Lobectomy to downsize donor lungs for use in small recipients

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Abstracts

⫹SEM) was 42.0⫹13.6pcg/ml in the “unused” group compared to 23.9 ⫹ 8.4 in the “used” donors (p⫽0.01). Mean BNP was 70.7 ⫹ 14.5 in the “unused” compared with 32.8 ⫹ 9.6 in the “used” (p⬍0.05). RNA abundance (delta ct)for ANP was 17.6⫾1.8 and 11.81⫾3.9 in used and unused donors respectively. For BNP the values were 17.0⫾3.0 and 10.7⫾3.1 respectively. Conclusion: Measurement of natriuretic peptides may be a rapid, simple and objective method to assess donor heart function and can be used as a point-of-care assay at the donor hospital. Further studies are indicated to determine its role in donor assessment and the response to treatment.

The Journal of Heart and Lung Transplantation January 2003 pA)were transplanted with “optimal” donor hearts. 84 pts (17%,Group B) received a graft from donors considered marginal because of one or more of the following:age⬎ 60 yrs (13pts), high inotropic support (6pts), coronary artery disease (5pts),2D echo abnormalities (LPW thickness ⬎⫽ 13mm and/or LVEF⬍45%) (44pts), hypernatremia ⬎170 mmol/L (12pts), ischemic time ⬎ 300’(4pts).Recipients’ age, gender,indication to HTx and immunosuppressive regimens were comparable in both groups. Mean follow up was 83.5⫹/-56 months Acute rejection scores on endomiocardial biopsies were calculated for each patient (ISHLT grade 0⫽0, 1A⫽1, 1B⫽2, 2⫽3, 3A⫽4, 3B⫽5, 4⫽6) and compared at 1 month and 12 months. CAV incidence was assessed by annual coronary angiography and by IVUS in selected cases. Survival curves and results are shown.

131 SHORT AND LONG TERM OUTCOMES USING MARGINAL PULMONARY ALLOGRAFT DONORS H. Luckraz,1 P. White,1 L.D. Sharples,2 P. Hopkins,1 J. Wallwork,1 1 Transplant Unit, Papworth Hospital, Cambridge, United Kingdom; 2 MRC Biostatistics Unit, Cambridge, United Kingdom Background: The establishment of lung transplantation as a treatment modality for end-stage lung disease has led to an imbalance in the demand and supply for such a procedure. Increasingly borderline donors are being accepted for transplantation. Aim: We assessed the short and long term outcomes with the use of lung donors with low PO2. Methods and Results: All heart-lung and double lung transplantations (n⫽362) carried out between 1984 and 2001 were included. Recipients were divided according to the optimised donor PO2 (on 100 % FiO2): PO2⫽ 30-40 KPa ⫽ low PO2 donors (n⫽50) and PO2 ⬎ 40KPa ⫽ normal PO2 donors (n⫽312). There were no differences in the sex distribution, CMV status, ischaemic time and intubation durations for the recipients and their respective donors between the two groups. The low PO2 donors were older (38 v/s 32 years, p⫽0.01) and the allografts were transplanted into younger recipients (33 v/s 38 years, p⫽0.01). 30 day mortality was different between the two groups but not significantly so (22% v/s 13%, p⫽0.08). The 1 and 5-year survival rates (SE) were 66 (7 %) and 52 (7 %) for the low PO2 group and 72 (3%) and 44 (3 %) for the normal PO2 group (p⫽0.97). Similar infection rates were recorded for the groups. Although rejection rates were similar in the first three months, there was a lower rate of rejection in the low PO2 group thereafter, hazards ratio of 0.52 (p⫽0.05). Risk of BOS onset was marginally increased in the borderline donors (HR⫽1.22) although this was not statistically significant. Conclusion: Lung allograft donors with optimised PO2 between 30 and 40 KPa on 100 % FiO2 can be used for lung transplantation without significantly compromising short and long term outcomes in our patient group.

132 MARGINAL DONORS IN SHORTAGE ERA: IMPACT ON RECIPIENT’S LONG-TERM OUTCOMES A. Gambino, G. Feltrin, G. Gerosa, G. Nesseris, G. Tarantini, D. Casarotto, Cardiovasc Surgery, Univ. Padua, Italy In era of organs shortage, increasing donor hearts availability becomes crucial. Usage of “marginal donors”(MD) may expand the donors pool. We evaluated recipient’s outcomes (overall survival, incidence of acute and chronic rejection(CAV)) when a MD is used.We retrospectively analized data of 491consecutive pts, with a minimum follow up of 3 years (yrs) who underwent HTx at our Institution.407pts (83%,Grou-

Rejection score 1 month post HTx Rejection score 1 year post HTx CAV incidence

Group A

Group B

p value

5.26 ⫾ 3.6 18.94 ⫾ 9.3 15.2%

5.65 ⫾ 3.4 21.8 ⫾ 8.2 26.5%

0.36 0.009 0.016

Conclusions: In our experience, use of MD increased risk of acute rejection at 1yr(p⫽0.009), and incidence of CAV(p⫽0.016), with only a trend to worse survival (p⫽ns).MD can be considered in selected groups of recipients at high risk for early mortality on waiting list.

