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We reviewed all tissue specimens from 163 transplant patients (108 double lung transplant [DLT], 55 single lung transplant [SLT]) between November 1983 and January 1994 for abnormalities indicating bronchiolitis obliterans organizing pneumonia (BOOP) and found 17 cases (14 DLT and 3 SLT). Of the three SLTs, BOOP was diagnosed by open lung biopsy (OLB) in two and one was found at autopsy. Of the 14 DLTs, BOOP was diagnosed by transbronchial biopsy (TBB) specimens (9), OLB specimens (2), autopsy (1), TBB and OLB specimens (1), and OLB specimens and autopsy (1). BOOP was found between 1 and 43 months posttransplantation; time of survival from diagnosis was between 2 and 36 months with 9 patients presently alive. Concurrent pathologic diagnosis at the time of BOOP findings were as follows: acute rejection (7) (grade 1 [4] and grade 2 [3]), BO and grade 1 rejection (2), BO and grade 2 rejection (2), BO and Aspergillus infection (1), acute alveolar injury (1), acute alveolar injury and pulmonary embolus (1), acute rejection (grade 1) and Burkholderia cepacia pneumonia (1). No other pathologic diagnosis was found in 1 patient. In total, 11 of 17 patients (65%) had associated acute rejection. Of the 17 patients, 7 subsequently developed BO and 3 had BO before the finding of BOOP. Death occurred in 8 patients (5 DLT and the 3 SLT) between 2 and 6 months after the diagnosis. We conclude that BOOP is an important complication after lung transplantation; it was present in 13% of DLTs and 5% of SLTs. BOOP was most often associated with acute rejection.

Damage to the phrenic nerve, either unilaterally or bilaterally, is a well-documented complication of cardiac operation, but less commonly reported after lung transplantation.A retrospective review of 185 single and sequential single lung transplant procedures was performed at The Toronto Hospital. Objective confirmation (fluoroscopy or ultrasound) of diaphragmatic paralysis was found in 6 patients. Paralysis was unilateral in 5 patients (all were left sided) and bilateral in 1 patient.The average length of ventilation was 8.2 +/- 9.2 days with an average intensive care unit stay of 11.2 +/- 10.6 days. Mean duration in the hospital was 37.5 +/- 11.1 days. The average length of intensive care unit stay and hospitalization were compared with all other sequential single transplantations performed from approximately the time of the first documented case of diaphragmatic paralysis. Intensive care unit stay and hospitalization for the other (no diaphragmatic paralysis) transplant recipients were significantly shorter (5.3 +/- 2.7 and 29.1 +/- 12.9 days, respectively; p0.05). One patient required noninvasive ventilatory assistance via bilevel positive airway pressure in the hospital. One other patient used bilevel positive airway pressure in the hospital and overnight for 6 months after discharge. All patients obtained acceptable lung function and were ambulatory upon discharge from the hospital.Clinically detectable diaphragmatic paralysis is an infrequent complication of lung transplantation and is associated with longer intensive care unit stay and hospitalization, but is not associated with significant adverse outcomes.

Cardiopulmonary bypass has been widely used in the management of isolated single and double lung transplantations. Although there are certain clear-cut preoperative indications for cardiopulmonary bypass, in many patients the decision to use this modality is based on the hemodynamic consequences of intraoperative pulmonary artery clamping. We have performed 109 isolated lung transplantations. In 69 patients (38 single lung transplantations and 31 double lung transplantations) cardiopulmonary bypass was initiated only on the basis of intraoperative hemodynamics. We have analyzed preoperative data From these 69 patients to determine whether an intraoperative requirement for cardiopulmonary bypass can be predicted. Of 38 single lung transplantations, 12 necessitated cardiopulmonary bypass (all patients had restrictive lung disease). No patients with obstructive lung disease who underwent single lung transplantation required cardiopulmonary bypass (p

Between November 1983 and March 1991, we performed 50 single and 40 double lung transplants in 82 recipients. Early deaths occurred in six (13 %) single and in eight (21 %) double lung transplant recipients. Late deaths occurred in 11 (28%) single and in one (3%) double lung recipients. Twenty-three of 37 (62%) single and 17 of 24 (71%) double lung transplant recipients have survived at least 1 year after the operation. In patients surviving at least 3 months after the operation (36 of 47 single lung transplant [77%] and 28 of 37 double lung transplant recipients [76%]), significant improvement occurred in arterial blood gases, pulmonary function tests, and exercise capacity. During our initial experience, airway anastomotic complications were the main cause of early morbidity and mortality. With newer surgical techniques and improved perioperative care, airway complications are now uncommon. Infectious complications, either bacterial (Pseudomonas cepacia) or viral (cytomegalovirus), are now the main cause of early mortality. Chronic rejection in the form of obliterate bronchiolitis has become a frequent cause of late morbidity. (J T horac C ardiovasc S urg 1992;103:295—306)

Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement.

