- Email: [email protected]
Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema
CLINICAL LUNG AND HEART-LUNG TRANSPLANTATION
Acute Native Lung Hyperinflation is Not Associated with Poor Outcomes after Single Lung Transplant for Emphysema David Weill, MD, Fernando Torres, MD, Tony N. Hodges, MD, Jennifer J. Olmos, and Martin R. Zamora, MD Background: Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. Methods: We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. Results: Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with ␣1antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P ⫽ 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/FIO2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9 ⫾ 14.6 hours vs 40.4 ⫾ 3.9, P ⫽ 0.02, ANOVA) and longer lengths of stay (19.3 ⫾ 2.1 days vs 13.7 ⫾ 1.3, P ⫽ 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. From Lung Transplant Program, The University of Colorado Health Sciences Center, Denver, Colorado Submitted April 13, 1999; accepted August 22, 1999. Reprint requests: David Weill, MD, The Heart and Lung Center, Medical City Hospital, 7777 Forest Lane Suite C-430, Dallas,
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TX 75230. Telephone: (972) 566-6409. Fax: (972) 566-7993. Email: [email protected]. Copyright © 1999 by the International Society for Heart and Lung Transplantation. 1053-2498/99/$–see front matter PII S1053-2498(99)00079-0
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Conclusion: Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation. J Heart Lung Transplant 1999;18:1080–1087.
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hronic obstructive pulmonary disease (COPD) has become the most common indication for lung transplantation. Despite excellent results of single-lung transplantation (SLT) for COPD, controversy remains regarding the best procedure for this disorder. The difference in compliance between the graft and the native lung may result in severe ventilation–perfusion mismatches leading to hemodynamic and/or respiratory insufficiency in the early postoperative period. Following the initial reports of successful SLT for COPD by Mal et al1 and Calhoon et al,2 incidences of acute native lung hyperinflation (ANLH) resulting in respiratory and hemodynamic compromise and subsequent increased morbidity and mortality have been reported. Recently, Yonan et al3 reported a series of 27 patients undergoing SLT for COPD, of whom approximately 30% developed severe ANLH requiring cardiopressor agents and independent lung ventilation (ILV). The mortality rate of patients developing ANLH was 42.6%. A preoperative FEV1 less than 15%, residual volume greater than twice the predicted value, and increased pulmonary artery pressures were predictive of the development of ANLH. These authors advocate the routine use of ILV, double-lung transplant (DLT), or rightsided SLT with contralateral lung volume reduction surgery (LVRS) for this subgroup of high-risk patients. However, these approaches all have inherent disadvantages. Independent lung ventilation can result in increased morbidity due to the inability to perform adequate pulmonary toilet with prolonged use of a dual lumen tube. Further, longer ischemic times during DLT may lead to an increased operative risk and may decrease the number of available donor lungs. Lung volume reduction surgery can cause prolonged postoperative air leaks and other problems unique to that procedure. Given the controversy as to the appropriate operation for COPD, our aim was threefold: to identify the incidence of ANLH in a larger series of patients, to identify
variables that preoperatively predict ANLH, and to comment on postoperative management strategies that limit its development.
PATIENTS AND METHODS We retrospectively reviewed 51 consecutive patients who underwent SLT for COPD at the University of Colorado Health Sciences Center between February 1992 and October 1998. Thirteen patients had ␣1-antitrypsin deficiency, and 38 had cigaretteinduced emphysema. Fourteen patients had bilateral bullous emphysema (13 had A1AT deficiency); 32 patients had no bullous changes; and 5 had unilateral bullous changes. Twenty-four right and 27 left SLTs were performed. Preference as to the side transplanted was determined by split-function ventilation–perfusion scans, the presence of previous major thoracic surgery or asymmetric bullous disease on computed tomography (CT) scan, and donor availability.
Definitions of Hyperinflation Acute native lung hyperinflation was defined as radiographic mediastinal shift and ipsilateral diaphragmatic flattening (Fig 1). Symptomatic ANLH was associated with either hemodynamic instability, defined as a systolic blood pressure ⬍ 90 mm Hg or a mean arterial pressure ⬍ 65 mm Hg requiring cardiopressor medications, or respiratory insufficiency requiring inhaled nitric oxide (iNO) or ILV. The presence of ANLH and the degree of lung injury by a lung injury score were determined by a radiologist unassociated with this study.
Outcome Variables We analyzed complete preoperative pulmonary function tests, hemodynamic parameters, the predicted donor to actual recipient total lung capacity (TLC) ratio, the need for cardiopulmonary bypass (CPB) or the use of iNO to prevent CPB, lung injury scores as determined by chest x-ray (CXR) and PaO2/FIO2 ratios, the need for iNO, and postoper-
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FIGURE 1 Acute native lung hyperinflation after a single left lung transplant for
emphysema. The respiratory insufficiency and hemodyamic instability resolved following extubation 2 hours postoperatively.
ative pulmonary artery pressures (PAP). The FEV1 and 6-minute walk tests were compared between the groups at 1 year. The incidence of acute rejection (AR), infection, and bronchiolitis obliterans syndrome (BOS) greater than grade 2 was also determined. Survival was compared at 30 days and 1, 2, and 3 years after transplant. Complete data were available on 38 of 51 total patients at the 3-year follow-up.
Statistical Analysis Preoperative and postoperative variables were compared using analysis of variance (ANOVA) and Schefe’s test. Survival, incidence of rejection and infection, and freedom from BOS were analyzed using Kaplan-Meier curves. P values less than 0.05 were considered significant.
Donor Criteria and Preservation Donor criteria included an age less than 60, PaO2 greater than 300 mm Hg on an FiO2 of 1.0 and
positive end-expiratory pressure of 5 cm H2O, clear chest radiograph, negative sputum gram stain, and an unremarkable bronchoscopic examination. Recipients and donors were matched by ABO compatibility and were of similar height and weight. No effort was made to match donors and recipients based on predicted TLC. Donors and recipients were instead matched within 15 to 20% of one another by vertical dimensions and by having a donor/recipient inframammary chest wall circumference ratio less than 1 and greater than 0.75.4 Modified Euro-Collins solution containing prostaglandin E1 was used to preserve the donor lungs.
