T evolved from en bloc heart-lung transplantation to en

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1 Double-Lung Transplantation in Children: A Report of 20 Cases Dominique Mktras, MD, Hani Shennib, MD, Bernard Kreitmann, MD, Jean Camboulives, MD, Laurent Viard, MD, Michel Carcassonne, MD, Roger Giudicelli, MD, Michel Noirclerc, MD, and the Joint Marseille-Montreal Lung Transplant Program HBpital Ste. Marguerite, Marseille, France; La Timone Children s Hospital, Marseille, France; and Montreal General Hospital, Montreal, Quebec, Canada In the last 3% years, we have performed 20 double-lung transplantations in children between 7 and 16 years old (mean age, 13 years). One patient had primitive bmnchiolitis obliterans and the other 19, cystic fibrosis. Eight patients were operated on in an emergency situation, 7 of them requiring ventilator support before transplantation. The procedures were en bloc double-lung transplantation in the first 11 patients with separate bronchial anastomoses in 10, and sequential bilateral lung transplantation in the later 9 patients. There were no operative deaths. Two patients died in the hospital on postopera- tive days 37 and 73, and there were four late deaths, which were due to infection, rejection, and bronchiolitis obliterans. The acceptable incidence of airway complications, the improvement in lung function of sumvors, and the acceptable midterm survival make double-lung transplantation an acceptable alternative to heart-lung transplantation in children. However, in very small children, heart-lung transplantation may be preferable because of the size of the airway anastomoses at risk. (Ann Thorac Surg 1993;55:352-7) he technique of bilateral lung transplantation has T evolved from en bloc heart-lung transplantation to en bloc double-lung transplantation and finally to sequential bilateral lung transplantation. Although heart-lung transplantation originally was advocated for all types of parenchymal diseases and for pulmonary vascular disease either isolated or caused by Eisenmenger syndrome, it has now been restricted to irreparable or irreversible heart defects associated with pulmonary disease. Single-lung transplantation is now advocated for many parenchymal and pulmonary vascular diseases, and double-lung transplantation is advocated when both lungs have to be removed, in particular for septic lung diseases such as cystic fibrosis or bronchiectasis. Lung transplantation has been done mostly in adult patients. The difficulty of looking after children with end-stage heart or lung disease and the uncertainty about the long-term outcome of the allografts have raised doubts about the usefulness of performing lung transplantation in children. It has been suggested [l] that children will experience more episodes of rejection, both acute and chronic, which will result in graft attrition and a disappointing long-term outcome. In the world experience, heart-lung transplantation has been by far the most frequent procedure reported for lung transplantation in children [Z] and in patients with cystic fibrosis in particular [3]. In 1988 in Marseille, we started a double-lung transplant program in children with cystic fibrosis [4]. Presented at the Twenty-eighth Annual Meeting of The sodety of Thoracic Surgeons, Orlando, FL., Feb %5, Address reprint requests to Dr Mhas, La Timone Children s Hospital, Blvd Jean Moulin, Marseille, C6dex 5, France. This article reports our experience and our intermediateterm results in 20 consecutive pediatric patients undergoing double-lung transplantation in the combined Marseille-Montreal lung transplant program. Material and Methods Between May 1988 and December 1991, 58 children were accepted for transplantation, including some very severely ill patients who required ventilation. Few children (only 3) were denied inclusion on the waiting list. Twenty-two patients (40%, 22/55) died while awaiting transplantation because of a lack of donors. During the same period, 20 patients underwent bilateral lung transplantation. There were 11 girls and 9 boys. The average age at transplantation was 13 years (range, 7 to 16 years). The average weight was 25 kg (range, 14 to 56 kg). The indication for transplantation was cystic fibrosis in 19 patients and primitive bronchiolitis obliterans in 1 patient. The nutritional status of most patients was poor, their growth pattern being well under the normal range for their age. Twelve patients were in stable condition and 8, in severe condition at transplantation. These 8 patients were in intensive care and receiving intravenous inotropic support necessitated by secondary right ventricular failure; 7 of them were on a ventilator with nasotracheal intubation for 1 day to 21 days before transplantation. The patient having ventilator support for 21 days had a tracheostomy 3 days before transplantation. Age of the donors ranged between 4 and 20 years (mean age, 11 years), and weight ranged between 17 and 70 kg (mean weight, 37 kg). After the first few patients, little by The Society of Thoracic Surgeons /93/$6.00

