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277 Lung Transplant Surgery on Cardiocirculatory Support: Extracorporeal Membrane Oxygenation Outcompetes Cardiopulmonary Bypass
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The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
risks for MRSA dz were ⫹ nasal (p⬍0.0001) or recipient sterility (p⫽0.02) cultures (cx). 33% (26/80) of MRSA colonized pts developed dz. Donor MSSA cx were protective against MSSA dz (p⫽0.006), likely due to tailored antibiotics post-LT. SA dz was associated with longer ICU and hospital stays (p⬍0.0001), acute and chronic rejection (BOS), and lower survival (MRSA⬃MSSA). Increased mortality is apparent up to 4 yrs post-LT. Conclusions: SA largely causes PNA (VAP in particular) and tracheobronchitis early post-LT. Early-onset SA dz is associated with longer stays and increased rejection (BOS in particular) and mortality. Risks for MRSA dz are ⫹ recipient nasal or sterility cx, suggesting that MRSA decolonization may reduce dz and be cost-effective. 276 Paired Donor Lung Expression Suggest Key Effectors in Primary Graft Dysfunction E. Cantu,1 L. Erhunmwunsee,2 R. Feng,3 N.J. Meyer,4 J.M. Diamond,5 R.J. Shah,5 S. Rao,6 S.S. Lin,2 R.D. Davis,2 J.D. Christie.4 1Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 2Department of Surgery, Duke University Medical Center, Durham, NC; 3Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 4Pulmonary, Allergy, and Critical Care Division, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 5 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 6Penn Molecular Profiling Facility Bioinformatics Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Purpose: Donor selection practices have become more subjective as use of extended criteria donors has become more prevalent. The risk of primary graft dysfunction (PGD) after lung transplantation significantly influences donor selection. We hypothesized that mRNA expression of donor organ injury transcripts prior to procurement would be associated with subsequent PGD. Methods and Materials: We performed a cohort study of sequential lung transplant donors. Open lung biopsies were obtained at the donor hospital prior to heparinization and within 30 minutes after reperfusion in the recipient. The primary outcome was development of grade 3 PGD within 72 hours. Results: Of the 17 donors evaluated, 4 recipients developed PGD (24%). Mean donor age (PGD:44.8; non-PGD 33.5, p⫽0.16), PaO&2 &(470; 466,p⫽0.94) and ischemic time (8.85; 6.82, p⫽0.12) did not significantly differ between groups. In donor samples, 1525 distinct transcripts were different in those donor organs that subsequently developed PGD. Of the 20 transcripts with the greatest differences between PGD and non-PGD, 6 were in known lung injury mediators, including chitinase 1(CHIT1), angiopoietin 2(ANGPT2), long pentraxin 3 (PTX3), interleukin 1 beta (IL1B), interleukin-8(IL8), growth arrest and DNA-damage-inducible beta (GADD45b). Prior to procurement of donor lung, increased fold-changes in CHIT1 (4), ANGPT2 (7) and PTX3 (2) were demonstrated. Further exploration within subjects between donor and post-implantation gene expression illustrated even greater up-regulation of these lung injury markers: CHIT1(60), ANGPT2 (10) and PTX3 (7). Conclusions: Up-regulation of lung injury transcripts in donor lungs that go on to PGD suggests that subclinical lung injury has begun in the donor prior to procurement. Increases in these same lung injury markers over the pre-procurement level after transplantation, suggests amplification of these injury mechanisms during the procedure. Pathways involving CHIT1, ANGPT2 and PTX3 should be prioritized for future studies of PGD after lung transplantation. 277 Lung Transplant Surgery on Cardiocirculatory Support: Extracorporeal Membrane Oxygenation Outcompetes Cardiopulmonary Bypass F. Ius,1 C. Kühn,1 I. Tudorache,1 W. Sommer,1 M. Avsar,1 T. Fuehner,2 T. Welte,2 J. Gottlieb,2 A. Haverich,1 G. Warnecke.1 1Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany; 2Department of Respiratory Medicine,
Hannover Medical School, Hannover, Germany. Purpose: In early 2010, we changed our standard for implementation of cardiopulmonary bypass (CPB) in lung transplantation (LuTx). Before, CPB was used in patients with severe pulmonary artery hypertension (PHT) or other important reasons for the CPB use. After March 2010, all LuTx patients who fulfilled the same criteria received extracorporeal membrane oxygenation (ECMO). Here, we analyzed the impact of this change of strategy on outcome. Methods and Materials: Between 08/2008 and 02/2010, 46 consecutive patients underwent LuTx with CPB and thereafter 46 consecutive patients with ECMO. Preoperatively, more ECMO patients presented PHT (37% vs 11%, p⫽0.003) as indication to transplantation and were admitted to the intensive care unit (ICU) (30% vs 13%, p⫽0.04). Results: Intra-operatively, CPB patients required more blood transfusions (12⫾11 vs 7⫾9 units p⫽0.01) and platelet concentrates (2.5⫾1.6 vs 1.5⫾1 bags, p⬍0.001). More CPB patients needed a secondary ECMO implant (26% vs 4%, p⫽0.004) and presented an acute renal failure requiring dialysis (41% vs 13%, p⫽0.002). CPB patients seemed to need longer mechanical ventilation and ICU stay times (days) (21⫾28 vs 14⫾19, p⫽0.4 and 29⫾32 vs 19⫾18, p⫽0.5, respectively), higher incidence of rethoracotomy for bleeding (30% vs 13%, p⫽0.09) and higher primary graft dysfunction scores (PGD) at 24 hours (PGD 2-3: 39% vs 30%, p⫽0.2). At 1, 3 and 9 months survival was 80⫾6% vs 98⫾2%, 70⫾7% vs 86⫾5% and 59⫾7% vs 86⫾5%, in CPB and ECMO patients, respectively (p⫽0.003).
