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J Thorac Cardiovasc Surg 2006;132:1441-1446
© 2006 The American Association for Thoracic Surgery
Cardiothoracic Transplantation |
Department of Allergy, Immunology, and Respiratory Medicine, Lung Transplant Unit, The Alfred Hospital, Melbourne, Australia.
Received for publication May 24, 2006; revisions received June 26, 2006; accepted for publication August 8, 2006. * Address for reprints: Gregory I. Snell, Department of Allergy, Immunology, and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, Victoria 3004, Australia. (Email: g.snell{at}alfred.org.au).
| Abstract |
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METHODS: Depending on posttransplant radiographic appearance, 144 patients who underwent bilateral lung transplantation were divided into 3 groups: no infiltrates (clear), unilateral infiltrates (unilateral), or bilateral infiltrates (bilateral).
RESULTS: Radiographic abnormalities were seen in 43% of donors and 61% of posttransplant recipients (sensitivity = 76%, specificity = 50%). The percentage of recipients in the unilateral, clear, and bilateral groups was 26%, 39%, and 35%, respectively. Lower posttransplant oxygenation (P < .05), longer intubation hours, and more intensive care unit days (P < .0001) were seen in the bilateral compared with the unilateral and the clear groups. A significant difference in the prevalence of primary graft dysfunction (P < .0001) was seen, depending on whether unilateral infiltrates were included or excluded from the primary graft dysfunction grading.
CONCLUSIONS: The incidence of unilateral infiltrates is relatively high after bilateral lung transplantation. The early posttransplant outcome of the unilateral infiltrates is similar to that in the group having a clear chest x-ray film and significantly better than that in those with bilateral infiltrates. In bilateral lung transplantation, only bilateral infiltrates should be used as part of the definition of primary graft dysfunction.
| Introduction |
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Unilateral infiltrates on chest x-ray films are occasionally seen after bilateral lung transplantation. In the absence of unilateral pulmonary venous anastomotic obstruction, pulmonary contusion, hemorrhage, atelectasis, or pneumonia, this phenomenon may be due to unilateral ischemia-reperfusion injury.
Theoretically, in the absence of cardiopulmonary bypass, during the second lung implantation the newly implanted first lung is exposed to the entire cardiac output with resultant doubling of normal pulmonary arterial blood flow, pulmonary hypertension, and increased microvascular hydrostatic pressure.11
In the first lung, this might amplify ischemia-reperfusion injury, resulting in a unilateral radiographic infiltrate; however, the actual incidence and etiology of these unilateral infiltrates remain unknown.
In the official ISHLT PGD grading system, the presence or absence of a radiographic abnormality has a critical role in determining the incidence and severity of PGD, as the absence of radiographic infiltrates is considered as grade 0 even if the ratio of arterial oxygen tension and inspired oxygen consumption (PaO
2/FIO
2) is less than 300.10
It is noted that this definition of PGD mimics that of the acute respiratory distress syndrome, which is based on bilateral disease. In this grading system, no consideration is given as to whether a unilateral infiltrate has the same impact and relevance as a bilateral infiltrate.
We therefore hypothesized that consideration of unilateral radiographic infiltrates as either "present" or "absent" in bilateral lung transplantation might influence the apparent severity of the PGD grading when compared with a clear chest x-ray film or one with bilateral infiltrates. Therefore, this study aims to describe the incidence, features, and outcomes of unilateral infiltrates on chest x-ray films and their effect on the novel PGD grading system.
| Patients and Methods |
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Study Group
All patients were divided into 3 groups depending on radiographic appearance: no infiltrates (clear group), unilateral infiltrates (unilateral group), or bilateral infiltrates (bilateral group). The presence or absence of radiographic infiltrates consistent with reperfusion edema was assessed by blinded reviewers at the time of arrival in the intensive care unit (ICU) (T 0), at 24 hours (T 24), and at 48 hours (T 48) after transplant. On the basis of the radiographic features (clear, unilateral, or bilateral), 3 patient groups were analyzed at each time point (T 0 to T 48).