2 Ann Thorac Surg 1993;55:352-7 MkTRAS ET AL 353 attention was paid to size and weight matching between donor and recipient, and more attention was given to the size of the chest. The criterion used for size matching was the circumference of the thorax at the nipple level, a variation of 10% being accepted. The lungs were procured as part of a multiorgan harvesting, the technique including crystalloid cardioplegia and a single flush of 4 C Euro-Collins solution in the pulmonary artery after an infusion of prostaglandin El. The ischemic time ranged from 2 hours 15 minutes to 7 hours (mean time, 4 hours * 1 hour 30 minutes). In the first 11 patients, the en bloc double technique [5] was used with a tracheal anastomosis in the first patient and bilateral bronchial anastomoses in the following 10 patients [6, 71. In the last 9 patients, bilateral single-lung transplantation [8] was performed through a bilateral transverse thoracotomy. In none of the patients was omentopexy or any wrapping of the airway anastomoses done. All operations were performed with cardiopulmonary bypass, moderate hypothermia, and a beating heart except during the left atrial anastomosis in en bloc double-lung transplantation, where cardioplegia was used. The immunosuppression regimen included induction with rabbit antithymocyte globulin (2.5 mg/kg) for 7 to 14 days and triple immunosuppression with cyclosporin A, azathioprine, and corticosteroids. Cyclosporin A was given preoperatively, intraoperatively, and postoperatively as a continuous intravenous administration until oral administration became possible after approximately 2 weeks. We aimed at a residual level of 150 to 250 ng in serum or 300 to 500 ng in total blood. The steroids were given intraoperatively (4 ng - kg-' - d-') and withheld thereafter for 2 to 3 weeks in the initial experience. In the last 7 patients, corticosteroid administration was started earlier at 0.6 mg/kg and tapered to 0.2 mg/kg after 4 to 6 months. Azathioprine was given at 2 mg/kg for the first week and then reduced to 0.5 to 1.5 mg/kg to obtain a white blood cell count in the range of 4,000 to 7,OOO/pL (4.0 to 7.0 x lo'/l). The postoperative antibiotic regimen included a double or triple association to obtain synergy and was usually identical to the pretransplantation treatment. The antibiotics commonly used, based on the most recent assessment of bacterial sensitivity in vitro, were a penicillin (ceftazidime, imipenem), an aminoglycoside (amikacin sulfate, tobramycin sulfate), and a quinolone (ciprofloxacin). Antifungal prophylaxis was also instituted for 1 month (amphotericin A, 0.2 mg/kg). Rejection monitoring included routine endoscopies and biopsies, the former being started after day 5 for inspection of the airway anastomoses. Biopsies were done systematically every week, then every month after the second month, and then every 3 months in the following year. Subsequently, routine lung function studies, computed tomographic scans, and scintigraphs were performed. Rejection episodes were treated with intravenous pulse steroid therapy (17 mg * kg-'. d-') and OKT3 when resistant to steroids. Four episodes of rejection were treated with OKT3. Results There were no operative deaths and two in-hospital deaths. One involved a 12-year-old patient with severe multiorgan failure preoperatively (coma, renal failure, artificial ventilation). This patient died on postoperative day 37 of multiorgan failure, infection, airway dehiscence, and cerebral anoxia. The other patient died of posttransplantation lymphoproliferative lung disease 73 days after transplantation. This patient had multiple episodes of rejection requiring augmentation of immunosuppression and repeated pulse steroid therapy. He also had one course of OKT3. There were four late deaths. One patient with cystic fibrosis but otherwise in excellent condition died of acute bronchopneumonia 4 months after sequential bilateral lung transplantation. The causative organism was unknown, as the death occurred in a remote community hospital where no bacterial investigation was done. The other three deaths were due to bronchiolitis obliterans at 1 year, 1 year 3 months, and 1 year 6 months. In 2 of these patients, it was associated with chronic infection and repeated episodes of rejection. Both patients also had a permanent left main bronchial stent. The postoperative course was difficult, with most patients requiring mechanical ventilation for l day to 54 days (mean duration, 16 days). Eight patients needed a temporary