Conclusions: The intra-operative use of ECMO in LuTx to substitute CPB is a superior alternative, confers a survival benefit and reduces postoperative complications. 278 Grade 3 Primary Graft Dysfunction after Lung Transplantation: A Heterogeneous Population M. Cypel, R. Zamel, K. Yasufuku, A. Pierre, M. DePerrot, L.G. Singer, M. Liu, S. Keshavjee, T.K. Waddell. University of Toronto, Toronto, ON, Canada. Purpose: Severe primary graft dysfunction (PGD, ISHLT grade 3) has been shown to adversely impact short and long term outcomes after lung transplantation (LTx). However, some patients with PGD 3 rapidly recover from this injury, whereas others persist with poor graft function for several days. The objective of this study was to determine the outcome of different PGD 3 phenotypes. Methods and Materials: Patients suffering from PGD 3 were classified in the following categories: A: PGD 3 on ICU arrival but PGD 3 free by 72hs; B: persistent PGD 3 throughout first 72h post LTx; and C: PGD 3 requiring use of extracorporeal membrane oxygenation (ECMO). Time of mechanical ventilation, ICU and hospital length of stay (LOS), 30 day mortality, and overall survival were compared among the 3 groups. Results: Between January of 2007 and October of 2011, 448 LTx were performed. Incidence of PGD 0-1, 2, and 3 on ICU arrival were 294
The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
risks for MRSA dz were ⫹ nasal (p⬍0.0001) or recipient sterility (p⫽0.02) cultures (cx). 33% (26/80) of MRSA colonized pts developed dz. Donor MSSA cx were protective against MSSA dz (p⫽0.006), likely due to tailored antibiotics post-LT. SA dz was associated with longer ICU and hospital stays (p⬍0.0001), acute and chronic rejection (BOS), and lower survival (MRSA⬃MSSA). Increased mortality is apparent up to 4 yrs post-LT. Conclusions: SA largely causes PNA (VAP in particular) and tracheobronchitis early post-LT. Early-onset SA dz is associated with longer stays and increased rejection (BOS in particular) and mortality. Risks for MRSA dz are ⫹ recipient nasal or sterility cx, suggesting that MRSA decolonization may reduce dz and be cost-effective. 276 Paired Donor Lung Expression Suggest Key Effectors in Primary Graft Dysfunction E. Cantu,1 L. Erhunmwunsee,2 R. Feng,3 N.J. Meyer,4 J.M. Diamond,5 R.J. Shah,5 S. Rao,6 S.S. Lin,2 R.D. Davis,2 J.D. Christie.4 1Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 2Department of Surgery, Duke University Medical Center, Durham, NC; 3Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 4Pulmonary, Allergy, and Critical Care Division, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 5 Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; 6Penn Molecular Profiling Facility Bioinformatics Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. Purpose: Donor selection practices have become more subjective as use of extended criteria donors has become more prevalent. The risk of primary graft dysfunction (PGD) after lung transplantation significantly influences donor selection. We hypothesized that mRNA expression of donor organ injury transcripts prior to procurement would be associated with subsequent PGD. Methods and Materials: We performed a cohort study of sequential lung transplant donors. Open lung biopsies were obtained at the donor hospital prior to heparinization and within 30 minutes after reperfusion in the recipient. The primary outcome was development of grade 3 PGD within 72 hours. Results: Of the 17 donors evaluated, 4 recipients developed PGD (24%). Mean donor age (PGD:44.8; non-PGD 33.5, p⫽0.16), PaO&2 &(470; 466,p⫽0.94) and ischemic time (8.85; 6.82, p⫽0.12) did not significantly differ between groups. In donor samples, 1525 distinct transcripts were different in those donor organs that subsequently developed PGD. Of the 20 transcripts with the greatest differences between PGD and non-PGD, 6 were in known lung injury mediators, including chitinase 1(CHIT1), angiopoietin 2(ANGPT2), long pentraxin 3 (PTX3), interleukin 1 beta (IL1B), interleukin-8(IL8), growth arrest