Recipient Operation and Immunosuppression The operation was performed as previously described2 with the use of a telescoped anastomosis and without the use of CPB. Patients with secondary pulmonary hypertension (PA mean ⬎ 25 mm Hg) do not receive DLT in preference to SLT in our program. Patients received standard triple-drug im-
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TABLE I Incidence of acute native lung hyperinflation by disease and side transplanted ANLH
COPD A1AT deficiency Left side Right side
Radiographic (Total)
Symptomatic
10 6 10 6
4 4 4 4
No ANLH
Incidence
28 7 17 18
26% 46%* 37% 25%
ANLH, acute native lung hyperinflation; COPD, chronic obstructive pulmonary disease; A1AT, ␣1-antitrypsin deficiency. *P ⫽ 0.10 vs COPD.
munosuppression with cyclosporine, azathioprine, and prednisone and did not receive lympholytic agents. Solumedrol, 500 mg/kg, was given intravenously prior to the release of the PA clamp, then 125 mg twice a day in 6 doses. Prednisone was then given at 1 mg/kg per day and tapered to 0.1 to 0.15 mg/kg per day by 1 month. Cyclosporine was maintained at trough levels of 350 – 450 ng/mL, and azathioprine given at up to 2.5 mg/kg per day to maintain a white blood cell count of 5000 cells/L.
RESULTS We reviewed 51 consecutive SLT patients for emphysema. A total of 16 patients (31%) developed radiographic evidence of ANLH; 8 (15.7%) developed symptomatic ANLH requiring cardiopressor agents (n ⫽ 6), iNO (n ⫽ 1), or ILV (n ⫽ 1). Radiographic ANLH occurred in 6 of 14 patients, with bullous emphysema versus in 10 of 37 patients without bullous disease (P ⫽ NS). There was a trend toward an increased incidence of symptomatic
ANLH in patients with bullous emphysema, but this was primarily accounted for by patients with A1AT deficiency (4/13 vs 4/38 with COPD, P ⫽ 0.10). The development of ANLH was not influenced by ischemic times or the side transplanted (Table I). No patient in either group required CPB or intraoperative iNO, and there was no difference in the requirement for intraoperative pressors between groups. Preoperative pulmonary function tests, pulmonary artery pressures or the predicted donor to actual recipient TLC ratio did not predict which patients would develop radiographic or symptomatic ANLH (Table II). Postoperative parameters evaluated did not reveal any difference between patients who did and did not develop ANLH. Specifically, lung injury scores as determined by PaO2/FIO2 ratio and CXR scores were similar between the two groups (Table III). Pulmonary artery pressures were also similar between groups. Only one patient with ANLH required postoperative iNO while 5 patients without
TABLE II Preoperative pulmonary function tests and pulmonary artery pressures
FEV1 (actual) (% Predicted) FEF25–75 TLC RV RV % predicted PDTLC/ARTLC Range PA pressures PAS PA mean Ischemic Time (minutes)
Total ANLH (n ⴝ 16)
Radiographic ANLH (n ⴝ 8)
Symptomatic ANLH (n ⴝ 8)
No ANLH (n ⴝ 35)
0.47 ⫾ 0.3 15.7 ⫾ 1.2 0.18 ⫾ 0.01 133 ⫾ 7 5.08 ⫾ 0.6 275 ⫾ 22 0.97 ⫾ 0.12 0.64–1.44
0.47 ⫾ 0.03 14.7 ⫾ 2.3 0.17 ⫾ 0.02 138 ⫾ 8 5.25 ⫾ 0.55 289 ⫾ 27 0.98 ⫾ 0.12
0.52 ⫾ 0.04 16.6 ⫾ 1.0 0.19 ⫾ 0.02 130 ⫾ 11 4.96 ⫾ 1.0 266 ⫾ 33 0.95 ⫾ 0.11 0.78–1.43
0.52 ⫾ 0.04 16.4 ⫾ 0.8 0.21 ⫾ 0.02 132 ⫾ 5 5.17 ⫾ 0.3 281 ⫾ 16 0.93 ⫾ 0.17 0.56–1.56
32.3 ⫾ 1.7 20.2 ⫾ 1.3 239 ⫾ 23
33 ⫾ 3 21.3 ⫾ 2.4 245 ⫾ 17
31.5 ⫾ 1.7 19.1 ⫾ 1.2 233 ⫾ 21
35.1 ⫾ 1.4 23.8 ⫾ 1.2* 220 ⫾ 11
ANLH, acute native lung hyperinflation; FEV1, forced expiratory volume in 1 second; FEF25–75, forced expiratory flow 25–75%; TLC, total lung capacity; RV, residual volume; RV % predicted, percent predicted residual volume; PAS, systolic pulmonary artery pressure; PA mean, mean pulmonary artery pressure; PDTLC/ARTLC, predicted donor TLC/actual recipient TLC. *P ⫽ 0.07 vs symptomatic PAP mean.
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TABLE III Early postoperative outcomes
Lung Injury CXR Immediate 24 hours 48 hours 7 days PaO2FIO2 Immediate 24 h PAS Need for iNO Mech Vent (hours) LOS (days)
Total ANLH (n ⴝ 16)
Radiographic ANLH (n ⴝ 8)
Symptomatic ANLH (n ⴝ 8)
No ANLH (n ⴝ 35)
1.88 ⫾ 0.3 1.94 ⫾ 0.36 1.68 ⫾ 0.33 0.44 ⫾ 0.13c
1.91 ⫾ 0.3 1.96 ⫾ 0.4 1.66 ⫾ 0.3 0.40 ⫾ 0.1c
1.85 ⫾ 0.4 1.89 ⫾ 0.3 1.70 ⫾ 0.31 0.49 ⫾ 0.1c
1.56 ⫾ 0.19 1.75 ⫾ 0.22 1.43 ⫾ 0.21 0.91 ⫾ 0.19c
253 ⫾ 21 239 ⫾ 18 27.5 ⫾ 1.0 1 51.8 ⫾ 8.3 15.9 ⫾ 1.8
272 ⫾ 27 247 ⫾ 22 27.5 ⫾ 1.4 0 38.9 ⫾ 5.9 12.6 ⫾ 1.9
244 ⫾ 34 228 ⫾ 36 27.4 ⫾ 1.4 1 64.9 ⫾ 14.6a 19.3 ⫾ 2.1b
248 ⫾ 26 237 ⫾ 31 30.4 ⫾ 1.2 5 40.4 ⫾ 3.9 13.7 ⫾ 1.3
CXR, chest radiograph; PaO2, arterial oxygen tension; FIO2, fractional inspired oxygen; PAS, systolic pulmonary artery pressure; iNO, inhaled nitric oxide; LOS, length of stay. a P ⫽ 0.02 vs no NLH. b P ⫽ 0.07 vs no ANLH. c P ⬍ 0.05 vs immediate, 24 h, 48 h CXR score.