tracheostomy. The duration of ventilator support after transplantation did not correlate with the time of ischemia or the need for preoperative ventilation. Four patients had renal failure requiring peritoneal dialysis. Patients had insulin-dependent diabetes, discovered during a pulse of intravenous steroid therapy. Two patients had a temporary unilateral diaphragmatic palsy. Cardiac function, even when impaired preoperatively, always improved. Fifteen patients required prolonged inotropic support after transplantation until the right ventricle recovered normal function. Postoperative lnfec t ions The duration of the initial course of antibiotics ranged from 10 to 35 days based on the negativity of bronchial secretions. Pulmonary infections caused by Pseudomonas aeruginosa developed in 5 patients during their initial hospital course. No patient died of this infection, but in 2 it became chronic, associated with bronchiolitis obliterans, and the patients died at 13 and 19 months. A late infection developed in 6 patients. One of them died at 4 months. A Pseudomonas aeruginosa infection developed in 5 patients, 2 of whom were cured. In the other 3, the infection was chronic and recurrent. A cytomegalovirus lung infection developed in 5 patients and was diagnosed by bronchoalveolar lavage (4 patients) or by transbronchial biopsy (1 patient). All were successfully treated by DHPG. Airway Complications Bronchoscopy under short general anesthesia, at bedside when necessary, was well tolerated and uneventful. The patient with a tracheal anastomosis had development of an anastomotic stricture 3 months after transplantation. This was treated with one session of laser therapy. Nine-

3 354 METRAS ET AL Ann Thorac Surg 1993: teen patients had 38 bronchial anastomoses at risk. Twelve patients had simple or uneventful healing, whereas 7 had airway complications. One patient had bilateral necrosis and dehiscence (the patient who died 37 days after transplantation). Two patients had bilateral bronchomalacia, predominant on the left side, and needed a permanent left main bronchial stent. Both later died of bronchiolitis obliterans and superimposed rejection and infection. Left main bronchomalacia developed in 4 patients, necessitating one permanent and three temporary endobronchial stents. All stents were the Dumon Silastic (Dow Corning, Midland, MI) stents [9]. In the initial experience, bronchial complications were found to be related to preoperative ventilation and younger age of recipients (less than 10 years). In the recent experience, and particularly with sequential bilateral lung transplantation, bronchial healing was generally uneventful. Rejection Episodes In the first month, 16 patients had one or two rejection episodes (0.9 episode per patient). At 1 year, rejection occurred at the rate of 0.2 rejection episodes per patient. After 1 year, there were no acute rejection episodes. Bronchiolitis Obliterans Bronchiolitis obliterans developed in 6 of 14 patients followed up for more than 6 months, an incidence of 42.9%. This diagnosis was based on a progressive, irreversible decline in pulmonary flow measurements. Histologic diagnosis was accomplished in 3 patients by transbronchial biopsy and in 3 by open lung biopsy. Three of the 6 died of infectious complications secondary to bronchiolitis obliterans. One patient underwent retransplantation after a year. Before the heart-lung retransplantation, he received ventilator support for 66 days. One year after retransplantation, he is in excellent condition. Two patients are awaiting retransplantation 2% years after initial double-lung transplantation. Eight patients are leading a normal life, but 2 of them are considered to have moderate and stable bronchiolitis obliterans. Lung Function After transplantation, there was significant improvement in forced expiratory volume in 1 second from 25.5% k 2.1% predicted before transplantation to 75% f 5.8% predicted at 3 months, 95.3% 2 7.4% predicted at 6 months, and 87.4% k 10.8% predicted at 1 year (p > 0.01 compared with pretransplantation values for all three periods) (Fig 1). The mild decline observed at 1 year is related to the development of bronchiolitis obliterans in 3 patients. Similarly, the forced vital capacity increased significantly from 41.4% * 2.3% predicted before transplantation to 84.5% * 4.8% predicted at 3 months, 101.2% f 4.8% predicted at 6 months, and 99.1% f 9.2% predicted at 1 year (p < 0.01 compared with pretransplantation value) (see Fig 1). Follow-up Overall, 13 patients, including 1 patient who underwent retransplantation, are doing well or reasonably well 3 to 40 MM Pre op Months Fig I. Changes in lung function during the first year after operation. Data are shown as percent predicted. (FEW = forced expiratory volume in 1 second; FVC = forced vital capacity.) 