- Email: [email protected]
LUNG TRANSPLANTATION
CARDIOTHORACIC AND VASCULAR SURGERY
0039-6109/98 $8.00
+ .OO
LUNG TRANSPLANTATION P. Michael McFadden, MD, and W. Brooks Emory, MD
Lung transplantation has been successful in the treatment of a variety of terminal restrictive, obstructive, and suppurative end-stage lung diseases, the management of which has until recently been only palliative at best. Experimental investigation in transplantation of the lung in animals, conducted in the 1940s, led to the first successful lung transplant in a dog by Metras12of France in 1950. Further experimental studies by Webb and Hardy in the United States led to the first canine heart-lung transplant in the late 195Os.I7These same investigators subsequently performed the first human lung transplant in 1963 at the University of Mississippi on a 58-year-old male with carcinoma of the lung7 The patient survived only 18 days, but this event ushered in a new enthusiasm for clinical lung transplantation. Human heart-lung transplantation was attempted by Cooley et a12 in 1968 and Lillehi9 in 1969. Although these initial efforts at lung and heart-lung transplantation were exciting technical accomplishments, none of the recipients survived long term. Immunosuppressive regimens in the 1960s and 1970s)largely consisting of azathioprine and high-dose steroids, predisposed to problems with bronchial healing: Deaths from infection frequently resulted from bronchial anastomotic leaks and dehiscence. Early enthusiasm for lung transplantation rapidly waned as unacceptable mortality from rejection, infection, and airway complications presented major obstacles to successful transplantation. The introduction of a new and more effective immunosuppressive agent, cyclosporine, and the first successful human heart-lung transplant
From the Department of Surgery (PMM) and the Department of Medicine (WBE), Ochsner Clinic and Tulane University School of Medicine; and the Department of Medicine, Louisiana State University School of Medicine (WBE), New Orleans, Louisiana
SURGICAL CLINICS OF NORTH AMERICA VOLUME 78 NUMBER 5 * OCTOBER 1998
749
750
McFADDEN & EMORY
performed by Reitz and Shumway and their team'* at Stanford University in 1981, catalyzed a 'resurgence of interest in both heart and lung transplantation (Fig. 1). Adoption of triple-drug immunosuppressive regimens that included cyclosporine, azathioprine, and lower steroid dosage reduced the incidence and severity of rejection and minimized the deleterious side effects of the drugs. Significant improvement in bronchial healing was observed with lower steroid doses. Although the first human lung transplant, attempted in 1963, preceded the first successful heart transplant in 1967 by 4 years, the lung is the last of the solid organs to be successfully transplanted. The first successful single- and double-lung transplants were performed in 1987 and 1989 by a team led by Cooper at the University of T ~ r o n t o . ~ , ~ Surgical technique to preserve the vascularity of the bronchial anastomosis, such as omental wrapping as proposed by Cooper and his group in Toronto,lo,l 3 telescoping of the bronchial anastomosis as advocated by Veith and Richards,I6 and the use of a vascularized intercostal muscle pedicle wrap as recommended by Fell et a1,6 were attempts to minimize bronchial anastomotic leaks and improve operative survival. The successes we now enjoy in the management of terminal respiratory conditions by the application of lung transplantation must be credited to the ingenuity and efforts of these dedicated experimental and clinical investigators.
Figure 1. Stanford Team, led by NE Shumway and BA Reitz, performing the first successful heart-lung transplant in 1981.
LUNG TRANSPLANTATION
751
INDICATIONS AND SELECTION
A wide variety of end-stage pulmonary parenchymal and pulmonary vascular disorders have been treated with lung or combined heartlung transplantation:
Obstructive lung disease Suppurative Cystic fibrosis Bronchiectasis Nonsuppurative Emphysema-idiopathic Emphysema-alpha,-antitrypsin deficiency Bronchopulmonary dysplasia Obliterative bronchiolitis Post-transplant Viral, fume, and drug-induced Restrictive lung disease Idiopathic pulmonary fibrosis Sarcoidosis Asbestosis Eosinophilic granuloma (histiocytosis X) Bronchiolitis obliterans organizing pneumonia (BOOP) Desquamative interstitial pneumonitis Lymphangioleiomyomatosis(LAM) Silicosis Pulmonary fibrosis with manageable connective tissue diseases Pulmonary vascular disease Primary pulmonary hypertension Eisenmenger’s syndrome (atrial septal defect, ventricular septal defect, patent ductus arteriosus, truncus arteriosus, other complex anomalies) Pulmonary hypertension secondary to thromboembolic disease Cardiomyopathy with pulmonary hypertension The majority of these procedures (greater than 90%) have been performed in patients with emphysema, idiopathic pulmonary fibrosis, cystic fibrosis, brochiectasis, primary pulmonary hypertension, and pulmonary hypertension secondary to congenital heart disease (Eisenmenger’s syndrome). Patients who are selected for lung transplantation suffer from a severe pulmonary parenchymal or vascular disorder with no potential for reversibility or alternative therapy. These patients generally have a life expectancy of less than 18 to 24 months and are classified as functional New York Heart Association class I11 or IV. Because of poor outcomes in patients with end-stage cardiopulmonary disease requiring mechanical ventilatory support, lung transplantation is generally not indicated for patients on a ventilator. The patient’s age is a consideration in the decision for transplantation. In our center patients less than 65
752
McFADDEN & EMORY
years of age may be considered for single lung transplantation, those less than 55 years for bilateral sequential lung transplantation, and those less than 45 years for heart-lung transplantation. Presence of coronary artery disease is considered a contraindication to lung transplantation, although we have successfully transplanted five patients with singlevessel coronary artery disease upon whom we performed coronary angioplasty or stenting. Severe emotional, financial, and physical stresses involved in the procedure and major psychosocial or family support problems may exclude patients from transplant consideration. Previous pleurodesis, pleurectomy, and lobectomy result in pleural adhesions and predispose the transplant recipient to the potential for bleeding at the time of native lung resection and increase the risk for anticoagulation. Patients who have had previous thoracic procedures require careful individual consideration prior to transplantation. Absolute contraindications to heart-lung or lung transplantation are a consequence of a number of factors: Age greater than 65 for single lung and age greater than 45 for heartlung transplantation; for bilateral sequential lung transplantation, may be up to age 55 Significant systemic or multisystem disease Active or extrapulmonary infection Significant hepatic disease (bilirubin >3.0 mg/dL) Significant renal disease (24-hour creatinine clearance <50 mL/ min). Exception is in patients with severe pulmonary hypertension and subsequent poor renal perfusion. A creatinine clearance down to 40 mL/min may be acceptable once intrinsic renal disease has been excluded. Cachexia or obesity Corticosteroid therapy greater than 20 mg/day Current cigarette smoking Chronic psychiatric illness Drug or alcohol abuse Severe osteoporosis Special selection considerations must be reviewed for patients who have cystic fibrosis: Indications Decline in physical status such that the life expectancy is between 1 and 2 years, suggested by: 1. Deteriorating pulmonary function (FEV, <30% of predicted) 2. Increasing hypoxia and hypercapnia 3. Increasing nunber of days of hospitalization for pulmonary infections 4. Decrease in ability to perform the activities of daily living 5. Recurring life-threatening pulmonary complications, such as pneumothorax or hemoptysis 6. Ability and desire to undertake a major medical endeavor