ANLH required iNO. Patients with symptomatic or asymptomatic ANLH had longer ventilator times than those without ANLH. There was a trend toward a longer hospital length of stay in the group who developed ANLH (see Table III), but 30-day survival was identical at 100%. Long-term survival (Fig 2) and functional outcomes (Table IV) were similar among the groups. There were also no differences in the episodes of AR, infection, or freedom from BOS greater than grade 2 (Fig 3). Four patients developed chronic NLH (3 had ANLH), and 2 underwent LVRS 3 and 4 years after transplant. FIGURE 2 Survival following single-lung transplant for
DISCUSSION
COPD. No difference in Kaplan–Meier survival between patients with (—) and without (----) acute native lung hyperinflation (P ⫽ NS).
In the early 1980s, heart-lung transplantation was considered the procedure of choice for COPD. By the late 1980s, DLT was used to avoid the hemody-
TABLE IV Long-term functional outcomes NLH (n ⴝ 16) FEV1 at 1 year 6-min walk at 1 year (feet) Episodes of AR Infection BOS (grade 2)
1.58 ⫾ 0.1 1276 ⫾ 89 0.22/100 patient days 0.40/100 patient days 5/16 (31%)
No NLH (n ⴝ 35) 1.52 ⫾ 0.07 1289 ⫾ 76 0.34/100 patient days 0.32/100 patient days 11/31 (35%)
ANLH, acute native lung hyperinflation; FEV1, forced expiratory volume in 1 second L/min; AR, acute rejection; BOS, bronchiolitis obliterans syndrome (BOS rates assume survival of at least 3 months).
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FIGURE 3 Incidence of bronchiolitis obliterans
syndrome following SLT for COPD. No difference in the percent freedom from BOS ⬎ Grade 2 between patients with (—) and without (----) acute native lung hyperinflation (P ⫽ NS).
namic and ventilatory consequences of performing SLT in patients with severe emphysema. Mal et al,1 and soon after Calhoun et al,2 reported successful SLT for COPD. Today, most centers consider SLT to be the procedure of choice, because SLT allows maximal use of donor organs, and patients receiving a SLT achieve a similar exercise tolerance5,6 and survival7,8 to those undergoing DLT. Despite the growing body of literature supporting SLT for emphysema, controversy still exists regarding the optimal procedure for this disorder. Recent reports have shown that SLT for this disease may be associated with increased morbidity and mortality secondary to excessive air trapping and hyperinflation of the native lung.3 In the present study, we found that ANLH was indeed common radiographically but was rarely clinically severe. The ANLH seen in our series was typically managed with cardiopressor agents, ventilator strategies aimed at allowing prolonged expiration, and early extubation. Further, ANLH was not associated with increased morbidity or mortality, or with suboptimal long-term graft function. Finally, similar to other anecdotal reports, we found a trend for symptomatic ANLH to occur more frequently in patients who had bullous emphysema, particularly those with A1AT deficiency. However, using standard preoperative pulmonary and hemodynamic parameters, we were unable to identify “high-risk” patients prone to develop ANLH. Recently, Yonan et al3 reported an incidence of symptomatic ANLH of up to 30% with an associated mortality rate of 42%. Preoperative parameters
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identifying this group included higher mean pulmonary artery pressures, FEV1 less than 15%, and residual volume greater than 200%. The authors recommended that alternative surgical and ventilatory strategies were necessary to optimize survival and functional outcomes. One such recommendation was the routine use of ILV in the high-risk subgroup of emphysema patients. Independent lung ventilation is complicated by the necessity of using a double-lumen endotracheal tube, which may prevent adequate pulmonary toilet. Maintaining proper positioning can be problematic, and acute malpositioning of the tube can result in lobar collapse or hypoventilation from an air leak around the bronchial cuff. Awake patients may not tolerate these tubes and will require more sedation and/or paralysis, which may delay weaning from mechanical ventilation. Finally, prolonged use of a dual-lumen tube can cause tracheal erosion or vocal cord injury because of the large caliber of these tubes. We were unable to identify a high-risk subgroup, so we cannot advocate the routine use of ILV. Our approach is to initially treat ANLH by disconnecting the endotracheal tube from the ventilatory circuit at various intervals to allow emptying of the native lung and to restore hemodynamic stability. If symptomatic ANLH persists in the absence of significant graft ischemia/reperfusion injury, we prefer early extubation. Late ischemia–reperfusion injury has been suggested as an impediment to early extubation; however, we have only experienced this problem in less than 2% of our patients. If a patient is unable to be extubated, either due to poor condition of the graft or due to muscular weakness or sedation caused by anaesthetic medications, ventilator manipulation can limit the amount of native lung hyperinflation and its negative consequences. Specifically, this is achieved by reducing tidal volume, decreasing ventilator breath frequency, increasing inspiratory flow rates, and reducing positive endexpiratory pressure. Frequent bronchodilator therapy is also employed in all COPD patients undergoing SLT in order to facilitate maximal native lung expiratory airflow. Some centers advocate alternative surgical approaches for the emphysematous patient. Bilateral lung transplant,7 SLT with contralateral LVRS,9 or the exclusive use of right-lung allografts has been advanced as the procedure to prevent the complications associated with SLT. However, these procedures may have several disadvantages. Double-lung transplantation has several disadvantages when compared to SLT, including longer ischemic times