133 LOBECTOMY TO DOWNSIZE DONOR LUNGS FOR USE IN SMALL RECIPIENTS C.L. Lau, T.J. Guthrie, M. Scavuzzo, E.P. Trulock, J.D. Cooper, G.A. Patterson, B.F. Meyers, Department of Surgery/ Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO Purpose: The shortage of donors currently limits the more widespread use of lung transplantation. One traditional criterion has been size matching between the donor and recipient. In this study we review our experience with the use of donor lungs requiring downsizing to reduce size discrepancy between donor and recipient. Methods: We retrospectively reviewed 202 patients who underwent bilateral lung transplants at our institution from 6/98 to 8/02. The outcomes of patients who had undergone lobectomy for donor downsizing were compared to those of the overall series. Wedge resections were not included.

The Journal of Heart and Lung Transplantation Volume 22, Number 1S Results: Ten recipients, 7 females and 3 males, received lungs that required lobectomies due to size mismatch (5%). Downsized donor lungs were estimated to be 139% of the desired size (range 110-178%). Disease indication for transplant was COPD(6), pulmonary fibrosis(2), pulmonary hypertension(1), and lymphangioleiomyomatosis (1). Donor allografts underwent right upper lobectomy(5), left upper lobectomy(3), or bilateral upper lobectomies(2) after procurement to reduce size discrepancy. Intraoperatively, between the downsized and the overall series there were no differences in the use of cardiopulmonary bypass (30% vs.16%, p⫽0.4) or mean ischemic times (260 vs. 276 minutes, p⫽0.4). Significantly more of the recipients in the downsized group did have ⬎1 liter blood loss (50% versus 19%, p⫽0.03) Postoperatively no differences were seen in reperfusion injury(40% vs. 27%, p⫽0.5), reintubation(10% vs. 12%, p⫽1.0), airleaks ⬎7 days(20% vs. 11%, p⫽0.3), hemothoraces(0% vs. 1%, p⫽1.0), or PaO2/FiO2 at 24 hours (288 vs. 346, p⫽0.2). There were no hospital mortalities and no anastomotic complications in recipients of downsized donor lungs. Conclusions: Downsizing of donor lungs for smaller recipients can be done safely with minimal morbidity. The use of lobectomy to downsize donor lungs is a potential method of increasing utilization of otherwise adequate donors. 134 DONOR PRETREATMENT USING THE AEROSOLIZED PROSTACYCLIN ANALOGUE ILOPROST OPTIMIZES POSTISCHEMIC FUNCTION OF NON HEART BEATING DONOR LUNGS T. Wittwer, U.F.W. Franke, T. Sandhaus, A. Schuette, S. Richter, J.M. Albes, T. Mueller, H. Schubert, T. Wahlers, Cardiothoracic and Vascular Surgery, Friedrich Schiller University, Jena, Germany Ischemia-reperfusion-injury accounts for one third of early deaths after lung transplantation. To expand the limited donor pool, lung retrieval from non-heart-beating donors (NHBD) has been introduced recently. However, due to potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods prior to preservation. After intravenous prostanoids are routinely used to ameliorate reperfusion injury, latest evidence suggests similar efficacy of inhaled prostacyclin. Therefore, the impact of donor pretreatment using the prostacyclin-analogue Iloprost on postischemic NHBD lung function and preservation quality was evaluated. Asystolic pigs (n⫽5/group) were ventilated for 180 minutes of warm ischemia (group 1). In group 2, 100 ␮g Iloprost were aerosolized during the final 30 minutes of ventilation using a novel mobile ultrasonic nebulizer (Optineb威). Lungs were then retrogradely preserved with Perfadex and stored for 3 hours. Following left lung transplantation and contralateral lung exclusion, hemodynamics, pO2/FiO2 and dynamic compliance were monitored for 6 hours and compared to sham-operated controls. Pulmonary edema was determined by wet-to-dry weight ratio (W/D), and extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA analysis with repeated measurements. Flush preservation pressures, dynamic compliance, inspiratory pressures and W/D were significantly lower in Ilomedin-treated lungs, while oxygenation and pulmonary hemodynamics were comparable between groups. EVLWI was within normal ranges in Iloprost-grafts. Alveolar deposition of Iloprost in NHBD lungs prior to preservation ameliorates postischemic edema and significantly improves lung compliance. This easily applicable innovative approach using a mobile ultrasonic nebulizer offers an important strategy for improvement of preservation quality.