LUNG TRANSPLANTATION
753
Contraindications Absolute 1. Pan-resistant respiratory flora 2. Poor renal function (creatinine clearance <50 mL/min) 3. Active viral infection (HIV, hepatitis) 4. Poor hepatic function (bilirubin >3.0 mg/dL) 5. Major nonpulmonary complications (portal hypertension, esophageal varices, other systemic diseases) 6. Lack of adequate social support and/or history of poor compliance with medical regimen Relative 1. Cachexia (weight <70% ideal for height) 2. Evidence of recurrent Aspergillus or fungal colonization of the sinuses or respiratory tract 3. Poorly controlled diabetes mellitus 4. Previous major cardiothoracic surgery or pleurodesis (caseby-case basis) 5. Mechanical ventilation for more than 3 days (case-by-case basis) An excellent overview of lung transplantation has recently been provided by Tru10ck.l~ The selection process is a multidisciplinary approach that involves the surgeon, pulmonologist, psychiatrist, infectious disease physician, transplant nurse coordinators, and social worker before a decision is made to list a patient for transplantation. The selection process is rigorous in order to ensure that the best candidates are given the opportunity to undergo transplantation. Because there is a great need for organs, the selection process must be as objective as possible. Approximately 8% to 10% of patients referred for consideration for lung transplantation are ultimately listed as candidates. Some patients become candidates for lung transplantation but have not yet reached the “transplant window.” These patients undergo close observation and follow-up and are listed once they become ill enough for transplantation. Surgical options for lung transplantation include combined heartlung, single lung, and bilateral sequential lung transplantation. Following is a list of the major indications for each: Bilateral sequential lung transplantation Cystic fibrosis/bronchiectasis Emphysema/chronic obstructive pulmonary disease Pulmonary hypertension without significant right heart dysfunction Usually any potential candidate less than 55 years of age Single lung transplantation Pulmonary fibrosis Emphysema Bronchopulmonary dysplasia Obliterative bronchiolitis
754
McFADDEN & EMORY
Heart-lung transplantation Severe Eisenmenger 's complex with right ventricular decompensation or uncorrectable congenital heart disease (e.g., truncus arteriosus, large ventricular septa1 defect) Severe primary pulmonary hypertension with right ventricular decompensation and/or cardiomyopathy Intercurrent cardiac and pulmonary disease In general, the indications for bilateral sequential lung and combined heart-lung transplant have remained fairly firm, whereas those for single lung transplant have expanded to include conditions previously treated medically or by other surgical options. Heart-lung transplantation is indicated for patients with severe Eisenmenger 's complex or severe primary pulmonary hypertension who suffer with right ventricular decompensation and/or cardiomyopathy and for patients with concomitant end-stage cardiac and pulmonary disease. Bilateral sequential lung transplantation is indicated for patients with suppurative lung conditions such as cystic fibrosis and/or bronchiectasis. It has also been applied in selected patients with emphysema and pulmonary hypertension who have relatively normal cardiac function (Table 1). Single lung transplantation is used for treatment of patients with pulmonary fibrosis, pulmonary emphysema, alpha,-antitrypsin deficiency, bronchial pulmonary dysplasia, sarcoidosis, and obliterative bronchiolitis. Idiopathic pulmonary fibrosis and other fibrotic lung conditions were once the most common conditions treated with lung transplantation, but currently the most common indication is emphysema. The initial concern that a mediastinal shift and crowding of the transplanted lung would result in ventilation-perfusion abnormalities in emphysema patients having a single lung transplant has not proved to be clinically relevant. Consequently, severe end-stage pulmonary emphyTable 1. INDICATION FOR LUNG TRANSPLANTATION BY DIAGNOSIS, 1990-1997 (N = 75) Emphysema Chronic obstructive pulmonary disease a,-Antitrypsin deficiency Cystic fibrosis Pulmonary fibrosis Idiopathic Sarcoidosis Scleroderma Hodgkin's lymphoma Silicosis Pulmonary hypertension Primary Secondary Bronchiectasis Bronchiolitis obliterans
24 23 1 22 20
13 4 1 1 1 6
1 5 2 1
LUNG TRANSPLANTATION
755
sema has become the most common indication for single lung transplantation. A single lung transplant is the simplest to perform technically and rarely requires the use of cardiopulmonary bypass. Enthusiasm and expanded indications for single lung transplantation have largely been driven by a scarcity of donor organs. Once a lung donor has been identified, the organ procurement team managing the donor provides the transplant surgeon and pulmonologist with vital information about the donor’s medical history, current status, and lung function to assist them in their decision to accept the organ for transplantation. Important considerations include blood type, size of the donor, mechanism of death, chest film status, distance from the transplant center, character of the bronchial secretions, sputum Gram stain results, hemodynamic status, presence of infection, lung dimensions, and oxygenation status. Lungs that are otherwise satisfactory and provide an arterial oxygen concentration greater than 350 mm Hg on a 100% oxygen ventilatory challenge are generally acceptable. DONOR OPERATION
The lung harvest is usually conducted in conjunction with multiorgan retrieval and requires appropriate evaluation, preservation, and transport of the lung for transplantation. Bronchoscopy is routinely performed by the lung procurement team to evaluate the donor airways and assess bronchial secretions. The heart and lungs are approached through a median sternotomy incision. The lungs are inspected for the presence of pulmonary pathology and are manipulated sparingly during the assessment and harvest to avoid lung injury and to maintain maximal functional and structural integrity. The transplant institution is briefed on the status of the donor and given an estimated time of arrival of the lung for transplantation. The lungs and heart are harvested simultaneously. Cannulas are placed for administration of cardiac and pulmonary preservation solutions. Once preparations for the harvest of abdominal and thoracic organs are complete, the donor is systemically anticoagulated and prostaglandin E, is infused into the pulmonary artery to facilitate pulmonary vasodilation. Coincident with cardioplegia administration, a rapid infusion of 4°C lung preservation solution (2 L of Eurocollins solution and 2 L of University of Washington solution) is infused by large-bore catheter into the pulmonary artery. The tip of the left atrial appendage is amputated to allow egress of blood and preservative from the pulmonary circulation. Gentle ventilation is continued to prevent atelectasis and to promote even distribution of preservation solution. The lungs are also cooled topically with iced 4°C saline solution. The lungs and heart are harvested after completion of the preservation infusion. A ”button” of the posterior left atrial wall containing the four pulmonary veins is left in situ as the heart is harvested. The pulmonary artery is divided proximal to its bifurcation. The supracarinal
756
McFADDEN & EMORY
trachea is divided between rows of staples. The lung block is removed and the left atrial cuff and pulmonary arteries are divided. The bronchi are stapled and divided near the carina to provide maximum length. The right and left lungs are stored separately in sterile iced solution and placed in a cooler for transport. If a heart-lung bloc is to be harvested, the pulmonary artery and venous connections to the heart are maintained. The trachea is stapled as previously described, and the heart-lung graft is taken en bloc. The lungs are transported to the recipient facility without delay. A complete operative note is dictated, noting pertinent observations or events that may later be correlated with graft function and patient outcome. RECIPIENT OPERATION