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and a higher perioperative mortality in some programs; DLT may not be as well tolerated in older, sicker patients. Furthermore, SLT allows optimal use of scarce donor organs. Although this study did not directly compare the efficacy of SLT and DLT, in our experience, we have not seen differences in long-term functional outcome or survival between these two procedures (data not shown). Comparing SLT and DLT in terms of exercise tolerance and survival is difficult, given that studies examining these issues are mainly generated from single centers and are conflicting. The FEV1 following DLT should be higher than with SLT as more lung tissue—and therefore a greater pulmonary reserve—is transplanted during DLT. Demonstration of an exercise benefit from DLT as compared to a SLT may be biased given that younger, healthier patients are more likely to receive DLT.7,10 Although performing simultaneous LVRS and SLT in emphysema patients is effective in reducing the size of the hyperinflated native lung and may lead to better expiratory flows in the native lung,11 prolonged air leaks and other postoperative complications associated with LVRS may offset any benefit derived by this procedure. Injury to the native lung due to surgical manipulation during the LVRS procedure may lead to native lung dysfunction, which could exacerbate the postoperative difficulties associated with ischemia–reperfusion injury. Lung volume reduction surgery may, however, be useful in patients experiencing more chronic graft compression from the hyperinflated native lung.12,13 It has been postulated that the problems encountered with SLT for COPD are more common when a left SLT is performed. Because the right hemidiaphragm cannot move downward due to the presence of the liver, a hyperinflated native right lung can only expand across the mediastinum and could be more likely to cause cardiac tamponade and graft compression. Conversely, an emphysematous native left lung would tend to hyperinflate downward, flattening an unimpeded left diaphragm. These theoretical concerns aside, the exclusive use of right SLT is not supported by our findings as the development of symptomatic or asymptomatic ANLH was not dependent on the side transplanted in our series. Our study did not address functional capacity beyond 1 year and survival beyond 3 years, so our results do not suggest that the routine use of the above approaches are warranted to prevent the acute effects of NLH. In younger patients with bilateral bullous disease (usually those with A1AT
The Journal of Heart and Lung Transplantation November 1999
deficiency in our cohort), these alternative approaches may be appropriate. The number of patients in our study may be inadequate to conclude definitively regarding this specific issue. When confronted with a patient with unilateral bullous changes, we of course chose to transplant the side with the bullae. The discrepancy between our results and those of Yonan et al3 is difficult to explain. The patient groups are similar with regards to severity of illness (mean FEV1 of 21% in our group vs mean FEV1 of 19.6% in Yonan’s cohort), and both included patients with secondary pulmonary hypertension. When analyzing small patient numbers (51 in the current study vs 27 in Yonan’s group), a type II () error may be present that could make detecting a difference between the two groups difficult. However, Yonan reported a 30-day mortality of 42% and commented that this rate was excessively high, while our 30-day mortality was zero. This survival difference suggests that perhaps there are other, unrecognized factors in donor and/or recipient selection or intra- or early postoperative management strategies that may account for the observed differences between the two studies. In conclusion, the purpose of this study was to identify the incidence of ANLH and potential preoperative variables that predict its occurrence. Our results support the following conclusions. First, although common radiographically, clinically severe ANLH is rare. Second, the preoperative variables we analyzed could not identify a subset of patients at risk for the development of ANLH. Third, although the development of either symptomatic or asymptomatic ANLH was associated with longer ventilator times and hospital lengths of stay, it was not associated with increased morbidity or mortality. These results do not support the routine use of ILV, DLT, or the exclusive use of right SLT for COPD. Further, simultaneous LVRS and SLT is not indicated for most patients. However, in young patients with bilateral bullous disease (particularly those with A1AT deficiency), alternative approaches to SLT may be indicated. Single-lung transplant for COPD can present challenging postoperative management issues, but several strategies can be employed that limit or eliminate the potentially deleterious effects of ANLH. REFERENCES 1. Mal H, Andreassian B, Pamela F, Duchatelle JP, Rondeau E, Dubois F, Baldeyrou P, Kitzis M, Sleiman C, Pariente R.
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2.
3.
4.
5.
6.
7.
Unilateral lung transplantation in end-stage emphysema. Am Rev Respir Dis 1989;140:797– 802. Calhoon JH, Grover FL, Gibbons WJ, Bryan CL, Levine SM, Bailey SR, Nichols L, Lum C, Trinkle JK. Single lung transplantation. Alternative indications and techniques. J Thorac Cardiovasc Surg 1991;101:816 –25. Yonan NA, El-Gamel A, Egan J, Kakadellis, Rahman A, Deiraniya AK. Single lung transplantation for emphysema: predictors for native lung hyperinflation. J Heart Lung Transplant 1998;17:192–201. Park SJ, Houck J, Pifarre R, Sullivan H, Garrity E, Kim SY, Zbilut J, Montoya A. Optimal size matching in single lung transplantation. J Heart Lung Transplant 1995;14:671–5. Low DE, Trulock EP, Kaiser LR, Pasque MK, Dresler C, Ettinger N, Cooper JD. Morbidity, mortality, and early results of single versus bilateral lung transplantation for emphysema. J Thorac Cardiovasc Surg 1992;103:1119 –26. Orens JB, Becker FS, Lynch JP 3rd, Christensen PJ, Deeb GM, Martinez FJ. Cardiopulmonary exercise testing following allogeneic lung transplantation for different underlying disease states. Chest 1995;107:144 –9. Waddell TK, Keshavjee S. Lung transplantation for chronic obstructive pulmonary disease. Semin Thorac Cardiovasc Surg 1998;10:191–201.
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8. Gaissert HA, Trulock EP, Cooper JD, Sundaresan RS, Patterson GA. Comparison of early functional results after volume reduction surgery or lung transplantation for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1996;111:296 –307. 9. Malchow SC, McAdams HP, Palmer SM, Tapson VF, Putman CE. Does hyperexpansion of the native lung adversely affect outcome after single lung transplant for emphysema? Acad Radiol 1998;5:688 –93. 10. Sundaresan RS, Shiraishi Y, Trulock EP, Manley J, Lynch J, Cooper JD, Patterson GA. Single or bilateral transplantation for emphysema. J Thorac Cardiovasc Surg 1996;112: 1485–95. 11. Todd TR, Perron J, Winton TL, Keshavjee SH. Simultaneous single lung transplantation and lung volume reduction surgery. Ann Thorac Surg 1997;63:1468 –70. 12. Anderson MB, Kriett JM, Kapelanski DP, Perricone A, Smith CM, Jamieson SW. Volume reduction surgery in the native lung after single lung transplantation for emphysema. J Heart Lung Transplant 1997;16:752–7. 13. Kuno R, Kanter KR, Torres WE, Lawrence EC. Single lung transplantation followed by contralateral bullectomy for bullous emphysema. J Heart Lung Transplant 1996;15:389 – 94.
