Lung Allograft Procurement Principles,Additional Donor Options and FutureDirections Marcelo Cypel MD MSc Assistant Profess...
Overview1. Principles of management of the multi-organ   donor2. Principles of Lung Preservation3. How can we improve on c...
Organ Shortage• Increasing demand = Insufficient supply• Shortage is compounded by a low utilization of  donor lungs      ...
SALTAmerican Journal of Respiratory and CriticalCare Medicine 2006;174:710174:710--716716
SALT protocol•Education: “Every donor is a potential lung donor”•Alveolar recruitment: pressure-controlled ventilation at ...
Conclusion from SALT study• The implementation of a lung donor management protocol  incorporating improved communication, ...
Current Concepts in the Careof the Multi-Organ Donor
“Conventional” (Old) Management      of the Multi-Organ Donor• Maintain BP / abdominal organ perfusion• Volume rehydration...
Donor Lung Injury• Completely “normal” donor lung unusual• Pre-existing diseases: asthma, COPD, Ca...• Trauma - pneumothor...
Motivated Nursing Care• Attentive nursing care• Strict aseptic technique• Frequent pulmonary suction• NG tube suction• Pre...
Cardiovascular Management• Restoration of an ADEQUATE circulating  volume• Goal is EUVOLEMIA not HYPERVOLEMIA!• Hemodynami...
Hemodynamic Targets• Mean arterial pressure        > 70 mmHg• CVP                          < 10 mmHg• PCWP                ...
Fluid and Electrolyte Management• Hypernatremia secondary to diabetes insipidus is  common• Avoid Normal Saline - use Dext...
Endocrine Management• Endocrine dysfunction contributes to hemodynamic  instability and cardiopulmonary dysfunction• Insti...
Pulmonary Management• Frequent turning and endobronchial suctioning• Bronchoscopy to remove mucous plugs• Sputum / BAL gra...
• Protective Vt 6-8cc/kg, PEEP 8-10cmH20 better than  Conventional Vt 10-12cc/kg, PEEP 5cmH2O.• 27% lungs harvested in Con...
Intraoperative Management• Same principles as ICU management• Maintain optimal organ perfusion and O2 delivery• Avoid inap...
Donor OR - Phase 1: Lung Assessment• Final assessment ABG’s on FiO2 1.0, PEEP 5, then  decrease FiO2 to 0.5• Bronchoscopy ...
Donor OR - Phase 2: Organ Flushing• Heparinization (300u/kg) when all teams ready• Pulmonary artery, cardioplegia and abdo...
Summary I• The lung is the most likely organ to be compromised in  the organ retrieval process• Lung donor care starts wit...
How can we improve on current practice?
Cold                    Ischemia                                     Brain death Mechanical Ventilation                   ...
Severe Primary Graft Dysfunction (PGD)
CURRENT PRACTICE IN ORGAN SELECTION AND  MANAGEMENT              Donor            Management                             D...
Lung Donors / Total Donors (USA)Utilization Rates  Year    Lung / Total Donors    % 2000        825 / 5985         13.7% 2...
WHAT’S NEXT?• Opportunities to improve donor  organs• Focus on repair and regeneration  - not death• Era of personalized m...
Normothermic Ex Vivo Lung Perfusion                (EVLP)• Time to accurately assess - diagnose• Option to treat/repair/re...
Concept of Ex Vivo Evaluation/Repair                    Donor                  Management                     Organ    Dec...
NEJM, April 14th 2011, vol. 364, no. 15, pp. 1431-1440.32
Human Ex vivo Lung Perfusion            HELP clinical trialProspective, non-randomized, non-inferiority trial; Safety of...
TORONTO EX VIVO LUNG            PERFUSION (EVLP) SYSTEMPerfusion : 40% COVentilation: 7cc/kg, 7BPM, PEEP 5, FiO2 = 21%    ...
Normothermic Ex vivo Lung Perfusion in Clinical Transplantation – HELP Trial
EVLP function was stable in transplanted lungs(n=20)
Bronchoscopy
LUNG X-Ray
Resolution of pulmonary edema during       EVLP                                   1h EVLPDonor P/F 230                    ...