Patients listed for lung transplantation are typically outpatients and must be called to the hospital when a suitable donor has been identified. A preoperative assessment of the current status of the recipient is performed by the transplant team. The recipient is prepared for surgery and monitored with radial and femoral arterial lines, central venous and urinary catheters, and a pulmonary artery catheter. A double-lumen endotracheal tube is used to allow for differential lung ventilation. Proper position and function of the endotracheal tube are confirmed by auscultation and fiberoptic bronchoscopy once the patient has been positioned for the operation. In single lung transplantation, the patient is placed in a standard lateral thoracotomy position. Exposure and preparation of the groin on the ipsilateral side allow access to the femoral vessels should cardiopulmonary bypass be required. The operation may commence once the transplant surgeon is assured that the donor lung is acceptable. The chest is entered through a posterior lateral thoracotomy incision. The pleural space, lung, and mediastinum are inspected for abnormalities. Contralateral single lung ventilation is initiated and the lung to be removed is decompressed. Should hypoxemia develop because of shunting through the atelectatic lung, intermittent ventilation or temporary occlusion of the pulmonary artery may be performed to resolve the ventilation-perfusion mismatch. The pulmonary artery and veins are approached intrapericardially posterior to the phrenic nerve. Care is taken to avoid devascularization when exposing the bronchus. Prior to removal of the lung, the patient is heparinized and the pulmonary artery is temporarily occluded. The pulmonary artery pressure, right ventricular hemodynamics, and oxygen saturations are closely monitored to determine whether ventilation and perfusion of the contralateral lung are sufficient to effect adequate oxygenation and allow normal hemodynamics during the procedure. If hypoxemia or elevated right heart pressures are observed, the initiation of inotropic drugs such as nitroprusside and prostaglandin El may be necessary. Patients who continue to demonstrate arterial oxygen desaturation, elevated right
LUNG TRANSPLANTATION
757
heart pressures, or systemic arterial hypotension are placed on femoralfemoral cardiopulmonary bypass. It is preferable in most instances to employ partial cardiopulmonary bypass and moderate hypothermia to allow the heart to beat and maintain a pulsatile pressure. Cardiopulmonary bypass is discontinued when the donor lung has been implanted and proved functional. On arrival of the donor lung, the pulmonary artery and superior and inferior pulmonary veins are stapled and divided. The bronchus is transected sharply. The bronchial arteries are controlled with either suture or electric cautery. The lung is removed and cultures of the bronchial secretions are obtained to assist in postoperative antibiotic therapy. The donor lung is then prepared for implantation. Intraoperative cultures are also taken from the donor bronchus. Topical cooling of the donor lung is continued throughout the procedure with iced laparotomy packs. Anastomoses are performed between the pulmonary veins and the recipient left atrial cuff, the bronchi, and the pulmonary arteries (Fig. 2).l The donor bronchus is trimmed as short as possible. Prior to completion of the arterial suture line, the left atrial clamp is released to allow retrograde venting of air and preservation solution from the lungs. This maneuver avoids flushing of potassium and prostaglandin El into
Figure 2. Surgical technique for single lung transplantation. Ao = aorta; LA = left atrium; LMB = left main bronchus; FA = pulmonary artery; FV = pulmonary vein. (From Calhoon JH, Trinkle, et al, J Thorac Cardiovasc Surg 101:816-825, 1991; with permission.)
758
McFADDEN & EMORY
the systemic circulation, which may result in hypotension and bradycardia. The vascular anastomoses are examined for bleeding, and the bronchial anastomosis is inspected for air leak as the lung is inflated. Bronchial reinforcement is rarely necessary but may be accomplished with either an omental or vascularized intercostal muscle pedicle wrap. Fiberoptic bronchoscopy is performed prior to closure of the chest to inspect the bronchial anastomosis for patency, angulation, or torsion. In patients who require cardiopulmonary bypass, arterial and venous cannulation is performed after systemic heparin anticoagulation. When transfusion is required during the transplant operation, it is accomplished with cytomegalic virus-free blood products and leukocyte filters. A bilateral sequential lung transplant is performed in a supine position via a bilateral transverse thoracotomy in the fourth intercostal space. The sternum is divided transversely, and the internal mammary arteries are suture-ligated. Removal of the recipient lungs and implantation of the donor lungs are carried out in a manner similar to that described for a single lung transplantation. If a significant difference in lung function exists between the right and left lungs on preoperative ventilation/perfusion lung scan, the less functional lung is transplanted first. Once adequate function of the new lung is assured, the second lung is transplanted. An operative note is dictated in a timely manner and should include details of the operation such as organ ischemic time, the hemodynamic response to pulmonary artery clamping, and related intraoperative physiology, transfusion, and fluid requirements as well as immediate postimplantation physiology. OCHSNER EXPERIENCE
The lung transplant program at the Ochsner Clinic began in 1990 with Louisiana’s first successful heart-lung transplant performed on a 39-year-old man with pulmonary hypertension at Ochsner Foundation Hospital in New Orleans.11Since that time the lung transplant program has grown steadily. Seventy-five lung transplants were performed during the period between November 1990 and January 1998 (Fig. 3). Lung transplantation was indicated for a variety of end-stage pulmonary conditions, including emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, sarcoidosis, and bronchiolitis obliterans (Fig. 4). A relatively large portion of our transplants have been “performed for cystic fibrosis, which accounts for the greater frequency of bilateral sequential lung transplants at our center. As in most other centers, emphysema is the predominant indication for lung transplantation. The overall 1-year and 3-year lung transplant survivals (KaplanMeier) at the Ochsner Clinic are 78% and 52%, respectively. The 1-year and 3-year actuarial survivals for our patients who were discharged
LUNG TRANSPLANTATION
759
25
cn 20
c.
C
a, .-c
2
15
v-
0 L
2
10
E
3
z
5
0 1990 1991
1992 1993
1994 1995
1996 1997
Figure 3. Ochsner lung transplant eight-year experience by volume and transplant type. Solid bar = heart-lung (1); hatched bar = bilateral sequential (38); open bar = single (36).
from the hospital were 93% and 63'7'0, respectively. These survival results compare favorably with those reported by other programs in the United States5 Early mortality (death 5 90 days) resulted from surgical complications (33%), sepsis (20%), organ failure (27%), and graft failure (20%). Late mortalities were the result of infection in only two patients; the remainder succumbed to bronchiolitis obliterans. None of the deaths resulted from acute rejection. Triple-drug immunosuppressive therapy that includes prednisone, azathioprine, and cyclosporine is our regimen of choice. However, patients with suppurative lung diseases such as cystic fibrosis and bronchiectasis first receive polyclonal induction therapy with antithrombocyte
Figure 4. Indications for lung transplantation at Ochsner by diagnoses.
