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Lung Transplantation

Alper Toker, M.D.Istanbul University

Istanbul Medical SchoolDepartment of Thoracic Surgery

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1963 (Hardy)

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First successful heart lung transplantation 1981

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Single lung transplantation 1985

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Sequential bilateral lung transplantation

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Lung transplantations region/year

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200

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1600

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85

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86

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91

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94

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95

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Nu

mb

er o

f T

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spla

nts South America

North America

Europe

Australia

Asia

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Lung transplantation in the world

Report of ISHLT year 2003 : • 931 bilateral lung transplantation• 772 single lung transplantation• 74 heart-lung transplantation

3 years survival• 1994-1998: % 55.7• 2000-2003: % 63.3

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Survival after lung transplantaion (1983-2000)

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25

50

75

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Years Post Transplantation

Sur

viva

l (%

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Bilateral lung tx

Single lung tx

All kind of lung tx

Bilateral 1/2-life = 4.5 YılSingle: 1/2-life = 3.6 YılAll Transplantations: 1/2-life = 3.8 Yıl

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Indications in years

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Myopathy

19821983198419851986198719881989199019911992199319941995

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1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Transplant Year

% o

f T

ran

spla

nts

Cystic Fibrozis IPF Emphysema A1A PPH

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Discussions in the country

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Transplantation and Turkey until January 2004 Karakayalı H and Haberal M. Transplant Proc, 2005

In 28 centers• 6686 renal• 696 liver• 13278 cornea• 2883 bone marrow• 132 Heart• 185 Cardiac Valve• 15 Pancreas

» Coordinating organ transplantation in Turkey:effects of national coordination center. Tokalak I, Prog Transplant 2005

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Outmoded attitudes toward organ donation among Turkish Health Care professionals

Topbas M,Transplant Proc, 2005

• Residents, nurses and interns• Rate of organ donation % 2.2

• No idea (%28.7)• Organ trading (%22.1)• Religious reasons (% 21.6)

• % 59 of the attendes would ask for an organ for himself if he needs.• % 57.6 of the attendes would not donate his realtive’s organ• This population should be the leading people in organ donation.

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Solution to organ shortage• The solution of Organ shortage in Turkey: Trained

transplant coordinators. Yücetin L, Transplant Proc 2004– 14 hospitals have tx coordinators – 88 % of donors are from these 14 hospitals– 65 % of donors are from 2 cities– There should be 1675 donors – In year 2002 there were 100 donors– 200 coordinators

• The role of the transplant coordinator on tissue donation in Turkey. Yücetin L. Transplant Proc, 2004

– 50 different tissues from a single donor– No coordinator for tissue transplantation– Skin, tendon, valve, cornea and bone

• How to improve organ donation in Mesot Countries Shaheen FA, Ann Transplant 2004

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Middle East Society for organ transplantation (MESOT) Transplant Registry, Masri MA ve ark. Exp. Clin Transplant, 2004

• 1986 Muslim theologist Al Aloma declared that donation from a cadaver is allowed (Amman Declaration)

• Transplantaion begin in Mesot Area except Egypt• The rate of organ donation card in Saudia is 10%• 5088 renal transplant per year• Liver, heart, pancreas and lung transplantion.

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Standart Donor

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Changing indications in donors

Marginal Donor Low PaO2: (225 – 300 mmHg)

High PaO2: 300 mmHg and over

Age over 50 years

Hbs Ag

Non-heart beating (9 – 12 hours ischemia)

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Indications of lung transplantation

• Obstructive Lung diseases– Emphsema– Alfa 1 antitripsin deficiency– Obliterative bronchiolitis

• Suppurative lung diseases– Cystic Fibrozis – Bronchiectasis

• Fibrotic lung diseases– IPF– Sarcoidozis– Collagen vascular diseases– Alveoler microlithiasis– Lymphangioleiomyomitosis

• Pulmonary hypertension– Primary pulmonary hypertansion– Eisenmenger Syndrom– Thromboembolic pulmonary hypertansion– Pulmoner veno occlusive diseases

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Indications

• Emphysema / Alpha-1 AT deficiency FEV1< 25% predicted

PaCO2 > 55 mmHg+/- cor pulmonale

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Indications

• Cystic Fibrozis / BronchiectasisFEV1 < 30 % predictedIf FEV1 > 30% predicted, Decline in

FEV1 or increased number of hospitalistions and periods or

• PaCO2 > 50 mmHg

• PaO2 < 55 mmHg

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Indications

• Pulmonary fibrozisUnsuccessful immunosuppressive therapy

• VC (TLC) 60-70% predicted• Diffusing Capacity of Lung for Carbon Monoxide• (DLCO) < 50% predicted• Early acceptance for the tx programme

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Indications

• Primary Pulmonary Hypertension– 2 years survival %60 and median time 2.8 years– NYHA Class 1 ve 2; median survival 6 years

NYHA III or IVCI < 2 L/min/m2RA pressure > 15 mmHgMean PA pressure >55 mmHgIncreased Bilirubin

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Indications

• Pulmonary hypertension and congenital heart diseases

Eisenmenger Physiology(right to left shunt)

• Timing is difficult.

