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Ann Thorac Surg 2000;70:1675-1678
© 2000 The Society of Thoracic Surgeons

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Original articles: general thoracic

Lung transplantation is warranted for stable, ventilator-dependent recipients

^a Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA
^b Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

Address reprint requests to Dr Meyers, Department of Cardiothoracic Surgery, Washington University School of Medicine, 3108 Queeny Tower, One Barnes-Jewish Hospital Plaza, St. Louis, MO 63110-1013
e-mail: meyersb{at}msnotes.wustl.edu

Presented at the Thirty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Lung transplantation for patients on ventilators is a controversial use of scarce donor lungs. We have performed 500 lung transplants in 12 years and 21 of these have been in ventilator-dependent patients.

Methods. A retrospective review of patient records and computerized database was performed. Living patients were contacted to confirm their health and functional status.

Results. Patients included 13 men and 8 women with a mean age of 43 years. Sixteen patients were considered stable awaiting lung transplant, whereas 5 patients were unstable with acute graft failure after prior lung transplantation. Stable patients had been ventilated for a mean of 57 ± 46 days whereas unstable patients had been supported for 10 ± 9 days. Half of the patients required cardiopulmonary bypass support during the transplant, and there was no statistical difference in the frequency of CPB in stable and unstable patients (p = 0.61). Three hospital deaths included 0 of 16 of the stable patients and 3 of 5 of the unstable patients (p = 0.01). Long-term actuarial survival was significantly better in stable versus unstable patients (p = 0.02), with 5-year survival 40% for stable patients and 0% for unstable patients.

Conclusions. Lung transplantation can be successfully conducted in stable patients who have become ventilator dependent after listing for transplantation. Acute retransplantation for early lung dysfunction is high risk and has produced poor long-term results.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
In the early years of clinical lung transplantation, the availability of donors exceeded the number of candidates. Patients were only referred for transplantation when life expectancy was short because the risk of transplantation itself was quite high. Results improved, referrals increased, and gradually demand outstripped donor availability, creating the present situation in which waiting lists for donor lungs exceed 2 years. If recent trends continue, transplant programs will be increasingly faced with the dilemma of proposed recipients deteriorating on the waiting list and requiring mechanical ventilation. The current report is a review of our institutional experience with lung transplantation specifically for patients supported on ventilators immediately before transplantation. Our early experience was reported several years ago, and this report includes the patients described in that paper [1].

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
We performed a retrospective review of all patients receiving a single or bilateral lung transplant from the start of our lung transplant program in July 1988 until January 2000. During that period, 505 transplants were performed, including 21 transplants for patients who were being supported with mechanical ventilation at the time of transplant. These patients included 16 patients who were considered stable and 5 patients considered unstable. For the purposes of this analysis, stable patients are those patients with respiratory failure in the absence of any immediate antecendent surgery, and unstable patients are those patients with acute allograft dysfunction immediately following lung transplantation. This report describes the experience with the 21 patients transplanted while being supported with mechanical ventilation.

Statistical methods
All normally distributed continuous data (FEV1, age, etc) are expressed as mean ± standard deviation. Two group comparisons of normally distributed, continuous data are made using the unpaired t test. Non–normally distributed data (ie, postoperative hospital stay) are expressed as median and interquartile range. The interquartile range (IQR) describes the limits that contain the subset of values between the 25th and 75th percentile. Two group comparisons in these data sets are made with the Mann-Whitney U statistic. Survival estimates were calculated with the Kaplan-Meier method. Comparison of survival of different groups of patients is done with the Mantel-Haenszel log rank test. Tabular data are compared using Fisher’s exact test. A p value less than 0.05 was considered statistically significant.

Recipient selection
The selection of recipients for lung transplant has become a relatively standard process, and selection criteria have been described in previous publications [2–4]. Briefly, patients are selected when they have disabling lung disease with a limited prognosis and no other systemic illness that would complicate, or be complicated by, lung transplantation and immunosuppressive therapy.

