Long-term outcomes of cadaveric lobar lung transplantation: helping to maximize resources.

BACKGROUND: Cadaveric lobar lung transplantation (CLLTx) represents a potential opportunity to address the bias against smaller recipients, especially children, on transplant waiting lists. The widespread use of CLLTx is hindered by the paucity of outcome data with respect to early complications and long-term lung function and survival. METHODS: We looked at the long-term outcomes in 9 patients undergoing CLLTx since May 2003, including early surgical complications, pulmonary function tests, and survival. Patients were analyzed by whether the decision to perform CLLTx was elective (made at the time of listing) or emergent (surgical decision). RESULTS: The incidence of early complications in the entire group was low, with the most common being atrial arrhythmias and prolonged thoracostomy tube. Lung function at 1 and 2 years (mean forced expiratory volume in 1 second % predicted +/- standard deviation of 73 +/- 18 and 60.5 +/- 27, respectively) was equivalent to living lobar transplant results. Overall survival was similar to 199 patients who received conventional cadaveric LTx during the same period. CONCLUSION: This study suggests that CLLTx has a low complication rate with acceptable lung function and long-term survival, especially in cases where consideration has been given to CLLTx at the time of listing. CLLTx warrants consideration more often for patients of smaller physique to improve their chance of receiving LTx.

The implications of pulmonary embolism in a multiorgan donor for subsequent pulmonary, renal, and cardiac transplantation.

BACKGROUND: Unexpected donor pulmonary embolism is suggested to be associated with primary graft dysfunction (PGD) after lung transplantation. In multiorgan donors with pulmonary embolism, multiple organs could potentially be at high risk for the development of post-transplant PGD. This study investigated (1) the association of donor pulmonary embolism with different organ transplant outcomes where a recipient received an organ (heart or kidney) from a lung donor, (2) the effect of different composition of pulmonary embolism (fat or thromboemboli) on multiorgan post-transplant PGD, and (3) the effect of removal of pulmonary embolism (therapeutic flush) on lung transplant outcomes. METHODS: The study included 130 multiorgan donors and 135 lung, 38 heart, and 172 kidney transplant recipients. RESULTS: Pulmonary embolism was detected in 40 of 130 (31%) multiorgan donors (10 fat emboli, 30 thromboemboli). A significant association between donor pulmonary embolism and PGD was seen in lung, but not in heart and kidney transplant recipients. A multivariate analysis showed that lung transplant recipients receiving lungs with fat emboli and thromboemboli were 20.6-fold (p = 0.0002) and 4.8-fold (p = 0.02) more likely to develop severe PGD, respectively, compared with those who received lungs without pulmonary embolism. Removal of pulmonary embolism reduced the incidence of PGD (p = 0.01) in lung transplantation. CONCLUSIONS: The deleterious effect of donor pulmonary embolism seems to be a local phenomenon, limited to the lung; therefore, the heart and kidneys can be safely used even from a donor with pulmonary embolism. When pulmonary embolism (especially fat emboli) is diagnosed, the likely effect on lung transplant clinical outcomes and the impact of further interventional strategies (therapeutic flush) must be considered.

Third-time lung transplant using extended criteria lungs.

There is an increasing requirement for lung re-transplants (re-LTx) related to the bronchiolitis obliterans syndrome. Nevertheless, re-LTx, especially second-time re-LTx, poses the dilemma of appropriate allocation of a scarce donor lung resource versus the desire to optimize outcomes for an individual patient. Extended donors have been used to partially alleviate a scarce donor lung supply with satisfactory outcomes for primary lung transplant. However, the usefulness of the extended donors remains unknown, including donation-after-cardiac-death donors for re-LTx. This report describes a second-time re-LTx using significantly extended donor criteria lungs from a Maastricht category IV donation-after-cardiac-death donor with resultant good clinical outcomes.

Feasibility and utility of a lung donor score: correlation with early post-transplant outcomes.