• Symptomatology.• Syncope, hemoptyzis, chest pain, arryhtmia,

cyanosis, polycythemia.

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Contrindications

• Multisystem diseases• Active infection• Hepatic and renal disease (creatine clearance

50 mg/ml/min)• >20mg prednisolone/daily• Malignancy (in 2 to 5 years)

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Contrindications

• Obesity or Cachexia: 20% of ideal weight • Drug abuse or alcoholism• Severe psychiatric disease• Smoking• CAD or valve disease

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Contrindications

• Severe chest wall deformity• Previous thoracic surgery*• Hepatitis B or C infection

• Symptomatic osteoporozis

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Contrindications and age

• Single lung 65 years• Bilateral lung 60 years• Heart - Lung 55 years

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2 single lung transplantations vs. 1 bilateral lung transplantation ?

Anyanwu AC et al. Does splitting the lung block into 2 SL grafts equate to doubling the societal benefit from bilateral lung donors?… Transplant Int 2000;13:S201-2.

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Surgical procedures

• Single lung transplantation

– Less morbidity, unilateral thoracotomy – Problems (Hyperinflation /infection/ cancer

risk of the native lung)

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Hyperventilation of the native lung

• Does donor lung cause a detoriation in the functions of native lung ?

Weill D et al. Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema. J Heart & Lung Transplant 1999;18:1080-7

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Surgical procedures

• Bilateral lung transplantations• Bilateral sequential lung Tx• Bilateral lung Tx

– Cystic Fibrozis,– Bronchiectasis,– PPH,– COPD.

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Surgical Procedures

• Heart Lung Transplantation; En-bloc– PPH, – Congenital heart disease

Survival is short, waiting list is long

( Avoidance from Heart – Lung transplantation in PPH)

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Single lung vs Double Lung (Emphysema)

• Short waiting list• Simple operation

• Long waiting list• Risky and long

operation • Better survival

Meyer et al. Single Vs Bilateral, Sequential Lung Txp for End-Stage Emphysema… J Heart & Lung Txp 2001;20:935-941

Bando et al. Comparison of outcomes after single & bilateral lung transplantation in obstructive lung disease. J of Heart & Lung Txp 1995;14:692-8

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Immunosuppresion (induction)

• Azathioprine 3-4 mg/kg pre-op

• Methylprednisone 500 mg with first lung transplatation, 125 mg iv x 3 for 24 hours

• Rabbit anti-thymocyte globulin (RATG) 2 mg/kg x 3 post-op

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Immunosuppresion (maintanence)

• Prednisolone (From 0.6 mg/kg to 0.2 mg/kg after 2nd day)

• Cyclosporine A: 3-5 mg/kg acc. to serum level

• Azathioprine 2-3 mg/kg

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Complications

• EarlyTheatre (hemorrhage )Ischemia/reperfusion injuryHyperacute rejection (HLA abs)Anastomosis problems

Acute rejection (+/- changes in PFT)

Infection (bacterial, viral, fungal)

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Ischemia reperfusion injury

Primary graft disfonction (PGD)• Leading cause of early posttransplant mortality• UNOS/ISHLT PGD % 10.2• Mortality % 42• No PGD rate of mortality is %6

Risk factors• Ischemic time more than 330 minutes• PaO2/FiO2 in posttransplant 6th hour • Recipients need for inotropics• PaO2/FiO2 of donor• Age of Donor

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Prognostic factors in PGD

• PaO2/FiO2 posttransplant 6th hour• Increasing CVP in first posttransplant 3 days

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Acute rejection

• Bronchoscopic follow ups (2,4,8, 12 weeks & 6 and 12 months)

• Methylprednisone bolus 500-1000 mg X 3

• Rebronchoscopy 2-3 weeks later

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Infectious complications

• Bacterial, viral, fungal• >50% bacterial, 10-35 % within first two weeks• Cultures of donor lung• If recipient was a cystic fibrozis patient treatment

acc. to last culture.

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Complications

• Early • Side effects of the medication• (Hypertension, Renal failure, tremor, hair growth,

bone marrow suppression, hypercholesterolemia, diabetes, osteoporosis)

• Delayed gastric emptying, aspiration.

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Complications

Late– Chronic rejection / obliterative bronchiolitis (FEV1,

FEF25-75, FEF50, Slope of N2 washout)

– Infection (generally Pseudomonas aeruginosa)

– Post-transplant lymphoma– Persistant side effects

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Results after transplantation

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20%

40%

60%

80%

100%

1 Year (N = 4,188) 3 Years (N = 2,486) 5 Years (N = 1,368)

Retired

Not Working

Working Part Time

Working Full Time

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Conclusion

• Lung transplantation is not something magic

• The leading cause of mortality is PGD .

• < 50% 5 years survival

• Immune-mediated rejection is limiting factor

• Progress in immonology will dominate the results in lung transplantation