Acute Native Lung Hyperinflation is Not Associated with Poor Outcomes after Single Lung Transplant for Emphysema David Weill, MD, Fernando Torres, MD, Tony N. Hodges, MD, Jennifer J. Olmos, and Martin R. Zamora, MD Background: Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. Methods: We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. Results: Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with ␣1antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P ⫽ 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/FIO2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9 ⫾ 14.6 hours vs 40.4 ⫾ 3.9, P ⫽ 0.02, ANOVA) and longer lengths of stay (19.3 ⫾ 2.1 days vs 13.7 ⫾ 1.3, P ⫽ 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. From Lung Transplant Program, The University of Colorado Health Sciences Center, Denver, Colorado Submitted April 13, 1999; accepted August 22, 1999. Reprint requests: David Weill, MD, The Heart and Lung Center, Medical City Hospital, 7777 Forest Lane Suite C-430, Dallas,
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TX 75230. Telephone: (972) 566-6409. Fax: (972) 566-7993. Email: [email protected]. Copyright © 1999 by the International Society for Heart and Lung Transplantation. 1053-2498/99/$–see front matter PII S1053-2498(99)00079-0
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Conclusion: Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation. J Heart Lung Transplant 1999;18:1080–1087.
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hronic obstructive pulmonary disease (COPD) has become the most common indication for lung transplantation. Despite excellent results of single-lung transplantation (SLT) for COPD, controversy remains regarding the best procedure for this disorder. The difference in compliance between the graft and the native lung may result in severe ventilation–perfusion mismatches leading to hemodynamic and/or respiratory insufficiency in the early postoperative period. Following the initial reports of successful SLT for COPD by Mal et al1 and Calhoon et al,2 incidences of acute native lung hyperinflation (ANLH) resulting in respiratory and hemodynamic compromise and subsequent increased morbidity and mortality have been reported. Recently, Yonan et al3 reported a series of 27 patients undergoing SLT for COPD, of whom approximately 30% developed severe ANLH requiring cardiopressor agents and independent lung ventilation (ILV). The mortality rate of patients developing ANLH was 42.6%. A preoperative FEV1 less than 15%, residual volume greater than twice the predicted value, and increased pulmonary artery pressures were predictive of the development of ANLH. These authors advocate the routine use of ILV, double-lung transplant (DLT), or rightsided SLT with contralateral lung volume reduction surgery (LVRS) for this subgroup of high-risk patients. However, these approaches all have inherent disadvantages. Independent lung ventilation can result in increased morbidity due to the inability to perform adequate pulmonary toilet with prolonged use of a dual lumen tube. Further, longer ischemic times during DLT may lead to an increased operative risk and may decrease the number of available donor lungs. Lung volume reduction surgery can cause prolonged postoperative air leaks and other problems unique to that procedure. Given the controversy as to the appropriate operation for COPD, our aim was threefold: to identify the incidence of ANLH in a larger series of patients, to identify
variables that preoperatively predict ANLH, and to comment on postoperative management strategies that limit its development.
PATIENTS AND METHODS We retrospectively reviewed 51 consecutive patients who underwent SLT for COPD at the University of Colorado Health Sciences Center between February 1992 and October 1998. Thirteen patients had ␣1-antitrypsin deficiency, and 38 had cigaretteinduced emphysema. Fourteen patients had bilateral bullous emphysema (13 had A1AT deficiency); 32 patients had no bullous changes; and 5 had unilateral bullous changes. Twenty-four right and 27 left SLTs were performed. Preference as to the side transplanted was determined by split-function ventilation–perfusion scans, the presence of previous major thoracic surgery or asymmetric bullous disease on computed tomography (CT) scan, and donor availability.
Definitions of Hyperinflation Acute native lung hyperinflation was defined as radiographic mediastinal shift and ipsilateral diaphragmatic flattening (Fig 1). Symptomatic ANLH was associated with either hemodynamic instability, defined as a systolic blood pressure ⬍ 90 mm Hg or a mean arterial pressure ⬍ 65 mm Hg requiring cardiopressor medications, or respiratory insufficiency requiring inhaled nitric oxide (iNO) or ILV. The presence of ANLH and the degree of lung injury by a lung injury score were determined by a radiologist unassociated with this study.
Outcome Variables We analyzed complete preoperative pulmonary function tests, hemodynamic parameters, the predicted donor to actual recipient total lung capacity (TLC) ratio, the need for cardiopulmonary bypass (CPB) or the use of iNO to prevent CPB, lung injury scores as determined by chest x-ray (CXR) and PaO2/FIO2 ratios, the need for iNO, and postoper-
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FIGURE 1 Acute native lung hyperinflation after a single left lung transplant for
emphysema. The respiratory insufficiency and hemodyamic instability resolved following extubation 2 hours postoperatively.
ative pulmonary artery pressures (PAP). The FEV1 and 6-minute walk tests were compared between the groups at 1 year. The incidence of acute rejection (AR), infection, and bronchiolitis obliterans syndrome (BOS) greater than grade 2 was also determined. Survival was compared at 30 days and 1, 2, and 3 years after transplant. Complete data were available on 38 of 51 total patients at the 3-year follow-up.
Statistical Analysis Preoperative and postoperative variables were compared using analysis of variance (ANOVA) and Schefe’s test. Survival, incidence of rejection and infection, and freedom from BOS were analyzed using Kaplan-Meier curves. P values less than 0.05 were considered significant.
Donor Criteria and Preservation Donor criteria included an age less than 60, PaO2 greater than 300 mm Hg on an FiO2 of 1.0 and
positive end-expiratory pressure of 5 cm H2O, clear chest radiograph, negative sputum gram stain, and an unremarkable bronchoscopic examination. Recipients and donors were matched by ABO compatibility and were of similar height and weight. No effort was made to match donors and recipients based on predicted TLC. Donors and recipients were instead matched within 15 to 20% of one another by vertical dimensions and by having a donor/recipient inframammary chest wall circumference ratio less than 1 and greater than 0.75.4 Modified Euro-Collins solution containing prostaglandin E1 was used to preserve the donor lungs.
