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Lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. The most common indications are COPD, idiopathic pulmonary fibrosis, cystic fibrosis, α1-antitrypsin deficiency, and primary pulmonary hypertension. Less common indications include interstitial lung disorders (eg, sarcoidosis), bronchiectasis, and congenital heart disease. Single and double lung procedures are equally appropriate for most lung disorders without cardiac involvement; the exception is chronic diffuse infection (eg, bronchiectasis), for which double lung transplantation is best. Heart-lung transplantation is indicated for Eisenmenger's syndrome and for any lung disorder with severe ventricular dysfunction likely to be irreversible; cor pulmonale is not an indication because it often reverses after lung transplantation. Single and double lung procedures are about equally common and are at least 8 times more common than heart-lung transplantation.
Relative contraindications include age (single lung recipients must be < 65; double lung recipients, < 60; and heart and lung recipients, < 55), active cigarette smoking, previous thoracic surgery, and, for some cystic fibrosis patients and at some medical centers, lung infection with resistant strains of Burkholderia cepacia, which greatly increases mortality risk.
Nearly all donated lungs are from brain-dead, heart-beating donors. Rarely, living adult (usually parent-to-child) lobar transplantation is done when deceased-donor organs are unavailable. Donors must be < 65 and never-smokers and have no active lung disorder as evidenced by oxygenation (Pao2/Fio2 > 250 to 300, with Pao2 in mm Hg and Fio2 in decimal fraction [eg, 0.5]), lung compliance (peak inspiratory pressure < 30 cm H2O at VT 15 mL/kg and positive end expiratory pressure = 5 cm H2O), and gross appearance by bronchoscopy. Donor and recipients must be size-matched anatomically (by chest x-ray), physiologically (by total lung capacity), or both.
Timing of referral for transplantation should be determined by factors such as degree of obstructive defect (FEV1
< 25 to 30% predicted in patients with COPD, α1-antitrypsin deficiency, or cystic fibrosis); Pao2 < 55 mm Hg; Paco2 > 50 mm Hg; right atrial pressure > 10 mm Hg and peak systolic pressure > 50 mm Hg for patients with primary pulmonary hypertension; and progression rate of clinical, radiographic, or physiologic disease.
Procedure
The donor is anticoagulated, and a cold crystalloid preservation solution containing prostaglandins is flushed through the pulmonary arteries into the lungs. Donor organs are cooled with iced saline slush in situ or via cardiopulmonary bypass, then removed. Prophylactic antibiotics are often given.
Single lung transplantation requires posterolateral thoracotomy. The native lung is removed, and the bronchus, pulmonary artery, and pulmonary veins of the donor lung are anastomosed to their respective cuffs. The bronchial anastomosis requires intussusception or wrapping with omentum or pericardium to facilitate adequate healing. Advantages include a simpler operation, avoidance of cardiopulmonary bypass and systemic anticoagulation (usually), more flexibility concerning size matching, and availability of the contralateral lung from the same donor for another recipient. Disadvantages include the possibility of ventilation/perfusion mismatch between the native and transplant lungs and the possibility of poor healing of the single bronchial anastomosis.
Double lung transplantation requires sternotomy or anterior transverse thoracotomy; the procedure is similar to 2 sequential single transplants. The primary advantage is definitive removal of all diseased tissue. The disadvantage is poor healing of the tracheal anastomosis.
Heart-lung
transplantation requires median sternotomy with cardiopulmonary bypass. Aortic, right atrial, and tracheal anastomoses are required; the trachea is anastomosed immediately above the bifurcation. The primary advantages are improved graft function and more dependable healing of the tracheal anastomosis because of coronary-bronchial collaterals within the heart-lung block. Disadvantages include long operative time with the need for cardiopulmonary bypass, the need for close size matching, and use of 3 donor organs by one recipient.
Methylprednisolone IV is often given to recipients before reperfusion of the transplanted lung. A common immunosuppressive regimen combines a calcineurin inhibitor ( cyclosporine or tacrolimus ), a purine metabolism inhibitor ( azathioprine or mycophenolate mofetil ), and methylprednisolone . Prophylactic antithymocyte globulin (ATG) or OKT3 may also be given during the first 2 wk after transplantation. Corticosteroids may be omitted to facilitate healing of the bronchial anastomosis; higher doses of other drugs (eg, cyclosporine , azathioprine ) are substituted. Immunosuppressants are continued indefinitely.
Rejection develops in most patients despite immunosuppressive therapy. Symptoms and signs are similar in hyperacute, acute, and chronic forms and include fever, dyspnea, cough, decreased SaO2, interstitial infiltrate on x-ray, and a decrease in FEV1 by > 10 to 15%. Hyperacute rejection must be distinguished from early graft dysfunction caused by ischemic injury during the transplantation procedure. Diagnosis is confirmed if bronchoscopic transbronchial biopsy shows perivascular lymphocytic infiltration in small vessels. IV corticosteroids are usually effective. Treatment of recurrent or resistant cases varies and includes higher corticosteroid doses, aerosolized cyclosporine , ATG, and OKT3.
Chronic rejection (after > 1 yr) occurs in up to 50% of patients; it takes the form of obliterative bronchiolitis or, less commonly, atherosclerosis. Acute rejection may increase risk of chronic rejection. Patients with obliterative bronchiolitis present with cough, dyspnea, and decreased FEV1 with or without physical and radiographic evidence of an airway process. Differential diagnosis includes pneumonia. Diagnosis is by bronchoscopy with biopsy. No treatment has proved effective, but options include corticosteroids, ATG or OKT3, inhaled cyclosporine , and retransplantation.
The most common surgical complication is poor healing of the bronchial or tracheal anastomosis. Up to 20% of single lung recipients develop bronchial stenosis that causes wheezing and airway obstruction; it can be treated with dilation or stent placement. Other surgical complications include hoarseness and diaphragmatic paralysis, caused by damage to the recurrent laryngeal or phrenic nerves; GI dysmotility, caused by damage to the thoracic vagus nerve; and pneumothorax. Supraventricular arrhythmias develop in some patients, probably due to conduction changes caused by pulmonary vein-atrial suturing.
Prognosis
At 1 yr, survival rates with living-donor grafts are 84% and with deceased-donor grafts 83%. At 5 yr, survival rates with living-donor grafts are 34% and with deceased-donor grafts 46%. Mortality rate is higher for patients with primary pulmonary hypertension, idiopathic pulmonary fibrosis, or sarcoidosis and lower for those with COPD or α1-antitrypsin deficiency. Mortality rate is higher for single lung transplantation than for double. Most common causes of death within 1 mo are primary graft failure, ischemia and reperfusion injury, and infection (eg, pneumonia) excluding cytomegalovirus; the most common cause between 1 mo and 1 yr is infection; and after 1 yr, it is obliterative bronchiolitis. Mortality risk factors include cytomegalovirus mismatching (donor positive, recipient negative), human leukocyte antigen (HLA-DR) mismatching, diabetes, and prior need for mechanical ventilation or inotropic support. Uncommonly, the disorder recurs, particularly in some patients with an interstitial lung disorder. Exercise capacity is slightly limited because of a hyperventilatory response.
With heart-lung transplantation, overall survival rate at 1 yr is 60% for patients and grafts.
Last full review/revision September 2008 by Martin Hertl, MD, PhD; James F. Markmann, MD, PhD; Paul S. Russell, MD; Heidi Yeh, MD
Content last modified September 2008
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