pulmoplegia, the aortic and pulmonary cannulae are removed and the heart is then extracted. The SVC is divided between the ligatures, the aorta is transected proximal to the cross-clamp and dissected off the right PA, and the distal main PA is transected, starting at the cannulation site (Figure 24.1).
   
2. Cooperation of the heart and lung teams is of paramount importance, especially regarding the site of division of the left atrial cuff and the site of cannulation and division of the main PA. The heart is retracted to the right and an incision is made in the LA, midway between the coronary sinus and the left pulmonary veins (PVs). The incision is extended superiorly over the roof of the LA, and inferiorly, parallel to the coronary sinus. An adequate cuff of LA should have a small rim of atrial muscle around each of the PV orifices (Figure 24.2).
   
3. Once the heart is removed, the trachea is encircled and doubly stapled using a TA stapling device, keeping the lungs at end-tidal inflation. The trachea is then divided between the staple lines, and all superior mediastinal tissue is incised. The pericardium is incised from one side to the other, the pulmonary ligaments are divided, and the donor lung block is removed after dividing the descending aorta (Figure 24.3).

SPLITTING THE DONOR LUNG BLOCK

Once on the back table, an additional retrograde flush is made. With the same PA cannula inserted into the PVs, the perfusate is vented through the main PA and continued until the effluent runs clear, with no clots. For DLT, the lung block is triple-bagged and placed on ice in the transport box. On occasion, the lung block must be split at the donor hospital, when two single lung recipients are going to be transplanted at different institutions (twinning procedures). In this case, the PA is divided at the level of its bifurcation, the LA is divided at midline, and the posterior pericardium is divided from below upward. Any residual mediastinal tissue is dissected free, and the proximal left main bronchus is doubly stapled and divided between the staple lines, which separates the two lungs. Then, the grafts are triple-bagged and transported as described.

Donation after circulatory death and the use of ex vivo lung perfusion

Recently, new strategies have been developed to potentially increase the lung donor pool, such as the use of lungs from donors after circulatory death—donation after circulatory death (DCD)—and the use of ex vivo lung perfusion (EVLP). ⁷ Controlled DCD is the most accepted and used DCD type for donation. ⁸ A warm ischemic time is added to the cold ischemic period. The process of DCD donor lung evaluation and procedure is as follows: life-sustaining therapies are withdrawn from the DCD donor at a planned time, which subsequently leads to patient death and then, organ retrieval can proceed; five minutes after the declaration of (a) cardiac death, the donor is reintubated and reventilated; finally, the lungs are procured and preserved in the standard way, with in situ antegrade flush and retrograde flush on the back table.

Another novel strategy to overcome the shortage of donor lungs is EVLP, which is used to optimize and recover organs initially deemed unsuitable for transplantation. ⁹ Contrary to standard cold static preservation, EVLP provides physiologic normothermic lung perfusion and allows for functional reassessment prior to implantation.

1. The lungs are perfused with a specifically designed solution (Steen solution) through the PA, and ventilated mechanically following a protective strategy. Clinically, the two most practiced EVLP methodologies are the Lund and the Toronto protocols ⁸ , ⁹ (Figure 24.4a and b).

SINGLE LUNG TRANSPLANTATION

Preoperative assessment and preparation

RECIPIENT SELECTION

Candidates must be free of significant comorbidities and sufficiently fit to tolerate the procedure. The most frequent conditions to be considered for SLT are COPD and interstitial lung diseases. Also, SLT may be the procedure of choice for older patients or those who would not tolerate the longer anesthetic time of DLT. Absolute contraindications are listed in Table 24.2. The side to be transplanted depends on several factors. Ideally, one should choose the lung that demonstrates the poorest function on lung perfusion scanning. However, for patients with previous thoracic operations like talc pleurodesis, the “virgin” side is preferable.

Anesthesia

Sedation outside of the operating room is not recommended as it may precipitate a cardiorespiratory arrest due to hypoxemia, hypercapnia or increased pulmonary vascular resistance resulting in acute right ventricular failure. A thoracic epidural catheter is usually placed once the patient arrives at the operating room. Standard monitoring is shown in Table 24.3. Transesophageal echocardiography (TEE) is also recommended to evaluate right ventricular function, distention, tricuspid regurgitation, leftand right-sided preload, the adequacy of left heart filling and volume status, assessment of air emboli after de-airing maneuvers, and to estimate right ventricular cardiac output, especially during and after PA clamping and unclamping. One-lung ventilation (OLV) is achieved with a double lumen endotracheal tube. In IPF patients, oxygenation can be maintained at the expense of increasing inflation pressures, which may result in hypercapnia or increased end-tidal partial pressure of carbon dioxide (PCO₂). In addition, hypotension during trial PA clamping anticipates the need for CPB. Monitoring of the patient undergoing DLT is as for SLT. However, bronchial toilet is of paramount importance for patients with septic lung disease. These patients are initially intubated with a single lumen endotracheal tube and fiber-optic bronchoscopy is performed to allow vigorous suctioning of purulent secretions. This maneuver reduces the need for CPB due to respiratory insufficiency while on OLV. Due to the risk of development of noncardiogenic pulmonary edema in the reimplanted lung, it is extremely important to avoid excessive fluid administration.

OPERATION

The patient is positioned in a lateral decubitus position, with a roll under the chest. Proper padding to the elbows and knees will avoid postoperative complications, such as venous thrombosis or nerve compression. In addition, a prophylactic venous compression system is placed on the lower extremities in every patient. A posterolateral thoracotomy is made, entering the chest through the 5th intercostal space. In patients with a small thorax, it is recommended to enter the pleural space through the 4th rather than the 5th intercostal space. A Finochietto retractor is placed and slowly opened to spread the ribs. Optionally, a Tuffier rib retractor can be placed in a perpendicular direction to retract the skin and the serratus anterior muscle. Double lung ventilation is continued whenever possible, to minimize the aggravation of hypoxia secondary to intrapulmonary shunt. Adhesions, if any, and the inferior pulmonary ligament are divided. Due to the small chest cavities of fibrotic patients, it is helpful to place a heavy traction suture (0 silk) into the fibrous dome of diaphragm, which is brought out of the chest and secured after pulling down the diaphragm with the suture. The pleura is incised anteriorly at the hilum, and special care should be taken to avoid injury to the phrenic nerve. Even if the patient is hemodynamically stable, the PA should be clamped for a trial period of 10-15 minutes to ensure that both ventilation and perfusion of the dependent lung only can be tolerated. If the patient does not tolerate OLV, in case of ventilatory compromise (acidosis, hypoxemia, hypercapnia), or hemodynamic instability (hypotension, dysrhythmias, right ventricular dysfunction, increased PA pressures) during this maneuver, they should be placed on extracorporeal lung support (ELS).

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