Recipient Operation and Immunosuppression The operation was performed as previously described2 with the use of a telescoped anastomosis and without the use of CPB. Patients with secondary pulmonary hypertension (PA mean ⬎ 25 mm Hg) do not receive DLT in preference to SLT in our program. Patients received standard triple-drug im-
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TABLE I Incidence of acute native lung hyperinflation by disease and side transplanted ANLH
COPD A1AT deficiency Left side Right side
Radiographic (Total)
Symptomatic
10 6 10 6
4 4 4 4
No ANLH
Incidence
28 7 17 18
26% 46%* 37% 25%
ANLH, acute native lung hyperinflation; COPD, chronic obstructive pulmonary disease; A1AT, ␣1-antitrypsin deficiency. *P ⫽ 0.10 vs COPD.
munosuppression with cyclosporine, azathioprine, and prednisone and did not receive lympholytic agents. Solumedrol, 500 mg/kg, was given intravenously prior to the release of the PA clamp, then 125 mg twice a day in 6 doses. Prednisone was then given at 1 mg/kg per day and tapered to 0.1 to 0.15 mg/kg per day by 1 month. Cyclosporine was maintained at trough levels of 350 – 450 ng/mL, and azathioprine given at up to 2.5 mg/kg per day to maintain a white blood cell count of 5000 cells/L.
RESULTS We reviewed 51 consecutive SLT patients for emphysema. A total of 16 patients (31%) developed radiographic evidence of ANLH; 8 (15.7%) developed symptomatic ANLH requiring cardiopressor agents (n ⫽ 6), iNO (n ⫽ 1), or ILV (n ⫽ 1). Radiographic ANLH occurred in 6 of 14 patients, with bullous emphysema versus in 10 of 37 patients without bullous disease (P ⫽ NS). There was a trend toward an increased incidence of symptomatic
ANLH in patients with bullous emphysema, but this was primarily accounted for by patients with A1AT deficiency (4/13 vs 4/38 with COPD, P ⫽ 0.10). The development of ANLH was not influenced by ischemic times or the side transplanted (Table I). No patient in either group required CPB or intraoperative iNO, and there was no difference in the requirement for intraoperative pressors between groups. Preoperative pulmonary function tests, pulmonary artery pressures or the predicted donor to actual recipient TLC ratio did not predict which patients would develop radiographic or symptomatic ANLH (Table II). Postoperative parameters evaluated did not reveal any difference between patients who did and did not develop ANLH. Specifically, lung injury scores as determined by PaO2/FIO2 ratio and CXR scores were similar between the two groups (Table III). Pulmonary artery pressures were also similar between groups. Only one patient with ANLH required postoperative iNO while 5 patients without
TABLE II Preoperative pulmonary function tests and pulmonary artery pressures
FEV1 (actual) (% Predicted) FEF25–75 TLC RV RV % predicted PDTLC/ARTLC Range PA pressures PAS PA mean Ischemic Time (minutes)
Total ANLH (n ⴝ 16)
Radiographic ANLH (n ⴝ 8)
Symptomatic ANLH (n ⴝ 8)
No ANLH (n ⴝ 35)
0.47 ⫾ 0.3 15.7 ⫾ 1.2 0.18 ⫾ 0.01 133 ⫾ 7 5.08 ⫾ 0.6 275 ⫾ 22 0.97 ⫾ 0.12 0.64–1.44
0.47 ⫾ 0.03 14.7 ⫾ 2.3 0.17 ⫾ 0.02 138 ⫾ 8 5.25 ⫾ 0.55 289 ⫾ 27 0.98 ⫾ 0.12
0.52 ⫾ 0.04 16.6 ⫾ 1.0 0.19 ⫾ 0.02 130 ⫾ 11 4.96 ⫾ 1.0 266 ⫾ 33 0.95 ⫾ 0.11 0.78–1.43
0.52 ⫾ 0.04 16.4 ⫾ 0.8 0.21 ⫾ 0.02 132 ⫾ 5 5.17 ⫾ 0.3 281 ⫾ 16 0.93 ⫾ 0.17 0.56–1.56
32.3 ⫾ 1.7 20.2 ⫾ 1.3 239 ⫾ 23
33 ⫾ 3 21.3 ⫾ 2.4 245 ⫾ 17
31.5 ⫾ 1.7 19.1 ⫾ 1.2 233 ⫾ 21
35.1 ⫾ 1.4 23.8 ⫾ 1.2* 220 ⫾ 11
ANLH, acute native lung hyperinflation; FEV1, forced expiratory volume in 1 second; FEF25–75, forced expiratory flow 25–75%; TLC, total lung capacity; RV, residual volume; RV % predicted, percent predicted residual volume; PAS, systolic pulmonary artery pressure; PA mean, mean pulmonary artery pressure; PDTLC/ARTLC, predicted donor TLC/actual recipient TLC. *P ⫽ 0.07 vs symptomatic PAP mean.
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TABLE III Early postoperative outcomes
Lung Injury CXR Immediate 24 hours 48 hours 7 days PaO2FIO2 Immediate 24 h PAS Need for iNO Mech Vent (hours) LOS (days)
Total ANLH (n ⴝ 16)
Radiographic ANLH (n ⴝ 8)
Symptomatic ANLH (n ⴝ 8)
No ANLH (n ⴝ 35)
1.88 ⫾ 0.3 1.94 ⫾ 0.36 1.68 ⫾ 0.33 0.44 ⫾ 0.13c
1.91 ⫾ 0.3 1.96 ⫾ 0.4 1.66 ⫾ 0.3 0.40 ⫾ 0.1c
1.85 ⫾ 0.4 1.89 ⫾ 0.3 1.70 ⫾ 0.31 0.49 ⫾ 0.1c
1.56 ⫾ 0.19 1.75 ⫾ 0.22 1.43 ⫾ 0.21 0.91 ⫾ 0.19c
253 ⫾ 21 239 ⫾ 18 27.5 ⫾ 1.0 1 51.8 ⫾ 8.3 15.9 ⫾ 1.8
272 ⫾ 27 247 ⫾ 22 27.5 ⫾ 1.4 0 38.9 ⫾ 5.9 12.6 ⫾ 1.9
244 ⫾ 34 228 ⫾ 36 27.4 ⫾ 1.4 1 64.9 ⫾ 14.6a 19.3 ⫾ 2.1b
248 ⫾ 26 237 ⫾ 31 30.4 ⫾ 1.2 5 40.4 ⫾ 3.9 13.7 ⫾ 1.3
CXR, chest radiograph; PaO2, arterial oxygen tension; FIO2, fractional inspired oxygen; PAS, systolic pulmonary artery pressure; iNO, inhaled nitric oxide; LOS, length of stay. a P ⫽ 0.02 vs no NLH. b P ⫽ 0.07 vs no ANLH. c P ⬍ 0.05 vs immediate, 24 h, 48 h CXR score.