BACKGROUND: A lung donor score may provide a numerical value of overall donor lung "quality" to allow comparison among different organizations and research protocols. This study aims to develop a simple scoring system and investigate its applicability on predicting donor selection and early post-lung-transplant (LTx) outcomes. METHODS: Data of all donors referred to our institution in 2001 were initially analyzed to create a LTx donor score. Five domains, age, smoking history, chest X-ray, secretions, and arterial blood gas results, were included. A larger cohort of transplant recipients (years 2002 to 2005) was analyzed to validate the score against early post-LTx outcomes. RESULTS: In the initial 2001 cohort, 36 of 87 (41%) donors were used for 41 LTx (used group) and 51 (59%) were declined for medical (lung-exclusion group, n = 31) and general (general-exclusion group, n = 20) reasons. The median donor scores in the used, general-exclusion, and lung-exclusion groups were 2.0, 2.0, and 10.0, respectively (p < 0.0001). In multivariate analysis of the validation cohort, the donor score in bilateral LTx was significantly associated with post-transplant ratio of arterial oxygen tension and inspired oxygen fraction (coefficient = -16.19, p = 0.002), primary graft dysfunction grade (coefficient = 0.21, p < 0.0001), and intubation hours (coefficient = 0.05, p = 0.04); however, a significant association was not seen in single LTx. CONCLUSIONS: A proposed simple donor scoring system, based on five major donor variables available at the time of donor selection, may be useful for data comparison between specific centers, quality control, evaluative research, and clinical decision making in donor selection and management in LTx.

Unilateral radiographic abnormalities after bilateral lung transplantation: exclusion from the definition of primary graft dysfunction?

OBJECTIVES: Unilateral infiltrates on chest x-ray films are occasionally seen after bilateral lung transplantation. In the primary graft dysfunction grading system, the presence or absence of a radiographic abnormality is crucial in determining the incidence and severity of primary graft dysfunction. However, no consideration is given as to whether unilateral infiltrates have the same impact and relevance as bilateral infiltrates. This study aims to describe the incidence, features, and outcomes of posttransplant unilateral infiltrates and their effect on the novel primary graft dysfunction grading system. 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.

Early outcomes comparing Perfadex, Euro-Collins, and Papworth solutions in lung transplantation.

BACKGROUND: Despite improved surgical techniques and medical management, primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after lung transplantation. Different types of lung preservation solutions have been developed and applied to clinical use; however, the relative clinical efficacy of these solutions to prevent PGD remains controversial. This study aimed to investigate the effect of the three solutions most commonly used (Perfadex [Vitrolife, Göteborg, Sweden], Papworth, and Euro-Collins [Baxter Healthcare, Old Toongabbie NSW, Australia]) on posttransplant outcomes. METHODS: Early outcomes from 157 consecutive lung transplants (113 bilateral and 44 single) performed at The Alfred Hospital were compared across three preservation solutions. RESULTS: Posttransplant oxygenation (p = 0.57), pulmonary vascular resistance (p = 0.34), intubation hours (p = 0.66), intensive care unit days (p = 0.34), severe PGD (grade 3) (p = 0.70), 30-day mortality (p = 0.87), and 3-month % predicted forced expiratory volume in 1 second (p = 0.58) were not statistically different; however, Perfadex trended toward superiority among the three solutions. After adjustment of donor, recipient, and operative factors in multivariate analysis, Perfadex was significantly associated with the prevention of moderate to severe PGD (grade 2 to 3) at 48 hours posttransplant (odds ratio = 0.26 [0.10 to 0.72], p < 0.01) compared with Papworth (odds ratio = 0.75 [0.32 to 1.75], p = 0.51) and Euro-Collins (reference) solutions. CONCLUSIONS: Although any advantageous effects of Perfadex on early posttransplant outcomes were generally subtle and statistically nonsignificant, Perfadex prevented moderate to severe PGD. Switching preservation solution from Euro-Collins (or Papworth) to Perfadex would appear to usefully contribute to a strategy to reduce PGD in lung transplantation.

Definitions of primary graft dysfunction after lung transplantation: differences between bilateral and single lung transplantation.