45 months after transplantation, this including the patient with retransplantation. The actuarial survival is 70% at 3 years (Fig 2). Nine of the 13 have resumed a normal life with considerable development and weight gain. They attend school, and some have taken up hobbies or sports requiring a high level of activity such as alpine skiing, tennis, soccer, or gymnastics. Comment The recent success of isolated lung transplantation reported by the Toronto group was followed by an explosion in the number of transplantations performed worldwide. Current registry data [2] indicate that as a consequence of the increase in the number of single- and double-lung transplantations performed, heart-lung transplantation has dwindled. Although single-lung transplantation can be suitable therapy for patients with nonseptic parenchymal or vascular lung disease, replacement of both lungs is thought to be essential for any patient with evidence of pulmonary infection. Contrary to the experience in adults, initial reports on pediatric lung transplantation have not been encouraging, with mortality attributed to a high incidence of acute rejection, airway complications, and infections [l]. In this series, we report our experience with bilateral lung transplantation in children less than 17 years of age. Bilateral lung transplantation without the heart was performed as the primary graft in all patients with parenchymal disease and a normal heart or a temporarily failing heart. The relatively low morbidity observed in this pediatric lung transplant experience may reflect the fact that children are generally more tolerant of surgical complications and the fact that the bacteria they harbor have not necessarily acquired the multiresistance to antibiotics observed in the adult population with cystic fibrosis. In addition, the absence of operative mortality in this pediatric group, which consists almost exclusively of patients with cystic fibrosis, may reflect the lack of extensive

4 Ann Thorac Surg 1993:55:352-7 MGTRAS ET AL 355 x (20) Fig 2. Actuarial survival curve for 20 children undergoing double-lung transplantation. Number of patients at risk is in parentheses ",. I. I. I. 1. I.,.. -. Months thoracic adhesions and hence the reduced bleeding and the lower cardiopulmonary bypass time compared with adults. Heart-lung transplantation was used as the second procedure for a recipient of a double-lung transplant in whom bronchiolitis obliterans developed. The choice of a heart-lung transplant rather than a redo double-lung transplant was made because the patient had had en bloc double-lung transplantation, and we did not wish to leave segments of bronchus from 2 donors. During the first 6 months, pediatric recipients of lung transplants appeared to experience the same complications seen in adults. Infection, rejection, and airway complications are not uncommon. Our methods of surveillance and investigation of pulmonary complications are no different from those in adult patients. We use fiberoptic bronchoscopy liberally when indicated. Transbronchial biopsy and bronchoalveolar lavage are routinely used at the time of bronchoscopy to rule out rejection or infection. Children are at the highest risk of the development of bronchopneumonia during the first month after transplantation. In this series, five episodes were observed to occur in the first month in 20 patients at risk. In the subsequent 6 months, only three episodes were noted in 14 patients at risk. These data suggest that as the incidence of rejection decreases and the doses of immunosuppression are lowered, and the patient is away from the hospital environment, the risks of infection decrease. Pediatric recipients of lung transplantation are also at highest risk of development of acute rejection during the first months. We noted 18 episodes in 20 patients at risk during this period. This is no different from the experience observed in other pediatric organ transplant programs or in adult patients [lo]. All episodes of rejection except for three were responsive to pulse steroid therapy. OKT3 was effective in treating steroid-resistant rejection on three occasions. In 1 child who received relatively high and repeated doses of steroid therapy for the treatment of rejection posttransplantation lymphoproliferative disorder developed and the patient died 73 days after transplantation. This 5% incidence of lymphoproliferative disorder is similar to that reported in adult patients [ll]. The frequency and severity of airway complications were within normal limits and have decreased substantially in the more recent experience with the bilateral single-lung technique. We therefore believe that airway complications are no different in children than they are in adults. Although our numbers