Preoperative treatment
Once patients are listed for lung transplantation, efforts are made to optimize their medical care to enhance survival and function while on the organ waiting list. For all patients, this involves enrollment and active participation in pulmonary rehabilitation. Adjustment of medications may include weaning of steroids to minimize the complications of corticosteroids during the time spent on the waiting list for donor lungs. Preoperative therapy ranges from ensuring continued compliance with pulmonary rehabilitation to acute management, including intubation and intensive care when deterioration occurs during the waiting period. Although patients will generally not be listed if they are intubated, patients who decline after listing for transplant are still considered if their general health is otherwise compatible with postoperative recovery from a transplant. Many of the patients in this report continued to be involved in physical therapy and pulmonary rehabilitation despite their need for mechanical ventilation.

Donor selection
The criteria that are used to evaluate lung donors are well established. Our donor lung selection criteria and our operative techniques for lung procurement have recently been reviewed [5]. We routinely classify a donor as ideal or marginal based on criteria published previously [6]. Review of donor classification in this article is pertinent to assess how the ventilated status of the proposed recipient affected the subjective decisions surrounding donor selection. Specifically, we wanted to test the hypothesis that more marginal donors were accepted in light of proposed recipient’s ventilator dependency.

Operative techniques and postoperative care
Our current operative technique has been described in previous publications [7]. Early postoperative care occurs in the intensive care unit with mechanical ventilation and invasive cardiac monitoring. We routinely extubate patients as soon as standard weaning criteria are met. Flexible bronchoscopy is performed at the time of extubation and again 7 to 10 days after transplantation. Immunosuppressive therapy consists initially of cyclosporin, corticosteroids, and azathioprine, with the addition of antithymocyte globulin during the first several postoperative days [3]. Patients who had tracheostomies preoperatively had the tracheostomy replaced at the end of the case, as their likelihood for early extubation is believed to be lower than that for nonventilated patients.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Demographics
We performed 21 transplants in 21 ventilator-dependent patients from July 1988 to January 2000. Selected pretransplant characteristics of these patients are described in Table 1. The pretransplant characteristics of the nonventilated patients and the stable ventilated patients were compared, and no significant differences were found. The 5 unstable ventilated patients were all acute retransplantations for early graft failure and represented such unique and unpredictable situations that statistical comparisons with stable patients did not make sense. The single retransplant in the stable group was a woman who developed bronchiolitis obliterans syndrome after an en bloc double lung transplant for chronic obstructive pulmonary disease and was relisted 17 months after her first transplant.

Three patients, all of them recipients of acute retransplant operations for early graft dysfunction, were considered operative deaths. Causes of death included a massive bleeding episode in 1 patient, fungal sepsis in 1 patient, and multisystem organ dysfunction in 1 patient.

In the first case, a 47-year-old man had a bilateral lung transplant for ₁-emphysema. He developed severe proximal graft bronchus ischemia and necrosis with dehiscence. On postoperative day 6 a bilateral retransplantion was performed using cardiopulmonary bypass. Renal and hepatic dysfunction developed postoperatively and dialysis was instituted. Pseudomonas was isolated from tracheobronchial secretions and Candida was isolated from all sites. On postoperative day 11 after the retransplant he suffered a massive bleed into the chest and arrested.

A 57-year-old woman had a bilateral lung transplant for ₁-emphysema. Severe reperfusion edema and hypoxemia in the first lung led to urgent CPB while implanting the second lung. Severe bilateral reperfusion injury led to prolonged mechanical ventilation. An air leak developed on the right and quickly became "massive," thus complicating ventilation of the stiff lungs. A dehiscence was noted, and concerns over reperfusion injury, viral pneumonitis, and hyperacute rejection led to retransplantation on postoperative day 8. Postoperative complications included duodenal perforation, mental status deterioration, repeat bronchial dehiscence, and fungal wound infection. She died 45 days after the retransplantation from Aspergillus sepsis due to foci of the fungus in lung abscesses, empyema, endocarditis, and peritonitis.