760
McFADDEN & EMORY
gamma globulin. Monoclonal therapy with OKT, has been reserved for patients with refractory rejection. This protocol has been successful in our hands, as we have experienced no early or late deaths from acute rejection. Cefazolin has been used for surgical infection prophylaxis in our patients unless preoperative sputum cultures have indicated another antibiotic based on sensitivities. General prophylaxis has included nystatin for oral Candida, acyclovir for herpes, trimethoprim-sulfamethoxazole for Pneumocystis carinii, and ganciclovir for cytomegalovirus infection. We believe that tight immunosuppressive control and diligent antibiotic prophylaxis not only lower rejection and infection rates but may also be of benefit in reducing insults to the transplanted lung, which may lead to chronic allograft dysfunction due to bronchiolitis obliterans. A recent review of our experience has indicated that bronchial complications are the major surgical morbidity following lung transplantation. A retrospective review of 65 consecutive patients transplanted at our institution between June 1991 and October 1997 was conducted. The analysis was limited to 54 patients (31 females, 23 males) who survived more than 14 days. Nonsurvivors had no bronchial complications. Seventeen complications (stenoses 13, dehiscence 2, bronchial arterial fistula 1, airway angulation 1) occurred in 15 patients with 79 airways at risk. The incidence of bronchial complications in this cohort was 21.570, which is consistent with that reported by others.* Median follow-up time was 450 days (range 22-228 days). The incidence of airway complications in single lung transplantation was 17.4% (5/29) and in bilateral lung transplantation it was 24% (12/50), which was not significantly different ( P = 0.57). Airway complications developed at a mean of 54 days following transplantation, with a range of 10 to 185 days. The preoperative diagnosis, gender, age, rejection, cytomegalovirus status, side of transplant, organ ischemic time, single versus bilateral transplant, use of cardiopulmonary bypass, and immunosuppressive regimen did not statistically influence the incidence of airway complications. Thirteen patients required endobronchial intervention (bronchoscopy 10, dilatation 13, stenting 7) or open surgical intervention (pneumonectomy 1, bronchial shortening 1, bronchoplasty 1) to manage the airway complications after transplantation. Two complications, a bronchoarterial fistula and a bronchial anastomotic infection with Aspergillus septicemia, were fatal. Two asymptomatic patients required no intervention. Survival in patients with and without airway complications was comparable, 84.8% versus 84.2% at 1 year and 56.6% versus 61% at 2 years, respectively. In these patients the incidence of surgical airway complications was similar for both single and bilateral lung did not influence operative morfor bronchial complications resulted in for patients with and without complications.
LUNG TRANSPLANTATION
761
SUMMARY
Although we have not yet obtained the survival results that have been observed in heart and renal transplantation, the survival rate in lung transplantation is improving. Because the lung is the only organ that is continuously exposed to the environment after transplantation, infection continues to be the major cause of early and late morbidity and mortality. Bronchiolitis obliterans, the second most common cause of late morbidity and mortality, is a progressive and currently untreatable condition resulting in lung dysfunction. The cause of this condition after transplantation is likely multifactorial and related to processes that result in allograft lung injury, such as rejection, bacterial infection, and cytomegalovirus infection. Future improvement in intermediate and longterm survival after lung transplantation will largely depend on prevention and long-term control of infection and subclinical rejection.
References 1. Calhoon JH, Grover FL, Gibbons WJ, et al: Single lung transplantation: Alternative indications and technique. J Thorac Cardiovasc Surg 101:816-825,1991 2. Cooley DA, Bloodwell RD, Hallman GL, et al: Organ transplantation for advanced cardiopulmonary disease. Ann Thorac Surg 8:3046, 1969 3. Cooper JD, Pearson GA, Grossman R, et al: Double-lung transplant for advanced chronic obstructive lung disease. Am Rev Resp Dis 139:303-307,1989 4. Cooper JD, Pearson FG, Patterson GA, et al: Technique of successful lung transplantation in humans. J Thorac Cardiovasc Surg 93:173-181,1987 5. Division of Transplantation, Bureau of Health Resources Development: 1995 Annual Report of the US Scientific Registry for Transplant Recipients and the Organ Procurement and Transplantation Network-Transplant Data: 1988-1994. Rockville, MD, US Department of Health and Human Services, 1995 6. Fell SC, Mollenkof FP, Montefusco CM, et al: Revascularization of ischemic bronchial anastomoses by an intercostal pedicle flap. J Thorac Cardiovasc Surg 90172-178, 1985 7. Hardy JD, Webb WR, Dolton ML Jr, et al: Lung transplantation in man: Report of the initial case. JAMA 186:1065-1074, 1963 8. Kshettry VR, Kroshus TJ, Hertz MI, et al: Early and late airway complications after lung transplantation: Incidence and management. Ann Thorac Surg 63:1576-1583, 1997 9. Lillehei CW: Discussion of Wildevuur CRH, Benefield J R A review of 23 human lung transplantations by 20 surgeons. Ann Thorac Surg 9:489-515, 1970 10. Lima 0, Goldberg M, Peters WJ, et al: Bronchial omentopexy in canine lung transplantation. J Thorac Cardiovasc Surg 83(3):418421, 1982 11. McFadden PM, Ochsner JL, Emory WB, et al: Lung transplantation in Louisiana: Report of the first 20 lung transplants performed in the state. J LA State Med SOC 1473742, 1995 12. Metras H: Note preliminaire sur la greffe totale du poumon chez le chin. Compt Rend Acad Sc 2301176-1177, 1950 13. Morgan E, Lima 0, Goldberg M, et al: Successful revascularization of totally ischemic bronchial autografts with omental pedicle flaps in dogs. J Thorac Cardiovasc Surg 84:204-210, 1982 14. Reitz BA, Burton NA, Jamieson SW, et al: Heart and lung transplantation: Autotransplantation and allotransplantation in primates with extended survival. J Thorac Cardiovasc Surg 80:360-372, 1980
762
McFADDEN & EMORY
15. Trulock El': Lung transplantation. Am J Respir Crit Care Med 155:789-818, 1997 16. Veith FJ, Richards K Improved technique for canine lung transplantation. Ann Surg 171:553-558, 1970 17. Webb WR, Howard HS Cardiopulmonary transplantation. Surg Forum 8:313, 1957
Address reprint requests to P. Michael McFadden, MD Division of Cardiothoracic Surgery Department of Surgery Ochsner Clinic 1514 Jefferson Highway New Orleans, LA 70121
0039-6109/98 $8.00
+ .OO
LUNG TRANSPLANTATION P. Michael McFadden, MD, and W. Brooks Emory, MD
Lung transplantation has been successful in the treatment of a variety of terminal restrictive, obstructive, and suppurative end-stage lung diseases, the management of which has until recently been only palliative at best. Experimental investigation in transplantation of the lung in animals, conducted in the 1940s, led to the first successful lung transplant in a dog by Metras12of France in 1950. Further experimental studies by Webb and Hardy in the United States led to the first canine heart-lung transplant in the late 195Os.I7These same investigators subsequently performed the first human lung transplant in 1963 at the University of Mississippi on a 58-year-old male with carcinoma of the lung7 The patient survived only 18 days, but this event ushered in a new enthusiasm for clinical lung transplantation. Human heart-lung transplantation was attempted by Cooley et a12 in 1968 and Lillehi9 in 1969. Although these initial efforts at lung and heart-lung transplantation were exciting technical accomplishments, none of the recipients survived long term. Immunosuppressive regimens in the 1960s and 1970s)largely consisting of azathioprine and high-dose steroids, predisposed to problems with bronchial healing: Deaths from infection frequently resulted from bronchial anastomotic leaks and dehiscence. Early enthusiasm for lung transplantation rapidly waned as unacceptable mortality from rejection, infection, and airway complications presented major obstacles to successful transplantation. The introduction of a new and more effective immunosuppressive agent, cyclosporine, and the first successful human heart-lung transplant