are too small to confirm such an observation statistically, we believe that younger children should be considered for a tracheal anastomosis rather than bronchial anastomoses. The age and weight of this group are not defined. Whether this is incorporated as part of a heart-lung or double-lung procedure remains to be determined. More recently, we have performed a successful heart-lung transplantation in a 6-year-old boy weighing 12 kg with cystic fibrosis (not included in this study) and employed a tracheal anastomosis for this small patient. Pulmonary function testing in our pediatric lung transplant series indicates significant improvement in forced expiratory volume in 1 second and forced vital capacity immediately after transplantation. There is continual improvement up to 6 months after operation, at which point lung volumes start to plateau. A slight drop in the percent predicted forced expiratory volume in 1 second and forced vital capacity observed at 1 year in our series may reflect the development of bronchiolitis obliterans in some patients. These objective findings indicate that bilateral lung transplantation in the pediatric population results in improvement in lung function and hence an expected better overall performance by these children. Among the 14 patients followed up for longer than 6 months, bronchiolitis obliterans developed in 6. We believe this incidence is no different from what can be expected in adults with our current methods of immunosuppression: cyclosporine, azathioprine, and low doses of prednisone. Three of the 6 patients are in stable condition with no further drop in forced expiratory volume in 1 second and are now studying and working full time. Two other patients with marked dyspnea and limited function are awaiting transplantation. The only patient in this series who has had retransplantation has regained normal function and is symptom-free 9 months after receiving a heart-lung transplant. Whether retransplantation should

5 356 MgTRAS ET AL Ann Thorac Surg 1993; be considered for patients with development of bronchiolitis obliterans in the primary grafts and which technique of retransplantation to use are controversial. As most patients with end-stage bronchiolitis obliterans will harbor fungal or bacterial infection, it is almost certain they would require replacement of both lungs. Whether heartlung or double-lung retransplantation is chosen will likely be addressed in the next few years as more patients with bronchiolitis obliterans are seen for retransplantation. The issue of the growth potential of transplanted lung allografts in children is not resolved. There is, however, experimental evidence to suggest that lung allografts show an increase in airway diameter and lung volumes with age [12]. Hislop and associates [13] reported an increase in both number and size of alveoli after allogenic single-lung transplantation in animals. Whether growth potential differences between donor and recipient bronchi will occur and lead to the risk of anastomotic stenosis must still be determined. Within the limited period of observation in this study, we can report normal clinical and radiologic thoracic development and the absence of airway complications, findings attributed to the development of donor lungs. Finally, the results in the severely diseased patients needing artificial ventilation and inotropic support before transplantation were not different from those in the other patients. This was true with reference to all variables, such as survival, complications, and difficulty of postoperative management. Therefore, we believe that mechanical ventilation per se before transplantation should not be considered a contraindication to transplantation. Multiorgan failure before transplantation, however, is a definite contraindication, and our patient who died on day 37 would not have been a candidate now for transplantation. We conclude from this study that bilateral lung transplantation is a valid option for the treatment of children with end-stage lung disease. Currently, sequential bilateral lung transplantation is our procedure of choice in all patients with septic lung disease. Heart-lung transplantation is rarely needed and should be restricted to patients with combined heart and lung disease or when bronchial anastomoses are likely to be at risk for the development of complications, as in retransplantation and in younger children with smaller airways. Although pediatric bilateral lung transplantation can result in good intermediateterm survival and function, research directed toward prevention and treatment of bronchiolitis obliterans is needed to achieve better long-term survival. Addendum Since this report was written, 2 patients have undergone retransplantation for bronchiolitis obliterans 2 and 2% years after double-lung transplantation. Both had heart-lung transplantation and died after operation. One died of an oversized graft and 1 of inability of the heart to resume normal function. The second patient was in multiorgan failure while on the ventilator for 4 weeks and had severe metabolic disturbances that may have caused the failure of an otherwise uneventful operation. Since then, a 14-year-old patient has had a successful sequential bilateral lung transplantation for cystic fibrosis. We have therefore updated the actuarial survival curve (Fig 3). 