Primary Graft Dysfunction Grading
Details of the grading of PGD severity have been described elsewhere.10
In brief, the classification scheme is based on the chest x-ray film and PaO
2/FIO
2: grade 0, PaO
2/FIO
2 greater than 300 without radiographic infiltrates; grade 1, PaO
2/FIO
2 greater than 300 with radiographic infiltrates; grade 2, PaO
2/FIO
2 between 200 and 300 with radiographic infiltrates; and grade 3, PaO
2/FIO
2 less than 200 with radiographic infiltrates. There are other specific inclusion/exclusion criteria: a requirement for supplemental oxygen via nasal cannula or with an FIO
2 less than 0.3 is graded as 0 or 1 depending on radiographic features; the absence of radiographic infiltrates is graded as grade 0 (even if PaO
2/FIO
2 ratio < 300); the requirement of extracorporeal membrane oxygenation (ECMO) or mechanical ventilation with FIO
2 greater than 0.5 on nitric oxide beyond 48 hours after transplant is graded as grade 3. Furthermore, when grading beyond 48 hours, venous anastomotic obstruction, pneumonia, hyperacute rejection, and cardiogenic pulmonary edema should be excluded or assessed separately.
Donor Assessment and Management
The lung donor assessment and management have been described elsewhere.12-15
Preoperative immunologic evaluation including donor-recipient T-cell and B-cell cross-matching was routinely performed and found to be negative in all cases. Active donor management, including an initial bronchoscopic examination and repeated suctioning, physiotherapy, revision of antibiotic therapy, and fluid management, are usually undertaken to optimize the donor for transplantation. A repeat assessment, including chest x-ray films and serial arterial blood gases, may need to be undertaken after donor management changes before a final decision is made to accept or decline donor organs.
Donor Lung Procurement and Preservation
Lung procurement and preservation followed previously described procedures.16,17
Perfadex (Kabi Pharmacia, Uppsala, Sweden) replaced Euro-Collins preservation solution in September 2004. An intravenous infusion of prostacyclin (Flolan; Wellcome, Sydney, Australia) at 40 to 80 ng · kg1 · min1 for approximately 10 minutes before crossclamp was performed when Euro-Collins solution was used for lung preservation. A single antegrade flush with cold preservation solution followed by heart-lung en bloc procurement was routinely performed.
Lung Transplant Surgical Technique and Perioperative Management
Lung transplant procedures have been described elsewhere.18,19
Cardiopulmonary bypass was only routinely performed in our institution for heart-lung transplantation and only otherwise considered when intolerance of single lung ventilation due to hemodynamic instability was seen. As a part of lung graft preparation, a retrograde exploratory flush was performed to detect any unexpected donor pulmonary artery embolism before implantation.4
Before completion of implantation, retrograde followed by antegrade reperfusion and deairing was performed via untied pulmonary vascular anastomotic suture lines. An evaluation of the venous anastomosis by transesophageal echocardiogram was routinely performed at the end of the operation. An additional reconstruction/repair of the pulmonary venous anastomosis was performed when the donor left atrial cuff was inadequate for single end-to-end anastomosis.16
Postoperative management in the ICU was performed to ensure satisfactory end-organ perfusion while maintaining a relatively low filling pressure (cardiac index > 2.4, pulmonary capillary wedge pressure < 10 mm Hg, and central venous pressure < 7 mm Hg). Patients with PGD received a standardized evaluation (including transesophageal echocardiogram) and therapy with increasing complexity depending on the degree of ventilatory and hemodynamic compromise (including ECMO and inhaled nitric oxide).20
Details of immunosuppression and transbronchial lung biopsy protocols are described elsewhere.3,4,12-14
Data Collection
Data were retrieved from the transplant database and a review of ICU and donor records. Data of arterial blood gas analysis and the existence of infiltrates on chest x-ray film at each time point of T 0, T 24, and T 48 after transplant were used to define PGD grade.
Statistical Analysis
Continuous data were reported as mean ± standard error of the mean, whereas categorical data were reported as count and proportions. Comparison among groups was performed with 1-way analysis of variance followed by post hoc analysis with the Fisher test for parametric continuous variables and the
2 test for categorical variables. Duration of intubation and length of ICU stay were estimated by the Kaplan-Meier method and the curves were analyzed by use of log-rank test. For analysis of pulmonary arterial pressure during the second lung implantation, data from patients without cardiopulmonary bypass were used. Intubation hours and ICU days were both found to be well approximated by a log-normal distribution. Univariate correlation analysis between PGD grades and log-transformed intubation hours and log-transformed ICU days was performed with Pearson correlation coefficients. Logistic regression analysis was used to estimate the relationship of individual factors with the occurrence of unilateral radiographic infiltrates. Analysis was performed with Statview 5.0 software package (SAS Institute, Inc, Cary, NC).
| Results |
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Donor and Recipient Demographics
Detailed demographics including donor, recipient, and operative factors in the 3 groups at T 0 are shown in Tables 1 and 2.
Significant differences among the 3 groups are seen in the presence of an abnormal donor chest x-ray film (P = .005), donor unexpected pulmonary emboli (P = .003), recipient underlying disease (P = .02), and cardiopulmonary bypass use (P < .001). There were no significant differences in donor PaO
2/FIO
2 before procurement and pulmonary arterial pressure during the second lung implantation (P > 0.2).