and DNA-damage-inducible beta (GADD45b). Prior to procurement of donor lung, increased fold-changes in CHIT1 (4), ANGPT2 (7) and PTX3 (2) were demonstrated. Further exploration within subjects between donor and post-implantation gene expression illustrated even greater up-regulation of these lung injury markers: CHIT1(60), ANGPT2 (10) and PTX3 (7). Conclusions: Up-regulation of lung injury transcripts in donor lungs that go on to PGD suggests that subclinical lung injury has begun in the donor prior to procurement. Increases in these same lung injury markers over the pre-procurement level after transplantation, suggests amplification of these injury mechanisms during the procedure. Pathways involving CHIT1, ANGPT2 and PTX3 should be prioritized for future studies of PGD after lung transplantation. 277 Lung Transplant Surgery on Cardiocirculatory Support: Extracorporeal Membrane Oxygenation Outcompetes Cardiopulmonary Bypass F. Ius,1 C. Kühn,1 I. Tudorache,1 W. Sommer,1 M. Avsar,1 T. Fuehner,2 T. Welte,2 J. Gottlieb,2 A. Haverich,1 G. Warnecke.1 1Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany; 2Department of Respiratory Medicine,
Hannover Medical School, Hannover, Germany. Purpose: In early 2010, we changed our standard for implementation of cardiopulmonary bypass (CPB) in lung transplantation (LuTx). Before, CPB was used in patients with severe pulmonary artery hypertension (PHT) or other important reasons for the CPB use. After March 2010, all LuTx patients who fulfilled the same criteria received extracorporeal membrane oxygenation (ECMO). Here, we analyzed the impact of this change of strategy on outcome. Methods and Materials: Between 08/2008 and 02/2010, 46 consecutive patients underwent LuTx with CPB and thereafter 46 consecutive patients with ECMO. Preoperatively, more ECMO patients presented PHT (37% vs 11%, p⫽0.003) as indication to transplantation and were admitted to the intensive care unit (ICU) (30% vs 13%, p⫽0.04). Results: Intra-operatively, CPB patients required more blood transfusions (12⫾11 vs 7⫾9 units p⫽0.01) and platelet concentrates (2.5⫾1.6 vs 1.5⫾1 bags, p⬍0.001). More CPB patients needed a secondary ECMO implant (26% vs 4%, p⫽0.004) and presented an acute renal failure requiring dialysis (41% vs 13%, p⫽0.002). CPB patients seemed to need longer mechanical ventilation and ICU stay times (days) (21⫾28 vs 14⫾19, p⫽0.4 and 29⫾32 vs 19⫾18, p⫽0.5, respectively), higher incidence of rethoracotomy for bleeding (30% vs 13%, p⫽0.09) and higher primary graft dysfunction scores (PGD) at 24 hours (PGD 2-3: 39% vs 30%, p⫽0.2). At 1, 3 and 9 months survival was 80⫾6% vs 98⫾2%, 70⫾7% vs 86⫾5% and 59⫾7% vs 86⫾5%, in CPB and ECMO patients, respectively (p⫽0.003).
Conclusions: The intra-operative use of ECMO in LuTx to substitute CPB is a superior alternative, confers a survival benefit and reduces postoperative complications. 278 Grade 3 Primary Graft Dysfunction after Lung Transplantation: A Heterogeneous Population M. Cypel, R. Zamel, K. Yasufuku, A. Pierre, M. DePerrot, L.G. Singer, M. Liu, S. Keshavjee, T.K. Waddell. University of Toronto, Toronto, ON, Canada. Purpose: Severe primary graft dysfunction (PGD, ISHLT grade 3) has been shown to adversely impact short and long term outcomes after lung transplantation (LTx). However, some patients with PGD 3 rapidly recover from this injury, whereas others persist with poor graft function for several days. The objective of this study was to determine the outcome of different PGD 3 phenotypes. Methods and Materials: Patients suffering from PGD 3 were classified in the following categories: A: PGD 3 on ICU arrival but PGD 3 free by 72hs; B: persistent PGD 3 throughout first 72h post LTx; and C: PGD 3 requiring use of extracorporeal membrane oxygenation (ECMO). Time of mechanical ventilation, ICU and hospital length of stay (LOS), 30 day mortality, and overall survival were compared among the 3 groups. Results: Between January of 2007 and October of 2011, 448 LTx were performed. Incidence of PGD 0-1, 2, and 3 on ICU arrival were 294