ANLH required iNO. Patients with symptomatic or asymptomatic ANLH had longer ventilator times than those without ANLH. There was a trend toward a longer hospital length of stay in the group who developed ANLH (see Table III), but 30-day survival was identical at 100%. Long-term survival (Fig 2) and functional outcomes (Table IV) were similar among the groups. There were also no differences in the episodes of AR, infection, or freedom from BOS greater than grade 2 (Fig 3). Four patients developed chronic NLH (3 had ANLH), and 2 underwent LVRS 3 and 4 years after transplant. FIGURE 2 Survival following single-lung transplant for
DISCUSSION
COPD. No difference in Kaplan–Meier survival between patients with (—) and without (----) acute native lung hyperinflation (P ⫽ NS).
In the early 1980s, heart-lung transplantation was considered the procedure of choice for COPD. By the late 1980s, DLT was used to avoid the hemody-
TABLE IV Long-term functional outcomes NLH (n ⴝ 16) FEV1 at 1 year 6-min walk at 1 year (feet) Episodes of AR Infection BOS (grade 2)
1.58 ⫾ 0.1 1276 ⫾ 89 0.22/100 patient days 0.40/100 patient days 5/16 (31%)
No NLH (n ⴝ 35) 1.52 ⫾ 0.07 1289 ⫾ 76 0.34/100 patient days 0.32/100 patient days 11/31 (35%)
ANLH, acute native lung hyperinflation; FEV1, forced expiratory volume in 1 second L/min; AR, acute rejection; BOS, bronchiolitis obliterans syndrome (BOS rates assume survival of at least 3 months).
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FIGURE 3 Incidence of bronchiolitis obliterans
syndrome following SLT for COPD. No difference in the percent freedom from BOS ⬎ Grade 2 between patients with (—) and without (----) acute native lung hyperinflation (P ⫽ NS).
namic and ventilatory consequences of performing SLT in patients with severe emphysema. Mal et al,1 and soon after Calhoun et al,2 reported successful SLT for COPD. Today, most centers consider SLT to be the procedure of choice, because SLT allows maximal use of donor organs, and patients receiving a SLT achieve a similar exercise tolerance5,6 and survival7,8 to those undergoing DLT. Despite the growing body of literature supporting SLT for emphysema, controversy still exists regarding the optimal procedure for this disorder. Recent reports have shown that SLT for this disease may be associated with increased morbidity and mortality secondary to excessive air trapping and hyperinflation of the native lung.3 In the present study, we found that ANLH was indeed common radiographically but was rarely clinically severe. The ANLH seen in our series was typically managed with cardiopressor agents, ventilator strategies aimed at allowing prolonged expiration, and early extubation. Further, ANLH was not associated with increased morbidity or mortality, or with suboptimal long-term graft function. Finally, similar to other anecdotal reports, we found a trend for symptomatic ANLH to occur more frequently in patients who had bullous emphysema, particularly those with A1AT deficiency. However, using standard preoperative pulmonary and hemodynamic parameters, we were unable to identify “high-risk” patients prone to develop ANLH. Recently, Yonan et al3 reported an incidence of symptomatic ANLH of up to 30% with an associated mortality rate of 42%. Preoperative parameters
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identifying this group included higher mean pulmonary artery pressures, FEV1 less than 15%, and residual volume greater than 200%. The authors recommended that alternative surgical and ventilatory strategies were necessary to optimize survival and functional outcomes. One such recommendation was the routine use of ILV in the high-risk subgroup of emphysema patients. Independent lung ventilation is complicated by the necessity of using a double-lumen endotracheal tube, which may prevent adequate pulmonary toilet. Maintaining proper positioning can be problematic, and acute malpositioning of the tube can result in lobar collapse or hypoventilation from an air leak around the bronchial cuff. Awake patients may not tolerate these tubes and will require more sedation and/or paralysis, which may delay weaning from mechanical ventilation. Finally, prolonged use of a dual-lumen tube can cause tracheal erosion or vocal cord injury because of the large caliber of these tubes. We were unable to identify a high-risk subgroup, so we cannot advocate the routine use of ILV. Our approach is to initially treat ANLH by disconnecting the endotracheal tube from the ventilatory circuit at various intervals to allow emptying of the native lung and to restore hemodynamic stability. If symptomatic ANLH persists in the absence of significant graft ischemia/reperfusion injury, we prefer early extubation. Late ischemia–reperfusion injury has been suggested as an impediment to early extubation; however, we have only experienced this problem in less than 2% of our patients. If a patient is unable to be extubated, either due to poor condition of the graft or due to muscular weakness or sedation caused by anaesthetic medications, ventilator manipulation can limit the amount of native lung hyperinflation and its negative consequences. Specifically, this is achieved by reducing tidal volume, decreasing ventilator breath frequency, increasing inspiratory flow rates, and reducing positive endexpiratory pressure. Frequent bronchodilator therapy is also employed in all COPD patients undergoing SLT in order to facilitate maximal native lung expiratory airflow. Some centers advocate alternative surgical approaches for the emphysematous patient. Bilateral lung transplant,7 SLT with contralateral LVRS,9 or the exclusive use of right-lung allografts has been advanced as the procedure to prevent the complications associated with SLT. However, these procedures may have several disadvantages. Double-lung transplantation has several disadvantages when compared to SLT, including longer ischemic times