Twelve single lung and nine double lung transplant recipients were studied before transplantation and at 3 months and 1 year after transplantation with serial right and left ventricular radionuclide angiograms. The resting right ventricular ejection fraction increased in the double lung recipients from 31% +/- 5% before transplantation to 43% +/- 11% at 3 months after transplantation (p less than 0.05) and then remained stable to 1 year. The single lung recipients also demonstrated a significant rise in ejection fraction from 25% +/- 11% before transplantation to 36% +/- 12% at 3 months after transplantation. Again, this remained stable to 1 year. The exercise right ventricular ejection fraction also showed a significant posttransplantation rise in the double lung recipients (p less than 0.005) that remained stable to 1 year. In the single lung recipients a trend was seen for a rise in the exercise right ventricular ejection fraction that did not reach statistical significance by 1 year after transplantation. Neither group had a significant change in rest or exercise left ventricular ejection fraction. The systemic blood pressure increased significantly by 1 year after transplantation in both groups. The heart rate increase with exercise at 3 months after transplantation was significantly greater in the single lung group (42 +/- 13 beats/min) than in the double lung group (14 +/- 13 beats/min) (p less than 0.005). These data indicate that a significant improvement in right ventricular function occurs after single and double lung transplantation.

SUMMARY Therapeutic challenges in the management of lung transplant recipients abound. Every new (and often seemingly niggling) symptom should be carefully considered as it may be the prelude to a life-threatening infection or rejection episode; the minor, but unexplained, abnormality in a laboratory result may be the precursor to a major drug reaction. Constant vigilance is critical, but most emerging crises can be successfully addressed, and the ultimate rewards are immeasurable.

We have had success with en bloc double lung transplantation in the management of selected patients with end-stage parenchymal pulmonary disease. Airway complications have been more prevalent in our own experience with double lung transplantation than in reports of combined heart-lung transplantation from other centers. Between November 1986 and March 1989, 16 patients underwent double lung transplantation. Allografts were preserved by topical hypothermic immersion in 12 patients and by pulmonary artery flush with cold crystalloid solution in the most recent four patients. Thirteen patients underwent tracheal anastomosis and the most recent three patients underwent bilateral bronchial anastomoses. Fatal ischemic necrosis of the donor trachea and both main bronchi developed in three patients. Preterminal airway ischemia developed in a patient who had systemic sepsis. Partial anastomotic dehiscence, which went on to form fibrous strictures necessitating endoscopic placement of silicone rubber airway stents, developed in two additional patients. Two other patients had late strictures and required subsequent placement of bifurcation stents. There was no relationship between development of airway complications and gas exchange in the donor lungs, lung ischemic time, early postoperative gas exchange, early postoperative mean pulmonary artery pressure, or frequency of early postoperative rejection. Severe postoperative hypotension occurred in five of eight patients with airway complications and in three of eight patients without airway complications.

Double lung transplantation has been successfully introduced for patients with end-stage pulmonary disease and preserved cardiac function. An advantage of this operation compared with heart-lung transplantation is retention of the recipient's heart. The operative dissection, however, may lead to interruption of sympathetic and parasympathetic pathways to the heart and consequent denervation of the native heart. The cardiac innervation of seven double lung transplant recipients was investigated by the heart rate response to carotid sinus massage, the Valsalva maneuver, intravenous injection of atropine, and exercise. Five single lung and two heart-lung transplant recipients were studied for comparison. Of the seven double lung transplant recipients, three had abnormal responses to carotid sinus massage, six to the strain phase of the Valsalva maneuver, and five to the release phase of the Valsalva maneuver. Three of six double lung transplant recipients tested had no response to intravenous injection of atropine, and five of seven patients had an abnormal recovery of heart rate after maximal exercise. No patient had a normal response to all interventions, and three patients had responses compatible with complete cardiac denervation. It is concluded that cardiac denervation may occur after double lung transplantation, most likely caused by surgical interruption of sympathetic and parasympathetic pathways during dissection of the recipient's trachea.