Ann Thorac Surg 1998;66:1755-1758
© 1998 The Society of Thoracic Surgeons
Original articles: general thoracic
Acute and chronic effects of bilateral lung transplantation without cardiopulmonary bypass on the first transplanted lung
Brett C. Sheridan, MDa,
Tony N. Hodges, MDa,
Martin R. Zamora, MDa,
David L. Lynch, MDa,
James M. Brown, MDa,
David N. Campbell, MDa,
Frederick L. Grover, MDa
a Divisions of Cardiothoracic Surgery, Pulmonary Medicine, and Department of Radiology, University of Colorado Health Sciences Center, and Department of Veteran’s Affairs Medical Center, Denver, Colorado, USA
Address reprint requests to Dr Grover, Cardiothoracic Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Box C-310, Denver, CO 80262
Presented at the Forty-fourth Annual Meeting of the Southern Thoracic Surgical Association, Naples, FL, Nov 6–8, 1997.
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Abstract
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Background. Bilateral lung transplantation (BLT) without cardiopulmonary bypass (CPB) may exacerbate reperfusion injury to the initially engrafted lung because of increases in pulmonary flow during implantation of the second graft.
Methods. In a retrospective review of 23 BLT patients, we hypothesized that BLT without CPB injures the first transplanted lung measured by acute and late graft dysfunction compared to the second transplanted lung. Of the 23 BLT, 19 underwent transplantation without CPB while 4 patients were placed on CPB secondary to hemodynamic instability.
Results. Acute graft function was assessed by radiographic scoring of lung quadrants (blinded radiologist; 0 = no infiltrate; 1 = infiltrate; maximum = 2 per lung) and by arterial/alveolar oxygen tension ratios (PaO2/FiO2) ratios. Late graft function was evaluated by quantitative perfusion scan. Lung perfusion was graded as abnormal if less than 50% on the right or less than 45% on the left (Fisher’s exact). Radiographic scores were not different between first and second implanted lungs at 1 and 24 hours, PaO2/FiO2 ratios at 1 and 24 hours were 273 ± 26 and 312 ± 23, respectively, and perfusion scans at 3 and 12 months revealed normal differential blood flow.
Conclusions. These findings suggest no acute or chronic differences occur between the first or second transplanted lung completed without CPB.
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Introduction
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Although several lung transplant centers [1–3] perform bilateral lung transplantation (BLT) without cardiopulmonary bypass (CPB) for patients without severe pulmonary hypertension, this approach remains controversial. During implantation of the second graft, the diversion of the entire cardiac output to the newly implanted lung may result in twice normal blood flow, pulmonary hypertension and increased microvascular hydrostatic pressure, possibly leading to amplification of the ischemia-reperfusion-induced injury. This potentially increases pulmonary edema and hypoxemia. To ameliorate this potential injury, investigators have advocated the routine use of CPB during BLT. Cardiopulmonary bypass, however, is associated with acute lung injury itself and has been shown to be potentially deleterious in human lung transplantation [1]. We hypothesized that BLT performed without CPB would manifest both acute and chronic evidence of enhanced injury in the first transplanted lung compared with the second graft in BLT patients. Therefore, we retrospectively reviewed the chest radiographs (1 and 24 hours, arterial blood gases, and perfusion scans (3 and 12 months) of 23 consecutive nonpulmonary hypertensive BLT patients (19 without CPB) comparing the initially engrafted lung with the second graft.
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Material and methods
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Patient population and operative details
The records of all 23 nonpulmonary hypertensive patients who underwent BLT at the University of Colorado Health Sciences Center from March 1994 to March 1997 were reviewed. The indications for BLT are as follows: cystic fibrosis (n = 15), 
1 antitrypsin (n = 5), chronic obstructive pulmonary disease (n = 2), and pulmonary fibrosis (n = 1). Preoperative patient characteristics and physiologic parameters are listed in Tables 1 and 2, respectively. Donor selection, lung procurement procedures, anesthetic management, immunosuppression, and recipient operation were consistent among the 23 BLT patients and have been previously described [3]. All patients were to undergo BLT without CPB a priori but 3 patients had hemodynamic compromise at the time of pulmonary artery clamping and one patient had deterioration of oxygenation and blood pressure during the dissection of the native lung requiring CPB. Therefore, 19 patients underwent BLT without CPB while 4 patients required CPB. There were no differences in total ischemia times between those patients without CPB and those with CPB. The mean total ischemia time without CPB was 214 min for the first lung and 290 min for the second lung.