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and a higher perioperative mortality in some programs; DLT may not be as well tolerated in older, sicker patients. Furthermore, SLT allows optimal use of scarce donor organs. Although this study did not directly compare the efficacy of SLT and DLT, in our experience, we have not seen differences in long-term functional outcome or survival between these two procedures (data not shown). Comparing SLT and DLT in terms of exercise tolerance and survival is difficult, given that studies examining these issues are mainly generated from single centers and are conflicting. The FEV1 following DLT should be higher than with SLT as more lung tissue—and therefore a greater pulmonary reserve—is transplanted during DLT. Demonstration of an exercise benefit from DLT as compared to a SLT may be biased given that younger, healthier patients are more likely to receive DLT.7,10 Although performing simultaneous LVRS and SLT in emphysema patients is effective in reducing the size of the hyperinflated native lung and may lead to better expiratory flows in the native lung,11 prolonged air leaks and other postoperative complications associated with LVRS may offset any benefit derived by this procedure. Injury to the native lung due to surgical manipulation during the LVRS procedure may lead to native lung dysfunction, which could exacerbate the postoperative difficulties associated with ischemia–reperfusion injury. Lung volume reduction surgery may, however, be useful in patients experiencing more chronic graft compression from the hyperinflated native lung.12,13 It has been postulated that the problems encountered with SLT for COPD are more common when a left SLT is performed. Because the right hemidiaphragm cannot move downward due to the presence of the liver, a hyperinflated native right lung can only expand across the mediastinum and could be more likely to cause cardiac tamponade and graft compression. Conversely, an emphysematous native left lung would tend to hyperinflate downward, flattening an unimpeded left diaphragm. These theoretical concerns aside, the exclusive use of right SLT is not supported by our findings as the development of symptomatic or asymptomatic ANLH was not dependent on the side transplanted in our series. Our study did not address functional capacity beyond 1 year and survival beyond 3 years, so our results do not suggest that the routine use of the above approaches are warranted to prevent the acute effects of NLH. In younger patients with bilateral bullous disease (usually those with A1AT
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deficiency in our cohort), these alternative approaches may be appropriate. The number of patients in our study may be inadequate to conclude definitively regarding this specific issue. When confronted with a patient with unilateral bullous changes, we of course chose to transplant the side with the bullae. The discrepancy between our results and those of Yonan et al3 is difficult to explain. The patient groups are similar with regards to severity of illness (mean FEV1 of 21% in our group vs mean FEV1 of 19.6% in Yonan’s cohort), and both included patients with secondary pulmonary hypertension. When analyzing small patient numbers (51 in the current study vs 27 in Yonan’s group), a type II () error may be present that could make detecting a difference between the two groups difficult. However, Yonan reported a 30-day mortality of 42% and commented that this rate was excessively high, while our 30-day mortality was zero. This survival difference suggests that perhaps there are other, unrecognized factors in donor and/or recipient selection or intra- or early postoperative management strategies that may account for the observed differences between the two studies. In conclusion, the purpose of this study was to identify the incidence of ANLH and potential preoperative variables that predict its occurrence. Our results support the following conclusions. First, although common radiographically, clinically severe ANLH is rare. Second, the preoperative variables we analyzed could not identify a subset of patients at risk for the development of ANLH. Third, although the development of either symptomatic or asymptomatic ANLH was associated with longer ventilator times and hospital lengths of stay, it was not associated with increased morbidity or mortality. These results do not support the routine use of ILV, DLT, or the exclusive use of right SLT for COPD. Further, simultaneous LVRS and SLT is not indicated for most patients. However, in young patients with bilateral bullous disease (particularly those with A1AT deficiency), alternative approaches to SLT may be indicated. Single-lung transplant for COPD can present challenging postoperative management issues, but several strategies can be employed that limit or eliminate the potentially deleterious effects of ANLH. REFERENCES 1. Mal H, Andreassian B, Pamela F, Duchatelle JP, Rondeau E, Dubois F, Baldeyrou P, Kitzis M, Sleiman C, Pariente R.
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2.
3.
4.
5.
6.
7.
Unilateral lung transplantation in end-stage emphysema. Am Rev Respir Dis 1989;140:797– 802. Calhoon JH, Grover FL, Gibbons WJ, Bryan CL, Levine SM, Bailey SR, Nichols L, Lum C, Trinkle JK. Single lung transplantation. Alternative indications and techniques. J Thorac Cardiovasc Surg 1991;101:816 –25. Yonan NA, El-Gamel A, Egan J, Kakadellis, Rahman A, Deiraniya AK. Single lung transplantation for emphysema: predictors for native lung hyperinflation. J Heart Lung Transplant 1998;17:192–201. Park SJ, Houck J, Pifarre R, Sullivan H, Garrity E, Kim SY, Zbilut J, Montoya A. Optimal size matching in single lung transplantation. J Heart Lung Transplant 1995;14:671–5. Low DE, Trulock EP, Kaiser LR, Pasque MK, Dresler C, Ettinger N, Cooper JD. Morbidity, mortality, and early results of single versus bilateral lung transplantation for emphysema. J Thorac Cardiovasc Surg 1992;103:1119 –26. Orens JB, Becker FS, Lynch JP 3rd, Christensen PJ, Deeb GM, Martinez FJ. Cardiopulmonary exercise testing following allogeneic lung transplantation for different underlying disease states. Chest 1995;107:144 –9. Waddell TK, Keshavjee S. Lung transplantation for chronic obstructive pulmonary disease. Semin Thorac Cardiovasc Surg 1998;10:191–201.
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8. Gaissert HA, Trulock EP, Cooper JD, Sundaresan RS, Patterson GA. Comparison of early functional results after volume reduction surgery or lung transplantation for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 1996;111:296 –307. 9. Malchow SC, McAdams HP, Palmer SM, Tapson VF, Putman CE. Does hyperexpansion of the native lung adversely affect outcome after single lung transplant for emphysema? Acad Radiol 1998;5:688 –93. 10. Sundaresan RS, Shiraishi Y, Trulock EP, Manley J, Lynch J, Cooper JD, Patterson GA. Single or bilateral transplantation for emphysema. J Thorac Cardiovasc Surg 1996;112: 1485–95. 11. Todd TR, Perron J, Winton TL, Keshavjee SH. Simultaneous single lung transplantation and lung volume reduction surgery. Ann Thorac Surg 1997;63:1468 –70. 12. Anderson MB, Kriett JM, Kapelanski DP, Perricone A, Smith CM, Jamieson SW. Volume reduction surgery in the native lung after single lung transplantation for emphysema. J Heart Lung Transplant 1997;16:752–7. 13. Kuno R, Kanter KR, Torres WE, Lawrence EC. Single lung transplantation followed by contralateral bullectomy for bullous emphysema. J Heart Lung Transplant 1996;15:389 – 94.