Early outcomes were similar in the 2 groupsNEJM, April 14th 2011
Overall survival                   100                                                                   Control (n=116)  ...
How Can We Apply This Clinically?• Organ Repair Center Model   Hospital Run?   OPO Run?
Launching the Organ Regeneration Laboratory        at TGH OR (Oct 2011) – assessment and        repair of all organs for c...
Number of Transplants             0                 20                      40                              60            ...
Utilization vs Outcomes    40                                                             Utilization of donor lungs      ...
Summary II• Era of “Personalized Medicine” for the organ• The opportunity to engineer better organs for transplantation• I...
Thank you
Marcelo Cypel  - Canada - Tuesday 29 - Organ Donor Care. New Alternatives
Marcelo Cypel  - Canada - Tuesday 29 - Organ Donor Care. New Alternatives
Marcelo Cypel  - Canada - Tuesday 29 - Organ Donor Care. New Alternatives
Marcelo Cypel  - Canada - Tuesday 29 - Organ Donor Care. New Alternatives
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Marcelo Cypel - Canada - Tuesday 29 - Organ Donor Care. New Alternatives

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  • In lung transplantation this is further aggravated because most of the potential donor lungs are injured during the process of brain death and ICU related complications and thus cannot be used for LTx.. This leads to a utilization rate of only 15% worldwide.
  • EVLP is a new technology that provides the opportunity for a better assessment of donor lungs. It also allows treatment and improvement of injured human donor lungs
  • Marcelo Cypel - Canada - Tuesday 29 - Organ Donor Care. New Alternatives

    1. 1. Lung Allograft Procurement Principles,Additional Donor Options and FutureDirections Marcelo Cypel MD MSc Assistant Professor of Surgery Staff Surgeon Division of Thoracic University of Toronto University Health Network Marcelo.cypel@uhn.ca
    2. 2. Overview1. Principles of management of the multi-organ donor2. Principles of Lung Preservation3. How can we improve on current practice? • Changing the paradigm: diagnosis, treatment, personalized medicine • Ex vivo organ repair
    3. 3. Organ Shortage• Increasing demand = Insufficient supply• Shortage is compounded by a low utilization of donor lungs 2000 1800 1600 1400 Number of Patients 1200 1000 800 600 400 200 0 Waiting List Transplants Donors TGLN, 2006
    4. 4. SALTAmerican Journal of Respiratory and CriticalCare Medicine 2006;174:710174:710--716716
    5. 5. SALT protocol•Education: “Every donor is a potential lung donor”•Alveolar recruitment: pressure-controlled ventilation at an inspiratory pressure of25 cm H2O and positive end-expiratory pressure of 15 cm H2O for 2 h. Ventilatorthen switched to conventional volume control ventilation with a tidal volume of 10ml/kg and a positive end-expiratory pressure of 5 cm H2O• Clinical assessment the donor fluid balance: minimized the use of crystalloids,and recommended the administration of diuretics to maintain a neutral or negativefluid balance after the initial hospital resuscitation.• Elevation of the head of the bed to 30 degrees• Bronchoscopy with bilateral bronchoalveolar American Journal of Respiratory and Critical Care Medicine 2006;174:710174:710--716716
    6. 6. Conclusion from SALT study• The implementation of a lung donor management protocol incorporating improved communication, active management of donors by a transplant pulmonologist and establishing a donor classification system, increased the number of lung donors and lung transplant procedures.• Lung recruitment maneuvers were significant in improving oxygenation and converting poor donors to extended or ideal donors.• The use of “poor to extended” or “poor to ideal” donor allograft allografts did not have adverse clinical effects on lung transplant recipient American Journal of Respiratory and Critical Care Medicine 2006;174:710174:710--716716
    7. 7. Current Concepts in the Careof the Multi-Organ Donor
    8. 8. “Conventional” (Old) Management of the Multi-Organ Donor• Maintain BP / abdominal organ perfusion• Volume rehydration, inotropes and pressors• “Auto-pilot”• This approach tends to trash donor lungs!
