344
Organ Preservation for Heart-lung and Lung Transplantation Th. Wahlers, H. -J Sc hiifers, J Cremer, M. Jurman, S. W Hirt, H. G. Fieguth, and A. Hav erich Division of Thoracic and Cardiovascular Surgery , Han nover Medical School. Ha nn over. Germa ny
One of th e most imp ortant restriction s in th e field of heart-lun gand lung-tran splantation remains the limited ischemic tolerance ofthe lun g. From Decemb er 1987 through February 1991, 44 patients underwent either single-, dcuble-. or heart-lu ng-transplant ation. All orga ns were harvested in multiorgan proce dures. For th e first 4 pati ents core cooling of the don or was used . For the rest pulmona ry artery flush with m odified Euro -Collins solution and prostacyclin was employed. Ischemia time varied from
3-6.5 hours (mean 241; 176- 390 minutes). Hearts were ar rested with St. Thomas cardio plegia. Oxygenation was satisfactory at 24 hours: p 0 2 > 100mmH g, FI O2 < 30 % oxygen. It is concluded th at for lung preservation modified EuroCollins solution and prostacyclin for flush perfusion of the pulmonary artery will res ult in excellent lung function ea rly postoperatively with ischemic times up to 6.5 hours. This method seems advan tageous compared to others due to the limited surgical and instr umental needs. Keywords Organ preservat ion - Euro-Collins solution - Lung transplantation - Heart-lung transplanta tion - Prostacyclin
Introduction In lung and heart lung transplantat ion seve ra l lung preservations techniques have been discussed with regard to th eir effectiveness and perform an ce in the clinical situa tion . Throughout the last 5 years various methods have been applied c1incially (1, 2, 8-10, 12, 21-23). Initially, auto perfusion was used by the Pittsburgh group , but the technical requirem ents of this set up have limited th e broad appli cation (14). In contrast, the Toronto gro up has used simple cold imm ersion of th e lun g, but the resulting preservation quality was not suita ble for long-term pr eserv ation (4, 5). Subse que ntly, oth er gro ups introduced cor e cooling of th e donor with good clinical outcome. In Har efield, Baltimo re , and also in our own han ds this method has r esulted in an adequate pr eserv ation with storage times up to 4 hours (2, 9, 22). Other gro ups have employed perfusion of th e pulmonary artery with an intracellular type of
Organkonservierung zur Herz -Lungenund Lungentransplantation Eine der wesentlic hen Einschrankungen einer gesteigerte n Aktivitat im Bereich der Herz-Lungen- und Lungen -Tran splantat ion stellt die geringe Verfligbarkeit geeigneter Organ e aufgrund limitierter Ischamiezeiten der Lunge dar . Vom Dezember 1987 bis zum Februar 1991 sind an unserer Klinik 44 Patienten einer Einzel-, Doppel- oder Herz-Lungen-Tran splantation unterzogen worden . AIle Organe wurden im Rahmen von Multiorganen tna hmen konserviert . Die Ischamieze it variierte zwischen 3 und 6,5 Stunden (X = 247 ± 49 Minuten: 176- 390 Minuten). w ahrend fiir die ersten vier Patienten die extr akorporale Zirkulation mit Ktihlung des Spenders verwe ndet wurde , konservierten wir die Organ e flir die letzten 40 Patienten mittels Perfusion der Pulmonalarterie durc h modifizierte Euro-Colllns-Losung unt er zuvoriger Gab e von Prostacyclin. Alle Herzen wurden durch St.-Tho mas Losung kard ioplegiert . Generell konnte eine gute Oxygenierung fruhpostoperativ erzielt werden (24 Stunden: p 0 2 > 100mmHg bei FI0 230% Sauerstoff). Es wird gefolgert, daBmit dem vorgestellten Verfahren eine exzellente pulmonale Friihfunkti on bei Konservierungszeiten von bis zu 6,5 Stunden erzielbar Ist. Diese Methode scheint an deren iiberlegen zu sein, da sie bel gerlngem chirurgischen und instrumentellen Aufwand durchftlhrb ar ist.