OBJECTIVE: The primary graft dysfunction definition has been applied to both bilateral lung transplantation and single lung transplantation. However, the differences between bilateral and single lung transplantation in terms of primary graft dysfunction remain unknown. This study aims to investigate the features and utility of the new primary graft dysfunction grading system by comparing early outcomes from bilateral and single lung transplantation. METHODS: The primary graft dysfunction grade of 228 consecutive lung transplants (149 bilateral and 79 single lung transplants) at multiple postoperative time points was analyzed. Subgroup analysis with chronic obstructive pulmonary disease was performed to further validate the difference between bilateral lung transplantation and single lung transplantation. RESULTS: The percentage of grade 3 primary graft dysfunction in bilateral and single lung transplants was 32% and 37% at 0 hours (T0), 9% and 33% at 12 hours (T12), 7% and 26% at 24 hours (T24), and 9% and 18% at 72 hours (T72), respectively. The prevalence of the grade 3 primary graft dysfunction (T24) was significantly different between those undergoing bilateral lung transplantation and those undergoing single lung transplantation (P = .02). The primary graft dysfunction grade (T0) significantly correlated with the duration of intubation in both bilateral (r = 0.35, P < .0001) and single (r = 0.42, P = .001) lung transplantation and length of intensive care unit stay in both bilateral (r = 0.31, P = .0002) and single (r = 0.33, P = .006) lung transplantation. These differences were validated by the subgroup analysis. CONCLUSIONS: The prevalence of primary graft dysfunction grade is different between bilateral and single lung transplantation and varies with time. Although the primary graft dysfunction grade correlated with the early posttransplantation outcomes, for the purposes of description and further studies, primary graft dysfunction in bilateral and single lung transplantation should be considered separately.

Unexpected donor pulmonary embolism affects early outcomes after lung transplantation: a major mechanism of primary graft failure?

OBJECTIVE: Primary graft failure remains a significant cause of morbidity and mortality after lung transplantation, and its mechanism is not understood. Previously 2 case reports described fatal primary graft failure due to donor-related unexpected pulmonary embolism. This study investigated the incidence, early outcome, and risk factors of unexpected pulmonary embolism in lung transplantation. METHODS: An exploratory retrograde donor lung flush before implantation to diagnose pulmonary embolism (emboli group) or no pulmonary embolism (no-emboli group) was performed in 74 of 122 consecutive lung transplantations. RESULTS: The incidence of macroscopic unexpected pulmonary embolism was 38% (28% clot and 9% fat). In the emboli group, significantly decreased oxygenation (P < .05), increased pulmonary vascular resistance (P < .001), an increased proportion of opacity on chest radiograph (P = .03), prolonged intubation (P < .001) and intensive care unit stay (P < .01), and decreased 1-year survival (P = .03) were seen after transplantation. In multivariate analysis, pulmonary embolism was an independent risk factor for prolonged intubation (hazard ratio, 2.42; P < .01). In logistic regression, death due to trauma with fracture and a smoking history of more than 20 pack-years were significant donor risk factors for pulmonary embolism (adjusted odds ratio, 8.77 and 5.64; P = .02 and .04, respectively). No deleterious effects of the exploratory flush were seen. CONCLUSIONS: Unexpected pulmonary embolism is relatively common, is potentially predicted by donor history (but not by arterial blood gas analysis or chest radiograph), and is associated with primary graft failure. Donor lungs with risk factors of pulmonary embolism should undergo an exploratory flush. When pulmonary embolism is diagnosed, further therapeutic strategies must be considered.

A donor history of smoking affects early but not late outcome in lung transplantation.

BACKGROUND: Liberalization of tobacco exposure history as an exclusion to lung donation has recently occurred to increase donor organ availability. This study investigated the effect of donor smoking status and current and cumulative cigarette dose on early and late outcomes in lung transplantation. METHODS: From 1995 to 2002, 173 heart-lung and bilateral single-lung transplant recipients were retrospectively reviewed. Seventy-seven (45%) of 173 donors were ever-smokers and 64 of those 77 were current smokers. These were divided into subgroups by current number of cigarettes smoked to investigate acute dose effects and by pack-year to investigate cumulative dose effects. Risks of smoking were assessed by univariate and multivariate hazard regression models. RESULTS: Univariate analysis revealed that there were significant differences between current and cumulative dose subgroups in early postoperative variables, including Pao2/Fio2 ratio, ventilation time, and intensive care unit stay. Additionally, these variables were dose dependent. There was no significant difference in 3-year survival between never-smokers and ever-smokers (73% versus 64%, P = 0.27), and a rate of decline of survival was similar. There was a trend for the percentage of patients dying of bronchiolitis obliterans syndrome to be lower in the ever-smokers group compared with the never-smokers group (6% versus 11%, respectively). Multivariate analysis revealed current and cumulative smoking as a risk factor for early but not late outcomes. CONCLUSIONS: Donor smoking history had a significant effect on early outcomes in lung transplantation in a current and cumulative dose-dependent fashion. However, no significant effect on late outcomes, including bronchiolitis obliterans syndrome, was seen.