From the Department of Surgery (PMM) and the Department of Medicine (WBE), Ochsner Clinic and Tulane University School of Medicine; and the Department of Medicine, Louisiana State University School of Medicine (WBE), New Orleans, Louisiana
SURGICAL CLINICS OF NORTH AMERICA VOLUME 78 NUMBER 5 * OCTOBER 1998
749
750
McFADDEN & EMORY
performed by Reitz and Shumway and their team'* at Stanford University in 1981, catalyzed a 'resurgence of interest in both heart and lung transplantation (Fig. 1). Adoption of triple-drug immunosuppressive regimens that included cyclosporine, azathioprine, and lower steroid dosage reduced the incidence and severity of rejection and minimized the deleterious side effects of the drugs. Significant improvement in bronchial healing was observed with lower steroid doses. Although the first human lung transplant, attempted in 1963, preceded the first successful heart transplant in 1967 by 4 years, the lung is the last of the solid organs to be successfully transplanted. The first successful single- and double-lung transplants were performed in 1987 and 1989 by a team led by Cooper at the University of T ~ r o n t o . ~ , ~ Surgical technique to preserve the vascularity of the bronchial anastomosis, such as omental wrapping as proposed by Cooper and his group in Toronto,lo,l 3 telescoping of the bronchial anastomosis as advocated by Veith and Richards,I6 and the use of a vascularized intercostal muscle pedicle wrap as recommended by Fell et a1,6 were attempts to minimize bronchial anastomotic leaks and improve operative survival. The successes we now enjoy in the management of terminal respiratory conditions by the application of lung transplantation must be credited to the ingenuity and efforts of these dedicated experimental and clinical investigators.
Figure 1. Stanford Team, led by NE Shumway and BA Reitz, performing the first successful heart-lung transplant in 1981.
LUNG TRANSPLANTATION
751
INDICATIONS AND SELECTION
A wide variety of end-stage pulmonary parenchymal and pulmonary vascular disorders have been treated with lung or combined heartlung transplantation:
Obstructive lung disease Suppurative Cystic fibrosis Bronchiectasis Nonsuppurative Emphysema-idiopathic Emphysema-alpha,-antitrypsin deficiency Bronchopulmonary dysplasia Obliterative bronchiolitis Post-transplant Viral, fume, and drug-induced Restrictive lung disease Idiopathic pulmonary fibrosis Sarcoidosis Asbestosis Eosinophilic granuloma (histiocytosis X) Bronchiolitis obliterans organizing pneumonia (BOOP) Desquamative interstitial pneumonitis Lymphangioleiomyomatosis(LAM) Silicosis Pulmonary fibrosis with manageable connective tissue diseases Pulmonary vascular disease Primary pulmonary hypertension Eisenmenger’s syndrome (atrial septal defect, ventricular septal defect, patent ductus arteriosus, truncus arteriosus, other complex anomalies) Pulmonary hypertension secondary to thromboembolic disease Cardiomyopathy with pulmonary hypertension The majority of these procedures (greater than 90%) have been performed in patients with emphysema, idiopathic pulmonary fibrosis, cystic fibrosis, brochiectasis, primary pulmonary hypertension, and pulmonary hypertension secondary to congenital heart disease (Eisenmenger’s syndrome). Patients who are selected for lung transplantation suffer from a severe pulmonary parenchymal or vascular disorder with no potential for reversibility or alternative therapy. These patients generally have a life expectancy of less than 18 to 24 months and are classified as functional New York Heart Association class I11 or IV. Because of poor outcomes in patients with end-stage cardiopulmonary disease requiring mechanical ventilatory support, lung transplantation is generally not indicated for patients on a ventilator. The patient’s age is a consideration in the decision for transplantation. In our center patients less than 65
752
McFADDEN & EMORY
years of age may be considered for single lung transplantation, those less than 55 years for bilateral sequential lung transplantation, and those less than 45 years for heart-lung transplantation. Presence of coronary artery disease is considered a contraindication to lung transplantation, although we have successfully transplanted five patients with singlevessel coronary artery disease upon whom we performed coronary angioplasty or stenting. Severe emotional, financial, and physical stresses involved in the procedure and major psychosocial or family support problems may exclude patients from transplant consideration. Previous pleurodesis, pleurectomy, and lobectomy result in pleural adhesions and predispose the transplant recipient to the potential for bleeding at the time of native lung resection and increase the risk for anticoagulation. Patients who have had previous thoracic procedures require careful individual consideration prior to transplantation. Absolute contraindications to heart-lung or lung transplantation are a consequence of a number of factors: Age greater than 65 for single lung and age greater than 45 for heartlung transplantation; for bilateral sequential lung transplantation, may be up to age 55 Significant systemic or multisystem disease Active or extrapulmonary infection Significant hepatic disease (bilirubin >3.0 mg/dL) Significant renal disease (24-hour creatinine clearance <50 mL/ min). Exception is in patients with severe pulmonary hypertension and subsequent poor renal perfusion. A creatinine clearance down to 40 mL/min may be acceptable once intrinsic renal disease has been excluded. Cachexia or obesity Corticosteroid therapy greater than 20 mg/day Current cigarette smoking Chronic psychiatric illness Drug or alcohol abuse Severe osteoporosis Special selection considerations must be reviewed for patients who have cystic fibrosis: Indications Decline in physical status such that the life expectancy is between 1 and 2 years, suggested by: 1. Deteriorating pulmonary function (FEV, <30% of predicted) 2. Increasing hypoxia and hypercapnia 3. Increasing nunber of days of hospitalization for pulmonary infections 4. Decrease in ability to perform the activities of daily living 5. Recurring life-threatening pulmonary complications, such as pneumothorax or hemoptysis 6. Ability and desire to undertake a major medical endeavor
LUNG TRANSPLANTATION
753