solution for pulmonary preservation (15, 16, 21). After th e additional introduction of pro staglandines to dilatate th e pulm onary bed pri or to th e flush perfusion even better results we re achieved (7, 8, 11). With this meth od , using eithe r Euro-Collins solution or modified cold blood solution, good clinical results were obtained by the Cambridge, Pittsburgh , Stanfo rd , and Newcas tle group s. In 1987 this method was adopted by us also, and this communica tion gives a summary of th e results obtained . Material and Methods From December 1987 thr ough Febru ary 1991 , 18 heart-lung transplantations, 23 single-lung, and 6 double-lung transplantations were performed in our unit on a total of 44 patients. In the heartlung patient grou p, underlying disease was primary pulmon ary hypertension in 5 pat ients, Eisenmenger 's syndrome in 6, chronic pulmonary embolism in 3, pulmonary dysplasia, cystic fibrosis,
This pa per was presented in pa rt at the 20th Ann ual Meeting of the German Society for Thoracic and Cardiovascular Surge ry, Bonn,
February 1991 Thorac. cardiovasc. Surgeon 39 (1991) 344-348 © Georg Thieme VerlagStuttgart · New York
Received for Publication: August 24, 1991
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Summary
Thorae. eardiovasc. S urgeon 39 (1991)
Organ Preservation/or Heart-lung and Lung Transplantat ion
Results The mean age of the donors was 30.13 ± 11.24 years (13 to 53). All donors were ventilated for a mean of 2.3 ± 1.4 days (0.5-6). The mean duration from brain death until harvesting was 17.8 ± 10.6 hours (4-48). Donors had a mean inspir atory oxygen concentration of 44 ± 24 % oxygen (21-100). The achieved oxygenation showed a mean of 190 ± 150mmHg(75-600). The mean ischemic time was 247 ± 49 min with a range of 176 up to 390 min. The median was calculated at 240 min (Fig. I) . Following tra nsplantation, the mean inspiratory oxygen fraction directly after admissio n to the
ICU was 69 % resulting in a pO, of 213mmHg. Subsequently, the inspired oxygen fraction could be stea dily reduced to 46 ± 16% after 3 hours , resulting in a pO, of 115 ± 25 mmHg (Fig. 2,3). Regression analysis of the pO, of the organ donors with the achieved pO, 6 hours postoperatively showed no significant correlation (p - 0.102, T - 1.672, Fig. 4). In addition, the inspired oxygen fraction of the organ donors showed also no correlation with the pO, achieved 6 hours postoperatively (p - 0.07, T - 1.9, Fig. 5).
min. 400 . --
-------;:- - - - = - - - -----,
IOLT X DAII
Pa tients Fig.1 Ischemiatimesfollowingpreservationwith Euro-Collinssolution (n- 40, incl. 6 double-lung-transplantations (DlTXIJ
100,-- - - - - - - - - - - - - -----, 80 i'
II
60
8 i:i: 40
1
20
I
o+-..LL,LJ.J.J'-'r'l..L.I 100 mmHg using a PEEP of Scm H20 at an FI0 2 of 30% oxygen. Radiograp hs were checked for signs of infection. The infectious statu s ofthe donor s was assessed by bronchoscopy, and cultures were taken by bro nchial aspiration. Aventilation time of less than one week was required. Donors were selected according to ABO blood group compatibility. and a size mismatch of less than 10 %, as measur ed by thora x dimensions, was admitted in the heart lung group. In the patients undergoing lung transplantation. donors up to 40 % bigger were accepted. The pulmona ry art ery flush was ap plied thro ugh a specially designed perfusion system using a 20 French pulmonary cannula after excision of the tip of the left atrium. Postoperative lung function was assessed with respect to the inspired oxygen concentration and the partial pressures of oxygen achieved. Regression analysis was performed comparing the postopera tive oxygenation at 6 hours postoperati vely with the inspired oxygen fraction of the donors. the oxygenation of the donors, and the ischemic times. In addition, multi-variate analysis was performed, including donor oxygenation variables, donor age. time from brain deat h until harvesting, and ischemia times, using the oxygenatio n 6 hours postoperatively as dependent variable. Postoperative oxygenation da ta were obtained on a 6-hour basis up to 72 hours postoperatively. For statistical calculations the 5PSS-software was used (3) for simple linear and multivariate regression anal ysis.
