Download LUNG TRANSPLANTATION

LUNG
TRANSPLANTATION
ISKANDER AL-GITHMI, M.D., FRCSC,
FRCSC (Ts & CDs), FCCP.
Assistant Professor of Surgery
Division of Cardiothoracic Surgery
King Abdulaziz University
History:
First human lung transplantation was
performed by Dr. James Hardy in June
1963 at the University of Mississippi.
Between 1963 & 1978, 38 lung transplant
were done around the world.
Two
recipients live longer than one month.
Lung and heart-lung transplantation were
introduced into clinical practice in 1981
CSA era.
History (con’t.)
First successful transplantation in the
world was done in 1983 at the
University of Toronto. J. Cooper
Over 15,000 lung transplantation have
now
been
performed worldwide.
(ISHLT) statistics.
What Are Lung
Transplantation For?
Indications:
Obstructive air way disease (29%)
- COPD
- Alpha 1 antitrypsin deficiency
Idiopathic pulmonary fibrosis (19%)
Septic pulmonary disease (16%)
- Bronchiectasis
- cystic fibrosis
Primary pulmonary hypertension (11%)
Other Varieties (11%)
e.g. - sarcoidosis
- lymphangioliomyomatosis
(LAM)
- eosinophilic granuloma
Who are not
transplantable?
Contra-indications:
Age > 65 years
Active smoking
Poor compliance with the treatment
Severe active infections (HIV,
Hepatitis B & C)
Con’t.
Active malignancy within the past two
years.
Drugs or alcohol abuse.
Dysfunction of major other organs
- renal dysfunction
- untreatable CAD or LV dysfunction
- liver dysfunction
Recipient Selective Criteria:
End-stage pulmonary disease with life
expectancy < 2 yrs.
Absence of severe extra pulmonary diseases.
Strong motivation towards the idea of lung
transplantation.
Severe functional limitation, but potential for
rehabilitation.
Excellent psychosocial support.
Donor Selective Criteria:
Age < 65 years
No significant lung diseases
Acceptable CXR
PaO2 > 300mm Hg on F102 1.0 and
PEEP 5 cm for 5 min.
Bronchoscopy - clear
Con’t.
Viral studies are negative (HIV and
Hepatitis B & C)
Donor – recipient size matching
Medical Conditions – Impact
on eligibility for treatment
Symptomatic osteoporosis
Corticosteroid
Nutritional issues
Psychosocial issues
Colonization of air ways with fungi or
atypical mycobacteria
Guidelines for Timing Referral
Chronic obstructive pulmonary disease and a1-antitrypsin deficiency amphysema
Postbronchodilator FEV1 < 25% predicted
Resting hypoxia: PaO2 < 55 to 60 mm Hg
Hypercapnia
Secondary pulmonary hypertension
Clinical course rapid rate of decline of FEV1 or life-threatening exacerbations
Cystic fibrosis
Postbronchodilator FEV1 < 30% predicted
Resting hypoxia: PaO2 < 55 mm Hg
Hypercapnia
Clinical course: increasing frequency and severity of exacerbations
Idiopathic pulmonary fibrosis
VC, TLC < 60-65% predicted
Resting hypoxia
Secondary pulmonary hypertension
Clinical, radiographic, or physiologic progression on medical therapy
Primary pulmonary hypertension
New York Heart Association functional class III or IV
Mean right atrial pressure > 10 mm Hg
Mean pulmonary arterial pressure > 50 mm Hg
Cardiac index < 2.5 L/min/m2
•Which transplantation
procedure?
Living Donor Lobar Lung
Transplantation (LDLT)
- The first living donor lung transplant
was reported in 1990. Throughout the
world there have been approximately
100 such procedure done to date.
- The outcomes for recipients are similar
to those who have received lungs from
Cadaveric donors.
- All living donor lung transplantation
have been done utilizing a single lower
lobe from each donor which account for
about 25% of TLC for each.
Recipients Selection for LDLT
- Similar as for cadaveric donors.
- All candidates are first assessed and
listed for cadaveric lung transplantation.
- Potential recipient must be large
enough to receive the lower lobe of an
adult donor – at least the size of an
average six year old (90 cm in height).
Selection of Potential Donors
- Age 18 – 60 years
- Blood group compatible with recipient
- Of sufficient size
- Have normal lungs by clinical, radiographic
and physiological assessment.
Con’t.
- No other significant medical illnesses
- No history of hepatitis or HIV
- Be willing to undergo complete psychological
and psychiatric assessment.
- Be willing to undergo complete physical
assessment.
What Are the Benefits of
LDLT?
- To reduce the number of patient dying while
awaiting cadaveric transplantation.
- Ability to schedule surgery on a non-urgent
basis.
- Ability to time transplantation before the
recipient becomes too ill.
Con’t.
- Shorter ischemic times.
- Avoidance of hemodynamic instability
associated
with
cadaveric donor.
maintenance
of
Operative goals:
The operation should provide the
highest degree of operative safety and
the greatest cardio pulmonary
rehabilitation.
Is the lung
transplantation safe?
Complications:
Early graft dysfunction – is an acute
lung injury that is related to preservation
and ischemia reperfusion.
- referred to a clinical scenario as
pulmonary
infiltrate
and
poor
oxygenation.
- main consideration are rejection and
infection.
Con’t.
Airway complications:
- Dehiscence
- Stenosis
- Bronchomalacia
Con’t.
Rejection
- is the single most important limitation
to long-term survival.
- Acute rejection
* incidence – high
* infrequently fatal
* the principal risk factor for chronic
rejection
Why might the lung be
prone to rejection?
Con’t.
- The lung has an extensive vasculature
and circulating immune system.
- The lung is constantly exposed to
extrinsic infectious agents.
Con’t.
Infection
- is the leading cause of early and late
morbidity and mortality.
- wide spectrum of pathogens.
- bacterial pneumonia and CMV
pneumonitis have been the most
problematic.
Why is the lung allograft so
prone to infection?
Con’t.
- The lung allograft is denervated – cough
reflex is depressed.
- Mucociliary clearance is depressed.
- Lymphatic drainage is disrupted.
- Immunisystems are suppressed by anti
rejection medications.
Con’t.
Lymphoproliferative Disease (PTLD)
- the prevalence is 6%
- most cases developed in the first year
- the risk has been marked by increased
in recipient who have had EBV-sero
negative before transplantation and
have acquired a primary EBV infection
afterwards.
Con’t.
Outcomes
- gauged by survival
- quality of life
- cost-effectiveness
Con’t.
Quality of life
- the usual way of measuring the quality
of life for lung transplantation is the
improvement of pulmonary function test.
Con’t.
Cost and Cost-effectiveness
Analysis conducted at the University of
Washington Medical Center
- mean charge was $164,989
- the average charges to post-transplantation
care were $16, 628 per month during first 6
months and $5,440 per month during the 2nd
month.
- Lifetime cost was projected to be $424,853
Con’t.
Conclusion:
- lung transplantation has expanded
rapidly in the last decade.
- chronic allograft rejection is a major
impediment to long term survival.
- progress in immunobiology will likely
determine the state of the art.