Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. (See also Overview of Transplantation)
The most common indications for lung transplantation are
Primary pulmonary hypertension
Less common indications include other 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.
Indications for heart-lung transplantation are
Any lung disorder with severe ventricular dysfunction likely to be irreversible
Cor pulmonale often reverses after lung transplantation alone and is therefore rarely an indication for heart-lung transplantation.
Relative contraindications include
Age (single lung recipients must be < 65; double lung recipients, < 60; and heart-lung recipients, < 55)
Current cigarette smoking
Previous thoracic surgery
For some cystic fibrosis patients and at some medical centers, lung infection with resistant strains of Burkholderia cepacia, which greatly increases mortality risk
Single and double lung procedures are about equally common and are at least 8 times more common than heart-lung transplantation.
Донори легенів
Nearly all donated lungs are from brain-dead (deceased), heart-beating donors.
Grafts from non–heart-beating donors, called donation-after-cardiac-death (DCD) donors, are being increasingly used because lungs from more suitable donors are lacking.
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 (fractional inspired O2) > 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 tidal volume (VT) 15 mL/kg and positive end-expiratory pressure = 5 cm H2O
Gross appearance: Using bronchoscopy
Donor and recipients must be size-matched anatomically (by chest x-ray), physiologically (by total lung capacity), or both.
Донори серця
Almost all donated hearts come from brain-dead donors, who are usually required to be < 60 years and have normal cardiac function and no history of coronary artery disease or other heart disorders. Donor and recipient must have compatible ABO blood types, and appropriate heart size is critical. Trials have successfully used an in vitro pump system that modifies cell metabolism in the donor heart to help preserve the explanted hearts during transport, and thus prolong transplant viability > 4 to 6 hours and greatly improve cardiac function after reperfusion. Recently, a few procedures have been done using grafts from donors after cardiac death; these grafts all are done using the in vitro pump before implantation.
Терміни направлення на трансплантацію
Timing of referral for transplantation should be determined by factors such as
Degree of obstructive defect: Forced expiratory volume in 1 second (FEV1) < 25 to 30% predicted in patients with COPD, alpha-1 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
Progression rate of clinical, radiographic, or physiologic disease
Процедура
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.
Трансплантація однієї легені
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 of single lung transplantation 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.
Трансплантація двох легень
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 lung tissue in the recipient.
The disadvantage is poor healing of the tracheal anastomosis.
Трансплантація серця і легенів
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.
Імуносупресія
A common 3-drug posttransplant immunosuppression regimen combines
A calcineurin inhibitor (cyclosporine or tacrolimus)
A purine metabolism inhibitor (azathioprine or mycophenolate)
Methylprednisolone or another corticosteroid
First, patients are given high doses perioperatively; methylprednisolone IV is often given intraoperatively before reperfusion of the transplanted lung. Lower doses are given for maintenance thereafter (see table Immunosuppressants Used to Treat Transplant Rejection).
Antithymocyte globulin (ATG) or alemtuzumab is often given as induction therapy. These drugs can also minimize immunosuppressive therapy posttransplantation. Often, tacrolimus monotherapy is sufficient for maintenance therapy if induction therapy is given.
Corticosteroids may be omitted to facilitate healing of the bronchial anastomosis; higher doses of other drugs (eg, cyclosporine, azathioprine) are then used instead. Immunosuppressants are continued indefinitely.
Complications of Lung and Heart-Lung Transplantation
(See also Posttransplantation Complications.)
Відторгнення
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 (arterial oxygen saturation), and a decrease in FEV1 by > 10 to 15% (see table Manifestations of Lung Transplant Rejection by Category).
Hyperacute rejection must be distinguished from early graft dysfunction caused by ischemic injury during the transplantation procedure, and acute rejection must be differentiated from infection. Interstitial infiltrate, seen on chest x-rays, is typical in patients with accelerated or acute rejection. Rejection is usually diagnosed by bronchoscopy, including bronchoscopic transbronchial biopsy. If rejection has occurred, biopsy shows perivascular lymphocytic infiltration in small vessels; polymorphonuclear leukocytes in alveolar infiltrates and infectious pathogens suggest infection. IV corticosteroids are usually effective for hyperacute, accelerated, or acute rejection. Treatment of recurrent or resistant cases varies and includes higher corticosteroid doses, aerosolized cyclosporine, and ATG.
Chronic rejection develops after > 1 year in up to 50% of patients; it manifests as obliterative bronchiolitis or, less commonly, as atherosclerosis. Acute rejection may increase risk of chronic rejection. Patients with obliterative bronchiolitis present with cough, dyspnea, and decreased FEF25-75% (forced expiratory flow during expiration of 25 to 75% of the forced vital capacity) or FEV1, with or without physical and radiographic manifestations . Differential diagnosis includes pneumonia. Diagnosis is usually by bronchoscopy with biopsy. No treatment has proved effective, but options include corticosteroids, ATG, inhaled cyclosporine, and retransplantation.
Прояви відторгнення трансплантата легенів за категоріями
Rejection Category | Manifestations |
|---|---|
Hyperacute | Poor oxygenation, fever, cough, dyspnea, decreased FEV1 |
Accelerated | Poor oxygenation, fever, cough, dyspnea, infiltrate seen on chest x-ray, decreased FEV1 |
Acute | Same as those for accelerated Interstitial perivascular infiltrate (detected by transbronchial biopsy) |
Chronic | Obliterative bronchiolitis, cough, dyspnea |
FEV1 = forced expiratory volume in 1 second. | |
Хірургічні ускладнення
The most common surgical complications are
Poor healing of the bronchial or tracheal anastomosis (diagnosed when mediastinal air or pneumothorax is detected)
Infection
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; gastrointestinal dysmotility, caused by damage to the thoracic vagus nerve; and pneumothorax. Supraventricular arrhythmias develop in some patients, probably because of conduction changes caused by pulmonary vein-atrial suturing.
Prognosis for Lung and Heart-Lung Transplantation
Patient survival rates are
At 1 year: 84% with living-donor grafts and 83% with deceased-donor grafts
At 5 years: 34% with living-donor grafts and 46% with deceased-donor grafts
Mortality rate is higher for patients with primary pulmonary hypertension, idiopathic pulmonary fibrosis, or sarcoidosis and lower for those with COPD or alpha-1 antitrypsin deficiency. Mortality rate is higher for single lung transplantation than for double.
Most common causes of death are
Within 1 month: Primary graft failure, ischemia and reperfusion injury, and infection (eg, pneumonia) excluding cytomegalovirus
Between 1 month and 1 year: Infection
After 1 year: 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 original disorder, particularly some interstitial lung disorders, recurs. Such recurrence impairs exercise capacity slightly because of a hyperventilatory response.
With heart-lung transplantation, overall survival rate at 1 year is about 80% for patients and grafts.