Contraindications Absolute 1. Pan-resistant respiratory flora 2. Poor renal function (creatinine clearance <50 mL/min) 3. Active viral infection (HIV, hepatitis) 4. Poor hepatic function (bilirubin >3.0 mg/dL) 5. Major nonpulmonary complications (portal hypertension, esophageal varices, other systemic diseases) 6. Lack of adequate social support and/or history of poor compliance with medical regimen Relative 1. Cachexia (weight <70% ideal for height) 2. Evidence of recurrent Aspergillus or fungal colonization of the sinuses or respiratory tract 3. Poorly controlled diabetes mellitus 4. Previous major cardiothoracic surgery or pleurodesis (caseby-case basis) 5. Mechanical ventilation for more than 3 days (case-by-case basis) An excellent overview of lung transplantation has recently been provided by Tru10ck.l~ The selection process is a multidisciplinary approach that involves the surgeon, pulmonologist, psychiatrist, infectious disease physician, transplant nurse coordinators, and social worker before a decision is made to list a patient for transplantation. The selection process is rigorous in order to ensure that the best candidates are given the opportunity to undergo transplantation. Because there is a great need for organs, the selection process must be as objective as possible. Approximately 8% to 10% of patients referred for consideration for lung transplantation are ultimately listed as candidates. Some patients become candidates for lung transplantation but have not yet reached the “transplant window.” These patients undergo close observation and follow-up and are listed once they become ill enough for transplantation. Surgical options for lung transplantation include combined heartlung, single lung, and bilateral sequential lung transplantation. Following is a list of the major indications for each: Bilateral sequential lung transplantation Cystic fibrosis/bronchiectasis Emphysema/chronic obstructive pulmonary disease Pulmonary hypertension without significant right heart dysfunction Usually any potential candidate less than 55 years of age Single lung transplantation Pulmonary fibrosis Emphysema Bronchopulmonary dysplasia Obliterative bronchiolitis
754
McFADDEN & EMORY
Heart-lung transplantation Severe Eisenmenger 's complex with right ventricular decompensation or uncorrectable congenital heart disease (e.g., truncus arteriosus, large ventricular septa1 defect) Severe primary pulmonary hypertension with right ventricular decompensation and/or cardiomyopathy Intercurrent cardiac and pulmonary disease In general, the indications for bilateral sequential lung and combined heart-lung transplant have remained fairly firm, whereas those for single lung transplant have expanded to include conditions previously treated medically or by other surgical options. Heart-lung transplantation is indicated for patients with severe Eisenmenger 's complex or severe primary pulmonary hypertension who suffer with right ventricular decompensation and/or cardiomyopathy and for patients with concomitant end-stage cardiac and pulmonary disease. Bilateral sequential lung transplantation is indicated for patients with suppurative lung conditions such as cystic fibrosis and/or bronchiectasis. It has also been applied in selected patients with emphysema and pulmonary hypertension who have relatively normal cardiac function (Table 1). Single lung transplantation is used for treatment of patients with pulmonary fibrosis, pulmonary emphysema, alpha,-antitrypsin deficiency, bronchial pulmonary dysplasia, sarcoidosis, and obliterative bronchiolitis. Idiopathic pulmonary fibrosis and other fibrotic lung conditions were once the most common conditions treated with lung transplantation, but currently the most common indication is emphysema. The initial concern that a mediastinal shift and crowding of the transplanted lung would result in ventilation-perfusion abnormalities in emphysema patients having a single lung transplant has not proved to be clinically relevant. Consequently, severe end-stage pulmonary emphyTable 1. INDICATION FOR LUNG TRANSPLANTATION BY DIAGNOSIS, 1990-1997 (N = 75) Emphysema Chronic obstructive pulmonary disease a,-Antitrypsin deficiency Cystic fibrosis Pulmonary fibrosis Idiopathic Sarcoidosis Scleroderma Hodgkin's lymphoma Silicosis Pulmonary hypertension Primary Secondary Bronchiectasis Bronchiolitis obliterans
24 23 1 22 20
13 4 1 1 1 6
1 5 2 1
LUNG TRANSPLANTATION
755
sema has become the most common indication for single lung transplantation. A single lung transplant is the simplest to perform technically and rarely requires the use of cardiopulmonary bypass. Enthusiasm and expanded indications for single lung transplantation have largely been driven by a scarcity of donor organs. Once a lung donor has been identified, the organ procurement team managing the donor provides the transplant surgeon and pulmonologist with vital information about the donor’s medical history, current status, and lung function to assist them in their decision to accept the organ for transplantation. Important considerations include blood type, size of the donor, mechanism of death, chest film status, distance from the transplant center, character of the bronchial secretions, sputum Gram stain results, hemodynamic status, presence of infection, lung dimensions, and oxygenation status. Lungs that are otherwise satisfactory and provide an arterial oxygen concentration greater than 350 mm Hg on a 100% oxygen ventilatory challenge are generally acceptable. DONOR OPERATION
The lung harvest is usually conducted in conjunction with multiorgan retrieval and requires appropriate evaluation, preservation, and transport of the lung for transplantation. Bronchoscopy is routinely performed by the lung procurement team to evaluate the donor airways and assess bronchial secretions. The heart and lungs are approached through a median sternotomy incision. The lungs are inspected for the presence of pulmonary pathology and are manipulated sparingly during the assessment and harvest to avoid lung injury and to maintain maximal functional and structural integrity. The transplant institution is briefed on the status of the donor and given an estimated time of arrival of the lung for transplantation. The lungs and heart are harvested simultaneously. Cannulas are placed for administration of cardiac and pulmonary preservation solutions. Once preparations for the harvest of abdominal and thoracic organs are complete, the donor is systemically anticoagulated and prostaglandin E, is infused into the pulmonary artery to facilitate pulmonary vasodilation. Coincident with cardioplegia administration, a rapid infusion of 4°C lung preservation solution (2 L of Eurocollins solution and 2 L of University of Washington solution) is infused by large-bore catheter into the pulmonary artery. The tip of the left atrial appendage is amputated to allow egress of blood and preservative from the pulmonary circulation. Gentle ventilation is continued to prevent atelectasis and to promote even distribution of preservation solution. The lungs are also cooled topically with iced 4°C saline solution. The lungs and heart are harvested after completion of the preservation infusion. A ”button” of the posterior left atrial wall containing the four pulmonary veins is left in situ as the heart is harvested. The pulmonary artery is divided proximal to its bifurcation. The supracarinal
756
McFADDEN & EMORY
trachea is divided between rows of staples. The lung block is removed and the left atrial cuff and pulmonary arteries are divided. The bronchi are stapled and divided near the carina to provide maximum length. The right and left lungs are stored separately in sterile iced solution and placed in a cooler for transport. If a heart-lung bloc is to be harvested, the pulmonary artery and venous connections to the heart are maintained. The trachea is stapled as previously described, and the heart-lung graft is taken en bloc. The lungs are transported to the recipient facility without delay. A complete operative note is dictated, noting pertinent observations or events that may later be correlated with graft function and patient outcome. RECIPIENT OPERATION