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135 C2 TARGETS AND MULTIVARIATE PREDICTORS OF C2 LEVELS IN STABLE HEART TRANSPLANT PATIENTS IMMUNOSUPPRESSED ON A C0-BASED REGIMEN A.L.P. Caforio,1 F. Tona,1 S. Piaserico,2 A. Gambino,3 G. Feltrin,3 A. Belloni Fortina,2 A. Angelini,4 A. Peserico,2 G. Thiene,4 S. Iliceto,1 D. Casarotto,3 1Cardiology-Dept Exp Clinical Medicine, University of Padua, Padua, PD, Italy; 2Dermatology, University of Padua, Padua, PD, Italy; 3Cardiac Surgery, University of Padua, Padua, PD, Italy; 4 Cardiac Pathology, University of Padua, Padua, PD, Italy Neoral dose monitoring in heart transplantation (HT) is based on trough levels (C0), since cyclosporine A (CsA) 2-hr peak (C2) targets have not been established. To identify C2 targets and clinical correlates of C0 and C2, we studied 314 stable HT pts (251 male, aged 50⫾14 yrs at HT, follow-up 6.8⫾4 yrs, range 1 mo-15 yrs), on a C0-based regimen. Mean C0 and C2 levels (ng/mL) were 268⫾80 and 1031⫾386 respectively for pts (n⫽19) in the first 3 mo; 230⫾49 and 955⫾239 in pts (n⫽10) between 4 and 12 mo; 157⫾53 and 745⫾235 in pts (n⫽285) after 1 yr. Our target C0 levels (ng/mL) are 150-400 (first 3 mo), 150-300 (4-12 mo), 100-250 (⬎12mo). For pts within the target C0 the corresponding C2 (ng/mL) were 600-1500 (first 3 mo), 600-1300 (4 to 12 mo), 500-1000 (⬎12mo). C2 correlated with C0 (Pearson, r⫽0.61, p⫽0.0001). C2 correlated better with CsA dose than C0 (r⫽0.50, p⫽0.0001 vs r⫽0.36, p⫽0.0001). Between pts CsA dose varied by a factor of 9.3; the C/dose ratio varied by a factor of 8.5 for C2 and of 15.6 for C0. Pts with higher C2 (⬎550) had higher rejection scores at 1 yr (p⫽0.04) and during whole follow-up (p⫽0.04) than pts with lower C2 (t-test). This did not apply to higher (⬎110) C0 vs. lower C0. Both C2 and C0 correlated with blood urea (r⫽-0.19, p⫽0.001; r⫽-0.18, p⫽0.002) and creatinine (r⫽-0.16, p⫽0.004; r⫽-0.20, p⫽0.0001 respectively). By logistic regression higher C2 (⬎550 ng/mL) was associated with higher CsA and steroid load (mg/Kg) at 1 yr (p⫽0.038; p⫽0.001 respectively), lower blood urea (p⫽0.003) and tended to be associated with high total severe rejection score (p⫽0.07). Regression analysis on higher C0 (⬎110 ng/mL) did not show associations. Thus, C2 showed better correlation with CsA dose, renal function, rejection profile and less variability between pts than C0. C2 may improve CsA-based immunosuppression in HT. 136 RAPAMYCIN (SIROLIMUS) AUC ESTIMATION IN HEART TRANSPLANT RECIPIENTS WITH CHRONIC RENAL IMPAIRMENT E.D. Moloney,1 U. O’Mahony,2 M. Kirwan,2 J. McCarthy,2 J. Hurley,2 A.E. Wood,2 J.J. Egan,2 1Adult ICU, Royal Brompton and Harefield NHS Trust, London, United Kingdom; 2Heart Lung Transplant Programme, Mater Misericordiae Hospital, Dublin, Ireland Rapamycin has a narrow therapeutic index with variable absorption, distribution, and elimination. Therapeutic drug monitoring of plasma levels optimises drug concentrations reducing the risks of toxicity or rejection. This study was undertaken to estimate the relationship between trough rapamycin levels and AUC in heart transplant recipients (HTR) with renal impairment. Seven male HTR, mean (SEM) age 61years(3.6), were studied. Rapamycin was initiated 9 years (1.5) after transplant. Renal impairment resulted from cyclosporin in 6 cases and renovascular disease in 1 case. Mean creatinine clearance was 43.6 ml/min (17.5). Cyclosporin was discontinued and rapamycin initiated aimed at a stable trough level of 10ng/ml. The mean (SEM) rapamycin dose was 3 mg/day (0.5). AUC estimation was calculated using 6 specific time points. There was a significant correlation between time 0 hours