Determination of acute and chronic lung injury
Assessment of acute lung injury was completed by analysis of chest radiographs at 1 and 24 h postoperatively by a radiologist blinded to the purpose of the study. Each lung field was divided into upper and lower lung quadrants and graded as 0 for no infiltrate or 1 for an infiltrate [4]. For comparison of first and second transplanted lungs each lung was assigned a score of 0, 1, or 2 based on the summated quadrant score. Acute lung function was also assessed by the determination of the ratio of arterial oxygenation to inspired oxygen concentration (PaO2/FiO2) at 1 and 24 h. These data were calculated at Denver’s altitude using an average barometric pressure of 433 mm Hg.
Chronic graft function was determined by lung perfusion scans of the transplanted grafts at 3 and 12 months. Lung perfusion was graded by the radiologist as abnormal if < 50% perfusion on the right or < 45% perfusion on the left. The first transplanted lung was compared to the second transplanted lung and the percentage of patients with abnormal perfusion was compared between groups.
Statistical analysis
Analysis of variance (ANOVA) using Bonferroni/Dunn post hoc testing was utilized to compare the radiographic scores and the PaO2/FiO2 ratios between groups. Fisher exact test was used to compare the percentage of patients with abnormal perfusion distribution within groups and between groups. A p value of less than 0.05 was considered significant. The data presented are mean values ± the standard error of measurement (SEM).
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Results
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Acute studies
The results of the acute radiographic studies are summarized in Table 3. We found no significant differences in radiographically apparent lung injury between the first and second transplanted lung in the patients undergoing BLT without CPB. The initially engrafted lung had a score of 0.84 ± 0.21 at 1 hour that slightly increased to 0.95 ± 0.21 at 24 hours. In comparison, the second transplanted lung yielded a score of 0.47 ± 0.14 at 1 hour that increased to 0.84 ± 0.21 at 24 hours. These radiographic scores were not different at the 1 hour (p = 0.15) or 24 hours (p = 0.72) postoperative time interval.
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Table 3. Postoperative Radiographic Scoring of First and Second Transplanted Lungs in 19 BLT Patients Performed Without CPB
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As illustrated in Table 4, the PaO2/FiO2 ratios trended lower at 1 h than at 24 h (276 ± 26 versus 312 ± 22, p = 0.23) postoperatively. However, these differences did not reach statistical significance.
Chronic studies
The results of the quantitative, split function lung perfusion scans are shown in Table 5. In the 19 BLT patients without CPB, 14 patients had scans at 3 months and 10 patients had scans at 12 months. We found no effect of BLT without CPB on the normal perfusion distribution of the lungs. At 3 months 3 (21%) of 14 patients had abnormal perfusion in the initially transplanted lung and 5 (36%) of 14 in the second transplanted graft (p = 0.44). The degree of diminished perfusion did not significantly change at 12 months as evidenced by 3 (30%) of 10 patients in the first transplanted lung and 2 (20%) of 10 patients with abnormal perfusion in the second engrafted lung (p = 0.65).
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Table 5. Semiquantitative Lung Perfusion of First and Second Transplanted Lungs in 19 BLT Patients Performed Without CPB at 3 and 12 Months
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Comment
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The results of this study demonstrate that BLT without CPB in nonpulmonary hypertensive patients may be performed without exacerbation of the obligatory ischemia/reperfusion injury that occurs in the first transplanted lung. We examined acute radiographic evidence of injury of the first transplanted lung and compared that to the second graft and found no significant radiologic differences. We also examined chronic evidence of injury by analyzing lung perfusion scans at 3 and 12 months and again found no differences in perfusion between the initially grafted and the second grafted lung.
