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EACTS 16th Annual Meeting Monte Carlo Advances in Lung Transplantation The best preservation solution for the worst graft University Hospital Gasthuisberg,

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Presentation on theme: "EACTS 16th Annual Meeting Monte Carlo Advances in Lung Transplantation The best preservation solution for the worst graft University Hospital Gasthuisberg,"— Presentation transcript:

1 EACTS 16th Annual Meeting Monte Carlo Advances in Lung Transplantation The best preservation solution for the worst graft University Hospital Gasthuisberg, Leuven, Belgium Dirk Van Raemdonck, MD, PhD, FETCS EACTS Postgraduate Courses Session 3: General Thoracic Surgery Sunday, 22 September 2002 Monte Carlo, Monaco

2 EACTS 16th Annual Meeting Monte Carlo This presentation is available online via

3 EACTS 16th Annual Meeting Monte Carlo Overview ischemia - reperfusion injury lung donors preservation techniques preservation solutions reperfusion techniques conclusions

4 EACTS 16th Annual Meeting Monte Carlo ischemia - reperfusion injury lung donors preservation techniques preservation solutions reperfusion techniques conclusions

5 EACTS 16th Annual Meeting Monte Carlo Definition post-transplant allograft dysfunction resulting from damage during ischemiaandreperfusion = pulmonary reimplantation response I-R injury (1)

6 EACTS 16th Annual Meeting Monte Carlo Incidence unpredictable 57% - 97% perihilar edema (Khan S. Chest 1999:116:187-94) (Anderson D. Radiology 1995:195:275-81) % clinically significant (Zenati M. Transplantation 1990;50:165-67) 2 - 5% mortality (Hosenpud J. J Heart Lung Transplant 1996;15:655-74) (Meyers B. Ann Surg 1999;230:362-71) I-R injury (2)

7 EACTS 16th Annual Meeting Monte Carlo Clinical Manifestation poor oxygenation (low PaO 2 /FiO 2 - high A-a DO 2 ) low pulmonary compliance (C dyn ) interstitial / alveolar edema (fluid loss) pulmonary infiltrates (injury score on CXR) increased vascular resistance (PVR) intrapulmonary shunt (QS/QT) acute alveolar injury (DAD) I-R injury (3)

8 EACTS 16th Annual Meeting Monte Carlo Mechanisms complex (myriad cellular and molecular events) endothelial cell dysfunction (increased microvascular permeability) alveolar type II cell dysfunction (pulmonary surfactant alterations) (Novick RJ. Ann Thorac Surg 1996;62:302-14) I-R injury (4)

9 EACTS 16th Annual Meeting Monte Carlo Differential Diagnosis hyperacute rejection (Frost AE. Chest 1996;110:559-62) early infection (Paradis IL. J Heart Lung Transplant 1992;11:S232-6) venous anastomotic obstruction (Leibowitz D. J Heart Lung Transplant 1994;13:S39) cardiogenic edema (left ventricular failure) I-R injury (5)

10 EACTS 16th Annual Meeting Monte Carlo Treatment increased ventilation (FiO 2 - PEEP) negative fluid balance (diuretics) pulmonary vasodilation (PG - inhaled NO) (Aoe M. Ann Thorac Surg 1994;58:655-61) (Adatia I. Ann Thorac Surg 1994;57:1311-8) surfactant replacement (nebulized synthetic) (Struber M. Intensive Care Med 1999;25:862-4) extracorporeal oxygenation (ECMO) (Meyers B. J Thorac Cardiovasc Surg 2000;120:20-8) urgent retransplantation (Novick RJ. Ann Thorac Surg 1998;65:227-34) I-R injury (6)

11 EACTS 16th Annual Meeting Monte Carlo Impact increased morbidity & mortality prolonged ventilation prolonged ICU & hospital stay increased costs (King RC. Ann Thorac Surg 2000;69:1681-5) I-R injury (7)

12 EACTS 16th Annual Meeting Monte Carlo Identified Risk Factors I-R injury (8) donor-related - quality donor lung (age, cause of death, ventilation) (Sundaresan S. J Thorac Cardiovasc Surg 1995;109: ) preservation-related - preservation solution? - ischemic time? recipient-related - pulmonary hypertension (Bando K. Ann Thorac Surg 1994;58: ) - cardio-pulmonary bypass (Francalancia N. J Heart Lung Transplant 1994;13:498-57)

13 EACTS 16th Annual Meeting Monte Carlo I-R injury (9) Early outcome ischemic time (0 – 40 points) recipient age (0 – 36 points) PaO 2 /FiO 2 (0 – 80 points) hemodynamic failure (0 – 18 points) Ischemia/Reperfusion Injury Severity Score IRISS (Thabut G et al. Chest 2002;121: )