345
Thome. cardiovasc. Su rgeon 39 (991)
Th. Wahlers. H.-J. Scbiifers. J. Cremer. M. Jurman. S. W Hire. H. G. Fieguth . and A. Hauerich Table 1 Results of the multivariate analysisof donor ralated factors on postoperative oxygenation at 6 hours Variable
p-value
Ischemia Timefrombraindeathuntilharvesting Oxygenpartial pressure Inspiredoxygenfraction Donorage
0.911 0.391 0.630 0.839 0.751
Analysisof variancetotest regressionrelation(F - 0.299; p - 0.98)
30 10
O +-~~~~~~--~-~~~~--
Organ Preservation for Heart-lung and Lung Transplantation Th. Wahlers, H. -J Sc hiifers, J Cremer, M. Jurman, S. W Hirt, H. G. Fieguth, and A. Hav erich Division of Thoracic and Cardiovascular Surgery , Han nover Medical School. Ha nn over. Germa ny
One of th e most imp ortant restriction s in th e field of heart-lun gand lung-tran splantation remains the limited ischemic tolerance ofthe lun g. From Decemb er 1987 through February 1991, 44 patients underwent either single-, dcuble-. or heart-lu ng-transplant ation. All orga ns were harvested in multiorgan proce dures. For th e first 4 pati ents core cooling of the don or was used . For the rest pulmona ry artery flush with m odified Euro -Collins solution and prostacyclin was employed. Ischemia time varied from
3-6.5 hours (mean 241; 176- 390 minutes). Hearts were ar rested with St. Thomas cardio plegia. Oxygenation was satisfactory at 24 hours: p 0 2 > 100mmH g, FI O2 < 30 % oxygen. It is concluded th at for lung preservation modified EuroCollins solution and prostacyclin for flush perfusion of the pulmonary artery will res ult in excellent lung function ea rly postoperatively with ischemic times up to 6.5 hours. This method seems advan tageous compared to others due to the limited surgical and instr umental needs. Keywords Organ preservat ion - Euro-Collins solution - Lung transplantation - Heart-lung transplanta tion - Prostacyclin
Introduction In lung and heart lung transplantat ion seve ra l lung preservations techniques have been discussed with regard to th eir effectiveness and perform an ce in the clinical situa tion . Throughout the last 5 years various methods have been applied c1incially (1, 2, 8-10, 12, 21-23). Initially, auto perfusion was used by the Pittsburgh group , but the technical requirem ents of this set up have limited th e broad appli cation (14). In contrast, the Toronto gro up has used simple cold imm ersion of th e lun g, but the resulting preservation quality was not suita ble for long-term pr eserv ation (4, 5). Subse que ntly, oth er gro ups introduced cor e cooling of th e donor with good clinical outcome. In Har efield, Baltimo re , and also in our own han ds this method has r esulted in an adequate pr eserv ation with storage times up to 4 hours (2, 9, 22). Other gro ups have employed perfusion of th e pulmonary artery with an intracellular type of
Organkonservierung zur Herz -Lungenund Lungentransplantation Eine der wesentlic hen Einschrankungen einer gesteigerte n Aktivitat im Bereich der Herz-Lungen- und Lungen -Tran splantat ion stellt die geringe Verfligbarkeit geeigneter Organ e aufgrund limitierter Ischamiezeiten der Lunge dar . Vom Dezember 1987 bis zum Februar 1991 sind an unserer Klinik 44 Patienten einer Einzel-, Doppel- oder Herz-Lungen-Tran splantation unterzogen worden . AIle Organe wurden im Rahmen von Multiorganen tna hmen konserviert . Die Ischamieze it variierte zwischen 3 und 6,5 Stunden (X = 247 ± 49 Minuten: 176- 390 Minuten). w ahrend fiir die ersten vier Patienten die extr akorporale Zirkulation mit Ktihlung des Spenders verwe ndet wurde , konservierten wir die Organ e flir die letzten 40 Patienten mittels Perfusion der Pulmonalarterie durc h modifizierte Euro-Colllns-Losung unt er zuvoriger Gab e von Prostacyclin. Alle Herzen wurden durch St.-Tho mas Losung kard ioplegiert . Generell konnte eine gute Oxygenierung fruhpostoperativ erzielt werden (24 Stunden: p 0 2 > 100mmHg bei FI0 230% Sauerstoff). Es wird gefolgert, daBmit dem vorgestellten Verfahren eine exzellente pulmonale Friihfunkti on bei Konservierungszeiten von bis zu 6,5 Stunden erzielbar Ist. Diese Methode scheint an deren iiberlegen zu sein, da sie bel gerlngem chirurgischen und instrumentellen Aufwand durchftlhrb ar ist.