Patients listed for lung transplantation are typically outpatients and must be called to the hospital when a suitable donor has been identified. A preoperative assessment of the current status of the recipient is performed by the transplant team. The recipient is prepared for surgery and monitored with radial and femoral arterial lines, central venous and urinary catheters, and a pulmonary artery catheter. A double-lumen endotracheal tube is used to allow for differential lung ventilation. Proper position and function of the endotracheal tube are confirmed by auscultation and fiberoptic bronchoscopy once the patient has been positioned for the operation. In single lung transplantation, the patient is placed in a standard lateral thoracotomy position. Exposure and preparation of the groin on the ipsilateral side allow access to the femoral vessels should cardiopulmonary bypass be required. The operation may commence once the transplant surgeon is assured that the donor lung is acceptable. The chest is entered through a posterior lateral thoracotomy incision. The pleural space, lung, and mediastinum are inspected for abnormalities. Contralateral single lung ventilation is initiated and the lung to be removed is decompressed. Should hypoxemia develop because of shunting through the atelectatic lung, intermittent ventilation or temporary occlusion of the pulmonary artery may be performed to resolve the ventilation-perfusion mismatch. The pulmonary artery and veins are approached intrapericardially posterior to the phrenic nerve. Care is taken to avoid devascularization when exposing the bronchus. Prior to removal of the lung, the patient is heparinized and the pulmonary artery is temporarily occluded. The pulmonary artery pressure, right ventricular hemodynamics, and oxygen saturations are closely monitored to determine whether ventilation and perfusion of the contralateral lung are sufficient to effect adequate oxygenation and allow normal hemodynamics during the procedure. If hypoxemia or elevated right heart pressures are observed, the initiation of inotropic drugs such as nitroprusside and prostaglandin El may be necessary. Patients who continue to demonstrate arterial oxygen desaturation, elevated right
LUNG TRANSPLANTATION
757
heart pressures, or systemic arterial hypotension are placed on femoralfemoral cardiopulmonary bypass. It is preferable in most instances to employ partial cardiopulmonary bypass and moderate hypothermia to allow the heart to beat and maintain a pulsatile pressure. Cardiopulmonary bypass is discontinued when the donor lung has been implanted and proved functional. On arrival of the donor lung, the pulmonary artery and superior and inferior pulmonary veins are stapled and divided. The bronchus is transected sharply. The bronchial arteries are controlled with either suture or electric cautery. The lung is removed and cultures of the bronchial secretions are obtained to assist in postoperative antibiotic therapy. The donor lung is then prepared for implantation. Intraoperative cultures are also taken from the donor bronchus. Topical cooling of the donor lung is continued throughout the procedure with iced laparotomy packs. Anastomoses are performed between the pulmonary veins and the recipient left atrial cuff, the bronchi, and the pulmonary arteries (Fig. 2).l The donor bronchus is trimmed as short as possible. Prior to completion of the arterial suture line, the left atrial clamp is released to allow retrograde venting of air and preservation solution from the lungs. This maneuver avoids flushing of potassium and prostaglandin El into
Figure 2. Surgical technique for single lung transplantation. Ao = aorta; LA = left atrium; LMB = left main bronchus; FA = pulmonary artery; FV = pulmonary vein. (From Calhoon JH, Trinkle, et al, J Thorac Cardiovasc Surg 101:816-825, 1991; with permission.)
758
McFADDEN & EMORY
the systemic circulation, which may result in hypotension and bradycardia. The vascular anastomoses are examined for bleeding, and the bronchial anastomosis is inspected for air leak as the lung is inflated. Bronchial reinforcement is rarely necessary but may be accomplished with either an omental or vascularized intercostal muscle pedicle wrap. Fiberoptic bronchoscopy is performed prior to closure of the chest to inspect the bronchial anastomosis for patency, angulation, or torsion. In patients who require cardiopulmonary bypass, arterial and venous cannulation is performed after systemic heparin anticoagulation. When transfusion is required during the transplant operation, it is accomplished with cytomegalic virus-free blood products and leukocyte filters. A bilateral sequential lung transplant is performed in a supine position via a bilateral transverse thoracotomy in the fourth intercostal space. The sternum is divided transversely, and the internal mammary arteries are suture-ligated. Removal of the recipient lungs and implantation of the donor lungs are carried out in a manner similar to that described for a single lung transplantation. If a significant difference in lung function exists between the right and left lungs on preoperative ventilation/perfusion lung scan, the less functional lung is transplanted first. Once adequate function of the new lung is assured, the second lung is transplanted. An operative note is dictated in a timely manner and should include details of the operation such as organ ischemic time, the hemodynamic response to pulmonary artery clamping, and related intraoperative physiology, transfusion, and fluid requirements as well as immediate postimplantation physiology. OCHSNER EXPERIENCE
The lung transplant program at the Ochsner Clinic began in 1990 with Louisiana’s first successful heart-lung transplant performed on a 39-year-old man with pulmonary hypertension at Ochsner Foundation Hospital in New Orleans.11Since that time the lung transplant program has grown steadily. Seventy-five lung transplants were performed during the period between November 1990 and January 1998 (Fig. 3). Lung transplantation was indicated for a variety of end-stage pulmonary conditions, including emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, sarcoidosis, and bronchiolitis obliterans (Fig. 4). A relatively large portion of our transplants have been “performed for cystic fibrosis, which accounts for the greater frequency of bilateral sequential lung transplants at our center. As in most other centers, emphysema is the predominant indication for lung transplantation. The overall 1-year and 3-year lung transplant survivals (KaplanMeier) at the Ochsner Clinic are 78% and 52%, respectively. The 1-year and 3-year actuarial survivals for our patients who were discharged
LUNG TRANSPLANTATION
759
25
cn 20
c.
C
a, .-c
2
15
v-
0 L
2
10
E
3
z
5
0 1990 1991
1992 1993
1994 1995
1996 1997
Figure 3. Ochsner lung transplant eight-year experience by volume and transplant type. Solid bar = heart-lung (1); hatched bar = bilateral sequential (38); open bar = single (36).
from the hospital were 93% and 63'7'0, respectively. These survival results compare favorably with those reported by other programs in the United States5 Early mortality (death 5 90 days) resulted from surgical complications (33%), sepsis (20%), organ failure (27%), and graft failure (20%). Late mortalities were the result of infection in only two patients; the remainder succumbed to bronchiolitis obliterans. None of the deaths resulted from acute rejection. Triple-drug immunosuppressive therapy that includes prednisone, azathioprine, and cyclosporine is our regimen of choice. However, patients with suppurative lung diseases such as cystic fibrosis and bronchiectasis first receive polyclonal induction therapy with antithrombocyte
Figure 4. Indications for lung transplantation at Ochsner by diagnoses.