14 EACTS 16th Annual Meeting Monte Carlo IRISS and mortality in ICU I-R injury (10) (Thabut G et al. Chest 2002;121: )

15 EACTS 16th Annual Meeting Monte Carlo I-R injury (11) Late outcome Independent Predictive Factor For BOS (Fiser SM et al. Ann Thorac Surg 2002;73: )

16 EACTS 16th Annual Meeting Monte Carlo ischemia - reperfusion injury lung donors preservation techniques preservation solutions reperfusion techniques conclusions

17 EACTS 16th Annual Meeting Monte Carlo Final Assessment bronchoscopy (endotracheal aspiration) imaging (recent chest x-ray) macroscopy (inspection - palpation) (Sundaresan S et al. Ann Thorac Surg 1993;56: ) gas exchange (pulmonary vein gas analysis) (Aziz TM et al. Ann Thorac Surg 2002;73: ) Lung Donors (1)

18 EACTS 16th Annual Meeting Monte Carlo Lung Donor Score Lung Donors (2) donor age smoking history PaO 2 /FiO 2 x-ray findings bronchoscopic findings Task Force in Pulmonary Committee of ISHLT (Waddell TK)

19 EACTS 16th Annual Meeting Monte Carlo Lung Donors (3) (Pierre AF et al. J Thorac Cardiovasc Surg 2002;123: ) Recipient Outcome

20 EACTS 16th Annual Meeting Monte Carlo ischemia - reperfusion injury lung donors preservation techniques preservation solutions reperfusion techniques conclusions

21 EACTS 16th Annual Meeting Monte Carlo Techniques (1) Graft Cooling topical (NHBD) donor core cooling on CPB single pulmonary artery flush (Hopkinson DN et al. J Heart Lung Transplant 1998;17: )

22 EACTS 16th Annual Meeting Monte Carlo Controversies flushing conditions (T°, volume, pressure) pulmonary and/or bronchial arteries anterograde and/or retrograde flush storage conditions (T°, oxygen, inflation) Techniques (2) (Novick RJ et al. Ann Thorac Surg 1996;62: ) (Kelly RF. J Lab Clin Med 2000;136: )

23 EACTS 16th Annual Meeting Monte Carlo Flushing Conditions high volume (60 ml/kg) - high rate (4 min) low PA pressure (10 – 15 mm Hg) low temperature (4°C - 8°C) ventilation (V T 10 ml/kg; PEEP 5 cm H 2 O) vasodilator (PGE 1 - PGI 2 - Nitroglycerine) Techniques (3) (Hopkinson DN et al. J Heart Lung Transplant 1998;17: )

24 EACTS 16th Annual Meeting Monte Carlo Bronchial Arteries preservation of bronchial tree cannula in isolated aortic segment ml/kg mm Hg Techniques (3) (Steen S. In Messmer K (ed). Progress in Applied Microcirculation, Basel, Karger, 1996, vol 22, 50-60)

25 EACTS 16th Annual Meeting Monte Carlo Retrograde Flush primary (via left atrial appendage) (Sarsam MA et al. J Heart Lung Transplant 1993;12: ) secondary (via pulmonary veins) (Varela A et al. J Thorac Cardiovasc Surg 1997;114: ) preimplantation (on back-table) (Venuta F et al. J Thorac Cardiovasc Surg 1999;118: ) Techniques (4)

26 EACTS 16th Annual Meeting Monte Carlo Storage Conditions low temperature (4°C) (no hyper)inflation (15-20 cm H 2 0) oxygen reserve (FiO 2 50%) Techniques (5)

27 EACTS 16th Annual Meeting Monte Carlo ischemia - reperfusion injury lung donors preservation techniques preservation solutions reperfusion techniques conclusions

28 EACTS 16th Annual Meeting Monte Carlo Controversies colloid or cristalloid intracellular or extracellular Solutions (1)

29 EACTS 16th Annual Meeting Monte Carlo Colloid or Crystalloid ? colloid (donor blood): + natural: buffer - substrates - scavengers - preparation prior to organ retrieval crystalloid : + simple method, minimum equipment + technique applicable to any cristalloid + wash out of harmful blood constituents + no interference with other teams - embolization of microvasculature (Mg) Solutions (2)

30 EACTS 16th Annual Meeting Monte Carlo Intracellular or Extracellular? high K : + minimize transmembrane ion shift - reflex pulmonary vasoconstriction - endothelial cell damage/permeability low K : + better distribution of flush solution + uniform cooling of the graft + lower PVR upon reperfusion + less hydrostatic edema Solutions (3) (Kimblad PO et al. Ann Thorac Surg 1991;52: )

31 EACTS 16th Annual Meeting Monte Carlo Types Intracellular Extracellular modified Euro-Collins(EC) Perfadex (LPDG) University of Wisconsin (UW) Celsior Wallwork Solutions (4)

32 EACTS 16th Annual Meeting Monte Carlo Survey colloid: donor blood (Wallwork - Papworth)(7%) crystalloid: modified Euro-Collins (m-EC) (78%) University of Wisconsin (UW) (15%) (Hopkinson DN et al. J Heart Lung Transplant 1998;17: ) Solutions (5)