30: 20 : 10 : Months alter transplant. We gratefully acknowledge the following surgeons, intensivists, pediatricians, and pulmonologists who have actively participated in the program: Marie-Ange Silicani, MD, Adrienne Pannetier, MD, Olivier Garbi, MD, Pierre Geigle, MD, Jean-Yves Marty, MD, Monique Badier, MD, Louise Garbe, MD, Jean-Fransois Dumon, MD, Jean-Pierre Chazalette, MD, David S. Mulder, MD, and Christ0 I. Tchervenkov, MD. We also thank Francoise Moucadel for secretarial assistance. References 1. Berendt DM, Billingham M, Boucek M, et al. Rejection/ infection: the limits of heart transplantation success. J Heart Lung Transplant 1991;10: Kriett JM, Kaye MP. The Registry of the International Society for Heart and Lung Transplantation: eighth official report J Heart Lung Transplant 1991; De Leva1 MR, Smyth R, Whitehead 8, et al. Heart and lung transplantation for terminal cystic fibrosis. J Thorac Cardiovasc Surg 1991;101: Noirclerc M, Chazalette JP, Metras D, et al. Les transplantations bi-pulmonaires: rapport de la premipre observation fransaise et rapport des quatre suivantes. Ann Chir Thorac Cardiovasc 1989;43: Patterson GA, Cooper JD, Goldman 8, et al. Technique of successful clinical double-lung transplantation. Ann Thorac Surg 1988;45:62& Noirclerc M, Metras D, Vaillant A, et al. Bilateral bronchial suture in double lung and heart-lung transplantations. Eur J Thorac Cardiovasc Surg 1990;4:31&7. 7. Metras D, Noirclerc M, Vaillant A, Brunet CH, Kreitmann B. Double lung transplantation. The role of bilateral bronchial suture. Transplant Proc 1990;22: Pasque MK, Cooper JD, Kaiser LR, Haydock DA, Triantafillou A, Trulock EP. Improved technique for bilateral lung transplantation: rationale and initial clinical experience. Ann Thorac Surg 1990;49: Dumon JF. A dedicated tracheobronchial stent. Chest 1990; Kaye M, Kriett JM. Pediatric heart transplantation: the world experience. J Heart Lung Transplant 1991; Armitage J, Kormos R, Stuart S, et al. Post-transplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporin-based immunosuppression. J Heart Lung Transplant 1991; Haverich A, Dammenhayn L, Demertzis S, Kemnitz J, Reimers P. Lung growth after experimental pulmonary transplantation. J Heart Lung Transplant 1991;10:28% Hislop AA, Odom NJ, McGregor CGA. Growth potential of the immature transplanted lung. J Thorac Cardiovasc Surg 1980;100:

6 Ann Thorac Surg 1993;55:352-7 MPTRAS ET AL 357 DISCUSSION DR R. MORTON BOLMAN 111 (Minneapolis, MN): I enjoyed your presentation very much, Dr Metras. My colleagues and I have also had some experience with retransplantation in children. In children with cystic fibrosis in whom obliterative bronchiolitis develops, is single-lung retransplantation adequate, or, in the likelihood of bronchiectasis and infection developing in the contralateral lung, would bilateral replacement be better? I notice you did a heart-lung transplantation in 1 child. Why did you do that? DR METRAS: In our experience, all these patients with cystic fibrosis have chronic infection, and we would not recommend single-lung transplantation. The problem is we do not know yet what to do-another sequential bilateral lung transplantation or a heart-lung transplantation. This is, of course, debatable. As for the patient who underwent heart-lung transplantation, we chose that procedure because the first operation was a double-lung transplantation by the technique of Dr Cooper. We did not want the patient to have bronchus from 3 people, 1 recipient and 2 donors, so we decided to do heart-lung transplantation. DR DONALD C. WATSON JR (Memphis, TN): I enjoyed your presentation very much. It reminds me of why people often go into cardiothoracic surgery, that is, to take basic and clinical research to solve new or difficult problems. You mentioned a limited donor supply, as did Dr Spray yesterday. I have one observation and two questions. About 2 years ago, my associates and I were asked to evaluate a 4fi-year-old girl with primary pulmonary hypertension. She ultimately was put on the recipient list. She waited until the parents asked, Why wait? We can help. Ten months ago, her mother donated a right lower lobe, and today that young girl is out of the hospital and back in school after