760
McFADDEN & EMORY
gamma globulin. Monoclonal therapy with OKT, has been reserved for patients with refractory rejection. This protocol has been successful in our hands, as we have experienced no early or late deaths from acute rejection. Cefazolin has been used for surgical infection prophylaxis in our patients unless preoperative sputum cultures have indicated another antibiotic based on sensitivities. General prophylaxis has included nystatin for oral Candida, acyclovir for herpes, trimethoprim-sulfamethoxazole for Pneumocystis carinii, and ganciclovir for cytomegalovirus infection. We believe that tight immunosuppressive control and diligent antibiotic prophylaxis not only lower rejection and infection rates but may also be of benefit in reducing insults to the transplanted lung, which may lead to chronic allograft dysfunction due to bronchiolitis obliterans. A recent review of our experience has indicated that bronchial complications are the major surgical morbidity following lung transplantation. A retrospective review of 65 consecutive patients transplanted at our institution between June 1991 and October 1997 was conducted. The analysis was limited to 54 patients (31 females, 23 males) who survived more than 14 days. Nonsurvivors had no bronchial complications. Seventeen complications (stenoses 13, dehiscence 2, bronchial arterial fistula 1, airway angulation 1) occurred in 15 patients with 79 airways at risk. The incidence of bronchial complications in this cohort was 21.570, which is consistent with that reported by others.* Median follow-up time was 450 days (range 22-228 days). The incidence of airway complications in single lung transplantation was 17.4% (5/29) and in bilateral lung transplantation it was 24% (12/50), which was not significantly different ( P = 0.57). Airway complications developed at a mean of 54 days following transplantation, with a range of 10 to 185 days. The preoperative diagnosis, gender, age, rejection, cytomegalovirus status, side of transplant, organ ischemic time, single versus bilateral transplant, use of cardiopulmonary bypass, and immunosuppressive regimen did not statistically influence the incidence of airway complications. Thirteen patients required endobronchial intervention (bronchoscopy 10, dilatation 13, stenting 7) or open surgical intervention (pneumonectomy 1, bronchial shortening 1, bronchoplasty 1) to manage the airway complications after transplantation. Two complications, a bronchoarterial fistula and a bronchial anastomotic infection with Aspergillus septicemia, were fatal. Two asymptomatic patients required no intervention. Survival in patients with and without airway complications was comparable, 84.8% versus 84.2% at 1 year and 56.6% versus 61% at 2 years, respectively. In these patients the incidence of surgical airway complications was similar for both single and bilateral lung did not influence operative morfor bronchial complications resulted in for patients with and without complications.
LUNG TRANSPLANTATION
761
SUMMARY
Although we have not yet obtained the survival results that have been observed in heart and renal transplantation, the survival rate in lung transplantation is improving. Because the lung is the only organ that is continuously exposed to the environment after transplantation, infection continues to be the major cause of early and late morbidity and mortality. Bronchiolitis obliterans, the second most common cause of late morbidity and mortality, is a progressive and currently untreatable condition resulting in lung dysfunction. The cause of this condition after transplantation is likely multifactorial and related to processes that result in allograft lung injury, such as rejection, bacterial infection, and cytomegalovirus infection. Future improvement in intermediate and longterm survival after lung transplantation will largely depend on prevention and long-term control of infection and subclinical rejection.
References 1. Calhoon JH, Grover FL, Gibbons WJ, et al: Single lung transplantation: Alternative indications and technique. J Thorac Cardiovasc Surg 101:816-825,1991 2. Cooley DA, Bloodwell RD, Hallman GL, et al: Organ transplantation for advanced cardiopulmonary disease. Ann Thorac Surg 8:3046, 1969 3. Cooper JD, Pearson GA, Grossman R, et al: Double-lung transplant for advanced chronic obstructive lung disease. Am Rev Resp Dis 139:303-307,1989 4. Cooper JD, Pearson FG, Patterson GA, et al: Technique of successful lung transplantation in humans. J Thorac Cardiovasc Surg 93:173-181,1987 5. Division of Transplantation, Bureau of Health Resources Development: 1995 Annual Report of the US Scientific Registry for Transplant Recipients and the Organ Procurement and Transplantation Network-Transplant Data: 1988-1994. Rockville, MD, US Department of Health and Human Services, 1995 6. Fell SC, Mollenkof FP, Montefusco CM, et al: Revascularization of ischemic bronchial anastomoses by an intercostal pedicle flap. J Thorac Cardiovasc Surg 90172-178, 1985 7. Hardy JD, Webb WR, Dolton ML Jr, et al: Lung transplantation in man: Report of the initial case. JAMA 186:1065-1074, 1963 8. Kshettry VR, Kroshus TJ, Hertz MI, et al: Early and late airway complications after lung transplantation: Incidence and management. Ann Thorac Surg 63:1576-1583, 1997 9. Lillehei CW: Discussion of Wildevuur CRH, Benefield J R A review of 23 human lung transplantations by 20 surgeons. Ann Thorac Surg 9:489-515, 1970 10. Lima 0, Goldberg M, Peters WJ, et al: Bronchial omentopexy in canine lung transplantation. J Thorac Cardiovasc Surg 83(3):418421, 1982 11. McFadden PM, Ochsner JL, Emory WB, et al: Lung transplantation in Louisiana: Report of the first 20 lung transplants performed in the state. J LA State Med SOC 1473742, 1995 12. Metras H: Note preliminaire sur la greffe totale du poumon chez le chin. Compt Rend Acad Sc 2301176-1177, 1950 13. Morgan E, Lima 0, Goldberg M, et al: Successful revascularization of totally ischemic bronchial autografts with omental pedicle flaps in dogs. J Thorac Cardiovasc Surg 84:204-210, 1982 14. Reitz BA, Burton NA, Jamieson SW, et al: Heart and lung transplantation: Autotransplantation and allotransplantation in primates with extended survival. J Thorac Cardiovasc Surg 80:360-372, 1980
762
McFADDEN & EMORY
15. Trulock El': Lung transplantation. Am J Respir Crit Care Med 155:789-818, 1997 16. Veith FJ, Richards K Improved technique for canine lung transplantation. Ann Surg 171:553-558, 1970 17. Webb WR, Howard HS Cardiopulmonary transplantation. Surg Forum 8:313, 1957
Address reprint requests to P. Michael McFadden, MD Division of Cardiothoracic Surgery Department of Surgery Ochsner Clinic 1514 Jefferson Highway New Orleans, LA 70121