33 EACTS 16th Annual Meeting Monte Carlo Electrolytes (mmol/L) m-ECUWPerfadexCelsior Na K Cl Mg Ca pH mOsm/l Solutions (6)

34 EACTS 16th Annual Meeting Monte Carlo Buffer (mmol/L) m-ECUWPerfadexCelsior HCO SO PO Histidine Solutions (7)

35 EACTS 16th Annual Meeting Monte Carlo Impermeants Solutions (8) (mmol/L) m-ECUWPerfadexCelsior mannitol lactobionate raffinose glucose

36 EACTS 16th Annual Meeting Monte Carlo Oncotic agents Solutions (9) (gm/L) m-ECUWPerfadexCelsior Dextran Pentastarch

37 EACTS 16th Annual Meeting Monte Carlo Anti-Oxydants Solutions (10) (mmol/L) m-ECUWPerfadexCelsior Glutathione

38 EACTS 16th Annual Meeting Monte Carlo Energy Precursors Solutions (11) (mmol/L) m-ECUWPerfadexCelsior Adenosine Glutamate

39 EACTS 16th Annual Meeting Monte Carlo Comparative Studies (1) Solutions (12) EC versus UW (Hardesty R et al. J Thorac Cardiovasc Surg 1993:105:660-6) historical comparison, non-randomized study (n = 100) EC: n= 30 >< UW n = 70 no differences (longer ischemic times UW)

40 EACTS 16th Annual Meeting Monte Carlo Solutions (13) Comparative Studies (2) UW versus Celsior (DArmini AM et al. J Heart Lung Transplant 2001:20:183) randomized study (n = 20) UW: n= 10 >< Celsior: n = 10 A-aDO 2 up to 24 hours better (p<0.05) in UW no other differences

41 EACTS 16th Annual Meeting Monte Carlo Solutions (14) EC versus Perfadex Comparative Studies (3) (Müller C et al. Transplantation 1999;68: ) (Strüber M et al. Eur J Cardiothorac Surg 2001;19: ) (Fischer S et al. J Thorac Cardiovasc Surg 2001;121: ) 3 historical comparative, non-randomized studies EC: ~ n= 50 >< Perfadex: ~ n = 50 better (p < 0.05) early graft function in Perfadex group better (NS) early survival in Perfadex group

42 EACTS 16th Annual Meeting Monte Carlo Solutions (15) EC versus Perfadex (1) Comparative Studies (4) (Rega F et al. Presented at 5th International Congress on Lung Transplantation, Paris, September 19-20, 2002) A-aDO 2 p = 0.59 p < 0.001

43 EACTS 16th Annual Meeting Monte Carlo Solutions (16) EC versus Perfadex (2) Comparative Studies (4) (Rega F et al. Presented at 5th International Congress on Lung Transplantation, Paris, September 19-20, 2002) Freedom from Acute Rejection p = 0.2 p = 0.66 p = 0.17

44 EACTS 16th Annual Meeting Monte Carlo Solutions (17) EC versus Perfadex (3) Comparative Studies (4) (Rega F et al. Presented at 5th International Congress on Lung Transplantation, Paris, September 19-20, 2002) Early Survival p = 0.92p = 0.59* p < 0.01

45 EACTS 16th Annual Meeting Monte Carlo Solutions (18) EC versus UW versus Celsior versus Papworth Comparative Studies (5) (Thabut G et al. Am J Respir Crit Care Med 2001;164: ) French multicenter, non-randomized study (n = 170) EC: n = 61 > < Papworth: n = 64 lower incidence of reperfusion edema in extracellular solutions no difference in 1-month mortality

46 EACTS 16th Annual Meeting Monte Carlo ischemia - reperfusion injury lung donors preservation techniques preservation solutions reperfusion techniques conclusions

47 EACTS 16th Annual Meeting Monte Carlo Reperfusion Controlled Conditions controlled reperfusion (Bhabra MS et al. Ann Thorac Surg 1998;65: ) low PA pressure during first 10 min - slowly releasing PA clamp - reperfusion on CBP controlled ventilation (de Perrot M et al. J Thorac Cardiovasc Surg 2002 in press)

48 EACTS 16th Annual Meeting Monte Carlo Conclusions Best Preservation – Worst Graft IR-injury: multifactorial (donor - recipient) new techniques (retrograde flush) new extracellular solutions (Perfadex - Celsior) decreased incidence in reperfusion edema more extended donors with less optimal grafts better early outcome (less acute rejection) better late outcome? (less BOS)

49 EACTS 16th Annual Meeting Monte Carlo Acknowledgments Dr F. Rega, research fellow Leuven Lung Transplant Group (www.longtransplantatie.be)

50 EACTS 16th Annual Meeting Monte Carlo Thank you for your attention


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