    9. 9. Donor Lung Injury• Completely “normal” donor lung unusual• Pre-existing diseases: asthma, COPD, Ca...• Trauma - pneumothorax, contusion, hematoma• Head injury - neurogenic pulmonary edema• Ventilator induced injury, bacterial colonization, infection• Aspiration - chemical pneumonitis, pneumonia
    10. 10. Motivated Nursing Care• Attentive nursing care• Strict aseptic technique• Frequent pulmonary suction• NG tube suction• Pressure area care, turning• Eye care (corneas)• Work with donor coordinators • Knowledgeable, motivated resource people
    11. 11. Cardiovascular Management• Restoration of an ADEQUATE circulating volume• Goal is EUVOLEMIA not HYPERVOLEMIA!• Hemodynamic monitoring • Minimum - arterial line and CVP • If required - Swan-Ganz catheter • CVP can be misleading • Rational use of inotropes, pressors and fluids
    12. 12. Hemodynamic Targets• Mean arterial pressure > 70 mmHg• CVP < 10 mmHg• PCWP < 12 mmHg• SVR 800-1200 dyn/sec/cm5• Cardiac Index > 2.4 L/min/m2
    13. 13. Fluid and Electrolyte Management• Hypernatremia secondary to diabetes insipidus is common• Avoid Normal Saline - use Dextrose solutions  also helps maintain hepatic glucose stores• Colloids to replace volume• pRBC to keep Hb > 80mg/L• Goal: Achieve the lowest CVP/PCWP consistent with adequate CO and BP
    14. 14. Endocrine Management• Endocrine dysfunction contributes to hemodynamic instability and cardiopulmonary dysfunction• Institute hormonal resuscitation as soon as donor identified • Methylprednisolone 1g iv bolus • Vasopressin Infusion – titrate to BP • Insulin Infusion - maintain normal glc, min 1u/hr • ADH - (if required) 1u bolus, then 1-4u/hr • Thyroid hormone• Improves hemodynamics and reduces dependency on inotropes
    15. 15. Pulmonary Management• Frequent turning and endobronchial suctioning• Bronchoscopy to remove mucous plugs• Sputum / BAL gram stain and culture• Minimal FiO2, Tidal volume 6-8ml/kg, PEEP 8-10 cm H2O, Peak Airway Pressure < 30 cmH2O• Recruitment maneuver after apnea test  recruit alveoli and prevent atelectasis
    16. 16. • Protective Vt 6-8cc/kg, PEEP 8-10cmH20 better than Conventional Vt 10-12cc/kg, PEEP 5cmH2O.• 27% lungs harvested in Conventional vs. 54% in Protective group
    17. 17. Intraoperative Management• Same principles as ICU management• Maintain optimal organ perfusion and O2 delivery• Avoid inappropriate volume loading• Neuromuscular paralysis - spinal reflexes
    18. 18. Donor OR - Phase 1: Lung Assessment• Final assessment ABG’s on FiO2 1.0, PEEP 5, then decrease FiO2 to 0.5• Bronchoscopy by lung team• Intraoperative assessment: • Sternotomy, direct inspection, palpation • Re-expand any areas of atelectasis - manual inflation
    19. 19. Donor OR - Phase 2: Organ Flushing• Heparinization (300u/kg) when all teams ready• Pulmonary artery, cardioplegia and abdominal flush cannulae placed• Bolus of PGE1 given directly into PA by thoracic surgeon• Once BP starts to drop (PGE1 effect), inflow occlusion, aortic cross clamp, vent, flush in sequence• Continue ventilation of the lungs throughout
    20. 20. Summary I• The lung is the most likely organ to be compromised in the organ retrieval process• Lung donor care starts with the admission of the potential donor to the ICU and continues in the OR• Consider the multi-organ donor as a whole - not as a series of separate organs• Objective: optimize hemodynamic, ventilatory, fluid, electrolyte and endocrine status - to maximize the protection and resuscitation of all organs for transplantation
    21. 21. How can we improve on current practice?