a complicated course and recovery from a lymphoproliferative disease related to Epstein-Barr virus. This isolated case was pushed by circumstances, but the pediatric patient does present some unique options. My two questions are the following: (1) Do you think that lung donation from a living relative is a real option, not necessarily for our particular scenario but for patients with cystic fibrosis? and (2) Will the type of scenario I described encourage a critical review of the organ donation base that we currently use? DR METRAS: I think the shortage of donors favors bilateral lung transplantation in patients with cystic fibrosis instead of heartlung transplantation. In France, the demand for hearts is so great that it is very difficult to find a heart-lung donor. However, once the heart has been donated, obtaining the lungs is relatively easy. 1 think the tendency to use bilateral lung transplantation instead of heart-lung transplantation is going to increase. As for your lobar transplant, I think it is a very nice success and I congratulate you for your beautiful experience, but I have some doubts. I believe it would be a lifesaving procedure only for a certain time, because it has been shown that multiplication and growth of the alveoli are finished after the age of 8 years. One lobe from an adult cannot develop in a child except by emphysema, and I do not see how such a lobe can make a normal lung for a growing child. Nevertheless, I am sure that in some cases this would be a lifesaving procedure that could be followed later by replacement with a whole lung. DR G. ALEXANDER PATTERSON (St. Louis, MO): Professor Metras, that was a beautiful presentation, and you are to be congratulated for those results, particularly considering that children with cystic fibrosis represent the overwhelming majority of your patients. I have two questions. First, we heard yesterday from Dr Spray that their pediatric group uses cardiopulmonary bypass routinely in all cases, and you have said the same. Can you explain why you use bypass to do sequential bilateral lung transplantation in these children and whether you have encountered any difficulty because of the use of bypass? Second, I was struck by the lack of septic complications in your patients with cystic fibrosis. What type of prophylaxis do you use? Do you treat the sinuses preoperatively, and what antibiotic regimen is used? DR METRAS: To answer your second question first, all the patients have the sinuses treated. There were, in fact, 12 patients who had complications, some of them very severe. Concerning the antibiotic regimen, 1 am a surgeon; the intensivists use antibiotics the names of which I do not even know, and there are always new antibiotics. In the postoperative prophylaxis three or four antibiotics are used. This is the best answer I have. DR PATTERSON: Is it true that there was only one perioperative death resulting from sepsis? DR METRAS: The patient died, but not of sepsis. Sepsis was one of several of his problems. It is true that no patient in our experience died of postoperative infection only. As for your first question on cardiopulmonary bypass, I am happy that you asked about this, because I think the use of cardiopulmonary bypass in the pediatric population in harmless and even useful. These children had no pleural adhesions. This is one characteristic of cystic fibrosis in children in our experience: there are very few adhesions. So cardiopulmonary bypass does not add any more risk of hemorrhage, and the recent patients bled very little postoperatively. We use cardiopulmonary bypass because most often the donor is a remote donor. At the appropriate time after a donor has been found, we put the patient on bypass, remove the two lungs, and prepare everything for the anastomoses. Then when the lungs arrive, we can rapidly perform the three anastomoses. Wc think this is a quicker, simpler procedure than to wait for the donor and then try to do sequential bilateral single-lung transplanhtion without bypass. DR HANI SHENNIB (Montreal, Que, Canada): Perhaps I can follow up on this question. In regard to Dr Patterson s questions as to what antibiotics we use and why we do not have a high incidence of sepsis in these patients, I think it is necessary to remember that what we are dealing with in this particular study is a population of children. We tend to see a higher incidence of multiresistant I~szrrdorrror?as infections in adults compared with children. Most of these children would have a combination of antibiotics that would be effective. We tend to use aggressive doses of aerosolized tobramycin or Coly-Mycin in the patients with cystic fibrosis (we put almost all our patients on aerosol therapy) in addition to intravenous antibiotics based on the multisensitivity in vitro.