solution for pulmonary preservation (15, 16, 21). After th e additional introduction of pro staglandines to dilatate th e pulm onary bed pri or to th e flush perfusion even better results we re achieved (7, 8, 11). With this meth od , using eithe r Euro-Collins solution or modified cold blood solution, good clinical results were obtained by the Cambridge, Pittsburgh , Stanfo rd , and Newcas tle group s. In 1987 this method was adopted by us also, and this communica tion gives a summary of th e results obtained . Material and Methods From December 1987 thr ough Febru ary 1991 , 18 heart-lung transplantations, 23 single-lung, and 6 double-lung transplantations were performed in our unit on a total of 44 patients. In the heartlung patient grou p, underlying disease was primary pulmon ary hypertension in 5 pat ients, Eisenmenger 's syndrome in 6, chronic pulmonary embolism in 3, pulmonary dysplasia, cystic fibrosis,
This pa per was presented in pa rt at the 20th Ann ual Meeting of the German Society for Thoracic and Cardiovascular Surge ry, Bonn,
February 1991 Thorac. cardiovasc. Surgeon 39 (1991) 344-348 © Georg Thieme VerlagStuttgart · New York
Received for Publication: August 24, 1991
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Summary
Thorae. eardiovasc. S urgeon 39 (1991)
Organ Preservation/or Heart-lung and Lung Transplantat ion
Results The mean age of the donors was 30.13 ± 11.24 years (13 to 53). All donors were ventilated for a mean of 2.3 ± 1.4 days (0.5-6). The mean duration from brain death until harvesting was 17.8 ± 10.6 hours (4-48). Donors had a mean inspir atory oxygen concentration of 44 ± 24 % oxygen (21-100). The achieved oxygenation showed a mean of 190 ± 150mmHg(75-600). The mean ischemic time was 247 ± 49 min with a range of 176 up to 390 min. The median was calculated at 240 min (Fig. I) . Following tra nsplantation, the mean inspiratory oxygen fraction directly after admissio n to the
ICU was 69 % resulting in a pO, of 213mmHg. Subsequently, the inspired oxygen fraction could be stea dily reduced to 46 ± 16% after 3 hours , resulting in a pO, of 115 ± 25 mmHg (Fig. 2,3). Regression analysis of the pO, of the organ donors with the achieved pO, 6 hours postoperatively showed no significant correlation (p - 0.102, T - 1.672, Fig. 4). In addition, the inspired oxygen fraction of the organ donors showed also no correlation with the pO, achieved 6 hours postoperatively (p - 0.07, T - 1.9, Fig. 5).
min. 400 . --
-------;:- - - - = - - - -----,
IOLT X DAII
Pa tients Fig.1 Ischemiatimesfollowingpreservationwith Euro-Collinssolution (n- 40, incl. 6 double-lung-transplantations (DlTXIJ
100,-- - - - - - - - - - - - - -----, 80 i'
II
60
8 i:i: 40
1
20
I
o+-..LL,LJ.J.J'-'r'l..L.I 100 mmHg using a PEEP of Scm H20 at an FI0 2 of 30% oxygen. Radiograp hs were checked for signs of infection. The infectious statu s ofthe donor s was assessed by bronchoscopy, and cultures were taken by bro nchial aspiration. Aventilation time of less than one week was required. Donors were selected according to ABO blood group compatibility. and a size mismatch of less than 10 %, as measur ed by thora x dimensions, was admitted in the heart lung group. In the patients undergoing lung transplantation. donors up to 40 % bigger were accepted. The pulmona ry art ery flush was ap plied thro ugh a specially designed perfusion system using a 20 French pulmonary cannula after excision of the tip of the left atrium. Postoperative lung function was assessed with respect to the inspired oxygen concentration and the partial pressures of oxygen achieved. Regression analysis was performed comparing the postopera tive oxygenation at 6 hours postoperati vely with the inspired oxygen fraction of the donors. the oxygenation of the donors, and the ischemic times. In addition, multi-variate analysis was performed, including donor oxygenation variables, donor age. time from brain deat h until harvesting, and ischemia times, using the oxygenatio n 6 hours postoperatively as dependent variable. Postoperative oxygenation da ta were obtained on a 6-hour basis up to 72 hours postoperatively. For statistical calculations the 5PSS-software was used (3) for simple linear and multivariate regression anal ysis.
345
Thome. cardiovasc. Su rgeon 39 (991)
Th. Wahlers. H.-J. Scbiifers. J. Cremer. M. Jurman. S. W Hire. H. G. Fieguth . and A. Hauerich Table 1 Results of the multivariate analysisof donor ralated factors on postoperative oxygenation at 6 hours Variable
p-value
Ischemia Timefrombraindeathuntilharvesting Oxygenpartial pressure Inspiredoxygenfraction Donorage
0.911 0.391 0.630 0.839 0.751
Analysisof variancetotest regressionrelation(F - 0.299; p - 0.98)
30 10
O +-~~~~~~--~-~~~~--