    22. 22. Cold Ischemia Brain death Mechanical Ventilation Activation ofPneumonia Inflammation and Hypotension Coagulation Aspiration Trauma Reperfusion Induced Lung Injury
    23. 23. Severe Primary Graft Dysfunction (PGD)
    24. 24. CURRENT PRACTICE IN ORGAN SELECTION AND MANAGEMENT Donor Management Decline OrganDecision Procurement  Slows down death Cold Static Unable to assess function Preservation (Questionable organs are declined at procurement) Transplantation
    25. 25. Lung Donors / Total Donors (USA)Utilization Rates Year Lung / Total Donors % 2000 825 / 5985 13.7% 2001 887 / 6080 14.6% 2002 920 / 6187 14.8% 2003 961 / 6457 14.9% 2004 1064 / 7150 14.9% 2005 1285 / 7593 16.9% 2006 1325 / 8022 16.5% Source: UNOS, www.optn.org 2007 1382/8086 17.3% 2008 1388/7984 17.4%
    26. 26. WHAT’S NEXT?• Opportunities to improve donor organs• Focus on repair and regeneration - not death• Era of personalized medicine for the organ –diagnostics, repair and engineering of superior donor organs Copyright 2010, Toronto Lung Transplant Program
    27. 27. Normothermic Ex Vivo Lung Perfusion (EVLP)• Time to accurately assess - diagnose• Option to treat/repair/recover• Opportunity to reassess - confirm results of treatment
    28. 28. Concept of Ex Vivo Evaluation/Repair Donor Management Organ Decision Procurement Cold Static Preservation •Evaluate / re-evaluate Ex vivo questionable organs Evaluation •Decline unsuitable organs only •Useful for DCDTransplantation Decline
    29. 29. NEJM, April 14th 2011, vol. 364, no. 15, pp. 1431-1440.32
    30. 30. Human Ex vivo Lung Perfusion HELP clinical trialProspective, non-randomized, non-inferiority trial; Safety of transplanting high risk donor lungs after EVLP; Brain death and cardiac death (controlled) donors;Inclusion criteria - any of the following:- Donor PaO2/FiO2 ≤ 300mmHg;- Bilateral infiltrates CXR- Poor deflation- Multiple blood transfusion- DCD No exclusion criteria for recipients; Primary endpoint: PGD 2 and 3 at 72h;
    31. 31. TORONTO EX VIVO LUNG PERFUSION (EVLP) SYSTEMPerfusion : 40% COVentilation: 7cc/kg, 7BPM, PEEP 5, FiO2 = 21% J Heart Lung Transplant 2008; 27(12):1319-25.
    32. 32. Normothermic Ex vivo Lung Perfusion in Clinical Transplantation – HELP Trial
    33. 33. EVLP function was stable in transplanted lungs(n=20)
    34. 34. Bronchoscopy
    35. 35. LUNG X-Ray
    36. 36. Resolution of pulmonary edema during EVLP 1h EVLPDonor P/F 230 3h EVLPRecipient P/F 420
    37. 37. Early outcomes were similar in the 2 groupsNEJM, April 14th 2011
    38. 38. Overall survival 100 Control (n=116) 80 EVLP (n=23)Percent survival 60 p=0.77 40 median f/u 635 days 20 0 0 200 400 600 800 1000 Days after transplantation
    39. 39. How Can We Apply This Clinically?• Organ Repair Center Model  Hospital Run?  OPO Run?
    40. 40. Launching the Organ Regeneration Laboratory at TGH OR (Oct 2011) – assessment and repair of all organs for clinical useLung Heart KidneyLiver
    41. 41. Number of Transplants 0 20 40 60 80 100 120 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97Year 98 99 0 0 0 1 0 2 0 3 0 4 0 5 0 6 Number of Transplants/ year TLTP 0 7 0 8 0 9 1 0 1 1
    42. 42. Utilization vs Outcomes 40 Utilization of donor lungs 30 day mortality 30% 20 10 0 01 02 03 04 05 06 07 08 09 10 00 20 Year
    43. 43. Summary II• Era of “Personalized Medicine” for the organ• The opportunity to engineer better organs for transplantation• Improve the number of organs we can use• Improve the quality, safety and outcomes of the transplants performed
    44. 44. Thank you

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