A 41-year-old man had a right single lung transplant for pulmonary fibrosis. Immediate, severe lung dysfunction led to extracorporeal membrane oxygenation support. Failure to improve more than 48 hours led to a decision to retransplant using a marginal but acceptable donor. His postoperative course after retransplantation was stormy with poor allograft function, continued extracorporeal membrane oxygenation support, bleeding, renal failure, and hepatic dysfunction. On postoperative day 6 after the second transplant, support was withdrawn and he died.

Some details regarding the postoperative hospital stay are recorded in Table 3. The postoperative length of intubation, intensive care unit stay, and overall hospital stay were significantly longer for the stable ventilated patients as compared to nonventilated patients. These analyses were not performed for the unstable patients, as 3 of the 5 such patients died postoperatively.

View larger version (22K): [in this window] [in a new window]   Fig 1. Kaplan-Meier survival estimates for lung transplant recipients at Washington University School of Medicine from 1988 to 2000. Survival is stratified according to whether the patient was not ventilated, stable on the ventilator, or unstable on the ventilator at the time of transplant. Log-rank probability of survival difference is 0.14 between stable ventilator-dependent versus nonventilated patients and was 0.013 between stable ventilator-dependent and unstable ventilator-dependent patients.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

Lung transplantation for patients in stable respiratory failure is more promising. In our 16 stable ventilated patients there were no postoperative hospital deaths and a long-term survival that is not statistically different from that of the general population of our program’s transplant recipients. These patients do seem to be more prone to prolonged intubation and hospitalization after the transplant, but the results indicate that these problems are surmountable and that long-term results are acceptable.

Our practice continues to be the same as described in this article: we will consider transplantation in stable patients who have declined on the waiting list, but we are skeptical of, and generally discourage, transplantation for acute lung dysfuction regardless of the etiology.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Low D.E., Trulock E.P., Kaiser L.R., et al. Lung transplantation of ventilator dependent patients. Chest 1992;101:8-11.[Abstract/Free Full Text]
2. Lynch J.P., Trulock E.P. Recipient selection. Sem Resp Crit Care Med 1996;17:109-117.
3. Trulock E.P. Lung transplantation. Am J Respir Crit Care Med 1997;155:789-818.[Medline]
4. Maurer J.R., Frost A.E., Estenne M., Higenbottam T., Glanville A.R. International guidelines for the selection of lung transplant candidates. J Heart Lung Transplant 1998;17:703-709.[Medline]
5. Sundaresan S., Trachiotis G.D., Aoe M., Patterson G.A., Cooper J.D. Donor lung procurement. Ann Thorac Surg 1993;56:1409-1413.[Abstract]
6. Sundaresan S., Semenkovich J., Ochoa L., et al. Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs. J Thorac Cardiovasc Surg 1995;109:1075-1080.
7. Meyers B.F., Patterson G.A. Technical aspects of adult lung transplantation. Semin Thorac Cardiovasc Surg 1998;10:213-220.[Medline]
8. Meyers B.F., Sundt T.M., Henry S., et al. Selective use of extracorporeal membrane oxygenation is warranted after lung transplantation. J Thorac Cardiovasc Surg 2000;120:20-28.[Abstract/Free Full Text]
9. Eriksson L.T., Steen S. Induced hypothermia in critical respiratory failure after lung transplantation. Ann Thorac Surg 1998;65:827-829.[Abstract/Free Full Text]

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This Article Abstract Full Text (PDF) Online Discussion Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Bryan F. Meyers Richard J. Battafarano Joel D. Cooper Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyers, B. F. Articles by Patterson, G. A. Search for Related Content PubMed PubMed Citation Articles by Meyers, B. F. Articles by Patterson, G. A. Related Collections Related Article