- The document discusses principles for managing multi-organ donors to optimize organ preservation for transplantation. It emphasizes cardiovascular and pulmonary management to minimize donor organ injury. - The SALT protocol increased lung donors and transplants by improving donor lung recruitment and classification. It showed donor lungs previously deemed "poor" could be used if given recruitment maneuvers. - New approaches like ex vivo lung perfusion now allow for evaluating and potentially repairing marginal donor lungs before transplantation instead of immediate decline. This may help increase the utilization and outcomes of donor lungs.

1. Lung Allograft Procurement Principles,
Additional Donor Options and Future
Directions
Marcelo Cypel MD MSc
Assistant Professor of Surgery
Staff Surgeon
Division of Thoracic
University of Toronto
University Health Network
Marcelo.cypel@uhn.ca

2. Overview
1. Principles of management of the multi-organ
donor
2. Principles of Lung Preservation
3. How can we improve on current practice?
• Changing the paradigm: diagnosis,
treatment, personalized medicine
• Ex vivo organ repair

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. SALT
American Journal of Respiratory and Critical
Care Medicine 2006;174:710174:710--716716

5. SALT protocol
•Education: “Every donor is a potential lung donor”
•Alveolar recruitment: pressure-controlled ventilation at an inspiratory pressure of
25 cm H2O and positive end-expiratory pressure of 15 cm H2O for 2 h. Ventilator
then switched to conventional volume control ventilation with a tidal volume of 10
ml/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 negative
fluid 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. 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. Current Concepts in the Care
of the Multi-Organ Donor

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!

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. • 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

19. Intraoperative Management
• Same principles as ICU management
• Maintain optimal organ perfusion and O2
delivery
• Avoid inappropriate volume loading
• Neuromuscular paralysis - spinal reflexes

20. 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

21. 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

22. 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

23. How can we improve on current practice?

24. Cold
Ischemia
Brain death
Mechanical
Ventilation
Activation of
Pneumonia Inflammation and Hypotension
Coagulation
Aspiration Trauma
Reperfusion Induced
Lung Injury

25. Severe Primary Graft Dysfunction (PGD)

26. CURRENT PRACTICE IN ORGAN SELECTION AND
MANAGEMENT
Donor
Management
Decline
Organ
Decision Procurement
 Slows down death
Cold Static Unable to assess function
Preservation
(Questionable organs
are declined at
procurement)
Transplantation

27. 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%

28. 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

29. Normothermic Ex Vivo Lung Perfusion
(EVLP)
• Time to accurately assess - diagnose
• Option to treat/repair/recover
• Opportunity to reassess - confirm results
of treatment

30. 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 DCD
Transplantation
Decline

31. NEJM, April 14th 2011, vol. 364, no. 15, pp. 1431-1440.
32

32. 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;

33. TORONTO EX VIVO LUNG
PERFUSION (EVLP) SYSTEM
Perfusion : 40% CO
Ventilation: 7cc/kg, 7BPM, PEEP 5, FiO2 = 21%
J Heart Lung Transplant 2008; 27(12):1319-25.

34. Normothermic Ex vivo Lung Perfusion in
Clinical Transplantation – HELP Trial

36. EVLP function was stable in transplanted lungs
(n=20)

37. Bronchoscopy

38. LUNG X-Ray

39. Resolution of pulmonary edema during
EVLP
1h EVLP
Donor P/F 230
3h EVLP
Recipient P/F 420

40. Early outcomes were similar in the 2 groups
NEJM, April 14th 2011

41. 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

42. How Can We Apply This Clinically?
• Organ Repair Center Model
 Hospital Run?
 OPO Run?

43. Launching the Organ Regeneration Laboratory
at TGH OR (Oct 2011) – assessment and
repair of all organs for clinical use
Lung Heart
Kidney
Liver

45. Number of Transplants
0
20
40
60
80
100
120
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
Year
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

46. 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

47. 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

48. Thank you