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Risk Factor Analysis for Unilateral Infiltrates
In the unilateral group, 1 patient required pulmonary venous anastomotic repair/reconstruction because of an inadequate donor left atrial cuff, with a widely patent anastomosis and adequate blood flow through the anastomosis confirmed by postoperative transesophageal echocardiography. The incidence of unilateral infiltrates seen in the individual paired right versus left lungs was 56% versus 44%, and in the first versus second implanted lungs was 41% versus 59%. Overall, no donor, recipient, or operative factors were significantly associated with the development of unilateral infiltrates.
| Discussion |
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This study demonstrates that a high proportion of donor chest x-ray films are abnormal and that this contributes to an abnormal posttransplant chest x-ray film (sensitivity = 76%, specificity = 50%). Although the present study is limited in not having sufficient detail available to determine whether donor radiographic infiltrates were unilateral or bilateral, interestingly, an abnormal donor chest x-ray film appears to be a more potent predictor of subsequent recipient PaO
2/FIO
2 than the traditional measure of preoperative donor PaO
2/FIO
2.12,21
An abnormal donor x-ray film cannot be the only explanation for the development of posttransplant unilateral infiltrates, because 23% of the patients with a clear donor chest x-ray film still had unilateral infiltrates after transplant. Indeed, many factors, including the use of cardiopulmonary bypass, pulmonary venous anastomotic obstruction, hyperacute rejection, ischemia-reperfusion injury, cardiac failure, atelectasis, and pneumonia, potentially contribute to the development of radiographic infiltrates within the first 48 hours after transplant.1-9,22,23
Theoretically, without cardiopulmonary bypass, the newly implanted first lung is exposed to an entire cardiac output, which may result in double the normal pulmonary arterial blood flow, pulmonary hypertension, and increased microvascular hydrostatic pressure during the second lung implantation. In contrast, the second implanted lung is susceptible to a longer ischemic time with resultant greater ischemic damage. These might contribute to amplify ischemia-reperfusion injury and result in unilateral radiographic infiltrates. Sheridan and colleagues11
investigated the effect of bilateral lung transplantation on the first transplanted lung in 19 patients without cardiopulmonary bypass. The authors found no difference in radiographically apparent lung injury at 1 and 24 hours after transplant and in quantitative lung perfusion scan at 3 to 12 months after transplant when comparing the first and second implanted lungs. In the current study, no donor, recipient, or operative factors (including the first or second implanted lungs and the side of implanted lungs) could be associated with the development of unilateral infiltrates after transplant. Further study is needed to clarify the cause of posttransplant unilateral infiltrates on chest x-ray films.
Whether radiographic changes are included or excluded from the PGD diagnostic criteria has a critical role in determining the apparent incidence and severity of PGD, particularly for grade 0. In the current study, the consideration of radiographic changes has an impact on the apparent incidence of PGD grade 0 across the whole first 48 hours after transplant, although there was also a significant effect on the apparent incidence of PGD grade 3 at T 0 (Figure 3). In fact, the incidence of PGD grade 3 in bilateral lung transplantation generally decreases over time postoperatively.23
Moreover, in this study, beyond 24 hours, and especially beyond 48 hours, a number of patients in PGD grade 3 fell into this category primarily because of the requirement for ECMO or nitric oxide. Therefore, the impact of the radiographic appearance on PGD grade 3 may be the strongest at T 0 and decrease beyond 24 hours after transplant.
In conclusion, the incidence of unilateral radiographic infiltrates is relatively high throughout the first 48 hours after bilateral lung transplantation. The donor radiographic abnormality plays a role in the recipient radiographic infiltrates, but the mechanism of the unilateral infiltrates remains unknown. The early posttransplant outcomes of those patients with unilateral infiltrates are similar to those with a clear chest x-ray film and significantly better than those with bilateral infiltrates. Therefore, in bilateral lung transplantation only bilateral infiltrates should be used as part of the PGD definition.24
| Acknowledgments |
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| References |
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This article has been cited by other articles:
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T. Oto and G. I. Snell Reply to the Editor J. Thorac. Cardiovasc. Surg., July 1, 2007; 134(1): 270 - 271. [Full Text] [PDF] |
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J. Shuhaiber Unilateral as well as bilateral infiltrates should remain part of the definition of pulmonary graft dysfunction J. Thorac. Cardiovasc. Surg., July 1, 2007; 134(1): 269 - 270. [Full Text] [PDF] |
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