The primary objective of this study was to determine whether BLT without CPB would exacerbate ischemia-reperfusion injury of the initially engrafted lung. After implantation, the first lung receives the entire cardiac output with a concomitant increase in hydrostatic pressure. This occurs after a significant ischemic period during which pulmonary capillary endothelial barrier function is impaired favoring enhanced permeability. Several investigators have experimentally examined the effect of high-flow reperfusion and hydrostatic pressure on lung vasculature. DeLima and colleagues examined the influence of high-flow reperfusion and Euro-Collins solution in an ex vivo rabbit model of lung ischemia-reperfusion [5]. Their study documented that high-flow reperfusion with or without Euro-Collins solution increased pulmonary vascular resistance, decreased dynamic airway compliance, and increased lung edema in the setting of ischemia-reperfusion. Similarly, Fullerton and coworkers created a 3:1 left to right shunt in dogs and examined pulmonary hemodynamics, and mechanisms of pulmonary vasorelaxation at 3 days, 2 weeks, and 5 months [6]. This study found that increased flow without increased pressure impaired mechanisms of pulmonary vasorelaxation beginning at 2 weeks and progressed over time. Taken together these studies suggest that increased flow and pressure may result in pathophysiologic changes acutely and over an extended period of time. These flow and pressure injuries may be exaggerated, however, with the additional insult of ischemia reperfusion and hyperkalemic preservation solutions. From this experimental evidence further investigation into the influence of BLT in patients with or without the use of CPB is warranted.
Whether controlled reperfusion would be protective in human lung transplantation is unknown. Supporting this notion is the work of Hopkinson and colleagues who showed that limiting the flow rate during reperfusion limited ischemia-reperfusion-induced injury. This was evidenced by improved oxygenation, decreased pulmonary vascular resistance and decreased wet/dry lung ratios in an isolated, blood-perfused rat lung model after a 24-hour cold ischemic injury to a lung preserved in U-W solution [7]. Although CPB may allow improved regulation of reperfusion pressures, CPB itself is associated with acute lung injury. Cardiopulmonary bypass is known to activate complement [8] and neutrophils [9, 10]. It also increases circulating levels of cytokines such as endotoxin [10, 11], interleukins [12, 13], and tumor necrosis factor [11]. Employing a canine model of autologous lung transplantation, Fullerton and coworkers demonstrated that the use of CPB in lung transplantation was associated with impaired pulmonary vasorelaxation compared to lung transplants performed without CPB [14]. Aeba and coworkers retrospectively reviewed 100 lung transplant recipients, 55 of whom underwent CPB [1]. Patients undergoing CPB had increased radiographic evidence of lung injury, lower mean arterial-alveolar oxygen tension ratios, prolonged intubation and decreased 1-month graft, and patient survival compared with those patients whose transplants were completed without CPB. Our results support and extend the work of Aeba and colleagues and suggests that CPB might not only be associated with an increase in acute lung injury but also be associated with chronic lung injury after BLT.
While this study offers evidence to support the current practice of BLT without the use of CPB in nonpulmonary hypertensive patients, it has several limitations. Although all patients receiving BLT were to undergo this procedure without CPB a priori, this analysis remains retrospective and was not designed to compare BLT patients with and without CPB. The study size is also small (n = 19 in the BLT without CPB) and because no differences were found between the observed groups (first transplanted lung versus second transplanted lung) it is subject to a ß or type II statistical error. Despite these limitations, our results suggest no short-term or long-term deleterious effects to the first transplanted lung in BLT without the use of CPB.
Bilateral lung transplantation remains a difficult clinical challenge. The optimal surgical approach requires clinical judgment, experience and knowledge of the potential injury that high-flow, high-pressure reperfusion may induce without CPB versus the reperfusion injury imposed by the use of CPB. The present study supports BLT in nonpulmonary hypertensive patients without the use of CPB as there appears to be no objective evidence of injury in the initially engrafted lung compared with the second transplanted lung.
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Footnotes
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This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/annals
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References
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- Grover F.L., Fullerton D.A., Zamora M.R., et al. The past, present, and the future of lung transplantation. Am J Surg 1997;173:523-533.[Medline]
- Murray J.F., Matthay M.A., Luce J.M., Flick M.R. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988;138:720-723.[Medline]
- DeLima N.F., Binns O.A.R., Buchanan S.A., et al. Eurocollins solution exacerbates lung injury in the setting of high-flow reperfusion. J Thorac Cardiovasc Surg 1996;112:111-116.[Abstract/Free Full Text]
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- Kirklin J.K., Westaby S., Blackstone E.H., Kirklin J.W., Chenoweth D.E., Pacifico A.D. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:845-857.[Abstract]
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Abstract
Introduction
